Vaccines & Biologicals Annual Report 1999

VACCINES AND BIOLOGICALS

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WHON&B/00.01 English only

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DEPARTMENT OF VACCINES AND BIOLOGICALS

The Department of Vaccines and Biologi,cals thanks. the donors whose unspecified financial support has made the production of this document possible.

Ordering code: WHON&B/00.01 Printed: April 2000

This document is available on the Internet at: www.vaccines.who.int/vaccines-documents/

Copies may be requested from: World Health Organization

Department of Vaccines and Biologicals CH-1211 Geneva 27, Switzerland

Fax: +22 791 4193/4192 E-mail: vaccines@who.ch

© World Health Organization 2000

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The views expressed in documents by named authors are solely the responsibility of those authors.

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lines represent approximate border lines for which there may not yet be full agreement.

Design & Layout: 1:N Communications, Morges, Switzerland

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Contents

Glossary

Acknowledgements

1. Director's statement

2. Highlights of 1999 2.1 New look to departmental structure

ANNUAL REPORT 1999

[I]

2.2 The Global Alliance for Vaccines and Immunization 2.3 New vaccines 2.4 New culture of immunization safety 2.5 Polio eradication - nearly there! 2.6 Advice from the Strategic Advisory Group of Experts 2.7 AMRO and the World Bank 2.8 Funding vaccines in the Americas 2.9 On the move again

3. New structure of the Department

4. The Global Alliance for Vaccines and Immunization

5. Biological standardization 5.1 Recommendations for the production and control of oral polio vaccine 5.2 Harmonization of antigen content and potency measurement of diphtheria and

tetanus vaccines 5.3 Criteria for quality control of oral cholera vaccines 5.4 Standardization of serological assays for the evaluation of immune responses to

pneumococcal and meningococcal conjugate vaccines 5.5 Progress with interferon and cytokine standards 5.6 International standards

6. Innovation 6.1 Vaccine research 6.2 Introduction of new vaccines

7. Immunization systems 7.1 Introduction 7.2 Defining the elements of an immunization service 7.3 Supply and quality 7.4 Logistics and the cold chain 7.5 Surveillance 7.6 Immunization coverage 7.7 Target diseases 7.8 Communication and advocacy 7.9 Service delivery

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V

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1 1 1 1 1 2 3 3 3 3

4

6

8 8

9 10

10 10 11

12 12 16

23 23 23 23 27 30 33 42 46 47

DEPARTMENT OF VACCINES AND BIOLOGICALS

7.10 Financing 7.11 Health sector reform 7.12 Immunization safety priority project

8. Accelerated disease control 8.1 Progress towards global polio eradication 8.2 Measles control 8.3 Neonatal tetanus 8.4 Vitamin A supplementation

Annex 1: Documents produced by the V&B Document Centre during 1999 Annex 2: Internet information

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49 51 53

59 59 71 80 82

85 89

Glossar ACHR ACIH AD AEFI AFP AMRO ATT AVI BASICS BBC BCT BCG CBER CDC CFC CFI CIDA CRS DANIDA DFID DTP ECBS ELISA EPI FDA GAVI GIS GMP GFCV GTN Hib HPIC HRS HSR HTP HVI ICC ISSS IFA IVR JICA MAPREC MECACAR MMR MNT MT NCC NCL NFP NID NORAD NPEV NRA

ANNUAL REPORT 1999

Advisory Committee on Health Research (SEARO) Agency for Cooperation in International Health auto-disable (syringes) adverse event following immunization acute flaccid paralysis Regional Office for the Americas (WHO/PAHO) Access To Technologies (Team) Accelerated Vaccine Introduction Basic Support for Institutionalizing Child Survival British Broadcasting Corporation Blood Safety and Clinical Technology Bacillus Calmette-Guerin (vaccine) Center for Biologics Evaluation and Research United States Centers for Disease Control and Prevention chlorofluorocarbon Canal France International Canadian International Development Agency congenital rubella syndrome Danish International Development Agency Department for International Development diphtheria-tetanus-pertussis (vaccine) Expert Committee on Biological Standardization enzyme-linked immunosorbent assay Expanded Programme on Immunization Federal Drug Administration (USA) Global Alliance for Vaccines and Immunization Graphic Information System good manufacturing practice Global Fund for Children's Vaccines Global Training Network Haemophilus influenzae type b Highly Indebted Poor Countries (initiative) Human Resources Services health sector reform Health Technology and Pharmaceuticals (cluster) HIV Vaccine Initiative lnteragency Coordinating Committee Immunization Safety Surveillance System Information for Action system lntercluster Vaccine Research (initiative) Japanese International Cooperation Agency mutant analysis by polymerase chain reaction and restriction enzyme cleavage Middle East, Central Asia and Caucasian Republics measles-mumps-rubella (combined vaccine) maternal and neonatal tetanus maternal tetanus national certification committee national control laboratory not-for-profit national immunization day Norwegian Agency for Development Cooperation non-polio enteroviruses national regulatory authority

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NT OECD OPV PATH PMS RFI QSB SAGE SEDES SIGN SMO SNID sos SWOT TAG TB TCG TOR TECHNET TT TST UNICEF UNRWA USAID V&B VAD VAM VII VVM WWW

DEPARTMENT DF VACCINES AND BIOLOGICALS

neonatal tetanus Organization for Economic Cooperation and Development oral polio vaccine Program for Appropriate Technology in Health Post Marketing Surveillance Radio France Internationale Quality Assurance and Safety of Biologicals (Team) Strategic Advisory Group of Experts Departmental Health Services (Bolivia) Safe Injections Global Network surveillance medical officer subnational immunization day sustainable outreach services strengths, weaknesses, opportunities and threats Technical Advisory Group tuberculosis Technical Consultative Group Special Programme for Research and Training in Tropical Diseases Technical Network for Logistics in Health tetanus toxoid time-steam-temperature (indicator) United Nations Children's Fund United Nations Relief and Works Agency for Palestine Refugees in the Near East United States Agency for International Development Department of Vaccines and Biologicals Vaccine Development (Team) Vaccine Assessment and Monitoring (Team) Vaccine Independence Initiative vaccine vial monitor World Wide Web

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ANNUAL REPORT 1999

Acknowledg_em_e_nt_s _____ _

The World Health Organization would like to thank:

The Governments of: Australia Belgium Canada China (the People's Republic of) Denmark Finland France Germany Ireland Italy Japan Korea (the Republic of) Luxembourg Netherlands New Zealand Norway Spain Sweden United Kingdom of Great Britain and Northern Ireland United States of America

And: 3M, Denmark Agency for Cooperation in International Health, Japan American Association for World Health, USA Atlas Medical Resources Corporation, Canada Becton Dickinson and Co., USA Bill and Melinda Gates Children's Vaccine Program, USA Centre International de l'Enfance et de la Famille, France Children's Vaccine Initiative CIP Industries International, South Africa De Beers, UK Electrolux AB, Sweden Electrolux, Luxembourg International Development Research Centre, Canada International Federation of Pharmaceutical Manufacturers Associations International Foundation for the Millennium Fund, Switzerland Lifelines Technologies Inc., USA Ms Martina Hingis Micronutrient Initiative Organization of Petroleum Exporting Countries (Fund for International Development)

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DEPARTMENT OF VACCINES AND BIOLOGICALS

Pa Hu Oy, Finland Program for Appropriate Technology in Health, USA Rhein Biotech NV, Netherlands Rockefeller Foundation Rotary International Rotary. of Japan Saatchi and Saatchi, UK Shinnyo-en, Japan Smith Kline Biologicals, Belgium Task Force for Sight and Life, Switzerland The World Bank Joint United Nations Programme on HIV/AIDS (UNAIDS) United Nations Children's Fund (UNICEF) United Nations Development Programme (UNDP) United Nations Fund for International Partnerships (UNFIP) United States Agency for International Development United States Centers for Disease Control and Prevention Univec, USA Vestfrost, Denmark

Photography:

Page 53: All other photos:

Anthony Battersby, Feilden, Health System Analysts (FBA) UK WHON&B

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ANNUAL REPORT 1999

1. Director's statement

I n my last report I highlighted the profound changes that accompanied the creation of the

new Department with all the accompanying read­justments. Last year we were restructuring; in 1999 we have been getting down to business. The pace has been set by the Director-General, Dr Gro Harlem Brunddand. For the Department of Vaccines and Biologicals it has been a phase of con­solidation in which staff have been adjusting to their new roles and activities. Some appointments still have to be made but, by and large, key staff have been appointed and are functioning well.

I am convinced that the cornerstones on which our work must be based are that immunization:

■ is the right of every child; ■ contributes to alleviating poverty; and ■ is a cost-effective investment in health.

These justifications are of particular relevance at a time when the international community is becom­ing increasingly concerned with human rights and when governments are striving to meet the O ECD target of halving poverty by 2015.

The bench-to-bush strategy of the Department is implemented by the Quality Assurance and Safety of Biologicals Team (QSB), the Vaccine Development Team (VAD), the Vaccine Assessment and Monitoring Team (VAM), the Access to

Technologies Team (ATT), and the Expanded Programme on Immunization (EPI).

The teams' efforts are aimed at achieving three major objectives: Innovation, i.e. facilitating the development of new vaccines, simplifying immu­nization and accelerating the introduction of new and improved vaccines; improving Immunization Systems, i.e. increasing overall immunization cov­erage to 90%, strengthening the system for

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epidemiological surveillance, assuring the safety of immunization, ensuring the functioning of cold chain and logistics systems and strengthening finan­cial mechanisms; and Accelerated Disease Control by eradicating poliomyelitis by the end of the year 2000, reducing measles cases worldwide by 90%, eliminating neonatal tetanus and increasing the use of vitamin A supplements.

Each of our major objectives contains a time-limited priority project, the work of which cuts across the spectrum of activities undertaken by the Department and thus requires the expertise of each team. The Department, along with our partners, is justifiably proud of spearheading the polio eradication effort. This global priority for all our participating partners is being given the highest possible priority within WHO and UNICEF and is enjoying support from the top level in both organizations. Excitement mounts as we head towards the finishing line. Much more is written about this later in the report.

We are also concentrating our activities on Accelerated Vaccine Introduction (within the Innovation objective) and Immunization Safety (within the Immunization Systems objective). These projects are strongly supported by partners such as bilateral and multilateral development agen­cies and international organizations (e.g. UNICEF, the World Bank, PATH, the Bill and Melinda Gates Children's Vaccine Program and the Joint United Nations Programme on HIV/AIDS).

The aim of the Accelerated Vaccine Introduction project is to hasten the introduction of specific vac­cines by developing the infrastructure, capacity and collaboration necessary to make new vaccine intro­duction an integral part of global immunization practice. The ultimate goal is the timely introduc­tion of vaccines of public health importance into the developing world.

DEPARTMENT OF VACCINES AND BIOLOGICALS

I could not present this report without acknowl­edging the teamwork that supports our endeavours in every WHO Region and at country level. We enjoy the participation of excellent people operating at various levels throughout the health infrastruc­ture in almost every country, making possible the task of reaching all target groups. I sincerely thank all of you. I am also delighted to acknowledge that V&B is just one of many partners and organizations participating in or supporting immunization efforts everywhere. What a privilege it is to be part of this family!

The teams have made a considerable effort over recent months in order to refine the strategic plan, our blueprint for the next biennium and beyond. I am confident that we will reap rich benefits from this plan, which underpins all our strategic activi­ties, and I want to thank my team of professionals who have laboured to put it together.

One of the most important events during the year was the formation of the Global Alliance for Vaccines and Immunization (GAVI), the first board meeting of which was held on 28 October 1999 in New York. This followed a one-year review of immunization and vaccine development activities undertaken by major interested partners and the identification of three major gaps:

■ the 25 million children born every year in poor countries who still do not have access to rou­tine immunization;

■ the growing disparity between industrialized and developing countries in the number of vaccines available to children;

■ the lack of investment in vaccine research and development for diseases prevalent in poorer countries, such as HIV/AIDS, malaria and tuberculosis.

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GAVI is not a new organization but an alliance that will hold accountable each of the partners and the constituencies they represent. I believe that it will help to deliver more than the partners could have done acting independently. With Dr Brundtland chairing the Board of GAVI for the next two years, V&B will be the operating arm of WHO in the Alliance. We will collaborate closely with all part­ners to ensure that the objectives of GAVI become the immunization and vaccine development para­digm for the new decade.

It is worth reflecting on the lessons learned over the course of the last decades in the area of vaccines and immunization. Some of the world's most senior politicians are now focusing on vaccines, and this makes it clear to me that we are entering a new epoch where vaccines and immunization are being given an appropriate place in health care. It is there­fore with a feeling of tremendous optimism that I look towards a future in which people from every country work together for a world in which all those at risk are protected against vaccine­preventable diseases.

B. Melgaard Director, Department of Vaccines and Biologicals

ANNUAL REPORT 1999

2. Highlights of 1999

2.1 New look to departmental structure

During 1999 the Department of Vaccines and

Biologicals consolidated its structure and matrix

management. The five teams work in support of

three objectives. For each objective, specific targets

have been set and one of them has been identified

as a priority project. The work of the Department

will be guided by the "2000-2003 Strategy for

Vaccines, Biologicals and Immunization" developed during the year and endorsed by the newly estab­

lished V&B Strategic Advisory Group of Experts

(SAGE), which met in November.

2.2 The Global Alliance for Vaccines and Immunization

In October 1999 the Global Alliance for Vaccines and Immunization (GAVI) held its first Board

Meeting in New York. This was the last in a series of meetings that had been held throughout the

world since March 1998 with a view to redefining

and revitalizing the international coalition of public

and private partners supporting immunization and vaccine development. The meeting set the tone for

a new type of partnership and defined very ambi­

tious objectives for the coming decade.

2.3 New vaccines

Along with the Polio Eradication Initiative and the

Safety of Immunization project, Accelerated Vaccine

Introduction has been chosen as a priority project by V&B. Over a number of years it has become appar­

ent that new vaccines were being developed which

could be of tremendous value to the world commu­

nity but were unlikely to reach those in greatest

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need if market forces were left to control their intro­

duction. These vaccines include hepatitis B, Haemophilus influenzae type b (Hib), and most

recently, the pneumococcal conjugate vaccines.

Several other vaccines that have been available for

longer periods are underutilized (such as rubella and yellow fever vaccines). New vaccines will soon

be available for other diseases as well. Creative ways

are being sought to overcome the many barriers to

the introduction of these vaccines.

2.4 New culture of immunization safety

Safety of Immunization has been chosen as a priori­

ty project, in order to strengthen and optimize the impact of immunization services as part of health

delivery systems. The main target is to establish a

comprehensive system to ensure the safety of all

vaccines given in national immunization pro­

grammes by the year 2003. To achieve this it is nec­

essary to generate an overall culture of safety, enabling staff to prevent reactions, detect them

quickly, achieve rapid responses, and diminish the

negative impact of reactions on health and pro­

grammes. Countries are the primary focus for this

project. The partner coalition already includes UNICEF, the World Bank, PATH, the Bill and Melinda Gates Children's Vaccines Program, the

industry, and national and imernational profession­

al organizations. Several development and/or tech­nical agencies, such as the Canadian International Development Agency (CIDA), the Japanese

International Cooperation Agency (JICA), the United States Agency for International

Development (USAID), and the United States

Centers for Disease Control and Prevention (CDC)

are also participating in this project.

DEPARTMENT OF VACCINES AND BIOLOGICALS

2.5 Polio eradication - nearly there!

Of the three priority projects, the Polio Eradication Initiative has the highest profile. The global initiative to eradicate polio by the end of 2000 has become the largest public health initiative in history. It is spearheaded by WHO, Rotary International, CDC and UNICEF. The number of countries in which polio was endemic declined from 50 in 1998 to 30 in 1999. Of the three types of poliovirus, type 2 reached the verge of extinction, the only known remaining foci being in northern India. Polio incidence declined to the lowest levels ever, although reported cases increased slightly to

2

6659 because of improvements in surveillance and because outbreaks occurred in Angola and Iraq. Existing challenges to the initiative included main­taining activities of high quality, gaining access to children in countries affected by conflict, and ensuring political and financial support until certi­fication is achieved in 2005. The additional chal­lenge of ensuring sufficient oral polio vaccine ( 0 PV) emerged as a result of a marked acceleration in immunization activities. The public-private sec­tor partnership supporting the initiative expanded to include the Bill and Melinda Gates Foundation, Mr Ted Turner's United Nations Foundation, the World Bank, Aventis Pasteur and De Beers.

ANNUAL REPORT 1999

2.6 Advice from the Strategic Advisory Group of Experts

In the 1980s the Global Advisory Group advised

the Expanded Programme on Immunization (EPI),

and during the 1990s the Scientific Advisory Group of Experts advised the Global Programme for

Vaccines and Immunization. Because a number of

highly technical committees now advise WHO's

Department of Vaccines and Biologicals (V&B) on

specific issues such as polio eradication and immu­

nization safety, a need was perceived for a commit­tee that could take a broad view ofWHO's vaccine­

related work. The Strategic Advisory Group of Experts (SAGE) was therefore established. The first

meeting of the group, whose members were select­

ed for their expertise and geographical representa­

tion, was convened on 1-3 November 1999 in

Geneva to advise V&B on the three main strategic

aspects of its programme.

2.7 AMRO and the World Bank

AMRO's partnership in immunization with the

World Bank grew to include two more countries.

Since 1998, AMRO has been working with the World Bank in Bolivia and more recently in Peru

and Paraguay in the immunization component of

the Bank's health sector reform projects. The

AMRO/World Bank collaboration in Bolivia is part

of a ten-year project seeking to improve the cover­

age and quality of service networks, empower com­munities to improve their health status, and

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strengthen local capabilities to respond to health

needs. Overall implementation of the World Bank project is being moniwred by the use of eight indi­

cators, three of which are related to immunization.

2.8 Funding vaccines in the Americas

The AMRO Revolving Fund for Vaccine

Procurement is playing an instrumental role in the

rapid introduction of new and other vaccines in the Americas at affordable prices, such as Hib, measles­

mumps-rubella (MMR), hepatitis B and yellow fever vaccines. The dramatic cuts seen in the prices

of these vaccines have resulted directly from

economies of scale derived from bulk purchasing

through the Revolving Fund.

2.9 On the move again

We hope that we have a reputation in V&B for per­

petually looking for new ways of doing things. However, this year saw the majority of the Geneva Headquarters V&B staff on the move in another

way. Nearly everyone moved to a new office at least

once during 1999, although the telephone numbers

and e-mail addresses remained the same. By mid-2000 the entire Department will be housed on four

floors of the M building. There was general agree­ment that the move was a good opportunity to con­

sign large quantities of paper to recycling and to dust off a few old files. D

DEPARTMENT DF VACCINES AND BIDLOGICALS

3. New structure of the Department

V B was established in July 1998 as a & successor to the Global Programme

for Vaccines and Immunization and the Biologicals Unit. It belongs to WHO's Health Technology and Pharmaceuticals cluster (HTP), and its mission is to create a situation in which all people at risk are pro­tected against vaccine-preventable diseases.

During 1998 and 1999 an in-depth review of WHO's work in the area of vaccines and immu­nization was undertaken. This included a SWOT analysis of WHO activities in the field of immu­nization and vaccine development (i.e. a review of strengths, weaknesses, opportunities and threats), and there has been a definition of objectives and priorities with broad participation of the partners from within and outside WHO. This has resulted in the development of the "2000-2003 Strategy for Vaccines, Immunization and Biologicals". The Department is managed through a matrix structure whereby all teams work to support well-defined objectives, targets and priority projects (Fig. 1).

V&B teams

V&B comprises five teams, each of which is headed by a coordinator, has a mission statement and man­ages a work plan with identified products that con­tribute to the overall objectives of the Department (Fig. 1).

Quality Assurance and Safety of Biologicals Mission: To ensure the quality and safety of vac­cines and other biological medicines through the development and establishment of global norms and standards.

Vaccine Development Mission: To coordinate and facilitate the develop­ment of new vaccines and immunization-related technologies.

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Vaccine Assessment and Monitoring Mission: To assess the strategies and activities for reducing morbidity and mortality of vaccine-pre­ventable diseases.

Access to Technologies Mission: To reduce financial and technical barriers to the introduction of new and existing vaccines and immunization-related technologies.

Expanded Programme on Immunization Mission: To develop policies and strategies for max­imizing the use of vaccines of public health impor­tance and their delivery, to help regions and countries to acquire the necessary skills, compe­tence and infrastructure for implementing these policies and strategies, and to achieve disease control/elimination and eradication objectives.

Figure 1: Structure and objectives of the Department of Vaccines and Biologicals

Objectives of the Department of Vaccines and Biologicals Some 130 million children are born every year, of whom 91 million live in the poorest countries and 30 million do not have access to routine

ANNUAL REPORT 1999

immunization services. Approximately three mil­

lion children die every year from diseases that can

be prevented by available vaccines. Several million additional lives could be saved if effective vaccines

were developed against a range of maladies such as

AIDS, tuberculosis, acute respiratory infections and

diarrhoeal diseases.

This is why the Department of Vaccines and

Biologicals has organized its work to achieve the three objectives of Innovation, Immunization Systems and Accekrated Disease Control Progress made in each of these areas is critical to successfully

accomplishing the Department's mission and contributing to saving children's lives.

First of all, we need to make strides in Innovation. We must ensure that there is continued research

into and development of new vaccines against

diseases of public health importance, and that these

vaccines can be incorporated easily into existing immunization systems. We must also focus on new

vaccine delivery technologies and approaches, as

these advances are essential for improving the

performance of immunization services.

Immunization Systems have been established in all

countries. The services must now be strengthened. V&B will place more emphasis on improving the

quality of the services within the context of overall

health services and under the pressures of health

care reform.

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The overall aim of immunization is to bring dis­eases under control and, in some cases, to eliminate

or even eradicate them. We have defined an objec­

tive of Accekrated Disease Control whereby we concentrate our efforts on those diseases for which

routine immunization services are supplemented

with campaigns and special activities in order to

achieve control or an elimination/ eradication goal.

The present strategic plan is structured in three sec­

tions, each covering the work to be accomplished

under the headings of Innovation, Immunization Systems andAccekrated Disease Control For each

of these objectives a time-limited priority project has been selected through broad consultation with

V&B partners inside and outside WHO. As defined

in the shaded areas of Fig. 1, the priority projects are Accelerated Vaccine Introduction, Safety of Immunization and Polio Eradication Initiative.

The priority projects are three of the main targets identified by V&B. Nine specific targets have been

delineated and each has been assigned a well­

defined and measurable outcome or critical indica­

tor. The targets encompass the expertise and contri­butions of all five teams and therefore require

collaborative activities.

For each target a limited number of "products" have

been defined in this document, representing the

areas that need to be tackled in order to achieve the

target and the measurable outcome of the teams'

work. D

DEPARTMENT OF VACCINES AND BIOLOGICALS

4. The Global Alliance for Vaccines and Immunization

I Global Aliance for I Yacdnes and Immunization

T he Global Alliance for Vaccines and Immunization (GAVI) was established after a

series of meetings (World Bank, Washington, March 1998; Bellagio, Italy, March 1999; Seattle, USA, July 1999) and a one-year, in-depth review of immunization-related activities. This was undertak­en by major interested partners, including WHO, UNICEF, the World Bank, and the Bill and Melinda Gates Foundation's Children's Vaccine Program.

The underlying principle of the Alliance is that partners agree on a set of shared objectives to which they will all contribute through joint action.

The Alliance is not a new organization but a group­ing that broadens the partnership for vaccines and immunization and enhances the synergy between the partners' contributions.

The strategic objectives of the Alliance are to: ■ improve access to sustainable immunization

services; ■ expand the use of all existing cost-effective vac­

cines; ■ accelerate the development and introduction

of new vaccines; ■ accelerate research and development efforts on

vaccines and related products specifically need­ed by developing countries;

■ make immunization coverage an integral part of the design and assessment of health systems and international development efforts.

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Milestones have been adopted for each target so as to assure, within a specific time frame, a reduction in the inequalities of access to vaccines, and to reduce the preventable disease burden, especially among the poor.

The Alliance will operate through the following mechanisms: ■ a governing Board, initially of 12 members,

expressing the highest political commitment of partners and providing a forum for decision­making on common objectives and strategies;

■ a coordinating secretariat accommodated in the Geneva premises of UNICEF, facilitating the work of the Board and helping to ensure the involvement and representation of all bod­ies involved in immunization activities;

■ a working group consisting of dedicated staff attached to each of the major partners, ensur­ing that the decisions of the Board are translat­ed into operational actions appropriate to each lead agency;

■ task forces of limited duration, addressing spe­cific issues (three task forces with agreed terms of reference are currently operating, on coun­try coordination under WHO leadership, on advocacy led by UNICEF, and on financing led by the World Bank, and the Board has requested that an analysis of gaps in research and development be completed within a year);

■ a Global Fund for Children's Vaccines (GFCV), established in December 1999 with an initial grant of US$ 750 million from the Bill and Melinda Gates Foundation to facili­tate the financing of underutilized and new vaccines, the strengthening of the immuniza­tion delivery infrastructure, and research into and development of priority vaccines for poor populations and countries;

ANNUAL REPORT 1999

■ an international meeting to be held approxi­

mately every two years in order to bring togeth­

er the broader immunization community.

The GAVI initiative provides a unique opportunity for the international community to make clear sus­

tainable strides towards saving millions of children's

lives and protecting people's health against vaccine­

preventable diseases. Greater equity and timeliness in protecting the children of the poorest countries

with vaccines is the most important challenge facing GAVI. The Fund will be one of the new and power­ful tools intended to meet this challenge and devel­

op a renewed global commitment to immunization.

Well in advance of the formal launch of GAVI at the World Economic Forum in Davos, Switzerland,

on 31 January 2000, intense work was under way in

the participating organizations in order to:

■ develop and substantiate key outcomes (reduc­

tions in mortality and disease burden, develop­ment benefits, research and development);

■ outline a new strategy for immunization in

relation to health sector development;

■ develop a strategy for reaching those previous­

ly unreached, in the light of experience of the

polio initiative;

■ establish research and development priorities.

The partners in GAVI will build on a comprehen­

sive multi-year immunization plan within the health sector in each country, supported by a

national interagency coordinating committee. This

plan will be used to explore various tools for

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strengthening the financing of national immuniza­

tion services, including national resources, coordi­

nated support by multilateral and bilateral partners,

the use of concessional development bank loans,

and debt relief funds. Where appropriate, there will

also be support from the Fund (which should be

both a means of applying leverage for additional financial resources for immunization and a catalyst

for improved performance at the country level).

The Fund is thus only one of a number of financ­ing tools that should be used in support of a com­

prehensive and well-coordinated plan.

The main challenges facing GAVI partners are to:

■ improve immunization coverage, building on

lessons of the polio initiative;

■ reduce the gap between the rich countries and the poor countries in the number of vaccines

used for children;

■ find new tools to secure research and develop­

ment in relation to diseases prevalent in poor countries, such as malaria and HIV/AlDS.

Forging new partnerships for health and focusing on poor and marginalized populations, GAVI is

emblematic of the new way forward for WHO and

the HTP cluster. V&B is WHO's operating arm in

GAVI, fully contributing to the Alliance's objec­

tives. V&B works in close collaboration with the

partners of the Alliance in order to ensure increased

synergy and optimum use of resources and thus to achieve GAVI's mission of fulfilling the right of

every child to be protected against vaccine­preventable diseases of public health concern. D

DEPARTMENT OF VACCINES AND BIOLOGICALS

5. Biological standardization

B iological medicines, which include vaccines, blood products and biological therapeutics,

have played a dominant role in improving health and are expected. to make an increasingly important contribution .to public health in the twenty-first century. Recent scientific and biotechnological developments have opened the way to novel products, new production methods and highly sen­sitive assay procedures. However, the nature of bio­logicals, especially new vaccines and therapeutics, raises particular questions regarding their standard­ization and quality control. These relate to both efficacy and safety, not only for the individual recip­ient but also for the population at large. Such advances highlight the complex issues that surround the standardization and control of biologicals.

A major international scientific review of the field was undertaken in 1996 by the National Biological Standards Board of the United Kingdom in collab­oration with WHO. This review (Biological Standardization and Control. WHO/BLG/97.1) indicated a range of emerging products and tech­nologies and clarified the need for new approaches to the evaluation and regulation of biological med­icines. It was also a contributing factor in WHO's own external review of its arrangements for the standardization and control of biologicals (Review of the Remit and Activities of WHO in the Biologicals Field and of the Biologicals Unit: Report of the Review Team, October 1998). Both reviews emphasized the need for international collaboration and consensus on key issues related to the safety and quality of vaccines and other biologicals, and for continued support for regulatory research to protect public health.

WHO works closely in this area with its two International Laboratories for Biological Standards, namely the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, and the National Institute for Biological Standards

8

and Control, Potters Bar, United Kingdom, as well as with its Collaborating Centre in Biological Standardization, the Center for Biologics Evaluation and Research (CBER/FDA), Bethesda. The responsibility for adopting WHO Recommendations for biological substances used in medicine and for establishing WHO International Standards and Reference Materials rests with the WHO Expert Committee on Biological Standardization (ECBS), established in 194 7, which held its fiftieth meeting in October 1999. Many of the items considered at this meeting reflected the increasing number and complexity of biological medicines.

5.1 Recommendations for the production and control of oral polio vaccine

Revised recommendations (formerly requirements) for the production and control of oral poliomyelitis vaccine (OPV) were developed in 1999 and adopt­ed by ECBS. New quality control procedures have been introduced which have the potential to increase the stringency of control and lead to the production of even safer vaccines. This is an impor­tant consideration, given the considerable success of the polio eradication initiative. The new quality control procedures will also decrease the time taken to complete vaccine testing and will thus make vac­cines available for use more quickly. As the demand for OPV is higher than ever, any procedure that shortens the supply time is welcome.

For the first time a test for the molecular consisten­cy of production of a live virus vaccine is now avail­able. Mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC) quan­tifies the reversion of a key base, 472C, which cor­relates in type 3 poliovirus vaccine with the results of the WHO neurovirulence test. Studies of the

ANNUAL REPORT 1999

method coordinated by WHO have shown it to b.e

a standardized, robust and reliable procedure. The

results showed that MAPREC provided a very valu­able additional test for consistency of production, and the method was endorsed as the in vitro test of

preference for the control of poliovirus type 3 vac­

cine. Excellent progress is also being made with

MAPREC assays for poliovirus types I and 2 and

the possibility of introducing MAPREC for these

serotypes will be considered as soon as possible.

The discovery of the gene for the cellular receptor

for poliovirus led to the development of a trans­genic mouse, TgPVR21, susceptible to poliovirus

infection. A neurovirulence test for poliovirus vac­

cine has been developed in the T gPVR2 l transgenic

mouse line and the test in such mice was shown in studies coordinated by WHO to be a suitable alter­

native to the neurovirulence assay in simians for

poliovirus type 3. It has therefore been introduced

into the new recommendations. The possibility of introducing the mouse neurovirulence test for

poliovirus types I and 2 is being pursued.

The entire cycle encompassing basic scientific

research, method development, standardization and

the application of MAPREC, and the transgenic

mouse model, were paradigms for regulatory

research. This work clearly illustrates the need for long-term commitment of resources if significant

advances are to be made in the control and stan­

dardization of biologicals.

A period of international cooperation and consulta­

tion is now being initiated under the auspices of

WHO to provide for a smooth and effective adop­tion of the new methodologies imo quality control

procedures. This will involve:

■ appropriate training for people using the methods and the provision of proficiency pan­els of samples to enable laboratories to validate

their performance with the new tests; ■ monitoring the consistency of the new meth­

ods in different laboratories;

■ the identification and resolution of technical problems.

9

5.2 Harmonization of antigen content and potency measurement of diphtheria and tetanus vaccines

The diphtheria and tetanus vaccines are among the

most commonly used vaccines. Their use has result­

ed in a tremendous decrease in disease in both

industrialized and developing countries.

Nevertheless, fundamental problems exist in stan­

dardizing and controlling the potencies of these tox­oids globally, even when the International Standards are used, and different approaches have

been adopted by different countries. Some follow

WHO and European Pharmacopoeia procedures,

while others take the USA approach. There has also

been much activity in recent years in simplifying

the tests and reducing the number of expensive ani­

mals used in control testing.

Despite many attempts to harmonize requirements there is still no universally accepted potency assay.

This leads to problems in the international

exchange of these vaccines and in their licensing.

With the development of new combination vac­cines and the internationalization of markets the

need for harmonization of diphtheria and tetanus

potency tests is heightened. It is considered that a

unique opportunity exists for resolving this long­

standing issue. Agreement is also needed on the lev­

els of diphtheria and tetanus antigens appropriate

for adult/adolescent formulations, bearing in mind

the safety implications.

With a view to resolving these difficulties a WHO

working group was established in 1999 to review data on current tests, evaluate progress with alterna­

tive potency methods and develop a plan of action for harmonizing future approaches globally. It was

agreed to pursue the development of a simple,

robust and standardized assay for demonstrating the consistency of the immunologcal characteristics of vaccines, which could replace traditional assays in

lot release. This work is now in progress. Further

work ·will be needed to evaluate the value and

appropriateness of the specified limits of the current

WHO and European Pharmacopoeia potency

DEPARTMENT OF VACCINES AND BIOLOGICALS

assays. The working group emphasized that any proposed changes to current practice should not introduce difficulties similar to those experienced with the current approaches.

5.3 Criteria for quality control of oral cholera vaccines

Two oral cholera vaccines have recently been devel­oped and licensed in a few countries. One is a live attenuated vaccine, the other a formaldehyde-inac­tivated whole cell vaccine consisting of Vibrio cholerae O l cells, and, in some formulations, including recombinant B subunit. WHO has a par­ticular interest in the new cholera vaccines because of their potential to offer protection in emergency situations and because of the possibility of stockpil­ing vaccine for use at short notice.

A WHO working group met in 1999 to review cur­rent production and quality control procedures for these vaccines. It was concluded that two new sets of recommendations were required, one for each type of vaccine. The killed oral preparation was a new type of vaccine and there was no precedent for controlling it. It was agreed that control procedures should be scientifically relevant. This underscores the need to develop standardized methods and appropriate criteria for assessing quality, particular­ly in respect of safety and stability.

The current requirements for the parenteral whole cell cholera vaccine were considered inappropriate for the oral vaccines. This traditional vaccine is not recommended for use by WHO, and a recommen­dation was therefore made that the requirements be discontinued in order to avoid confusion and the possible use of inappropriate tests to control the new products. ECBS agreed to their discontinua­tion. Work is now required to develop more appro­priate quality control procedures for the killed oral vaccines.

10

5.4 Standardization of serologi­cal assays for the evaluation of immune responses to pneumococcal and meningo­coccal conjugate vaccines

The development and introduction of pneumococ­cal conjugate vaccine is a priority for WHO. Trials are being organized in developing and industrial­ized countries. In these and future studies, serologi­cal assays will play a pivotal role in the licensing procedure. A working group on the standardization of serological assays for pneumococcal conjugate vaccines met in 1999 to consider progress in this difficult but crucial area. There are two types of serological assays: a functional assay based on opsonic activity and an immunoassay based on ELISA. In order to standardize the assays a panel of sera has been prepared and is under evaluation in a small collaborative study for suitability as run con­trols. The intention is to use these reagents to cali­brate the assays. The possibility is also being con­sidered of establishing a standard WHO cell line for opsonic assays.

Similar difficulties exist in relation to the standard­ization and validation of serological assays for the evaluation of immune responses to conjugate vac­cines against Neisseria meningitidis serogroup NC. A working group is in place to coordinate activities in this area.

5.5 Progress with interferon and cytokine standards

A large and complex study has been undertaken in order to resolve longstanding problems with the cal­ibration of the current International Standards for interferon alphas and to see if a single standard might be suitable for the whole of this family of therapeutically important proteins. Statistical analy­ses of the data indicated that a number of important distinctions existed between the bioassays used and confirmed discontinuities among the International Units of some of the current WHO standards. The data were extensively discussed by the manufactur­ers of interferons, the WHO Consultative Group on Cytokines and ECBS. Agreement was reached that separate International Standards were still required for the different molecular species of inter-

ANNUAL REPORT 1999

feron alphas. The issue of the discontinuity of the

International Units has also been resolved to the

general satisfaction of the interested parties. As a result, new International Standards for the interfer­

on alphas were established by ECBS, minimizing as

far as possible any discontinuities with the units

most widely used in clinical practice and maintain­

ing the continuity of interferon products used for

research and therapeutic purposes.

ECBS also considered progress in the standardiza­

tion of other biological therapeutics and endorsed proposals to establish reference materials for a num­ber of these molecules. Given the rapidly expanding

cytok.ine field and the limited resources available for

developing standards, ECBS considered a policy to prioritize work in this area. A decision tree, devel­

oped by the WHO Consultative Group on

Cytok.ine Standards, was considered helpful and

was modified for use in setting priorities for work on all biological standards. There is increasing clin­

ical concern about patients who develop neutraliz­

ing antibodies to therepeutic proteins, including

cytok.ines, most of which are recombinant DNA

molecules. The measurement of immunogenicity

and the validation of methods for screening serum

and plasma samples remain controversial and this

area should be carefully monitored in the future.

Figure 2: WHO web pages on biological subtances

Biological Substances International Standards and Reference Reagents

Health TechnolQ!IY and Phamaceuticals homepage

11

5.6 International Biological Standards

In 1999, ECBS established 28 new or replacement

International Standards and Reference Materials

covering a wide range of products. Additionally, several International Standards and Reference

Materials that are no longer needed were discontin­

ued following a public consultative process.

The review of"WHO International Standards and

Reference Materials, initiated two years ago, has

now been completed and the catalogue has been fully updated and made available on the Internet

(http:/ /www. who. int/technology/biological.html) Fig. 1. The entire list was made available as an

interactive web page allowing searches to be made

either alphabetically or by class of substance. This

database allows easy worldwide access to the list of

WHO International Standards and gives relevant

information about the contents and characteristics of the reference preparations. Future developments

will include linkages to the laboratories holding

the reference materials and to relevant WHO

documents and publications and to reports in the scientific literature. D

0 WHO International Biological Reference Preparations

0 Meeting Reports

DEPARTMENT OF VACCINES AND BIOLOGICALS

6. Innovation

6.1 Vaccine research

For many years, research and development activities in the field of vaccines against major infectious dis­eases prevailing in developing countries have been undertaken by two WHO programmes, V&B and the Special Programme for Research and Training in Tropical Diseases (TDR), while work on HIV/AIDS vaccines fell under the responsibility of UNAIDS. Today, the UNAIDS HIV/AIDS vaccine unit has joined the HTP cluster at WHO and is known as the WHO-UNAIDS HIV Vaccine Initiative (HVI). The work of all these groups has now been consolidated into a single, interactive, integrated and efficient effort, termed the Intercluster Vaccine Research Initiative (IVR). A common strategy is being developed for: (a) pri­oritization of objectives, (b) rationalization and simplification of management structures and review systems, and (c) a single resource mobilization strategy for the support of activities agreed to be necessary for the accomplishment ofIVR objectives.

IVR will be compatible with WHO's priorities in tackling the diseases that cause the highest burden in developing countries (AIDS, malaria and tuber­culosis, these being among the highest priorities for WHO; and acute respiratory infections, diarrhoeal diseases and measles). This effort will be extended to areas often neglected by industry because of the lack of potential market return, for which WHO's role can be critical. These include dengue, leishma­niasis, shigellosis and schistosomiasis. IVR will also be concerned with new vaccination approaches to facilitate immunization.

IVR aims to make the best possible use of existing resources in a revamped, focused fashion. The cur­rent organizational and line management structures for V&B/VAD,TDR/CRD and HVI/HTP will remain the same, as IVR will operate on a func­tional matrix system. An IVR project leader is being

12

recruited and will be responsible for good function­al 'management, maintaining the overview, ensuring that interfaces mesh, troubleshooting, collating plans and reports and mobilizing resources

In this way, WHO's core competences are being harnessed to the task of consolidating efforts in vac­cine research ad development which will reduce the disease burden in developing countries. IVR is thus a good example of the new strategy of working across organizational boundaries within WHO and in external health organizations to deliver excellent results.

6.1.1 New tuberculosis vaccines

V&B provides support to tuberculosis vaccine development in the area of WHO's core compe­tence, i.e. normative guidance, coordination of the global research agenda and definition of required vaccine profiles. However, this is not enough. A number of research bottlenecks must be cleared before a new TB vaccme 1s introduced. WHO/V&B, having global outreach to both the vaccine research and vaccine user communities, is best placed to address some of them. The scientific gaps include:

• the need for preclinical vaccine evaluation models and facilities;

• the need for immunological markers indicat­ing that a vaccine provides protection from dis­ease;

• the need to identify and develop clinical trial sites where the efficacy of new vaccines can be evaluated in human populations where TB is endemic.

In all these areas V&B has established research net­works that are guided by a working group of high­level international experts. The following progress was made over the last year:

ANNUAL REPORT 1999

Preclinical models and facilities: A network of labo­ratories was established together with a system for

validating laboratory facilities that can perform ani­

mal testing of TB vaccines under standardized con­

ditions. A vaccine-screening model was designed

with a view to limiting the use of primates to a

strictly necessary minimum.

Immunological markers: A trial was initiated in order

to detect immunological differences in response to

BCG vaccination between a population where the vaccine protects (United Kingdom) versus one

where it is completely ineffective (Malawi). Comparison of the results of the two arms of the

trial should allow the identification of immunolog­

ical correlates of protection against TB.

Clinical trials: Guidelines for performing clinical

trials are being edited for publication. They include

very specific identification of potential geographical

sites and human populations that could be targeted for evaluation of a future TB vaccine.

6.1.2 A meningococcal serogroup A vaccine for Africa

The technology for producing a safe and effective

polysaccharide-protein conjugate vaccine for

serogroup A Neisseria meningitidis disease has been available for more than ten years, yet little progress

has been made towards achieving this goal. The dis­

ease is largely limited to persons living in the poor­

est countries of the world, and the potential returns

on investment are perceived by traditional manu­

facturers to be too low. Several vaccine companies

are developing multivalent meningococcal conju­gate vaccines that include a component for the pre­

vention of serogroup A disease. However, it is

unlikely that rhese vaccines will be available for the

prevention of disease in Africa. They are intended

for sale in industrialized countries and will be

expensive. It therefore seems unlikely that the pri­

vate sector will develop a meningococcal vaccine for use in Africa. Even if a commercial company

received funds from international donors its com­

mitment would be compromised by competing projects with a higher return on investment.

An attractive alternative for developing a meningo­

coccal A conjugate vaccine would be to establish a

not-for-profit (NFP) company funded by interna­

tional donors. It would be dedicated to the licens­

ing of a meningococcal A conjugate vaccine intend­

ed for use in Africa, and would serve as a model for vaccine or drug development against diseases that

primarily occur in poor countries where traditional market forces are insufficient to stimulate private

investment. An advantage of the NFP approach

would be its ability to focus on the development of

a single product. Thus delays from work on com­

peting projects of higher priority could be avoided.

Another advantage would be that the NFP compa­

ny would be free to design the product specifically for use in Africa, rather than adapting a product

originally designed for an industrialized country.

For example, a meningococcal A conjugate vaccine

Figure 3: Cases of meningitis in the epidemic meningitis belt of Africa, 1950-1996

170000

140000

100000

80000

60000

40000

20000

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88 939 80743

DEPARTMENT OF VACCINES AND BIOLOGICALS

for Africa would require consideration of special problems of maintaining vaccine stability where refrigeration may not be dependable or where the practice of reuse of needles poses a major health risk. This matter is currently at an exploratory stage: potential partners are being consulted and a business plan is being prepared.

6.1.3 Measles vaccine research

Important progress has been made towards the def­inition of a global research strategy for the elimina­tion of measles. While obstacles to global measles eradication are perceived to be predominantly polit­ical and financial, there are also scientific and tech­nical questions. These include: the refinement of measles elimination strategies in the light of recent outbreaks in the Americas; the implications of the HIV epidemic for measles elimination, issues around injection safety, and concerns about the possibility that secondary vaccine failures will con­tribute to sustaining transmission in highly vacci­nated populations. The global priorities are to improve measles control in low-income countries, increase awareness of the importance of measles among industrialized countries, and conduct stud­ies on technical aspects of measles elimination strategies.

An inventory has been prepared of all measles-relat­ed research activities. This represents a step towards ensuring that all the priority research issues are addressed in good time and that the results are wide­ly distributed to support the development and implementation of strategies for measles control and elimination. Measles research studies have addressed the whole spectrum of priority issues for measles control and elimination, but in some key areas there are only a few studies or progress is slow. This is true for the areas of new safer vaccine delivery systems, vaccines for alternative routes, tests for differential diagnosis, rapid diagnostic field tests, and implica­tions of HIV infection. Developing countries accounted for 88 of the 210 studies (42%) in the inventory, and only 20% of the principal researchers in the studies conducted in developing countries were actually from developing countries. The prepa­ration of the inventory is a first step in a continuing process. We hope that it will encourage researchers all over the world to contact us.

14

6.1.4 Haemophilus influenzae type B and pneumococcal vaccines

VAD's work mostly relates to the planning and monitoring of l;uge field trials. In the Hib field, the Lombok Hib intervention study and - through sup­port from the International Vaccine Institute - Hib disease burden studies got underway during 1999. In the area of pneumococcal conjugate vaccines, two trials are currently ongoing - the trial of a 7-valent vaccine among the Navajo and Apache populations in the USA, and the South African trial of a 9-valent vaccine being conducted in Soweto (South Africa). Other pneumococcal trials are being planned, e.g. in the Gambia (using the 9-valent vaccine) and the Philippines (using an 11-valent vaccine). The Gambian trial is due to start in April 2000 and it will be the only trial to study all cause mortality as the primary endpoint. VAD has been closely involved with the development of the Gambian study as well as in the development of the trial site for the study to be performed in The Philippines.

In addition to the above activities the work of the Pneumococcal Vaccine Trialists Group, which was set up by WHO in 1997, expanded during 1999. Standardization of procedures for radiological examination, image storage and image interpreta­tion is now seen as a key outcome measure for pneumococcal vaccine trials and other internation­al groups are now relying on this group to resolve the longstanding problems in this area. In this area VAD is working in partnership with BCT to devel­op agreed guidelines that will eventually form the basis for future pneumonia burden studies that can be linked in interpretation with the current vaccine trials. In addition to this activity, another working group has been formed to work towards agreed guidelines for the conduct of economic evaluation in the context of pneumococcal and Hib vaccine trials.

Other acnvmes relate to defining pneumococcal burden in early infancy, such as the recent comple­tion and publication of a WHO sponsored multi­centre study of serious infections in young infants. Furthermore, work is ongoing to plan the next round of Hib and pneumococcal studies.

ANNUAL REPORT 1999

6.1.5 Diarrhoeal disease vaccines

Rotavirus: There is only one licensed vaccine that

has 85-90% efficacy against severe disease and 55% efficacy against all rotaviral gastroenteritis.

However, following the identification of a possible

association between the vaccine and intussusception

in September 1999, VAD immediately terminated

all WHO-sponsored rotavirus trials in developing

countries ( Bangladesh, India). In October 1999 the

United States Advisory Committee on Immunization Practices revoked its recommenda­tion for the use of this vaccine. However, there is an

urgent need for an effective vaccine in developing countries, where 650 000 children die each year

from rotaviral gastroenteritis. Data are needed on

the incidence and risk factors for intussusception in

developing countries, as well as on the attributable

risk of intussusception with the current vaccine. It

is also necessary to consider whether intussuscep­

tion will be associated with all rotavirus vaccines

and whether alternative vaccine schedules might be used to minimize or eliminate the risk.

Shigel/a: A live oral vaccine candidate against

Shigella jlexneri 2a (SC602) has been tested in phase 1 and 2 studies in North American adult volun­

teers. A single oral dose of the vaccine was shown to be safe and immunogenic. It conferred 100% pro­

tection against severe shigellosis and 50% protec­

tion against any diarrhoea after an experimental challenge with S. jlexneri 2a. An inpatient clinical

phase 1 study using the SC602 vaccine was com­

pleted in 20 healthy Bangladeshi adults. They were randomized to receive a single oral dose of 1 x 104,

1 x 105 or 1 x 106 cfu of SC602 or placebo in a

double-blind controlled trial. There were no signif­icant side-effects in any of the volunteers. None of

the volunteers had diarrhoea, fever or significant

abdominal pains.

Typhoid: An important development during the

last five years has been the transfer of the technolo­gy for production of typhoid (Vi) vaccine to China

and Viet Nam. China currently produces the vac­

cine in six of its vaccine production institutes.

Several phase 2 trials and two phase 3 efficacy trials

of the locally produced vaccine were performed. Each randomized, placebo-controlled efficacy trial,

involved over 100 000 participants and demon­strated levels of protection of about 70% during

approximately two years of follow-up. This was

15

similar to the level of protection observed for the

Aventis Pasteur Vi vaccine tested in Nepal and South Africa. Promising newer-generation vaccines

under development include both injectable subunit

and genetically engineered live oral vaccines. A Vi­

protein conjugate vaccine has yielded encouraging

results when given in two-dose regimens to United

States and Vietnamese volunteers. It has also been

safe and immunogenic when given as a single dose

to United States adults.

Cholera: Another line of development of killed oral cholera vaccine has been undertaken in Viet Nam by the National Institute of Hygiene and

Epidemiology, which, in collaboration with the

University of Gothenburg and SBL, has produced a killed oral whole cell vaccine similar to the Swedish

vaccine but lacking the cholera toxin B subunit. An

early generation version of this vaccine, which con­

tained only O 1 serogroup cells, conferred ca. 60%

protection against El Tor cholera when tested as a

two-dose regimen in an open field trial in Hue dur­ing the early 1990s. Interestingly, young children

were as well protected as older persons, in contrast

to the findings in Bangladesh for the Swedish BS­

WC vaccine, which did not protect young children

as well as older persons.

More recently, the Vietnamese killed oral whole cell

vaccine has been made bivalent (01 + 0139) by the

addition of formalinized 0139 killed whole cells.

This vaccine is similar to the first-generation

Vietnamese vaccine except that it is bivalent with respect to serogroups and that it contains twice the

content of El Tor 01 cells. Phase 2 studies of two­dose regimens of this vaccine in Hanoi demonstrat­

ed that the vaccine was safe and induced at least

fourfold vibriocidal seroconversions to the O 1 com­

ponent in ca. 60% of adults and ca. 90% of children aged 1-10 years. Because these anti-01 responses

were similar in magnitude to those seen in volun­teers concurrently given the monovalent SBL vac­

cine, it seems that the 0139 component of the vac­cine does not interfere with responses to the 01

component. Analyses of serum vibriocidal responses to the 0139 component have demonstrated sero­

conversions in ca. 40% of adults and ca. 60% of

children receiving the vaccine. A randomized, place­bo-controlled field trial of the effectiveness of a two­

dose regimen of this vaccine was initiated in March

1997 in Viet Nam. In this trial the effectiveness of a

two-dose primary series followed by boosting at two

DEPARTMENT OF VACCINES AND BIOLOGICALS

years is being evaluated in ca. 300 000 persons aged 12 months or more in Nha Trang.

6.1.6 South-East Asia Region

The Twenty-fourth Session of South-East Asia Advisory Committee on Health Research (ACHR) recommended that: WHO/SEARO should (i) explore strategic ways of enhancing intercountry cooperation in areas of vaccine production, research and delivery, and (ii) set up a working group or task force of experts with the purpose of proposing a vaccine policy that would be comprehensive and specific to the region.

The guiding principles of developing a regional vac­cine policy would be equity, self-reliance and regional solidarity. The policy should cover the areas of vaccination research, vaccine development, and vaccine mix as well as the sustainability of expanded programmes of immunization in Member States.

To this end, a core group was constituted and its first meeting was held in Bangkok on 11-12 October 1999. The group discussed various aspects of immunization programmes, · ranging from vac­cine selection to delivery. Among the subjects cov­ered were vaccine policy, the introduction of new available vaccines, disease burden of vaccine-pre­ventable diseases, supply of vaccines in emergencies, and re-emerging diseases.

The core group concluded that each country in the Region needed to develop a national vaccine policy, which should then form the basis of a regional policy. The national policy could be best developed by promoting dialogue and constructive discussion with the major stakeholders in an immunization programme, namely the medical personnel involved with vaccine selection and use, the public health programme responsible for vaccine delivery, the National Regulatory Authority (NRA) responsible for vaccine quality, and those involved in vaccine supply, including procurement officers, agents and local producers.

The meeting agreed on the next steps in the devel­opment of national and regional policies. The members suggested a meeting of a small group of experts in early 2000 to discuss and select key pri­ority areas. The expert group would have sufficient regional and external experts and would have the

16

flexibility to take responsibility for specific areas if necessary and to set the stage for consultations and activities at country level. The group would report to ACHR on status and progress.

• A review in the following key areas would be conducted on a country-by-country basis over a period of several months: • vaccine-preventable disease burden; • vaccine research and development initiatives

within the region; • vaccine clinical trials within the region; • vaccine production and supply sources; • vaccine regulation; • networking among vaccine regulatory

authorities.

• The review would include meetings with con­cerned individuals in three or four selected countries. Consultants with expertise in rele­vant areas would be contracted to conduct the studies.

• Dialogue and meetings at country level would be initiated to prioritize and prepare the ground for implementation.

A meeting at the regional level would be conducted in order to constitute the regional policy. It was expected that by this time there would be adequate acceptance of issues and emerging recommendations at the level of ministers of health, and that the poli­cy would be discussed at the Regional Committee later in the year or early the following year.

6.2 Introduction of new vaccines

New vaccines that can prevent major causes of mor­bidity and mortality in the developing world are not being used widely in poorer countries. These include hepatitis B, Hib, and, most recently, the pneumococcal conjugate vaccines. Other underuti­lized vaccines have been available for a long time (rubella and yellow fever vaccines). Additional new vaccines will soon be available for other diseases. In order to take maximum advantage of these valuable prevention tools a number of barriers must be over­come. These include a lack of efficacy or impact data in developing country settings, a lack of bur­den and cost-effectiveness information, a lack of

technical assistance on introduction, issues related

ANNUAL REPORT 1999

to logistics, supply and quality control, and a lack of sustainable funding for vaccines.

Remarkable changes are taking place m national

routine immunization programmes in the Americas with the introduction of new vaccines of public

health importance. In 1999, over 90% of the chil­

dren born in the Americas will benefit from Hib

and hepatitis B vaccines as part of their regular vac­

cination schedule. MMR vaccine is now included in almost every country's routine programme. A

more aggressive yellow fever strategy is aiming to achieve prompt vaccination of the entire population in areas of endemicity and the incorporation the

vaccine into the routine immunization programme

for children under 1 year of age. The availability of

a new combination vaccine that includes the five

antigens of DTP, Hib and hepatitis B, has further facilitated the uptake of these new vaccines in

national immunization programmes. The AlvfRO

Revolving Fund for Vaccine Procurement has

played a fundamental role in the introduction of

these vaccines. Through its system of bulk purchas­

ing the Fund has secured the supply of high-quality

vaccines for national immunization programmes at affordable prices.

Some of these vaccines, however, such as the MMR,

yellow fever and hepatitis B vaccines, have already

been on the international market for 15 years. Their

introduction in the Americas, as in other develop­

ing countries, has been slow because of high prices

and the lack of additional resources to support the

expansion of surveillance systems for collecting

information on the burden of the diseases. MMR vaccine has been made available in response to

urgent requests from countries for vaccination

against rubella. The surveillance system established by AMRO with a view to measles eradication con­

tinues showing widespread circulation of rubella virus in most countries in the Americas.

Reliable epidemiological data, for instance on bur­den of disease and cost-effectiveness in relation to

the use of specific vaccines, is recognized as the key

information required by decision-makers allocating

resources for vaccine introduction and guaranteeing

their sustainability. Many countries are now work­ing to strengthen the capabilities of surveillance sys­

tems and laboratories in monitoring vaccine-pre­

ventable diseasesand the impact of vaccine intro­

duction. These efforts will play a catalytic role in

17

the introduction of combined vaccines against

S. pneumoniae, N meningitidis A and C, and rotavirus, which are scheduled to be released short­

ly and are also expected to have a substantial impact

on disease burden. The current surveillance systems for measles, polio and rubella could become the

basis for the surveillance of other viral diarrhoeal

(rotavirus) or respiratory diseases (respiratory syncy­tial virus , influenza), and the system in place for

H injluenzae and S. pneumoniae could be extended to include other bacterial pathogens (such as

Shigella and E. coli.)

6.2.1 The Accelerated Vaccine Introduction priority project

The Accelerated Vaccine Introduction (AVI) priori­

ty project was developed by V&B in 1999 to address critical issues in new vaccine introduction.

The goal of the project is to implement a mecha­

nism for accelerating the introduction of new and

underused vaccines of public health importance in

the developing world by 2003. This involves the

development of an infrastructure to complete a set of activities on vaccines at various stages of the

introduction process. The project focuses on critical

points in the vaccine evaluation and introduction continuum at which WHO could make a substan­

tial difference and involves activities in each of V&B's teams.

The work of AVI during 1999 has been divided

into five activity areas, corresponding to V&B's five

teams:

• VAD has focused on efficacy evaluation. During 1999 this work included a series of

coordination meetings on methodological issues in the ongoing pneumococcal vaccine

trials, and initiation of the trial in the Gambia which will identify impact on mortality. Work

on rotavirus vaccine issues includes the evalua­tion of burden and serotype distribution.

• VM1 activities have been directed at the assess­

ment of disease burden data for hepatitis B,

Hib, and other diseases of interest, and inte­

grating the data with economic analysis tools

to facilitate decision-making at the country

level. A database on hepatitis B burden, and

collaboration with CDC to produce a

cost/benefit tool for developing countries, have

DEPARTMENT OF VACCINES AND BIOLOGICALS

been promoted in the last year. Studies on the burden of Hib disease in Russia were initiated. The collation of available data on Hib menin­gitis burden was undertaken.

• QSB has developed guidelines for the produc­tion and control of Hib vaccine and has initi­ated parallel work on pneumococcal conjugate vaccines.

• ATT activities in 1999 included provision of global guidance on financing mechanisms and vaccine demand, and country-level input into supply, financing and planning.

• EPI activities focused on technical assistance with new vaccine introduction. They included: the development of a set of guidelines for immunization programme reviews; convening, with VAD, an international group of experts to outline the next steps required for accelerating the development and introduction of Hib and pneumococcal vaccines; and supporting posi­tions for persons devoted to new vaccine intro­duction in four of WHO's regions.

Major funding partners of the project include USAID and the Bill and Melinda Gates Children's Vaccine Program.

The priority project highlights the above activities and others for special focus but does not include all V&B activities in the field of new vaccines. WHO continues to publish position papers on new and underused vaccines. A total of eight such papers have been published, including, most recently, doc­uments on pneumococcal and hepatitis A vaccines. These papers provide background information and guidance to policy-makers, national programme managers and others.

6.2.2 Hepatitis B

Three major obstacles must be overcome so that hepatitis B vaccine can be introduced into the poor­est countries:

• lack of appreciation of the burden of disease associated with hepatitis B virus infection;

• weaknesses in the infrastructure of immuniza­tion programmes which limit coverage;

• insufficient financial support for countries to

Figure 4: Global status of routine hepatitis B vaccination implementation, September 1999

.. :~.

,J•. ~

',ii /

Routine Hepatitis B immunization status:

No routine immunization

■ Routine immunization

18

ANNUAL REPORT 1999

purchase a more expensive vaccine. Although the price of a dose of hepatitis B vaccine in

1999 was only US$ 0.58-0.99, compared to $8-12 ten years ago, the price for the three­

dose series is more than that of all other rou­tine EPI vaccines combined.

In the African Region the disease burden of hepati­

tis B has been well established, as has the high to

very high (2-8%) chronic carrier rate throughout

the Region. In addition the efficacy of vaccines has

been demonstrated and the benefits have been made abundantly clear.

Six countries (Botswana, Gambia, Seychelles, South Africa, Swaziland, and Zimbabwe) have

introduced hepatitis B vaccination inro their

routine programmes.

A new goal of at least 75% coverage by 2005 was

recommended for the African Region. Countries

were classified to allow for prioritization according

to whether they had expressed interest in the vac­

cine or had already included hepatitis B vaccine in

their programmes, had a DTP coverage higher than

50%, and had a per capita GNP below USS 1000.

The following actions were identified as increasing

the uptake of the hepatitis B vaccine:

• identification of the potential for financing vaccine purchase, including the development

of partnerships with the private sector, opti­

mizing support from national ICCs, and assur­ing that ministries of finance considered the

high cost-benefit of hepatitis B vaccine during

their strategic planning;

• increased education on the efficacy/ safety of the vaccine;

• promotion of the inclusion of hepatitis B vac­cine in vaccine supply agreements with part­ners;

• advocacy at all levels, including partnerships with professional associations and concerned

groups;

• use of evaluations conducted in countries that

have already introduced the vaccine, in order to demonstrate its impact to other countries.

In the South-East Asia Region, hepatitis B vaccine

is now routinely given in four countries: Bhutan (81 % coverage in 1998), Indonesia, Maldives (45%

coverage in 1998), and Thailand. V&B/SEARO

19

intends to fully integrate hepatitis B vaccine into

the routine immunization schedule in all countries

by 2003. In order to achieve this the following steps have been planned: 1) a technical visit to assess the

constraints on introducing hepatitis B vaccine in the national immunization programmes; 2) an

advocacy meeting on hepatitis B vaccine with high­

level officials in the priority countries; 3) support

for an operational study of a new financing mecha­

nism for hepatitis B vaccine; 4) use of the ICC

mechanism to make the vaccine available to the countries at an affordable price; 5) provision of

technical support for a review of the national

immunization programmes in Bangladesh, the Democratic People's Republic of Korea, India,

Myanmar, and Nepal; 6) follow-up and support of hepatitis B studies in countries.

India is conducting a pilot project for the introduc­

tion of the vaccine on a limited scale. Bangladesh

and Myanmar are planning a similar study. Bhutan has planned to conduct a hepatitis B efficacy study.

Hepatitis B is being locally produced in Indonesia

and the Democratic People's Republic of Korea. A

feasibility study of Myanmar's capability to produce hepatitis B vaccine was concluded in 1999. A com­

pany in India is planning to produce a combined DTP-HB vaccine by processing DTP manufac­

tured in India with bulk hepatitis B vaccine pro­

cured from abroad. These local productions will improve self-sufficiency in vaccine in the region and will help to reduce costs.

The most critical needs for hepatitis B control in the Western Pacific Region are to get the vaccine introduced in national immunization programmes

and to ensure an adequate uninterrupted, supply of

vaccine. All the countries in the region except for Cambodia and the Lao People's Democratic Republic, have introduced hepatitis B vaccines into

their national immunization programmes, and cov­

erage in most countries is good. However, coverage remains less than optimal in China, Papua New

Guinea, the Philippines and Viet Nam, primarily

because of inadequate vaccine supply or difficulties

in accessing the vaccine. Most countries have

secured hepatitis B vaccines for the immediate

future but long-term sustainability remains prob­

lematic, primarily because of the cost.

In nearly all countries of the Western Pacific

Region where comprehensive vaccine requirement

DEPARTMENT DF VACCINES AND BIOLDGICALS

Figure 5: Hepatitis B vaccine supply, Western Pacific Region, 1992-1997

calculations have been undertaken they have been

used to identify government and partner agency funds to meet vaccine requirements. The availabili­

ty of vaccine throughout the region has improved (Fig. 5). In Cambodia and the Lao People's

Democratic Republic the calculations have been

incorporated into five-year immunization plans to

form the basis of government planning and to be

used in negotiations with partner agencies to ensure

adequate vaccine supplies in the medium term. It is likely that in both countries the introduction of hepatitis B vaccine will commence in 2000.

Many countries in the region .are now achieving high immunization coverage levels with hepatitis B

vaccine. In 1998, 26 countries reported over

50% coverage with three doses in infants, and 23

countries reported over 80% coverage Fig 6.

Figure 6: Hepatitis B coverage (% receiving three doses of hepatitis B vaccine), Western Pacific Region, 1992-1998

20

Although original estimates had suggested HbsAg

prevalence of2-8%, results ranged from 2% carriers

in Baltic and northern countries, 2-7% in Russia, and 5-10% in Bulgaria, Romania, Albania,

Moldova and some central Asian republics. Various

routes of transmission of HBV to patients have

been documented. The contribution of unsafe

injection practices to the burden of hepatitis B globally is unknown but likely to be substantial.

Implementation of hepatitis B vaccine in these

countries could be seen as a highly effective use of

health resources. A Viral Hepititis prevention Board (WHO/VHPB) meeting was conducted to review the allegation that hepatitis B vaccine might be

associated with demyelinating disorders. The claim was refuted and recommendations made to contin­

ue to vaccinate target groups.

6.2.3 Haemophilus influenzae type b

Haemophilus influenzae type b (Hib) is the most common cause of bacterial meningitis and the

second commonest cause of bacterial pneumonia

among children. The vaccine was adopted in North

America and most of Western Europe by the early

1990s, primarily because of its ability to prevent meningitis. Uptake has been much slower in the

developing world, where its major impact is in the

prevention of pneumonia. By late 1999 more than

44 countries had adopted Hib vaccine for routine infant immunization, including South Africa, the

second African country to introduce the vaccine

and the first to support its introduction from its

own budget. Recent data from the Gambia con­firmed a 90% decrease in meningitis caused by Hib

as a result of the introduction of the vaccine on a national scale. The current status of Hib vaccine

introduction is shown in Fig 7.

The following issues continue to affect the pattern of Hib vaccine use.

• The burden of disease is either unknown or

not appreciated in much of the world. This is

partly attributable to the difficulty in diagnos­

ing the disease. Diagnosis of Hib meningitis requires laboratory material and the ability to

perform bacterial cultures on sick and febrile

children, which is lacking in many developing

countries. V&B results from five countries

should be available in 2000, and an additional study on Hib meningitis was initiated in

ANNUAL REPORT 1999

Figure 7: Countries that had introduced Hib into routine immunization schedules by July 1999

Routine HIB implementation status:

No policy

■ Routine policy

Russia in 1999. The main form of Hib disease in the developing world, pneumonia, is also caused by other bacteria; confirming that a specific case is caused by Hib is impossible in most situations, even with the best laboratory support. Our best information on the burden of Hib disease in the developing world has come from vaccine introduction studies in Chile and the Gambia. Additional information should be available soon from a study in Indonesia in which WHO is playing an advi­sory role. WHO has begun collaborating with CDC to develop a rapid assessment tool for use in countries wishing to estimate Hib dis­ease burden on the basis of local data.

• Additional efforts are needed to emphasize and clarify the burden of pneumonia in the devel­oping world. V&B is participating in a cross­cluster effort to clarify this burden, a particu­larly critical matter because of the licensing of the pneumococcal conjugate vaccine in early 2000. We now have the tools to reduce most of the mortality from pneumonia in the develop­ing world, but the case for disease burden and for the impact of these vaccines must be clear-

21

ly made to ensure rapid acceptance. • As with hepatitis B, sustainable financing for

Hib vaccines in the developing world is a major problem. New initiatives by the World Bank, the Bill and Melinda Gates Children's Vaccine Program and others have made it pos­sible to introduce Hib vaccine into countries where this was financially impossible previous­ly. Important issues remain, however, about the prioritization of funding for Hib vaccines and the gradual acquisition by national gov­ernments of financial responsibility for th~se vaccines.

In the Region of the Americas, 81 % of the coun­tries have Hib vaccine in their national immuniza­tion programmes, reaching 90% of children born. There is a possibility that this level will go up to 96% by the end of year 2000, representing 90% of the countries in the region. This noteworthy achievement took place in less than ten years since the licensing and availability of Hib vaccines in the developed world.

A Regional surveillance system developed in order to monitor bacterial pneumonia and meningitis is

DEPARTMENT OF VACCINES AND BIOLOGICALS

Figure 8: Collaborative research projects on polysaccharide conjugated vaccine research in the Americas

H. influenzae type b

e S. pneumoniae

e QC of conjugated vaccines

providing feedback for monitoring the impact of Hib vaccination on meningitis. Case-control stud­ies have been initiated to evaluate the impact of the vaccine on pneumonia in Brazil, Colombia, and Mexico. The results of these studies will be impor­tant in confirming the public health importance of Hib vaccine and promoting its use in other regions. Other surveillance systems are being formed to monitor vaccine-preventable diseases in relation to

vaccines to be released shortly and others still in development, namely pneumococcal, meningococ­cal and rotavirus vaccines. Data generated from the systems will be used for measuring disease burden and conducting cost-effectiveness studies.

The introduction of vaccines against Hib, which is responsible for many of the region's cases of bacter­ial pneumonia and meningitis, provides a useful example of the issues surrounding the sustainable introduction of a vaccine in a national immuniza­tion programme. Considering that the first conju­gated vaccines against this pathogen were licensed in Canada, Europe, and the USA as recently as 1991, their introduction has been remarkably rapid. AMRO played a leading role in promoting

22

Brazil

the establishment of Hib surveillance in the region and in evaluating the introduction of Hib vaccine in routine immunization pro­grammes. These initiatives were supported by recommendations of the Organization's Directing Council and the Technical Advisory Group on Vaccine-Preventable Diseases (TAG). The exchange of experi­ences among countries at meetings spon­sored by AMRO has become an important catalyst stimulating the introduction ofHib vaccine into routine immunization sched­ules. Furthermore, the establishment of an epidemiological surveillance network to monitor invasive pneumococcal diseases in children aged under five years in six coun­tries of the region has had a positive impact on Hib surveillance.

At the country level, decisive factors behind the speedy introduction of the Hib vaccine include: heightened awareness on meningitis diseases among parents; knowledge in the medical profession and health ministries of several clinical trials pointing to the vaccine's safety, efficacy and effectiveness; and previ­ous experience with the vaccine in the private

sector. Having a well-structured surveillance system that provides the pertinent epidemiological informa­tion in advance about the disease is also a critical fac­tor. Countries meeting these requirements have been able to analyse the cost-effectiveness of Hib vaccina­tion quickly and obtain government commitment to finance the vaccine on a routine basis.

Reliable data are not available among the countries of the South-East Asia Region on the burden of invasive Hib disease. Nevertheless, a study of the effect of Hib vaccination on the incidence of pneu­monia among children aged under five years is now progressing in Indonesia. Thailand is preparing a study on community surveillance for Hib meningi­tis with a view to ascertaining the burden of the dis­ease among children aged under five years. India and Indonesia are conducting similar studies. V&B/SEARO aims to introduce Hib vaccine into the routine immunization schedules in Thailand and Indonesia during 2003. The remaining eight countries will have at least a plan of action on Hib introduction by the year 2003. The high cost of Hib vaccine is still a major constraint on its introduction in national immunization programmes. D

ANNUAL REPORT 1999

7. Immunization systems

7. 1 Introduction

As part of Immunization Services there have been

two overall foci of work. The first involves strength­ening the infrastructure for immunization service

delivery. The second is the priority project on Safety

of Immunization. This infrastructure strengthening

process involves: • defining the elements of an immunization

service;

• determining the characteristics of an immu­nization service that is performing well;

• costing the elements of such a service;

• developing an assessment tool to assist coun­tries in analysing their immunization services,

• identifying gaps and • developing plans for dealing with them.

Future activities will follow these six steps, focusing

on further assessments, the development of plans,

and collaboration with partners in immunization in

order to address the gaps through the provision of technical and financial resources. Finally, the

Immunization Systems priority project has been

developed in the area of safe immunization, thereby integrating with all the other work areas of the

Department.

7 .2 Defining the elements of an immunization service

In this analysis an immunization service is divided into five components: supply and quality, logistics,

surveillance, communication and advocacy, and service delivery. Two additional elements that are

part of the external environment, namely financing

and the overall health system, have also been defined. For each of these components, key indica­

tors for identifying well-performing systems have

been defined in order to aid the assessment process.

The assessment tool is now being field-tested. This

23

division into concrete elements has been very use­

ful to V&B in defining interventions. The activi­ties pursued in each element throughout 1999 are

summarized below.

7 .3 Supply and quality

7.3.1 Global situation

Critical indicators: • proportion of countries using vaccmes of

assured quality;

• proportion of countries monitoring vaccines by means of vaccine vial monitors (VVMs) when

relevant;

• for OPV: ~ 175/190 countries using vaccines of assured quality, 82/164 with VVMs;

• for other vaccines: proportion of countries

using vaccines of assured quality varies with product, 0 to date with VVMs (to be imple­

mented in 2000-2001).

One ofV&B's critical targets is to ensure that by the

year 2000 all countries have access to vaccines of

assured quality and that the quality is maintained

up to the time of administration in the target pop­ulation. A vaccine of assured quality is one that is

produced in a country where an NRA exercises the six critical control functions identified by WHO,

with no unresolved problems reported.

A number of strategies have been developed to enable countries to obtain vaccines of assured qual­

ity; Others are in place or under development in

order to help countries to implement the proce­

dures ensuring that quality is maintained during the

storage, distribution, handling and administration

of vaccines:

(1) A centralized procurement system is offered by

UN procuring agencies. The UN procuring system

DEPARTMENT OF VACCINES AND BIOLOGICALS

uses the technical support of WHO/V&B to con­tinuously monitor the quality of vaccines being purchased. The system covers not only the vaccines traditionally included in national immunization programmes but also new and underused vaccines and combinations. Fifteen new applications for vac­cine assessment were received during 1999 and three have been completed. Twelve manufacturers' products were reassessed and one was removed from the pre-qualified list.

Critical indicators: .,. proportion of pre-qualified vaccines under con­

tinuous surveillance and re-evaluation - 100%; .,. proportion of candidate vaccines evaluated -

20%.

(2) Appropriate regulatory functions must be in place to assure the quality, safety and efficacy of the products used in countries obtaining vaccines by direct procurement or by local production. WHO/V&B has defined these functions and devel­oped indicators for assessing their effectiveness through an expert meeting held in 1999; Assessments against indicators were performed in eight countries during the year and the information obtained was added to a global database maintained in V&B.

Critical indicators: .,. percentage of vaccine doses of assured quality

- 56% for BCG, 73% for DTP, 69% for hepatitis B.

(3) WHO has identified 53 countries that are meet­ing at least some of their national vaccine needs by local production. A survey of the characteristics of these producers, usually belonging to the public sector, has revealed problems in the quality and reli­ability of the vaccines, as well as an inability to manage change, access new technologies and appro­priately assess the cost of production. In the long term it is unlikely that many of these local produc­ers will continue to be viable and relevant sources of national vaccine supply. In order to assess the relia­bility of suppliers, WHO has identified seven criti­cal components of local manufacturer viability. To date, 37 local vaccine producers have been assessed and 13 (35%) were identified as viable, having attained a minimum viability score of 70% as mea­sured by the critical functions. Progress is indicated in Fig. 9. Viability assessments were carried out in

24

four countries during 1999, and two papers (Donor Inputs to Local Vaccine Production, Motivations for Local Production) based on extensive global sur­veys were published.

Critical indicators: .,. percentage of local producers with a viability

rating of at least 70%: 35%.

Figure 9: Number of local vaccine manufacturers achieving 70% viability rating 1996-1999

(4) The Global Training Network (GTN) was developed in 1996 as a means of providing educa­tional resources to vaccine regulatory and produc­tion staff throughout the world. To date, 387 staff of NRA.s and vaccine manufacturers have partici­pated in GTN, 165 of them during 1999. The number of centres was increased by three to 17. Three of the standardized curriculum manuals already available in English were published in Spanish, one was published in French, and two new documents were published in Spanish and English. A new curriculum, specially designed for national regulatory staff in procuring countries, was devel­oped, and three courses were held. An important part of GTN's work is continuing evaluation and follow-up to monitor the impact of training on vac­cine quality. This was done in 1999 through two follow-up workshops, held in Egypt and Nigeria, and through a study of the proficiency of testing measles and pertussis vaccines. Recognizing the need for training in the management of adverse events at country level, GTN has provided a course

ANNUAL REPORT 1999

on the implementation of a system for monitoring

such events.

Critical indicators: • percentage of countries with independent, fully

functioning NRAs - 47/190 (25%).

(5) WHO is the focal point for reports of adverse

events following immunization (AEFI) wii:h vac­

cines supplied through UNICEF and other UN

agencies. V&B staff give quick responses to the

considerable number of reports received each year. The majority of cases are attributable to program­matic errors putting at risk the quality of vaccines

at country level, usually at the time of reconstitu­tion and administration. To improve the situation

in countries experiencing such problems. WHO

and UNICEF will perform country surveys on the

quality of vaccines at the point of use. A protocol

developed in 1999 includes a review of procedures in place at country level for the receipt, release,

storage, distribution and administration of vac­cines. Furthermore, WHO and UNICEF devel­

oped a vaccine arrival report for all vaccines, and

this was attached to the updated invii:ation-to-bid

documents.

Critical indicators: • proportion of field complaints received annual­

ly that have been addressed and resolved -

100%;

• number of countries with effective monitoring

systems for AEFis - 71/190.

(6) The National Vaccine Supply Plan is a new tool

assisting countries to assure an adequate supply of vaccines of high quality through their planning

processes. It was tested in five countries before

being used in another four. A monitoring system for use of the plans is being developed with regional

offices.

Critical indicators: • percentage of countries regularly producing and

updating national vaccine supply plans; not yet measured, but systems are being developed and

regional offices are to perform monitoring.

7 .3.2 African Region

Vaccines for routine immunization are mostly

procured through UNICEF. Certain countries are

25

providing most or all of their vaccine needs from their own budgets. Some countries in the African

Region are actively involved in UNICEF's Vaccine

Independence Initiative (VII).

The status of vaccine production in the four pro­

ducing countries of the region is as follows:

• South Africa has the capacity to produce

rei:anus toxiod (TT), DTP and BCG;

• as well as producing yellow fever vaccine for its

own use, Senegal supplies UN agencies;

• Cameroon will begin producing TT in 2000; • Nigeria stopped producing yellow fever

vaccine in 1997.

The number of countries contributing to their

national needs increased from seven in 1995 to 25

in 1998. This was achieved through established

budget lines and/or the adoption of financing

schemes proposed by partners in development e.g. VII of LTNICEF and the European Union in the Sahel countries of West Africa. However, there were

very strong limitations in the financing of new and

underutilized vaccines e.g. yellow fever, hepatitis B

and Hib vaccines, because of their relatively high

cost.

During the next five years, therefore, it will be nec­

essary to consolidate the gains of financing routine

immunization and to accommodate the financing

of new and more expensive vaccines, through the

promotion of established budget lines, financing

schemes with partners in development, and the pro­

posed global vaccine initiative.

7 .3.3 Region of the Americas

.AJ.\1RO collaboration with countries emphasizes

the need to strengthen activities related to the qual­ity control and production of vaccines. Special emphasis ·was placed on vaccines used in national

and regional immunization programmes.

In the area of quality control, efforts were made to assisi: the national control laboratories (NCLs) of

Argentina, Brazil, Chile, Colombia, Cuba, Ecuador,

Mexico, and Venezuela in achieving the desired lev­

els of proficiency and qualification. The support

was aimed at standardizing laboratory methodolo­gies, the production and distribution of reference

reagents, training on the control of new vaccines,

validai:ion of alternative in vitro potency tests, and

DEPARTMENT OF VACCINES AND BIOLOGICALS

improving the communication and exchange of information between participating laboratories. A certification programme assessing the proficiency and performance of laboratories in the regional net­work was developed and initiated in order to guar­antee access to vaccine testing at qualified laborato­ries, either by AMRO or by NRAs in the region. A database developed for the registration of all vaccine lots released and circulating in the Region was improved and is currently being evaluated by selected NRAs and laboratories.

In the area ofNRAs, AMRO is working towards the harmonization of regulatory activities for the licens­ing of vaccines in non-producing countries, specifi­cally in Central America and the Dominican Republic. A generic document with harmonized procedures for vaccine licensing was developed and some countries are already using these recommen­dations for their licensing requirements. In order to strengthen the regulatory functions in these coun-

Figure 1 O: NRAs and NCLs of vaccine-producing countries in the Americas

Non producers

NCA/NCL complying with at least S of the 6 basic functions

■ NCA/NCL complying with less than 5 basic functions

I?"' Source:PAHO

26

tries, workshops were held on topics that included vaccine licensing processes, lot release and good manufacturing practice (GMP). Computers and access to the Internet were provided to improve communication and implement the database system for registering circulating vaccine lots.

In the area of vaccine production, AMRO contin­ued to highlight the need for strong political com­mitment to improving local vaccine production and ensuring compliance with international require­ments and GMP. This commitment will lead to the availability of resources for necessary improvements and investments, as well as for the implementation of managerial, administrative and organizational changes that are more in line with the productive processes. AMRO is promoting technical and eco­nomic feasibility studies of vaccine producers in the region in order to obtain information that can jus­tify the continuation or termination of production activities. Mexico conducted such a study and

Brazil has requested assistance with a similar study. Peru is considering the possibility of producing yellow fever vaccine, and for this reason has also requested a study. Colombia, Ecuador, and Venezuela have been recommend­ed to consider this kind of study.

Two countries in the Americas have initiated the WHO assessment for UN vaccine suppliers: CIGB in Cuba for hepatitis B vaccine and BioManguinhos/Fiocruz in Brazil for yellow fever vaccine.

7 .3.4 Eastern Mediterranean Region

Assessment of the vaccine NRAs in this region's countries continued in 1999. Furthermore, the first consultation on vaccine supply, quality and local pro­duction in the Eastern Mediterranean Region was held in September 1998 with the objective of reviewing the sta­tus of vaccine supply and production in the region and the development of country plans of action to ensure.vac­cine quality. The consultation was attended by representatives from EPI programmes, the NRAs of Egypt, the

ANNUAL REPORT 1999

Islamic Republic of Iran, Jordan, Kuwait, Oman,

Pakistan, Saudi Arabia, the Syrian Arab Republic,

Sudan, and Tunisia, as well as representatives of local producers. Continued support was directed

towards the strengthening of the NRAs, with spe­

cial emphasis on vaccine-producing countries. The

NRA in the Islamic Republic of Iran is performing

all six functions; that in Tunisia is performing four

(licensing, PMS, lot release and clinical evaluation);

that in Egypt is performing three (licensing, PMS and GMP inspection); and that in Pakistan is per­

forming two (licensing and GMP inspection). Follow-up is maintained in the interest of further improvement.

7.3.5 South-East Asian Region

Achieving self-sufficiency means promoting the

ability to expand national efforts independently of outside donor support. By the countries in this

region had achieved rapid gains in self-sufficiency,

approximately 80% of funds being contributed by

the governments. India, Indonesia, and Thailand

are among the countries improving their NRAs'

capacity to perform regulatory functions assuring high-quality vaccine production. In order to

achieve self-sufficiency in supply, countries will need to be able to forecast their vaccine demand for

the near future.

7 .3.6 Western Pacific Region

The (NRAs of China, the Philippines, and Viet Nam have made progress in strengthening their vac­

cine regulatory functions. Through participation in

GTN a loose network of NRAs has been formed

and specific vaccine regulatory needs have been identified for countries. The WHO guidelines on

establishing immunization safety surveillance have been adapted in the Philippines to form the frame­

work for a national Immunization Safety

Surveillance System (ISSS).

7 .4 Logistics and the cold chain

The term "logistics" refers to the equipment and

management necessary for the safe and efficient

delivery of vaccines. It covers the cold chain and distribution systems, devices and policies which

affect the management of logistics systems, such as

VVMs, and the selection, use and disposal of

injection equipment.

27

Critical indicator: • The ratio of targeted countries implementing

satisfactory safe injection practices as defined by

a WHO standardized survey- currently 0/6.

7 .4.1 Cold chain and distribution systems

To assess the potential impact of the integration of

cold rooms for drugs and vaccines a study on the

integration of vaccine and drug storage and distrib­ution was performed in two countries in Africa.

Another initiative to certify cold rooms is designed to prepare countries for stocking future vaccines.

The final draft protocol for cold room assessment

and certification was developed and preparations for field trials in selected countries were initiated.

A vaccine management study was completed in another African country. A WHO/UNICEF

document entitled "Quality of cold chain WHO­

UNICEF" was printed.

A TECHNET consultation was held during 1999 in

Harare, Zimbabwe. There was a record number of

participants and all facets of logistics were consid­ered. The recommendations included a call to for­

malize TECHNET and to develop a strategic frame­

work for its activities. This will be done in 2000.

7 .4.2 Vaccine vial monitors

VVMs are now on all OPV supplied by UNICEF

and also on OPV provided by a number of produc­

ers not supplying vaccines to UNICEF, including all doses filled in India. Activities are now focused on

the assessment of impact, the completion of testing, and the translation and printing of information doc­

uments entitled "Testing correlation between VVM

and vaccine potency'' and "Temperature monitors for vaccines and the cold chain''.

A study carried out in India in connection with a cold chain review confirmed the effectiveness of

VV1v1s in indicating vaccines that should not be used because of the possibility of reduced potency.

Critical indicators: • Percentage of OPV distributed through inter­

national suppliers and fitted with VVMs - vir­

tually 100% unless the purchaser requests that they should not be supplied.

• Percentage of OPV doses from local producers

which are fitted with VVMs - >50%

DEPARTMENT OF VACCINES AND BIOLOGICALS

7 .4.3 African Region

The presence of a logistics manager with the skills

necessary for carrying out increasingly complex tasks is essential for EPI operations. Only 23 of 46

countries (50%) have such managers, and only

about half of them have had the training and expe­

rience needed to carry out the functions listed above

Another element essential to EPI operations is the

quality of the cold chain. As indicated by invento­

ries made in several countries, much cold chain equipment currently in use was provided in con­

nection with the Universal Childhood

Immunization Initiative lead by UNICEF in the late 1980s. Many units are nearing the end of their

useful life and should be replaced.

Studies of low-coverage areas frequently identify a lack of transport as the main barrier to the achieve­

ment of targets for coverage and disease reduction.

Programme requirements for timely transportation

of heat-labile vaccines, outreach in rural areas, and

active surveillance mean that EPI is dependent on transport. Level-specific transport planning is there­

fore essential for the effective implementation of

EPI tasks. As the effectiveness of outreach sessions

depends on the health system meeting its commit­ment to communities, reliance on vehicles that are

not always available is bad management.

The following proposals are being made with a view to establishing effective logistics and a reliable cold

chain:

• ministries of health should appoint adequate logistics managers and provide the resources

required, including those needed for transport

and cold chain management;

• training in logistics practices, planning and monitoring should be provided;

• aging cold chain equipment should be replaced entirely in most countries.

7 .4.4 Region of the Americas

AMRO's technical cooperation with countries dur­

ing 1999 focused on improving the management of

the cold chain. Emphasis was also placed on

increasing the capacity of cold chain storage facili­

ties at the central level, to accommodate new vac­

cines, such as pentavalent vaccines (DTP/hepatitis

B/Hib), and increased volumes of other vaccines.

Population increase is overwhelming the capacity for safe storage, as many cold rooms in the Americas

were built more than a decade ago.

During national programme evaluations carried out in various countries, one of the major problems

identified was an ageing cold chain infrastructure and a lack of suitable plans for its renovation.

Several countries have not made the investments

needed to update cold chain equipment since the

late 1970s or early 1980s. There is also a need to focus more on strengthening the supervision of

management. In both cases, AMRO is working

Figure 11: Samples of oral polio vaccine vials showing vaccine vial monitors in place

28

ANNUAL REPORT 1999

with countries to begin the renovation of the cold

chain and to improve the training of supervisors. A few countries in Central America have already initi­

ated this process by switching to the use of solar­

powered refrigeration. In Brazil, on-the-job training

of health care workers was initiated in 1999 as part

of an overall effort to improve the management of

the cold chain. In support of these efforts, AMRO

will update its cold chain module in 2000.

In the area of vaccine stock management, At\1RO

continues to improve national management capabilities through the installation of a software

package (CLM) for vaccine inventory and manage­

ment. Training on this package was given in Panama during 1999. Three more countries will

adopt the CLM software in 2000.

7 .4.5 South-East Asia Region

VVMs have been used with polio vaccme smce

1996. It has been found that in addition to assuring

vaccine potency they have significantly reduced vac­

cine wastage. They make it possible to conduct

immunization campaign activities in areas where the cold chain infrastructure is weak or even non­

existent.

During 1999 all polio vaccmes provided in the

Region had VVMs. Capitalizing on the training for

polio NIDs, V&B/SEAR assisted with the develop­

ment of training materials on VVMs and supported

the mass training of health workers and vaccinators.

V&B was closely involved in the VVM impact study in the Kingdom of Bhutan. Lessons learnt from this

study have helped V&B in the development of fast­chain strategy during NIDs. In 2000, V&B will 1)

participate in organizing a training workshop on VVM for mid-level EPI staff; 2) distribute VVM

manuals and guidelines to countries; 3) support

funding for training trainers at the central level; and

4) provide training modules for trainers.

7 .4.6 Western Pacific Region

WHO has facilitated the provision of partner

agency support for cold chain equipment and train­

ing in China, the Pacific Island Countries and

Areas, and Papua New Guinea. In most countries in the Region, cold chain requirements are largely met

for the short term, although China and the

29

Philippines still have major needs. In Cambodia,

the Lao Peoples' Democratic Republic, and Viet Nam, injection practices during measles cam­

paigns have been significantly improved through the introduction of auto-disable syringes and safety

boxes. This followed successful introductions in Papua New Guinea, the Pacific Island Countries

and Areas, and the Philippines (safety boxes only)

between 1997 and 1999. Major improvements in injection equipment have been made in several

provinces of China through projects supported by

partner agencies.

7 .5 Surveillance

7 .5.1 AFP/polio surveillance

Surveillance for polio eradication remains the prin­

cipal priority. By 31 December 1999 all countries

where polio was endemic had established AFP / polio

surveillance. Many countries are now using experi­

ence in this field to strengthen surveillance for other communicable diseases. (See also Section 8.1.)

7 .5.2 Estimation of burden associated with vaccine-preventable diseases

In order to ascertain the actual or potential impact

of immunization systems, to document the effec­

tiveness of immunization services, and to provide a

tool for local decision-makers, V&B is working

with other WHO clusters, WHO Regional Offices

and other agencies and institutions to develop country-specific estimates of vaccine-preventable

diseases, recommendations for improving the esti­

mates and methods and materials for making local

estimates of burden.

7 .5.3 Monitoring routine immunization systems

In collaboration with UNICEF, V&B has estab­

lished a common standard reporting system that covers information on the occurrence of vaccine­

preventable diseases, and immunization services

and policies. Included is information on the quality

of reported coverage data, on progress in the intro­

duction of new vaccines, on the safety of immu­

nization services, and on managerial, sustainability

and policy indicators.

DEPARTMENT OF VACCINES AND BIOLOGICALS

7 .5.4 Monitoring immunization safety

Establishing systems for ensuring and monitoring

immunization safety was a priority during 1999 and will continue in the coming years. Materials

have been developed for detecting problems with

immunization safety and for rapid investigation and

response to programmatic failure and vaccine safe­

ty. Interventions involve working not only with

national officials responsible for vaccine safety and

immunization services but also with the media. Workshops were held for the countries of WHO's Eastern Mediterranean Region on the detection of

problems, response and working effectively with the

media.

7 .5.5 Monitoring supplemental immunization activities

Increasingly, immunization services include not

only the provision of routine immunization but also supplemental activities (usually time-limited, target­

ed campaigns). While NIDs for polio are the dom­

inant example, supplemental activities for measles and neonatal tetanus immunization as well as vita­

min A distribution are becoming increasingly com­

mon. In order to facilitate the forecasting of vaccine

needs, monitor the impact of immunization strate­

gies and improve the estimation of disease burden,

V&B has begun routine and structured monitoring

of supplemental immunization activities.

7 .5.6 Improving the accuracy of data

On the basis of past analyses of the reliability, con­

sistency and completeness of reported immuniza­tion coverage, V&B has begun a project to improve

the accuracy of these estimates. The project includes an active search for alternative data, the

documentation and review of methods used to derive reported coverage, the eliciting of expert

opinion, the cataloguing and promotion of various

interventions and recognized statistical methods for the improvement of coverage estimates, and the

development of tools for evaluating the accuracy of

coverage estimates at the national level.

7 .5. 7 Graphic Information System

In order to improve the analysis and presentation of

epidemiological and programmatic data related to the control of vaccine-preventable diseases, V&B

30

has been working with regional offices and other

WHO dusters to establish a library of base maps

formatted for use by popular GIS computer pro­

grammes. The library now contains maps at the sec­

ond subnational administrative level for the Western Pacific Region, the South-East Asia

Region, the Eastern Mediterranean Region and the

African Region. These data are currently being

fitted into a global standard.

7 .5.8 Building consensus and coordinating

During 1999, V&B continued to work closely with Regional Offices and UNICEF on issues related to

surveillance and monitoring. A meeting was held to

identify future needs and reach agreement on sur­veillance and monitoring activities. These activities

concern burden estimation, immunization safety

monitoring, and the accuracy of reported coverage

data.

7 .5.9 Pneumonia surveillance

A surveillance network initiated in.1993 to moni­

tor the prevalence and antimicrobial resistance of

S. pneumoniae serotypes from invasive diseases in

children under 5 years of age in Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay is serving

as the basis for a network of sentinel hospitals, pub­

lic health laboratories and epidemiological surveil­

lance units in these countries' Ministries of Health.

The objective is to monitor bacterial pneumonia

and meningitis caused by S. pneumoniae, H injluenzae and N meningitidis. The system will provide reliable national, subregional and regional

epidemiological information and will monitor sea­

sonal and geographical changes in these infectious microorganisms and their antimicrobial resistance.

A regional quality control system, developed to assure the quality of the information, has the

National Center for Streptococcus in Alberta,

Canada, as its main reference centre, while three

laboratories in the region (in Brazil, Colombia, and Mexico) act as subregional centres. Meetings

were held at the centres with all the countries con­cerned, in order to define the basis of the surveil­

lance and the standardized procedures, and to

identify needs for further training. To date, almost

all countries have established a surveillance system for meningitis and pneumonia with varying

degrees of complexity.

ANNUAL REPORT 1999

By-products of the initial surveillance have been

collaborative studies with Rockefeller University on

the genetic relatedness of pneumococcal penicillin­

resistant clones in the region, and, in cojunction with the University of Alabama at Birmingham, a

study on the distribution of pneumococcal surface protein families among the isolates obtained so far.

This information will be valuable for the design of

alternative protein vaccines against pneumococcal

infections.

7 .5.1 D Measles surveillance

A sensitive epidemiological surveillance system for suspected cases of measles is critical for the success­

ful conclusion of the measles eradication strategy. It

is also necessary to provide support for countries in their efforts to generate reliable official epidemio­

logical data on measles, including detailed informa­

tion on suspected measles cases with laboratory data

on each. AMRO is therefore working with countries to improve the quality and use of epidemiological

data. The objective is to establish and/or enhance

networks of communication that guarantee the con­

tinuing and rapid flow of information between countries. The availability of data of high quality

will facilitate the preparation of national weekly bulletins on measles surveillance, which should be

distributed to health workers, including those in border areas. This information will enable policy­

makers and other health staff to obtain surveillance

of high quality on measles outbreaks and other

vaccine-preventable diseases and to coordinate

public health responses.

As part of the measles eradication initiative, AMRO

and national health authorities are implementing:

• periodic and intensive active searches for cases

to find remaining chains of transmission, par­ticularly in municipalities at high risk for measles outbreaks (including those where there

were cases during the preceding 12 weeks);

• intensive measles (mop-up) vaccination in municipalities with disease transmission and in

those that failed to reach 95% vaccination

coverage (estimated on the basis of either reported coverage or house-to-house monitor­

ing of vaccination in high-risk areas).

Among other strategies being implemented by

AMRO is the thorough investigation of all out­

breaks through:

31

• field investigation of the households, work­

places and/or schools where cases occur, and

vaccination as appropriate;

• monitoring of vaccination in all these areas and performing mop-up vaccination if necessary;

• field investigation of places where cases have occurred 7-18 days prior to the onset of rash,

and of places visited by cases during the week

following the onset of rash.

In order to ensure the sustainability of the eradica­

tion effort and the equity of vaccination, AMRO is stressing the importance of setting a target of high

(~95%) routine vaccination coverage for all vac­

cines. This should be achieved through strengthen­ing the routine vaccination services and education of

the community on the importance of vaccination.

Virological surveillance is a critical component of the measles surveillance system. To determine the

characteristics and probable origins of measles viruses are circulating in the Americas, enhanced

efforts are being made to collect appropriate clinical

specimens for measles virus isolation from every

chain of measles transmission that is detected by the

surveillance system. Surveillance personnel are

receiving special training on the collection of clini­

cal samples. AMRO's efforts to strengthen laborato­

ry diagnostic capabilities and the exchange of infor­mation under the measles eradication initiative will

serve as the foundation for establishing surveillance

for other emerging and re-emerging viral diseases in

the Region and elsewhere.

An active search for measles cases was conducted

during November and December 1999 in the eight largest cities in Colombia to determine whether the

measles virus was circulating. This action was taken

in response to laboratory-confirmed measles cases that occurred in isolation during 1998 and 1999 without any known source of infection. Following

the decentralization of health services there are many new health care providers who are not part of the formal national surveillance system and whose

measles surveillance work is still of unknown quali­ty. Ai\1RO and Ministry of Health officials

reviewed all available cases and surveillance data for

both years and determined that only one depart­

ment had a clustering of measles cases, especially in

an urban area, which suggested measles virus circu­

lation. A review of case and laboratory data from

the other sporadic laboratory-confirmed measles

DEPARTMENT OF VACCINES AND BIOLOGICALS

cases with no source of infection indicated that the majority occurred after vaccination. No additional confirmed laboratory measles cases were found.

7 .5.11 Measuring the impact of Haemophilus influenzae vaccine

Following AMRO recommendations the Ministry of Health in Colombia initiated the use of a conju­gated vaccine against Hib in May 1998, targeting children under 1 year of age. By December 1998, vaccination coverage had reached 50%. With the purpose of evaluating the impact of this interven­tion a trend analysis of the disease was carried out, utilizing data of the laboratory network for MBA. The number of MBA cases due to Hib (laboratory­confirmed) in children under one year occurring between June 1994 and May 1999 was analysed. The quality of the surveillance system was evaluat­ed by comparing the cases of MBA caused by Hib with those caused by S. pneumoniae in children under five years of age during the same period.

Between June 1994 and May 1999 the microbiolo­gy group confirmed 1166 bacterial isolations: 505 (43.3%) of H influenzae; 361 (31 %) of S. pneumo­

niae; and 300 (25.7%) of Nei;seria meningitidis. Of the 464 H influenza.e isolations for which there was information on the patient's age, 286 (62%) corre­sponded to children under 1 year of age and 99% of them were of Hib.

Between June 1994 and May 1999 the annual numbers ofHib isolates were 45, 37, 61, 64 and 31. The trend analysis of the disease indicated that the expected number of cases in children under 1 year for this last period was 52; however, only 31 cases were observed (p < 0.0005). During the same years there were 25, 18, 33, 37 and 25 cases of MBA caused by S. pneumoniae in children under 1 year of age, and 32, 26, 43, 48 and 42 in children under 5 years of age. According to the trend analysis of the disease for the last period, 28 cases were expected in the under one age group, while 25 occurred (p < 0.74); and in the under 5 age group 37 were expected and 42 were observed (p < 0.22).

The results of this analysis showed a 40% reduction in the number of MBA cases caused by Hib in the under-1 age group during the period studied. This reduction was not attributable to changes in the sur­veillance system, as demonstrated by the isolations

32

of S. pneumonia.e, for which a slight increase occurred between the expected and observed num­bers. It was concluded that the introduction of the conjugated vaccine had possibly led to a reduction of MBA cases caused by Hib.

7 .5.12 Eastern Mediterranean Region

Efforts to improve EPI disease .surveillance in Member States were sustained during 1999, and technical support for strengthening national sur­veillance systems for EPI target diseases continued. Issues and constraints facing the EPI target diseases surveillance activities and proposed solutions were discussed during various intercountry meetings. Country visits were made by regional office staff and short-term consultants to assess the surveillance systems and advise about methods for strengthen­ing them. Support for the newly developed com­puterized national surveillance data management systems was continued. The surveillance systems are sufficiently sensitive in some Member States but remain weak elsewhere, and the timeliness and completeness of reporting require improvement.

7.5.13 Routine data collection in the South-East Asia Region

The Information for Action (IFA) system has been established in all Member States. Although it can be u.sed to, create databases for the other EPI target dis­eases, it is currently being employed for polio sur­veillance by all Member States. Every Member State sends a weekly data report on AFP and polio to SEARO; seven countries use electronic mail for this purpose and the others send faxes.

Indonesia, Myanmar, and Sri Lanka have linked measks and neonatal surveillance to AFP surveil­lance. This integration strategy requires evaluation.

Information on vaccination coverage, vaccine-pre­ventable diseases and immunization systems is col­lected by means of the joint WHO/UNICEF data collection form and the reporting tables required for the regional TCG meeting each year.

Feedback to countries is provided in the region's Weekly Polio Bulletin. At the regional TCG meet­ing a forum is provided for the exchange of coun­try-level information.

ANNUAL REPORT 1999

In 1999, V&B/SEARO conducted a workshop on mapping for disease surveillance based on GIS Arciew software.Efforts will be made in 2000 to provide a dynamic link ofIFA to GIS. Virologists of the region's Polio Laboratory Network will attend an IFA workshop organized by V&B/SEARO.

Table 1: Measles and yellow fever vacdne coverage, 1998

Yelfowfffer Mfas/es

WICcint ,accjne awerage (96) awerage (%)

Angola 36 65 Benin 82 Bolivia 80 Brazil 38 96 Burkina Faso 27 68 Burundi 44 Cameroon 47

.Cape Verde 66 Central African Republk 36 39 Chad 25 30 Colombia 75 Congo Cote d'Ivoire 57 66 Demoaatic Republk of Congo Ecuador Equatorial Guinea Eritrea Ethiopia .French Guiana Gabon

• Gambia 91 /Ghana 67 ~uinea 58 • Guinea-Bissau Guyana 7 93 Kenya 61 Liberia 31 Mali 10 58 Mauritania Niger 85 Nigeria 26 Panama 10 95 Peru 93 Rwanda Sao Tome & Principe 59 Senegal 50 6S Sierra Leone 68 Somalia 47 Sudan 63 Suriname 82 Togo 33 Trinidad & Tobago 91 90 Uganda 30 United Republic ofTanzania 72 Venezuela 79 94

33

7 .6 Immunization coverage

7 .6.1 Global immunization coverage

Reported immunization coverage trends remained stable except in the South-East Asia Region and the African Region (Fig. 12). Global coverage with DTP3 in 1998 was reported to be 7 4%, the Regional figures ranging from 47% to 93%.

The downward trend in the South-East Asia Region is explained primarily by the fact that three large countries (Bangladesh, India, and Indonesia) used survey data instead of administrative data. The discrepancies between survey and administrative coverage data reflect the problems encountered in many countries with regard to coverage data quality (Fig. 13).

In Africa, 13 countries experienced declining cover­age, including two of the largest countries, namely Ethiopia and Nigeria, and this probably explains the slight overall downward trend (Fig. 14).

Of the 163 countries reporting to WHO in 1999 on DTP-3, 50 (30%) did not achieve 80% cover­age. This means that 52% of the global birth cohort live in countries where immunization systems need strengthening. Most of these countries are in the African Region (Fig. 15).

WHO and UNICEF collected information during 1999 on key indicators of the sustainability, quality and safety of immunization systems in 1998. Fig. 16 shows countries reporting the proportion of vaccines financed by government, and Fig. 17 shows countries having injection safety as a compo­nent of their annual work plans.

Only six of the 31 countries at risk for yellow fever outbreaks in the African Region and neither of the two at such risk in the Eastern Mediterranean Region reported yellow fever immunization cover­age figures. None of these countries achieved yellow fever coverage that was at least equal to measles cov­erage (Table 1), despite the fact that the vaccines were given during the same immunization visits. In the Americas, five of the ten countries considered at risk for yellow fever outbreaks reported coverage figures.

DEPARTMENT DF VACCINES AND BIDLDGICALS

Figure 12: Reported DTP3 coverage by WHO Region, 1989-1998

Figure 14: Reported DTP3 coverage in countries of South East Asia Region with the largest birth cohorts, 1980-1998

34

ANNUAL REPORT 1999

Figure 14: Countries in sub-Saharan Africa reporting decreasing DTP-3 coverage, 1996-1998

... ... ... ... -60 -50 -40 -30

Percentage (%) point decrease in DTP3 coverage

Figure 15: Reported DTP-3 global coverage in infants, 1998

>80%

■ 50-80%

■ <50%

No data

Data as of August 1999

---

... ... ... -20 -10 0

35

Ethiopia

Cote d'Ivoire

Gabon*

Zimbabwe

Central African Republic*

Uganda

Zambia*

Burundi*

Rwanda*

Mauritania*

Nigeria

Liberia*

Congo*

DEPARTMENT OF VACCINES AND BIOLOGICALS

Figure 16: Percentage of routine vaccines financed by governments

■ 0-49%

50-79%

>80%

No data

Sauret: Joint WH0/1/NICEF r,porting from 1999

Figure 17: Inclusion of a safe injections component to the national workplans

Sauret: Joint WH0/1/NICEF reporting from 1999

36

'.), ._1•:i,.

' ,,. ..... . )'

ANNUAL REPORT 1999

7.6.2 Immunization coverage in the African Region

Immunization coverage rates have generally been

stagnant or on a slight decline since 1995, although

there have been important variations between geo­

graphical areas. For BCG, 22 of 46 countries

reported 280% coverage, six reported an increase and 22 reported a decline (Table 2). For DTP3,

eight of 46 countries reported 280% coverage, ten reported an increase and 21 reported a decline. For

measles, seven countries reported 280% coverage, 13 reported an increase and 23 reported a decline. For TT2+, three countries reported 280% coverage,

14 reported an increase and 19 reported a decline.

Table 2: Numbers of countries in the African Region reaching 280% reported routine coverage in 1998 and numbers of countries with a change in reported coverage (25%) from 1995 to 1998, by antigen

Antigen Reaching >80% Increase Decline No change

!!CG 22 18

~i:!1/ /.)··· 22 8 7

6 10 11 13 14

21 15 20 15 23 10 19 13

While there are specific local reasons for these

changes, several issues cut across many areas and may have had a large effect on coverage. These

issues should be considered when the strategies for re-energizing EPI in the region are being addressed.

• Civil unrest continues in many countries in Africa. The Organization of African Unity

estimated that in 1999 civil conflict was taking place in 22 countries and that 90% of the

victims were civilians.

• Health sector reform (HSR) occurred in many

countries during the previous four years, notably in the Eastern Block countries.

Decentralization has disrupted logistics, plan­

ning and financial mechanisms. EPI was not well prepared for this transition. At the district

level, EPI now has to compete with other

district priorities for staff and funding. These

local priorities may legitimately be different

from national and global priorities, particular-

37

ly with regard to demands for curative care at the local level. Only in Ghana has HSR had a

positive effect on EPI coverage; this instance

should be studied further and the lessons learnt

should be used for guidance in other countries.

• Staff morale is very low in several countries ..

Peripheral and central level staff have been reduced in numbers. There are reports of staff

not being paid, of high staff turnover, and of

inadequate training.

• In some countries there may be fewer financial resources available for routine immunization

services, partly because of changes in donor

priorities and a lack of government resources

dedicated to EPI.

• It is unclear what the net effect of polio eradi­cation has been on routine coverage: the intro­

duction of activities such as polio NIDs,

together with other new priorities in EPI, may

have taken the focus away from achieving high

routine coverage.

7 .6.3 Region of the Americas

Provisional data for 1999 show an increase in vacci­

nation coverage for all antigens in the Americas

(Fig. 18).

Overall regional DTP vaccine coverage in 1998 was

86%; 23 of 39 reporting countries (59%) had cov­erage of 2 90%. The following countries reported

DTP3 coverage below 80%: Bolivia (76%),

Colombia (70%), the Dominican Republic (74%), Haiti (39%), and Venezuela (39%).Overall region­

al OPV3 vaccine coverage in 1998 was 89%; 25 of 38 reporting countries (66%) had coverage 2 90%

The following countries reported OPV3 coverage below 80%: Bolivia (75%), Colombia (72%), the

Dominican Republic (73%), Haiti (37%), and Venezuela (64%).

Overall regional BCG vaccine coverage in 1998 was

99%; 22 of 32 reporting countries (61 %) had coverage of at least 90%. Overall regional measles

vaccine coverage in 1998 was 86%; 22 of 39 report­

ing countries (56%) had coverage of at least 90%.

Under 80% coverage was reported by Colombia

(75%i), Haiti (42%), and Paraguay (78%).

DEPARTMENT OF VACCINES AND BIOLOGICALS

7.6.4 Eastern Mediterranean Region

The improvement in regional immunization cover­age observed since 1996 for all EPI antigens was maintained in 1998, mainly because of the sus­tained high coverage rates in most Member States. The reports received from Member States for 1998 indicate that the average regional coverage rates were 90% for BCG and 82% for OPV3/DTP3 and measles in children aged up to 1 year. Provisional data for 1999 indicate similar coverage rates.

Data for 1998 indicate that 17 countries were able to achieve an immunization coverage rate of90% or more for DT3/OPV3 (Bahrain, Cyprus, Egypt, Islamic Republic of Iran, Iraq, Jordan, Kuwait, Lebanon, Libyan Arab Jamahiriya,

fully integrated into national immunization pro­grammes for children under one year of age in 16 Member States (Bahrain, Cyprus, Egypt, Islamic Republic of Iran, Iraq, Jordan, Kuwait, Libyan Arab Jamahiriya, Oman, Qatar, Saudi Arabia, Syrian Arab Republic, Tunisia, United Arab Emirates, Yemen and the Self-Ruled Areas in Palestine and the popu­lation served by UNRWA). These countries account for about 47% of the total infant population of the region. Coverage rates of90% or more were report­ed from nine of them, and the overall regional average was 88%. Member States that have not yet included hepatitis B vaccine in their EPI schedules were urged to give a high priority to doing so. Lebanon, Morocco, and Pakistan are planning to introduce hepatitis B vaccine into their routine programmes.

Morocco, Oman, Qatar, Saudi Arabia, Syrian Arab Republic, Tunisia, United Arab Emirates, and the Self-Ruled Areas in Palestine and the population served by UNRWA). Sixteen countries report­ed a measles coverage rate of 90% or more (Bahrain, Cyprus, Egypt, Islamic Republic of Iran, Iraq, Jordan, Kuwait, Libyan Arab Jamahiriya, Morocco, Oman, Saudi Arabia, Sudan, Syrian Arab Republic, Tunisia, the United Arab Emirates, and the Self-Ruled Areas in Palestine and the population served by UNRWA). Some improvement was observed for coverage rates in Pakistan and Yemen. However, low coverage rates were still reported from Afghanistan, Djibouti, and Somalia.

Figure 18: Immunization coverage of children underl year of age, Region of the Americas*, 1995-1999**

The average regional TT2+ coverage among pregnant women during 1998 was maintained at approximately 50%. However, it should be borne in mind that the proportion of immune women in the communities is higher than that calculated from TT2+ annual immu­nization coverage and that it could be estimated through monitoring the pro­tection of children at birth.

Efforts are being made to expand the use of existing vaccines and to incorporate new ones into immunization pro­grammes. Hepatitis B vaccine is now

38

Source: Country reports • Exduding Canada and USA

.. Provisional

ANNUAL REPORT 1999

Hib conjugate vaccines have been intro­duced into routine infant immunization schedules in four countries (Bahrain, Kuwait, Qatar, and the United Arab Emirates). Oman and Saudi Arabia have prepared plans for inclusion of the vac­cine by 1999-2000. A pilot project was started in Syria for inclusion of the vac­cine in routine immunization in a limit-

Figure 19: Immunization coverage, Eastern Mediterranean Region 1992-1998

lmmunllltioo roverage%

100

80

60

ed geographical area, which will be 40

expanded later. It was recommended that countries should implement infant 20

immunization in accordance with their capacities, national priorities and disease burdens. Rubella vaccine combined with measles and mumps vaccine is included in the routine immunization pro­grammes of 12 countries in the Region.

In addition to routine immunization activities, other supplementary immu­nization activities were conducted, including polio NIDs and mopping-up operations and campaigns in areas at high risk for neonatal tetanus and measles.

0 '91

Immunization coverage%

100

80

60

40

20

0

'93 '94 '95 Ytor

BCG

'96 '97 '98

Measles

Immunization ·cowrage%

100

80

60

40

20

0 '91

Immunization coverage%

100

80

60

40

20

0

'93 '94 '95

Year

'.:' :,

'96 '97

During 1999 all Member States except Cyprus conducted supplemental immu­nization activities. NIDs were organized with high coverage in all Member States exceptthe Islamic Republic of Iran and Tunisia, where subnational immuniza-

'91 '93 '94 '95 '96 '97 '98 '91 '93 '94 '95 '96 '97•,.

tion activities were conducted in border and high­risk areas. Most significantly, immunization activi­ties were accelerated in all remaining countries of endemicity. This included improving the quality of campaigns through better planning, increased resources and house-to-house vaccine delivery, and increasing the number of campaign rounds. Two NIDs were conducted in both Afghanistan and Egypt. In response to the outbreak that began dur­ing May 1999 in Iraq, two additional NID rounds were conducted. Pakistan, Sudan, and the Syrian Arab Republic conducted additional mop-up oper­ations in high-risk and/or border areas. WHO pro­vided technical assistance in all aspects ofNID plan­ning, implementation and evaluation, particularly to countries where the virus was still circulating.

During 1999, coordinated immunization and sur­veillance activities continued under Operation

39

Year Year

MECACAR, involving countries of the European Region and the Eastern Mediterranean Region. Coordinated NIDs and mopping-up campaigns were conducted jointly by Afghanistan, the Islamic Republic of Iran, and Pakistan, and by the Islamic Republic of Iran, Iraq, the Syrian Arab Republic, and Turkey. Different Regional and inter-Regional epidemiological blocks coordinated immunization acrivities under the auspices of several organizations including the Gulf Cooperation Council, the Maghrebian Union and the South Asian Association for Regional Cooperation. Attention is currently focused on strengthening coordination between the countries of the Horn of Africa, espe­cially Eritrea, Ethiopia, Djibouti, Somalia, and Sudan.

The high-risk approach to the elimination of neonatal tetanus, involving two rounds of immu-

;;

I! {9f •·

, ... I

I

DEPARTMENT DF VACCINES AND BIOLOGICALS

nization of all women of childbearing age in identi­fied high-risk areas, was implemented in some Member States, including Egypt and Sudan. However, only limited areas were covered, and not all identified high-risk areas were covered. Plans of action for nationwide neonatal tetanus elimination, based on the high-risk approach, are available for all Member States needing them. District microplans were formulated with detailed costings for Egypt, Pakistan, Sudan, and Yemen.

Kuwait and Oman conducted national mass catch­up campaigns during 1994. In Oman, the campaign included all children aged 9 months to 18 years and was followed by the administration of a second dose within the immunization schedule. Very low inci­dence was maintained in Oman and there was no indication of a need to conduct a follow-up cam­paign. In Kuwait the initial campaign included chil­dren aged 6 to 18 years; in response to an outbreak that began in 1998 a catch-up campaign including children aged 6 to 11 years was conducted. Bahrain and Jordan conducted the first phase of their cam­paigns in late 1997 and early 1998 respectively, tar­geting school-age children; the second phase, target­ing preschool children, was conducted in both coun­tries during May 1999. Catch-up campaigns were conducted during 1998 in Syria (targeting children aged 9 months to 15 years), Tunisia (targeting chil­dren aged 7 to 15 years), the United Arab Emirates (targeting children aged 9 months to 4 years), and Saudi Arabia (targeting children aged 12 to 15 years). During 1999 the second phase of the catch-up cam­paigns was completed in Saudi Arabia (targeting chi!-

Figure 20: Percent vaccination coverage by antigen, SEAR, 1995-1998

40

dren aged 6 to 12 years) and the United Arab Emirates (targeting children aged 4 to 15 years).

Countries were encouraged to deliver vitamin A supplementation in routine EPI schedules and sup­plementary immunization activities, including polio NIDs and anti-measles campaigns. Vitamin A was included in NIDs in Afghanistan, Pakistan, Somalia, and Yemen. Vitamin A was included in the routine immunization programmes in Egypt and Oman during 1999.

The question of unsafe lllJection practices was discussed during most intercountry meetings. Assessments of lllJection practices during immunization ~essions were conducted in Egypt, Sudan, and Yemen. Support is being provided for countries to develop plans for safe immunization.

7.6.5 South-East Asia Region

Coverage declined for OPV3, DTP3, BCG and measles vaccines from over 80% of children in their first year oflife during 1995-1997 to about 70% in 1998. Preliminary data for 1999 showed that 63% of districts in Bangladesh achieved routine coverage of more than 80 %. In India, coverage of more than 80% was reported for BCG by 47% of districts, for OPV3 by 44%, for DTP3 by 37 % and for measles by 9% only. Myanmar reported that 85% of dis­tricts achieved over 80% routine coverage. In Nepal, 80% of districts reported over 80% coverage for BCG but only 50% for OPV3 and DTP3. About 70% of districts reported over 80% coverage

ANNUAL REPORT 1999

Table 3: Immunization coverage by country,South-East Asia Region, 1997-1998

BCG DTP3 Country/Area 1997 1998 1997 1998

: Bangladesh 100 92 98 78 '.:Bhutan 92 94 87 86 : ·. DPR KKorea n.a. 64 n.a. 37 ( India 96 79 90 73 '.'Indonesia 99 85 90 65 ',,,,''

• Maldives 99 99 97 97 : Myanmar 94 91 90 87 '(Nepal 96 86 78 76

,.,,;,',,,

.. :~r!,La.nka 96 90 97 94 /:!:.TMiland 99 n.a. 98 n.a ::R~gion. 97 81 90 72

for measles. V&B/SEAR will attempt to increase and maintain high coverage in 2000.

7.6.6 Western Pacific Region

In 1998, reported routine immunization coverage

for all antigens remained high. Most countries reported routine coverage of infants with all anti­

gens at over 80%. Some, however, including

Cambodia, the Lao People's Democratic Republic,

and Papua New Guinea, reported less than optimal coverage.

7. 7 Target diseases

In 1998, 2091 cases of diphtheria were reported in

the South-East Asia Region. This represented an increase in comparison with the fig-

ures for 1993-1996 but a decline

OPV3 Measles TT2 1997 1998 1997 1998 1997 1998

98 78 97 72 94 86 87 85 84 71 70 80

n.a. 77 n.a. 34 n.a. 5 91 73 81 66 80 87 77 93 76 78 97 97 96 98 96 91 90 88 88 85 83 78'· 78 70 85 73 19 65 98 94 94 91 89 95 n.a. n.a. n.a. 83 n.a:· 84 67 91 74 79 60

While these figures can easily be used to monitor a

trend, it is likely that the real incidence was higher.

The difficulty in diagnosing these diseases and the

poor quality of routine reporting are major reasons

for the production of inaccurate data. With regard

to pertussis, other sources have calculated that the

true incidence in the South-East Asia Region is

closer to 8.5 million cases and that 90 000 deaths are attributable to the disease.

7. 7 .1 Yellow fever

In 1998, reported routine immunization coverage

for all antigens remained high. Most countries reported routine coverage of infants with all anti­

gens at over 80%. Some, however, including Cambodia, the Lao People's Democratic Republic,

from the 6549 cases reported in

1997. Countries in this Region reported 46 666 pertussis cases,

Figure 21: Reported cases of vaccine preventable diseases in SEAR

substantially more than in the pre­

vious two years ( 41 940 cases in

1997 and 22 479 in 1996). The bulk of cases in 1998 were in India (31 199 cases) and Nepal (14 339

cases). In 1998 the numbers of

reported cases of measles, neonatal

tetanus and polio were 62 722,

3324 and 4777 respectively. A small

outbreak of pertussis was reported in Sri Lanka in 1997. However, no

outbreak of diphtheria was reported

during that year.

Cases

12000

10000

8000

6000

4000

2000

0 Pertussis*

41

■ 1995 ■ 1996 ■ 1997 1998 1999

Diphtheria Measles* NNT Polio

•numb,rofcas,s should be muttiplied by 10

DEPARTMENT DF VACCINES AND BIOLOGICALS

and Papua New Guinea, reported less than optimal coverage.

In 1988 the joint WHO/UNICEF Technical Group on Immunization in Africa recommended that yellow fever vaccination be integrated into EPI in countries considered to be at risk. Only 17 of these countries have given effect to the recommen­dation. In 1998 only eight countries reported immunization coverage, the estimated average being 40%.

The following strategies are proposed: • prevention of outbreaks by increasing routine

immunization coverage to at least 80%; • control of outbreaks through early detection

and laboratory analysis of blood specimens taken from suspected cases;

• emergency response to outbreaks through mass campaigns;

• prevention of outbreaks in high-risk areas through mass campaigns.

Yellow fever remains a major public health concern in Africa. Outbreaks occur periodically in the yel-

low fever belt, especially in the West African block. In general there has been poor surveillance and delayed response, sometimes resulting in cata­strophic outbreaks. There has been marked under­reporting of the disease. It is estimated that 200 000 cases and 30 000 deaths are attributable to yel­low fever annually in sub-Saharan Africa.

The capacity for laboratory confirmation of epi­demics has been strengthened in Africa. Of 31 countries at risk for yellow fever, 22 have benefited from training through the Regional Polio Laboratory Nerwork. Participants were provided with diagnostic reagents at the end of the course. There are 15 laboratories in the region with the facilities and expertise required for yellow fever serology. Polio laboratories in countries at risk for the disease are also capable of isolating the yellow fever virus. Sentinel surveillance systems have been created in some countries (e.g. Kenya, Senegal), allowing for constant monitoring of the yellow fever situation.

The lack of achievement in the control of yellow fever has been ascribed to the following factors:

Figure 22: Geographical distribution of yellow fever cases in South America, 1986-1999

1 dot = 1 case:

No case

■ With case

Source: Ministry of Htalth, data as of J 1 Dtcember 1999 (Bolivia, Colombia, Ewador, Ptru and Venezu,la)

1

Total: 204 cases !

42

1999 Yellow Fever Cases

Brazil 72 cases

Bolivia 68 cases

ANNUAL REPORT 1999

• a lack of motivation, commitment and politi­

cal will, and of public and professional

awareness;

• competing priorities of other vaccines; • a lack of effective country plans of action, weak

surveillance and reliance on emergency vacci­

nation;

• a lack of finance for the integration of yellow

fever vaccine into the routine EPI.

The risk of urbanization of yellow fever m the

Americas remains a concern because of the wide dissemination of Aedes aegypti in the 11 countries

located inside the enzootic area (Bolivia, Brazil,

Colombia, Ecuador, French Guiana, Guyana, Panama, Peru, Suriname, Trinidad and Tobago, and

Venezuela). Only Canada and Chile are free of

A. aegypti. The growing number of travellers by

road and air between countries in the region facili­tates the introduction of yellow fever into urban

areas outside the traditional enzootic areas, where

there are heavy infestations of A. aegypti at present.

A more aggressive yellow fever strategy was recom­

mended by AMRO's Technical Advisory Group on Vaccine-Preventable Diseases (TAG) with a view to

achieving prompt vaccination of the entire popula­

tion in areas where yellow fever is endemic (Bolivia, Brazil, Colombia, Ecuador, Guyana, Peru, and

Venezuela). It was also recommended that the

vaccine be incorporated into the basic routine

Figure 23: Yellow fever cases per year in selected countries, 1985-1999"

Number of Cases

600

500

400

300

200

100

0

Source: HVP/PAHO

immunization schedule for children under one year

of age by administration with measles vaccine.

In 1999 there were reports of 204 cases and 97 deaths. Bolivia, Brazil, and Peru accounted for

96% of reported cases; Colombia and Ecuador also

reported cases. These numbers are close to the

averages reported during the last 10 years.

Underreporting is still a problem and the

differences between countries in disease incidence

have much to do with differences in the sensitivities

of surveillance systems.

AMRO is collaborating closely with national

authorities to enforce the TAG recommendations.

The following major obstacles exist: a lack of polit­

ical commitment in some countries, partly attribut­

able to a failure to recognize the severity of the cur­rent situation; financial difficulties in purchasing

yellow fever vaccine; and serious shortages of yellow

fever vaccine in the international market.

7. 7 .2 Rubella

AMRO's technical cooperation in the rubella field

focused on the introduction of rubella vaccine in

routine immunization programmes and on the inte­

gration of measles and rubella surveillance. The objective of rubella surveillance is the detection of

circulating virus rather than of each case. Countries

were presented with options for either rapidly

*Data as of 10 December 1999 for Bolivia, Brazil, Colombia, Ecuado~ French Guyana, Peru and Venezuela

43

DEPARTMENT OF VACCINES AND BIOLOGICALS

controlling rubella or for preventing cases of con­

genital rubella syndrome (CRS). AMRO has rec­

ommended a one-time mass campaign with

measles- and rubella-containing vaccine aimed at

females aged 5-39 years in countries wishing to achieve rapid control of CRS. Countries wishing to

control both rubella and CRS should also conduct

mass campaigns with such vaccine for males and

females aged 5-39 years.

The majority of countries in the region now have MMR vaccine in their national immunization schedules. Bolivia, Guatemala, and Paraguay plan

to introduce MMR vaccine during 2000. Still

pending are Haiti and Peru.

Chile carried out a preventive vaccination campaign

for CRS, targeting females aged 10-29 years. The

campaign achieved 98% coverage with rubella vac­

cine, thanks to the strength of the national immu­

nization programme and a highly successful social

mobilization campaign. The Ministry of Health is

implementing a surveillance system in order to: provide information on the effectiveness of the

campaign and policies; measure its impact on the

occurrence of rubella and CRS; identify groups of

people or geographical areas in need of additional

control efforts to reduce disease incidence; and eval­

uate vaccine effectiveness, duration of vaccine­

induced immunity, and other aspects of the efficacy

and safety of the vaccine.

Costa Rica carried out an MMR campaign follow­

ing a rubella outbreak during 1999 in which over 250 cases were reported. The campaign targeted

children aged 1-14 years. Selective adult vaccination

among risk groups (health workers, people working in educational establishments, tourist workers and

migrants) with MMR vaccine was also undertaken.

The rubella outbreak in Costa Rica highlighted the

need for all countries to adjust their surveillance

systems for suspected measles cases so as to include rubella. The outbreak in Costa Rica was accompa­nied by an increase in rubella activity in almost all

other Central American countries. The countries of

Central America are planning to move rapidly towards the integration of measles and rubella sur­

veillance, creating a fever and rash surveillance sys­

tem. AMRO is adapting the Measles Eradication

Surveillance System software and expects to provide

technical cooperation in the collection of proper

specimens for virus isolation and in the supply of lgm rubella kits to all laboratories.

The objectives of integrated measles and rubella surveillance are: to know where the virus is circulat­

ing; to obtain timely detection of cases; to ensure

adequate outbreak control; to prevent CRS; to mea­

sure the magnitude of the disease burden; and to

provide evidence of the impact of various interven-

Figure 24: Annual reported rubella cases, Latin America and the Caribbean, 1984-1998

Source: PAHO/MH

44

ANNUAL REPORT 1999

tions. Besides the Central American countries, other

F.gre2B: CaE3 cf dipJ. fur :iantreEurcpEmREgXJJ, 1991-19.'B

countries in the Region are

integrating measles and rubel-

la surveillance. AMRO

expects this integration to

have the added benefit of

greater reporting of suspected measles cases. For surveillance

purposes it has been decided

that any patient in whom a

health care worker suspects measles or rubella infection

should be considered to have

measles until the contrary has been proved. A blood speci­

men should be obtained from

every patient who fits the case

definition of suspected rubella

25cm

:;n cm

JS cm

JO cm

or measles, unless the case is linked epidemiologi­

cally. All sera from suspected measles cases that test

negative for measles IgM antibodies should be test­

ed for rubella IgM antibodies and vice versa.

7. 7 .3 Diphtheria

Based on sound epidemiological projections, It 1s

estimated that the implementation of aggressive measures in the 15 diphtheria-epidemic countries

of the European Region has prevented more than 560,000 cases and more than 15,000 deaths. In

1999 there were 1,121 reported cases. All countries

have made significant efforts towards fully immu­

nizing their child and adult populations. The European Laboratory Working Group on

Diphtheria, formed at the initiative of the \VHO

European Office in July 1993 is still very active in monitoring the microbiological surveillance of

diphtheria and typing the causative agent, leading to the establishment of a database of isolates of

C. diphtheriae.

The declining trend of epidemic diphtheria in the NIS reflects the resource mobilization and immu­

nization activities undertaken by the affected coun­

tries in close collaboration with the international

community. The situation in Armenia, Azerbaijan, Kazakhstan, Estonia, Lithuania, Moldova,

Turkmenistan and Uzbekistan shows that the epi­

demic is clearly coming under control. During

1998/99, the situation greasdy improved in

Georgia. The trend in Russia is a clear decrease.

■ Rl!)crrtfrlcclffi PJg3!::tfrlcam

1932

45

However, an average of 100 cases are still being

reported every month, demonstrating gaps of

immunity, continuing circulation of C. diphtheriae and the potential for further spread. The situation

in Kyrgyzstan, Ukraine, and Tajikistan has also

improved. Epidemic control is still yet fully achieved, however. Concerns have been expressed

on the endemic status of Latvia. This country

showed an rising trend in 1998 and 1999, probably

due to the low acceptance of vaccination by hard­

to-reach adulr populations. In December 1999, the

situation was reviewed and innovative ways were carefully considered of immunising the high risk

group 35-50 years of age.

7 .8 Communication and advocacy

WHO's Direcrnr-General declared war on polio

during the lvfarch 1999 Polio Management ;-.freeing. In Mar she met health ministers of coun­

tries where the disease is endemic and of donor

countries at an extraordinary meeting during the \XTorld Health Assembly. Member States voted

unanimously to endorse acceleration of the initia­tive on the year 2000 target; India announced a

fast-track plan for NIDs to be held in four consec­

utive months, followed by two monthly mop-ups in

eight high-risk states.

During the year the Director-General travelled to

Bangladesh and C6ce d'Ivoire in order to participate

DEPARTMENT DF VACCINES AND BIOLOGICALS

in NIDs, thus expressing her commitment to the initiative. In July a joint announcement by Mr Kofi Annan, Dr Gro Harlem Brundtland and Ms Carol Bellamy, issued by the UN Secretary-General's Office and UNICEF, called on belligerents to secure Days of Tranquillity in the Democratic Republic of Congo so that polio vaccination could be carried out. Dr Michael Scholtz travelled to this country to participate in the second round ofNIDs, while Dr Bjorn Melgaard performed the same func­tion in India.

In July a press conference was held in London to introduce new partners in the initiative, namely the diamond mining and trading company De Beers and the world-renowned British photographer Lord Snowdon, who in May photographed polio suffer­ers in the Angola outbreak. In October a donation of 50 million doses of polio vaccine from a leading manufacturer, Aventis Pasteur, was announced. In the same month there was a public announcement of donations totalling US$ 78 million from the Bill and Melinda Gates Foundation and Mr Ted Turner's United Nations Foundation.

Effective implementation of immunization strate­gies has generally entailed strengthening the capac­ity of countries, making resources available, and re­enforcement at global and regional levels. Achievements in 1999 included:

• the strengthening of national core teams from ministries of health, UNICEF and WHO through regional training and planning work­shops;

• the strengthening of communication and social mobilization planning in countries by means of support for the development of research-based integrated plans for EPI/NIDs/surveillance which ensure that activities are organized throughout the year;

• high-level advocacy through regional leaders and bodies; heads of state and agencies were invited to preside over NID launches;

• advocacy through media relations and sports; WHO partnership with football became glob­al when the Federation Internationale de Football Association (FIFA), the world govern­ing body of football, decided to support the Kick Polio Out of Africa initiative. This unique contribution will dramatically boost the polio eradication campaign, ensuring that it will receive maximum attention and backing from

46

both the football world and millions of foot­ball fans.

Partnerships with media organizations have become stronger. Activities have been implemented with RPI, CFI, AITY, BBC and Africa No. 1, including educational programmes and tour visits to report on NIDs in some of the countries where there are particularly difficult conditions. Work with BBC has resulted in a project in Tanzania and may lead to one in Ethiopia, while work with RFI and Africa

No. I on the production of programmes could serve as a reference for future collaborative efforts.

The challenge for advocacy, social mobilization and communication in the coming years will be in expanding the gains made in political commitment and partnership relating to routine immunization.

7.9 Service delivery

7.9.1 Programme planning

After extensive deliberation and review during 1999, V&B developed a four-year Strategic Plan for 2000-2003, encompassing a broad range of activi­ties linked to the objectives of Innovation, Immunization Systems and Accelerated Disease Control. Nine specific goals or targets were identi­fied and each was assigned a well-defined and mea­surable outcome or critical indicator. The targets encompass the expertise and contributions of all five teams in V&B and therefore require the inte­gration of activities. Three of these targets are time­limited priority projects, namely Accelerated Vaccine Introduction, Safety of Immunization and the Polio Eradication Initiative. For the purposes of the Strategic Plan a limited number of products were also defined, identifying the areas of work to be tackled in order to achieve the targets. These products represent the measurable outcome of the work of the V&B teams.

7.9.2 Programme assessment

The environment in which immunization systems operate is changing. Health sector structure, the location of authority and responsibility, and the mix of public and private participation are changing sig­nificantly in many countries.

ANNUAL REPORT 1999

As new vaccines, equipment and technologies

become available the need increases to determine the readiness of immunization systems to introduce

and sustain these innovations. New goals demand

new strategies. The capacity of existing services

must be assessed in order to determine whether they

can achieve new goals and implement new strategies (e.g. the need for stronger surveillance).

A common assessment tool is needed. Health sector

officials, managers of services, development part­

ners and nongovernmental organizations have asked for a common assessment tool with a view to

identifying where improvements are needed and

planning individual and joint inputs.

A new methodology has been developed to examine the health systems and the external environments in

which immunization systems operate, as well as the

services themselves. Assessments carried out under

these guidelines should provide sufficient informa­

tion to prepare or update long-term plans of action

or to prepare proposals for securing the support of

partners in order to:

• increase the accessibility and use of routine immunization services, especially for people

who are not reached at present;

• improve the efficacy of immunizations and the quality of immunization services;

• increase the availability of new vaccines and new technologies in countries that have the

capacity to integrate them;

• ensure adequate and reliable financing of national immunization activities;

• support the development of health systems.

The assessment methodology is based on a number

of concepts. First, the focus is on performance. Quantifiable information alone, for instance on the

number of vehicles assigned to a district office or on whether a national policy on safe injections exists,

does not provide evidence of service effectiveness

or safety.

The inquiry concentrates on the level at which ser­

vices are provided, and problems are traced to the

level (service delivery, subnational or national) of

their origin. The assessment process involves the

people who know what the problems are and who

will participate in implementing the solutions. This methodology involves service providers, their

supervisors and other major stakeholders through

47

individual discussions and group work sessions at

every level.

Immunization operations, the health system and

the external environment are included in assess­ments. Immunizations are provided in a context

consisting of three components: the immunization

operations themselves, the health system and the

external environment. Because this context influ­

ences who receives immunizations and how they are

provided, a comprehensive assessment must exam­

ine all three. An assessment of immunization oper­ations may include an examination of the costs of

services and financing.

On the basis of experience gained in an initial assessment the tool will be streamlined and simpli­

fied for ease of use in guiding data collection and in

compiling reports.

7.9.3 Management

When EPI was launched, most countries were

introducing national immunization programmes. Their problems were mostly technical and mostly

the same because the countries were at similar stages

in controlling the target diseases. For example, it

was necessary to determine what strategies to use for providing routine immunization services and

how to ensure vaccine potency. Twenty years later,

managers are dealing with many of the same prob­

lems but the environment in which they work is

more complex. They need to devise more effective

strategies for vaccinating against diseases at different

stages of control, the number of diseases covered by EPI is expanding, and government systems are

changing. All managers need more sophisticated

skills in forecasting, influencing and responding to,

for example: • changes in vaccines, equipment and procedures;

• problems, e.g. unsafe injection practices; • changes in the organization of health services,

e.g. increasing privatization;

• government reform, e.g. decentralization.

To meet these needs, managers must have access to

information that is accurate and up-to-date and

must have sharper skills in using information to plan

and execute strategies and meet programme goals.

A project to be implemented in eight African coun­

tries will: 1) develop a comprehensive set of man-

DEPARTMENT OF VACCINES AND BIOLOGICALS

agement tools and materials enabling public health

personnel to strategically plan, manage and coordi­

nate national immunization programmes; 2) con­

duct extensive training of vaccine managers at the national and subnational levels, using the tools and

materials developed; and 3) establish an electronic

capacity that links vaccine managers at country level

with each other and with Headquarters in order to

provide immediate management support.

The goal of the proposed project incorporates three

major elements: • the collection and consolidation of informa­

tion that can guide managers in decision-mak­

ing and is presented in an accessible format;

• the promotion and dissemination of the infor­mation to all managers electronically and/or

via reference documents;

• keeping the information timely.

These elements require the development of three

products:

• a reference manual; • an electronic component; • a plan for updating information in the manual.

The reference manual will be the major product of

the proposed project.

7 .9.4 Sustainable outreach

Remote populations are exposed to specific health risks because of a combination of risk factors, such

as low coverage of health services. The aim of sus­

tainable outreach services (SOS) is to bring immu­

nization and a basket of minimum health interven­tions to populations physically beyond the reach of

the regular health system. The strategy was first pro­posed in 1998 and is now well developed. UNICEF

has adopted it as one of the strategies aimed at increasing immunization coverage, especially

among remote populations. The additional inter­

ventions to be included in the basket may be deter­mined by:

• the needs expressed by and/or found in the

community;

• the benefits, complications and conditions of including specific interventions;

• the operational constraints on bringing these interventions to the community.

48

The interventions may be of a non-medical nature,

including cattle immunization, sanitation or any

other service meeting community needs and comply­ing with a defined set of operational constraints. SOS

is heavily based on community participation in:

• expressing specific needs; • facilitating the arrival of teams;

• appointing persons as focal points who can be trained to provide simple services on a more

continuous basis with the support of profes­sional health staff making periodic visits.

SOS can be permanent if cost-benefit analyses show that a fixed health structure is not feasible

(e.g. periodic campaigns in Latin America), or tem­

porary, exploring the possibilities of and leading to

a fixed structure. The approach is not completely new: lessons have been drawn from a number of

experiences, and SOS can be seen as their synthe­

sis, to be applied and adapted in other Regions. All

the examples mentioned below are similar in that

several interventions have been brought to remote

populations:

• village health days in Tanzania; • periodic campaigns in the river area in Ghana;

• permanently rotating teams in Colombia; • periodic visits by health workers and midwives

in Benin, using the opportunity to train per­sons serving as dracunculiasis focal points;

• community health centres in Mali;

• certain vaccines beyond- the cold chain for Indonesian midwives working in remote

populations;

Figure 25: Diagrammatic representation of how SOS might work in different situations

ANNUAL REPORT 1999

• polio NIDs, based on flexible strategies and community participation, reaching cover­

age figures far exceeding those of routine

immunization.

The elements of sustainability and system-building

vital to the development of SOS include strength­

ening the capacity of the community to express and

demand needs and manage service delivery/imple­

mentation, a sustainable transport management system, and capacity-building through the training

of staff.

SOS does not aim to bring global guidelines or pre­scriptions to countries, but rather to give support by

providing product specifications and experiences

from elsewhere, thus allowing countries to devise

health systems specifically for remote populations. In

1999, four countries were chosen to implement SOS

pilot projects jointly with UNICEF: Chad, Mali,

Mozambique, and Uganda. A WHO/UNICEF meeting was held in Nairobi to finalize the strategies

and to prepare for the project, which will last 30

months, beginning in 2000. SOS is a dialogue, open

to all suggestions aimed at the improvement of health among unreached populations.

7 .10 Financing

Critical indicators: • Number of countries having had at least one

ICC meeting to obtain financial support for routine immunization services. Current status

= 75/190.

1999 saw a major change in the focus on financing of immunization programmes and the promise of

more funds available, especially for the purchase of new vaccines. V&B financing activities were largely centred on activities for and with GAVI and its Task

Force on Financing. Attention was also paid to immunization costs in actual programmes and to

various financing mechanisms.

A paper on options for a global fund was published. The fund, called the Global Fund for Children's

Vaccines, was set up through GA\11. V&B staff

were involved in this process and helped to develop

a proposal to the Bill and Melinda Gates Foundation which resulted in substantial financial

support. V&B staff participated in the GA\11 Task

49

Force on Financing and collaborated in the devel­

opment of a country assessment tool along with

critical indicators for its use.

Costing studies were conducted on immunization

programmes in conjunction with similar studies on

safe injections in several countries. The findings

provided important information about the sources

of funding for immunization, the proportions of

funding provided by countries and donors, and

breakdowns of costs in several types of immuniza­

tion delivery situation. A preliminary analysis of costs for introducing new vaccines to countries that

might benefit from the Heavily Indebted Poor Countries initiative (HPIC) was completed and

used as the basis of a paper presented to the GAVI

Board.

Although the new Global Fund will be an impor­

tant source of financing it is only one tool for

immunization funding. V&B is collaborating with other GA VI partners to definine the characteristics

of key financing methods for countries.

Typical of the efforts by Regions to fund immu­nization ,vas the annual intercountry meeting of

EPI managers held in Damascus in June 1999. The meeting was also attended by representatives from

UNICEF's Middle East and Northern Africa

Region and other collaborating agencies, including

Rotary International. Discussions were held on

progress in EPI activities relating to routine

and supplemental immunization, target disease

occurrence and the status of achievement of global goals in Member States. Recent advances and rec­

ommendations for the improvement of EPI were

explained and discussed. The impressive progress

towards the eradication of poliomyelitis in the Eastern Mediterranean Region of WHO is a result of extensive efforts of national authorities and the

support provided by the consortium of partners for

polio eradication.

The largest share of human and financial resources

for eradication efforts in the Region has been com­mitted br the ;-.,fember States. WHO/EMRO con­

tinued to play a central coordination role and pro­

Yided continuing technical and operational support

to all :'vfember Srates. During 1999, eight interna­tional staff and over 50 short-term consultants were

deployed in the priority countries that had not

achieved interruption of poliovirus transmission.

DEPARTMENT DF VACCINES AND BIOLOGICALS

About 100 national staff were recruited to support polio eradication activities, particularly AFP surveil­lance. WHO/EMRO further strengthened its part­nership with international agencies and govern­ments supporting polio eradication, particularly Rotary International, CDC, Mr Ted Turner's United Nations Foundation and the governments of Canada, Japan, and the United Kingdom. The central role of WHO/EMRO in polio eradication in the Region is highlighted by the fact that, during 1998 and 1999, voluntary funds amounting to nearly US$ 23 million were channelled through EMRO by partner agencies, mainly for Member States requiring external financial support. EMRO also played a key role in facilitating bilateral support to countries and in raising funds for the purchase of OPV through UNICEF in several Member States. It should be noted with special appreciation that the Council of Arab Ministers of the Gulf has agreed to provide US$ 1.5 million in support of polio eradi­cation in the Region. It is hoped that this contribu­tion will be followed by similar contributions from Regional organizations.

The meetings of the lnteragency Coordination Committee at both national and Regional levels have led to the identification and bridging of shortfalls in funding. Joint planning by national authorities, WHO and UNICEF has been instru­mental in the identification of external support required to address national needs for polio eradica­tion. The outcome of this dose collaboration was the development of a three-year plan for 2000-2002, representing a comprehensive budget for polio eradication in the priority countries and forming the basis of fund-raising for countries in need of external support.

7 .11 Health sector reform

Health reforms, taking place in most countries around the world, are changing the way health ser­vices are delivered. In 1998-99, EPI commissioned studies that were conducted in Kyrgyzstan, Uganda, and Zambia in collaboration with USAID/ BASICS. These studies aimed at drawing general lessons from the reform process, reviewing EPI in relation to the health reform process, and develop­ing a reference guide for national immunization

programmes during health reforms.

50

No single model encapsulates health reform. It sometimes involves radical constitutional and struc­tural changes in health services and other sectors. The reforms do not occur in a linear fashion; usual­ly there are multiple streams of change. There are, however, similarities from which lessons can be drawn for strengthening immunization services. These lessons can be used to devise approaches ensuring that services of adequate quality are provided effectively, not only in reformed health systems but also during the process of change.

Health reform should be seen as an occasion and opportunity for reanalysing immunization priori­ties and policies. When this is done, due considera­tion must be given to financial and operational parameters.

A meeting entitled "Health Sector Reform and Priority Health Interventions: the Case of Immunization Services" was held in Washington DC on 15-16 November 1999. It was organized jointly by V&B/Health Technology and Pharmaceuticals, and the Cluster of Evidence and Information for Policy, both of WHO Headquarters, and the Division of Vaccines and Immunization and the Division of Health Systems and Services Development, both of PAHO.

The expected outcomes of the meeting included the identification of key issues in health sector develop­ment-reform, a review of the health sector develop­ment-reform perspectives from development part­ners, and a discussion on key steps and best prac­tices whereby countries and regions can sustain effective immunization coverage and quality of ser­vices during the health reform process. Country case studies were presented which highlighted the key issues that immunization services are facing in a rapidly changing socioeconomic environment. Excerpts of the major recommendations are presented below.

• A posltlon paper should be prepared that includes information on best practices for pri­ority health interventions using the case of immunization programmes as an example within the context of major health systems development issues (e.g. financing health sec­tor reform, policy and advocacy).

ANNUAL REPORT 1999

• Fact sheets will be prepared to assist countries and their development partners to facilitate

and guide discussions and dialogue on health

systems development and priority health inter­ventions.

• WHO and development partners should work with countries to ensure that the assessment of

priority health interventions incorporates

essential issues relating to health systems devel­

opment.

• Countries should invite development partners

to participate in joint planning processes for the health sector, including priority health interventions and their financing. The latter

should include ensuring that the financial

envelope for immunization programmes is part of the overall financial framework. This should

be the first step in ensuring that national pri­orities are based on evidence and reflect peo­

ple's health needs. Development partners

should ensure flexibility in financing priority health interventions and should avoid ear­

marking.

• Countries and development partners should ensure that national immunization plans

become an integral part of national health sec­

tor development plans and that the indicators

of performance of national immunization plans form a key part of the overall monitoring

system for the sector.

• Countries and development partners should

identify key indicators for monitoring the per­

formance of the overall health system. Immunization indicators should be a part of

these indicators.

• Countries and development partners should work to ensure that the capacit:y for specific

technical skills and functions, planning and management are strengthened at all levels

so that they help all units to effectively and efficiently implement priority health interven­

tions such as immunization.

• Countries should focus on developing manage­rial capacity at the district level, and this should

include integrated in-service training and the

development of performance incentives.

AMRO is monitoring the progress of health reform and decentralization in the Americas through its

evaluations of national immunization programmes.

In the past year, evaluations were performed in the

51

Dominican Republic, Ecuador, Paraguay, and Peru.

Extensive interviews conducted at the central and

local levels, as well as the political, managerial and beneficiary levels, allow AL\1RO to obtain a com­

prehensive view of a country's national immuniza­

tion programme within the context of ongoing

strucmral processes.

lessons learnt from these exercises point to changes

in some of the key instruments used by immuniza­

tion programmes and to the addition of new instru­

ments for planning, financing and delivering immunization programmes. National plans of action, for example, have been used as a template

for country planning, monitoring and evaluation of

national immunization programmes at the central

level. The plans, prepared for five-year periods, out­line objectives and activities and provide estimates

of human and financial needs, investments and

sources of funding. The process of health sector

reform and decentralization is leading to changes in the development and implementation of these

plans, the make-up of partners and the funding

mechanisms used.

In Peru the Ministry of Health seeks to strengthen

the decentralization of basic health services through Committees of local Administration by

increasing the participation of communities,

municipalities and local health entities in the plan­

ning, management and monitoring of health pro­

grammes and services. The role of these commit­

tees is to work with health providers to develop

local health plans, determine resources and moni­tor expenditures and the provision of health ser­

vices. Ecuador is forming a system of decentralized health care networks to handle the delivery of

essential health services, especially maternal and

child health services. In Bolivia the Departmental Health SerYices are the main mechanism for

improving the coverage and quality of health ser­vices and developing health programmes that

respond better to the needs of the population at the local level. The results are measured by means of

specific indicators included in performance agree­

ments, these being contracts signed between cen­

tral health authorities and state governors as part of

the process of decentralization. The contracts are

being used in decision-making on resource alloca­tion benveen the central and local levels.

DEPARTMENT DF VACCINES AND BIOLOGICALS

Table 4: Functions of immunization services and levels at which the responsibilities should be held

AMRO's collaboration with ministries of health has

been geared towards the clarification of roles, the

accountability of new partners, and assurance of the

delivery of immunization programmes that are effective and of high quality. Mexico, for example,

is showing positive results in the sharing of respon­

sibility between vaccination and epidemiological

surveillance at the state level and planning, priority­

setting and evaluation at the national level. Bolivia is also sharing roles and responsibilities at the sub­

national level with departments and municipalities,

which, in turn, share roles and responsibilities

among themselves.

52

AMRO continued its dialogue with countries in order to ensure that clear mechanisms were in place

for transferring and managing financial and human

resources, and for managing the planning and implementation of the surveillance and delivery

components. Furthermore, advocacy will continue

to incorporate immunization indicators, especially

DTP3 coverage and drop-out rates, in performance

agreements. Bolivia and Nicaragua, for example, have included the indicator of DTP3 coverage in

their performance agreements.

ANNUAL REPORT 1999

7 .12 Immunization safety priority project

7.12.1 Global activities

Immunization programmes are among the most effective and safest of all health interventions. Yet

their implementation on a worldwide basis faces

many challenges. Immunization safety must be con­sidered by those advocating the use of vaccines to

lessen the burden of vaccine-preventable diseases.

Adverse events following immunization (AEFis)

have been known to occur since the first vaccines

were administered. These events may be local (at the site of injection) or generalized. Common

adverse events are mild while certain rare events may be more serious. Some of them are caused by the vaccines themselves but many eYents reported as

being related to vaccines are actuallr coincidental,

occurring for other reasons. Countries are adminis­

tering more doses of vaccine than ever before. Higher educational levels of parents and the greatly

increased speed and sophistication of communica­tion have helped to produce a ne,v and sometimes

extremely hostile climate for vaccines.

53

Formerly, the first inclination after an adverse event

was to blame the quality of the vaccine that had

been administered. Because of the need to assure

and improve vaccine quality, WHO and the NRAs have devoted much energy and resources to work­

ing with vaccine producers in order to enhance

their compliance with good manufacturing prac­

tices, thus ensuring the highest possible quality of

vaccines. The availability of vaccines of good quali­ty is, however, not enough. It has been reported that

up to a third of vaccine injections are not given in a

way that can guarantee sterility. Furthermore, there have been reports of mistakes in programmes.

The main target of the priority project is to estab­

lish a comprehensive system ensuring the safety of all vaccines given in national immunization pro­

grammes by the year 2003. To achieve this an over­

all culture of safety has to be developed so as to

encourage prevention, early detection and quick

response ro adverse events related to immunization programmes and thereby to lessen their negative

impact on health and on the programmes.

To coordinate these activities, WHO has earmarked

human and financial resources and has established

strong collaboration between its Headquarters and

Regional Offices. An internal cross-cluster coordi­

nation group meets regularly to share information

and monitor progress.

The principal areas of activity of the project are:

• ensuring vaccine safety at all stages from clini­cal trials to point of use;

• research into and development of safer and

simpler vaccine delivery systems; • expanded access to safe and effective delivery

technologies and their disposal;

• identification and management of risks related to immunization.

The first three areas are concerned with prevention, ,vhile the fourth involves the early management of events . .tvfuch effort is being dedicated to defining

proper methods and indicators for assessing all the

elements of immunization safety so as to monitor

progress. In themselves, immunization safety assess­

ments will be critical for highlighting problems and paving the way ro intervention. The third of the

above areas of activity is also one of concerted

action within the common strategic framework of

DEPARTMENT DF VACCINES AND BIDLDGICALS

Figure 27: Participants in the "Partnership-building with the media" workshop, Islamabad, September 1999

the newly launched Safe Injections Global Network

(SIGN), the mission of which is to achieve safe and

appropriate use of all injections throughout the

world.

The project emphasizes the importance of advocat­ing safety and building capacity at national level. It supports the implementation of a series of training activities, the development of a standard set of

information documents, and the fostering of col­laboration between various interested parties at the global, national (particularly between immuniza­

tion managers and NRAs) and subnational levels.

Two committees have been set up to guide the work

of V&B in this area: the external Steering

Committee on Immunization Safety has been creat­

ed to provide technical and scientific advice on

strategies, activities, constraints and requirements of

the priority project, and the global Vaccine Safety

54

Advisory Committee has been established to

enhance WHO's ability to react to allegations of

adverse events related to immunization by provid­

ing impartial scientific advice of high quality to WHO on specific issues related to vaccine safety as

they arise.

The Steering Committee on Immunization Safety

met for the first time on 25-26 October 1999. The importance of delivering safe vaccines of high qual­ity was underlined, as was the need to concentrate

on prevention and safety assurance during all stages

of development and at the point of use. Also highlighted was the importance of prompt moni­

toring and management of AEFis and of strength­

ening NRAs and fostering proper collaboration

between vaccine NRAs and managers of immuniza­

tion programmes. Among the recommendations

made were the following:

ANNUAL REPORT 1999

• The appropriate levels (e.g. ministers through the World Health Assembly and the Regional Committees) should be targeted as part of the

strategies for advocacy.

• All costs of safe delivery of vaccines, including

the disposal of residual waste, should be

encompassed in strategies for financing immu­

nization services. It is important to promote

the concept of the cost of the safely immunized child.

• Immunization safety should be emphasized as a core function of immunization systems dur­ing the process of health services reform.

• Capacity for assessing and managing immu­nization safety should be enhanced at all levels.

• WHO, UNICEF and national immunization

programmes should expand access to training as a core element of immunization safety.

• A standard assessment tool of immunization safety should be developed for use by national

managers and other stakeholders.

• National immunization plans should include policies on waste management.

• Early detection, proper response and timely management of vaccine safety concerns, in par­ticular the correction of programmatic errors,

should be implemented.

Because it was recognized that increased public

interest in immunization safety had altered the envi­

ronment in which programme managers operated, specific media training workshops were held in the

Eastern Mediterranean Region. The holding of fur­

ther workshops during the coming biennium is under consideration in all WHO Regions. Major

progress has been achieved in the area of training for

the monitoring and management of immunization safety, with the development of a curriculum on

immunization safety monitoring and management

as part of GTN. A course was held in Cape Town and training should be expanded during 2000.

Many activities were undertaken to improve the safety of injection devices. WHO's preferred syringe

for mass immunization campaigns is the auto-dis­able (AD) syringe. Overall, this syringe helps to

decrease the transmission of bloodborne pathogens

between patients by preventing reuse and resale,

both common practices in developing countries. However, AD syringes lack protection for the nee­

dle and do not eliminate the hazards of sharp waste

in the environment. Furthermore, they are still

more expensive than other types of syringe,

55

although an effort is being made to reduce their cost

through technology transfer. WHO is contributing

to the process of technology transfer by means of manufacturer assessments, liaison between intellec­

tual property owners and manufacturers, market

assessment in collaboration with health ministries,

the provision and modification of specifications,

and laboratory qualification testing. Studies to

assess the comparative (internal/external) costs of different injection strategies (disposable, sterilizable

and AD) have been performed in three African

countries. A joint WHO/UNICEF statement on the safety of all injections related to immunization

recommends that only AD syringes should be used in national immunization programmes.

Other strategies for improving immunization safety

that are under investigation as part of the project include:

• the use of monodose, prefilled vaccine presen­tations integrated with the injection device;

• the use of multidose injection systems, such as jet guns drawing vaccine from multidose vials

of vaccine;

• safe disposal of injection equipment.

7.12.2 African Region

Although a majority of past cases of reported AEFis

were mild and treated at the peripheral level, a few

serious cases necessitating vaccine withdrawal

and/or detailed investigation were also reported.

Examples are widespread BCG lymphadenitis in Uganda and Zimbabwe, and death after mass cam­

paigns against measles in Zimbabwe.

The major needs for the monitoring and manage­ment of AEFis include:

• responding to field reports of inadequacies attributable to vaccines and/or immunization service delivery;

• reducing the heightened level of suspicion and rumours surrounding immunization during mass campaigns, and boosting confidence in

immunization in general;.

• establishing an effective post-marketing sur­veillance system that, in addition to meeting

safety concerns, facilitates the monitoring and

assessment of vaccine efficacy during field use.

An essential requirement of EPI is that every injec­

tion be given safely with a sterile needle and syringe.

Although EPI injections are recognized as being

DEPARTMENT OF VACCINES AND BIOLOGICALS

among the safest, there are numerous studies docu­

menting unsafe immunization injection practices in

Africa.

For countries where national data were available

(Table 8), 18-60% of health centres did not meet

sterility standards and 25-55% recorded abscesses.

Factors contributing to the failure to achieve 100%

compliance with requirements include a lack of

knowledge, the aging of sterilization equipment,

shortages of spare parts, equipment, needles and

syringes, and inadequate training and supervision.

AD syringes are recommended for all immunization

activities. The use of sterilizable syringes is a safe

and cost-effective strategy for ensuring safe injec­

tion. However, time-steam-temperature (TST)

spots, which are very effective indicators of ade­

quate sterilization, are not widely used in the

Region. The waste disposal problems associated with AD syringes are being addressed.

Current issues related to the quest for safe injections

include the following.

• Assuring safe injections appears not to be a pri­ority in national programmes, despite the

availability of adequate technology and

resources for this purpose.

• Methods for the routine monitoring of injec­

tion safety have not been implemented.

7.12.3 Region of the Americas

The Region of the Americas continues to work with

countries to improve safe injection practices. A

major impediment remains the lack of adequate safety boxes to collect properly used injection

equipment. AMRO is emphasizing to managers of national immunization programmes the dangers to

health workers of needle-stick injuries resulting

from the recapping of needles.

AMRO's Technical Advisory Group Meeting, held in Canada in April 1999, recommended the follow­

ing actions to secure safe injection practices:

• single-use auto-destruct syringes should be used;

• all health care workers should be informed about the danger of recapping needles;

56

• funds should be provided for the procurement of sufficient syringes and safety boxes, for the

supervision and documenting of safe syringe

disposal, and for the proper disposal of used

equipment;

• support should be given for developmental studies on needle-free injection devices.

Countries are starting to purchase AD syringes but

the cost is still considered too high. AMRO is work­ing to improve the advocacy of the use of AD

syringes and to stop the recapping of used needles by health workers. Much remains to be done to

make this advocacy campaign effective. AMRO will intensify its collaboration with countries in the

Region, especially in the area of supervision, with a

view to improving safe syringe practices, and will urge countries to allocate more resources in their

budgets for the introduction of products such as

safety boxes and small clinic incinerators.

7.12.4 Eastern Mediterranean Region

Notwithstanding the fact that vaccination is one of

the safest health interventions and that the risks of

vaccine-related adverse events are extremely rare

when set against the risk of complications arising

from natural disease in unprotected children, such

events, if not properly addressed, could seriously undermine public confidence in immunization.

The topic of adverse events was considered during

several intercountry meetings. Oman established a

surveillance system in 1996 and is reporting regu­larly to the Regional office. Egypt and Syria started

adverse events surveillance systems in mid-1998. A

series of intercountry workshops on AEFis were organized with a view to developing national plans

of action for the establishment/strengthening of adverse events surveillance. The first workshop was

held in December 1998 and the other two were

held in Cairo in February 1999 and in Oman in March 1999. National plans were developed for the

establishment/strengthening of adverse events sur­veillance systems in each Member State. Systems are functioning in Bahrain, Egypt, Kuwait, Oman,

Saudi Arabia, Syria, and Tunisia.

ANNUAL REPORT 1999

Late in 1998 reports about adverse events that were

considered to be related to vaccination activities

were received from Egypt and Jordan. These events were investigated and it was concluded that

although they were related to immunization there

was no direct association. It was also noted that

these events reflected negatively on immunization

activities and that the media mishandled the inci­

dents. The national EPI managers faced numerous

difficulties in dealing with the events and the reac­

tions of the media and the public. In response to

this situation,two workshops, each lasting two days, were conducted during 1999 with the aim of

strengthening the capabilities of the national EPI

managers in these areas.

7.12.5 European Region

There is an acknowledgement of the increasing

importance of the adverse events in the management

of national immunization programmes. In future

more opportunities for discussion of surveillance

techniques for detecting adverse events, analysis of data, and handling of risk communication in this

regard will be considered. The role of the media and

our relationships with them need to be included.

7 .12.6 South-East Asia Region

Injection safety and waste disposal are top priorities

for V&B/SEARO in terms of providing technical

support to Member States. Furthermore, this pre­

sents an excellent opportunity to promote sustain­

ability in systems development. A Regional plan of action is being developed to refocus attention on a

public health problem that requires the involve­ment of several curative and preventive disease

strategies. In the meantime, SEARO is promoting

the bundling of vaccines with equipment that helps to ensure safe injection and waste disposal. A prior­

ity activity for 2000 will be an intercountry plan­ning workshop to be held in collaboration with

WHO Headquarters. Other opportunities for sys­

tems development include strengthening the man­

agement and replacement of the cold chain. To this

end, SEARO has employed a full-time cold chain

consultant. A major challenge is that none of the countries has an adequate plan for converting to a

CFC-free cold chain.

57

The global movement for the strengthening of immunization activities has brought the issue of

cold chain management and equipment replace­mem into focus. V&B/SEAR was actively involved

with the World Bank in formulating strategies for

strengthening immunization activities and the cold chain system in India. V&B also supported a num­

ber of cold chain technician training courses using

a CFC-free system in Bangladesh and India.

Intensified NIDs in a number of countries called

for the strengthening of the cold chain system in areas of greatest need. While other agencies such as

UNICEF provided cold chain supplies and equip­

ment to India, V&B/SEAR took the opportunity to conduct a rapid cold chain assessment in Uttar

Pradesh and Bihar, to ensure the timely installation

of the equipment, and to train local cold chain

technicians.

7.12.7 The Safe Injection Global Network

Because injection safety is essential to immuniza­

tion programmes, efforts to achieve safe injections initially focused on the field of immunization.

Equipment developed for introduction in the field

included plastic sterilizable syringes (1982), steam

sterilizers (1984), AD syringes (1985), and TST indicators (1991). In addition, training materials

and injection survey materials were developed.

At the end of the 1990s, public health professionals

recognized that the safety of immunization injec­tions could not be addressed in isolation. Efforts

had to reach beyond the field of immunization so as

to address therapeutic injections, these representing the majority of injections administered worldwide.

Simultaneously~ evidence became available suggest­ing that, in a number of countries where hepatitis B

virus or hepatitis C virus infections were highly endemic, the overuse of therapeutic injections com­

bined with unsafe injection practices to account for

a large proportion of new cases of infection. Preparatory work in ATT resulted in public health

professionals from various backgrounds sharing a

common interest in a safe and appropriate use of

injections. On 4-5 October 1999 these groups

joined forces during the initial meeting of the Safe Injection Global Network (SIGN). A secretariat

based in the Blood Safety and Clinical Technology

DEPARTMENT OF VACCINES AND BIOLOGICALS

Department now coordinates this network because:

• 95% of injections administered each year are given for therapeutic purposes;

• injection safety fits well with blood transfusion safety in the prevention of infections from

blood-borne pathogens through all potential

percutaneous exposures.

WHO's Immunization Safety priority project sup­

ports the initiative provided by SIGN for achieving safe immunization injections and is collaborating

closely with the SIGN secretariat. D

Figure 27: Disposable syringes and needles waiting to be re-used without sterilization in a container of tepid water

58

ANNUAL REPORT 1999

[I] 8. Accelerated disease control

8.1 Progress towards global polio eradication

The global effort to eradicate polio is the largest pubic health initiative in history. It was launched in 1988 by the World Health Assembly with the goal of eradicating polio while strengthening capacity to control other major childhood diseases. Extraordinary progress has been made towards achieving polio eradication by 2000 and global cer­tification of eradication by 2005.

In 1988, polio existed in over 125 countries on five continents, and more than 350 000 children were paralysed that year. By the end of 1999 the number of polio-infected countries had fallen to 30

Figure 28: Polio eradication progress, 1988-1999

...

59

(Fig. 28), polio had been eliminated from three more continents, and the number of reported cases was 6659 (the estimated maximum number was 20 000). When polio is eradicated and polio immu­nization ceases the world will save US$ 1.5 billion per year.

Status of polio transmission

The number of countries in which polio was known or suspected to be endemic decreased from 50 in 1998 to 30 in 1999. Type 2 poliovirus (one of three types) is on the verge of extinction, the only known foci being in northern India. Polio incidence declined to the lowest levels ever in 1999, although reported cases increased slightly to 6 659 because of

• I

6 659 * cases *as of 21 February 2000

DEPARTMENT DF VACCINES AND BIOLOGICALS

improvements in surveillance and a large outbreak in Angola. Polio was eliminated from the fifth of the seven continents, more than a year having elapsed since the last case in Europe.

Polio-free Regions

Three of the six WHO Regions, representing 115 countries, have been polio-free for more than a year.

Region of the Americas: The last case of polio

occurred in 1991. During 1999 a polio outbreak in Angola appeared to threaten the polio-free status of the Americas when two suspected cases were reported in Brazil. Neither case was confirmed.

Western Pacific Region: The last case of endemic

polio was reported in 1997. A case in China in 1999 was associated with a poliovirus imported from India. The implications for Regional certifica­tion will be considered during 2000. No Region is safe from polio until all Regions are polio-free.

European Region: The last known case of polio

occurred in Turkey during November 1998.

Regions where polio is still endemic

African Region: Polio is endemic or probably

endemic in 20 of the 46 countries in the Region. In 1999, 2718 cases were reported and 218 of them were laboratory-confirmed (Table 5). Poliovirus cir­culation was confined largely to the Horn of Africa, West Africa and Central Africa. The most intense transmission occurred in Chad, the Democratic Republic of Congo, and Nigeria. Following is a summary of the situation in the

Region by countries in special circumstances and by epidemiological blocks.

Countries in special circumstances

Nigeria reported 951 cases during 1999, including 83 laboratory-confirmed cases. Intense polio trans­mission continues in nearly all parts of the country. Nigeria is a major reservoir of poliovirus and exports the virus to countries throughout West and Central Africa.

Angola reported 1103 cases and 89 deaths when a polio epidemic swept the country early in 1999. Displaced children who had never been vaccinated were at the highest risk during this outbreak.

The Democratic Republic of Congo, which reported 45 cases in 1999, is a major reservoir of poliovirus. The reported cases understated the actu­al incidence because surveillance was inadequate in most parts of the country. Poliovirus transmission in the Democratic Republic of Congo represents a continuing threat to the apparently polio-free status of neighbouring countries in East Africa.

Ethiopia reported 125 cases of polio in 1999 but none were laboratory-confirmed. Despite the lack of poliovirus isolates the real epidemiological situa­tion remains unclear because surveillance sensitivity and laboratory capacity are inadequate.

Epidemiological blocks

Ail 14 countries of the southern Africa block appear. to be polio-free. The last confirmed case was reported from Madagascar in 1997. However, there

Table 5: Reported AFP cases, surveillance quality indicators and confirmed poliomyelitis cases 1998-1999, by WHO Region*

60

ANNUAL REPORT 1999

is a high risk of unrecognized low-level polio trans­

mission in Madagascar, Malawi, and Mozambique in particular, because surveillance remains inade­

quate. The cessation of NIDs in some southern

African countries coupled with poor routine OPV

coverage increases the risk that polio may become

re-established.

The East Africa block countries of Burundi,

Kenya, Rwanda, Tanzania, Uganda, and Zambia, appear to be polio-free. The last confirmed cases

occurred in Uganda in 1996 and in Tanzania and Zambia in 1995. Polio transmission continued to occur at low levels in Eritrea, which reported seven

cases in 1999. However, all seven countries in the

block are sat risk of importation and/or re-estab­

lishment of polio because they border an area of

endemicity and have low coverage with the three childhood doses of O PV

The Central Africa block comprises six countries.

Intense polio transmission continued in Chad,

which reported 99 cases of which 34 were laborato­

ry-confirmed; 66% of AFP cases for which speci­mens were collected proved positive for poliovirus

in that country. Cameroon and the Central African

Republic appeared to have low levels of polio trans­mission, but remained at risk because of their prox­

imity to countries with high transmission levels.

Although Congo, Equatorial Guinea, and Gabon

had no virologically confirmed cases, surveillance

was extremely weak and there was a very high risk

of unrecognized transmission.

Polio transmission continues in the West Africa block, which comprises 16 countries. It is most intense in Benin, Liberia, Niger and, probably,

Sierra Leone. Ghana, Mali, Senegal, Sierra Leone,

and Togo reported low levels of transmission involv­ing laboratory-confirmed cases. Because of to low

levels of poliovirus transmission and good AFP sur­

veillance quality, six countries are poised to enter the mop-up phase of eradication (Cote d'Ivoire, Ghana, Guinea, Mali, Senegal, and Togo). Sub­

optimal AFP surveillance quality limited the detec­

tion of probable virus in Burkina Faso, Gambia,

and Guinea-Bissau.

Eastern Mediterranean Region: In 1999, 829

cases were reported in the Eastern Mediterranean

Region (Table 5), including 449 laboratory -con­

firmed cases. Polio transmission continues to be

61

intense in Pakistan, which reported 466 cases and is

a major reservoir of poliovirus. There was wide­spread circulation in Afghanistan, where 141 cases

were reported and rhe virus had marked genotypic

similarity to that in Pakistan. Poliovirus from

Afghanistan was epidemiologically linked to the

three polio cases reported in Iran during 1999.

Although t\vo of these cases appear to have been

attributable to imported viruses, low-level endemic

transmission of poliovirus may be continuing. No

cases were reported from Iraq in 1998 but in 1999

there was a widespread outbreak in the country, involving 127 reported cases, including 72 labora­

tory-confirmed cases.

Sudan reported 51 cases and Somalia reported 16

cases. Egypt has made substantial progress, report­

ing irs lowest transmission ever, although focal transmission continued in Assiut and Minya in the

Upper Nile area.

South-East Asia Region: In 1999, 3111 polio cases

were reported, including 1072 laboratory-con­firmed cases from four countries (Table 5). There

were 2628 reported cases in India, a 40% decline from 1998; intense transmission continues in the

states of Bihar and Uttar Pradesh, which are the

only known remaining foci of poliovirus type 2 transmission. Polio transmission has markedly

decreased in the southern part of India, which is

now entering the mop-up phase of eradication.

Bangladesh reported 335 cases in 1999. Despite this large number, genetic typing demonstrated that several poliovirus lineages were nearing extinction

and that rhe biodiversity of the virus had decreased substantially. Nepal reported only one laboratory­

confirmed case in 1999 and appeared to have focal

transmission only along its border with India. In .i\1yanmar an imported case was detected and rapid mass vaccination was subsequently carried out. No

additional cases have been reported. The polio situ­

ation in the Democratic People's Republic of Korea remains unclear because of a lack of surveillance

and laboratory data.

Status and quality of strategy implementation National immunization days

• Full NIDs or subnational immunization days

(SKIDs) were conducted in 83 countries,

DEPARTMENT OF VACCINES AND BIOLOGICALS

reaching more than 470 mil­lion children (Fig. 30). Full NIDS were conducted in 70 countries, often with SNID rounds in high-risk areas. In India alone, over a billion OPV doses were distributed during four NIDs and two SNIDs (October 1999 to March 2000). Thirteen mostly polio­free countries in the European Region and the Western Pacific Region conducted SNIDs only.

Figure 29: Accelerated polio immunization efforts, 1999-2000

• Vitamin A supplementation was given in 50 of the 83 coun­tries conducting supplemen­tary immunization activities during 1999.

1

,

• In order to accelerate polio eradication activities the num­ber of NID rounds was increased in reservoir and other priority countries (Fig. 29). Afghanistan and India con­ducted four rounds of NIDs, and India conducted two addi-

Extra 'intensified' NIDs

II NIDs + SN IDs or 'Mop-ups'

tional SNID rounds early in 2000. Three rounds of NIDs were conducted in Angola and the Democratic Republic of Congo. However, many children were not immunized in Angola as a consequence of internal disturbances.

• The quality ofNIDs and SNIDs was improved by strengthened planning at provincial and district levels and by extensive use ofhouse-to­house vaccination strategies. These intensified NIDs and SNIDs were held in Afghanistan, Nigeria, and Pakistan, with resulting increases of up to 50% in the number of children reached in some provinces.

• The quality ofNIDs was threatened by a glob­al OPV shortfall that resulted from uncertain­ty of supply, cancelled shipments and resched­uling of major orders. Many countries were adversely effected by the uncertainty of the vaccine supply, including cancelled or delayed rounds in Chad and Ghana, inconsistent

62

presentations of the vaccine (e.g. Spanish labels in non-Spanish-speaking countries, vials with 10 instead of20 doses), and the postponement of routine orders.

• The evaluation of the quality of NIDs was improved by monitoring the number of chil­dren vaccinated for the first time (zero-dose monitoring), process evaluations, and limited use of coverage surveys. However, high-quality AFP surveillance remains the best means of evaluating the quality and effectiveness of NIDs and SNIDs.

Acute flaccid paralysis surveillance

AFP surveillance is used to detect polio cases. Certification standard is reached if the non-polio AFP rate is> 1/100 000 population aged< 15 years, if adequate specimens are collected from 80% or

ANNUAL REPORT 1999

more of AFP cases, and if the specimens are evalu­ated on a timely basis in accredited laboratories (Fig 31). High-quality surveillance was achieved in the Western Pacific Region, the European Region, the South-East Asia Region, and the Region of the Americas. At Regional and country levels, delay in achieving surveillance of certification standard can result in late detection of polio-infected areas. High priority must therefore be given to rapidly achieving this standard.

Regions where polio is endemic

• The African Region improved surveillance dramatically, the non-polio AFP rate more than doubling from 0.30 in 1998 to 0.70 in 1999. The increase in AFP surveillance was the result of extra funding for this purpose late in 1998, the initiation of active surveillance at the provincial level in some countries, the support of STOP teams in some countries, and the arrival of transport for active surveillance in 1999. However, adequate specimens were col­lected in respect of only 31 % of AFP cases. Priority countries for surveillance improve­ment include Burundi, Ethiopia, Madagascar, Malawi, Mozambique, and Rwanda. (Fig. 30).

• In the Eastern Mediterranean Region the non-polio AFP rate increased from 0.88 in 1998 to 1.13 in 1999. Among the six polio­endemic countries, Egypt, Iraq, and Pakistan achieved a non-polio AFP rate > 1; for Afghanistan the figure was close at 0.95. Somalia and Sudan reported rates of 0.79 and 0.52 respectively. Over the Region as a whole the percentage of cases with adequate speci­mens rose slightly from 64% in 1998 to 69% in 1999. The continued surveillance achieve­ments in Afghanistan, Somalia and Sudan demonstrate that high-quality surveillance can be implemented even in the most difficult circumstances.

• The South-East Asia Region increased its non-polio AFP rate from 1.25 in 1998 to 1.52 in 1999. Two of the four polio-endemic coun­tries, India and Nepal, achieved the standard for reported non-polio AFP rates with values of 1.8 and 1.9 respectively. Nepal substantially improved surveillance, its non-polio AFP rate

increasing from 0.41 in 1998 to 1.91 in 1999.

63

Bangladesh also improved its AFP surveillance, from 0.33 in 1988 to 0.63 in 1999. AFP sur­veillance in the Democratic People's Republic of Korea remains inadequate. For the Region as a whole the percentage of cases with ade­quate specimens increased from 60% in 1998 to 71 % in 1999. During 2000 the priority countries for improving surveillance will be Bangladesh, the Democratic People's Republic of Korea, and Myanmar (Fig. 30).

Mop-up immunization campaigns

Mop-up is the final strategy for polio eradication where high-quality AFP surveillance information is used to identify remaining pockets of virus trans­mission. Intense house-to-house immunization activities are then targeted to eliminate the final chains of virus transmission. During early 1999, mop-up was conducted in south-east Turkey and neighbouring provinces of the Islamic Republic of Iran, Iraq, and Syria following a case reported in Turkey in late 1998. No additional cases have been reported since then in Iran, Syria, or Turkey.

NOTE: Although house-to-house immunization was conducted during NIDs or in response to a detected case in many countries during 1999, this was intended to improve the quality of activity and reach previously unreached children. It did not meet the criteria of classic mop-up to stop the final chains of poliovirus transmission.

Status of the Global Polio Laboratory Network

The Global Polio Laboratory Network was fully operational in all the WHO Regions, comprising a total of 148 laboratories, including 126 national or subnational laboratories, 16 Regional reference lab­oratories, and six global specialized laboratories (Fig. 32). By the end of 1999, 108 laboratories (73%) were fully accredited, 16 (11 %) were provi­sionally accredited, 14 (9%) had been reviewed but could not be accredited, and 10 (7%) remained to be reviewed. Only the Democratic People's Republic of Korea still lacks an accredited laborato­ry or access to an accredired laboratory outside the country.

Standard guidelines, procedures, cell lines and reagents have been introduced in laboratories at

DEPARTMENT OF VACCINES AND BIOLOGICALS

Figure 30: Endemic or recently endemic ciountry priorities for improving surveillance in the year 2000

■ Good quality surveillance or marked improvement*

Inadequate surveillance*

• Data as of February 1000, WHO/HQ

•

Figure 31: Global laboratory network for polio eradication, 2000

* Specialised reference laboratory e Regional reference laboratory A National/Sub-national laboratory

• Proposed National laboratory

64

ANNUAL REPORT 1999

each level of the network. During 1999, almost all

stool specimens from AFP cases were processed in

WHO-accredited laboratories. Over 50 000 speci­

mens were processed for viral isolation, and over 3000 poliovirus isolates and over 10 000 non-polio

enterovirus isolates were obtained; serotyping and

intratypic differentiation were carried out on all

poliovirus isolates, and genomic sequencing infor­

mation was provided on nearly all programmatical­

ly important wild poliovirus isolates. There were marked increases in laboratory workloads between

1997 and 1999. Thus in India the number of spec­imens increased from 1570 in 1997 to 15 800 in 1999, a tenfold increase, and in Nigeria the corre­

sponding numbers were 7land 923, a 13-fold

increase.

At the end of 1999, 123 (83%) laboratories had

international telephone or fax lines and/or access to e-mail, but 25 (17%) continued to have inadequate

communications. Arrangements are being made to

Figure 32: Polio-endemic countries and low OPV-3 coverage

The problem

D Known or probable poliovirus at end 1998

(millil Very high risk

65

ensure that wild-type poliovirus isolates are being

shipped promptly and frequently to specialized lab­oratories with the capacity to sequence isolates.

Routine immunization

Both reported and survey-confirmed routine

immunization coverage with OPV3 is low and

stagnating in the remaining priority countries. ImproYements in routine immunization are

urgemly needed. Efforts to accelerate polio eradi­

cation proYide a useful opportunity to boost rou­tine immunization, strengthen EPI target disease

surveillance together with AFP surveillance,

improve the cold chain, and train health workers

and middle-level programme managers. The

absence of reliable basic immunity to polio through routine immunization is one of the main

reasons underlying the need for additional nation­wide immunization campaigns (Fig. 32).

The challenge

□ OPV3 <80% in large areas or nationwide

DEPARTMENT DF VACCINES AND BIOLOGICALS

Optimizing the impact of polio eradication on health systems

In 1998 the Forty-first World Health Assembly committed WHO to the goal of polio eradication by the year 2000 "in ways which strengthen nation­al immunization programmes and health infrastruc­ture". WHO and partner organizations, have con­tinued working to ensure that polio eradication activities complement and support efforts to strengthen routine health services. In December 1999, WHO convened a meeting entitled The Impact of Targeted Programmes on Health Systems: a Case Study of the Polio Eradication Initiative, the key elements of which are outlined below.

• WHO, with support from USAID, DANIDA, NORAD and DFID, initiated a study in 1997 to develop a methodology and country case studies in the Lao People's Democratic Republic, Nepal, and Tanzania. These studies found both positive and negative impacts of polio eradication activities, and it was conclud­ed that, with better planning and objectives, positive impacts could be increased and nega­tive ones could be reduced.

• The evaluation of the Pulse Polio Immunization Programme by The All India Institute of Medical Sciences indicated that the polio eradication initiative had strengthened management capacity, improved social mobi­lization, and increased confidence in the health care system. It was recommended that there should be better planning in order to minimize the disruption caused by NIDs.

• A study funded by USAID found that the implementation of polio eradication activities was not associated with a decrease in funding for routine EPI in Bangladesh, Cote d'Ivoire, and Morocco. Indeed, overall funding for immunization activities increased.

• A report on lessons learnt in the development of the global polio eradication network con­cluded that the principles of quality assurance and laboratory accreditation used in the labo­ratory network could be used to improve the quality of other health programmes.

• A UNICEF study in Benin and Niger found no strong evidence on the impact of the polio eradication initiative on routine coverage, but recognized that opportunities to link polio

66

eradication with other programmes and to strengthen EPI had been missed.

• There was broad recognition that NIDs had served as a vehicle for Vitamin A supplementa­tion. In the African Region, vitamin A supple­mentation had increased more than fivefold since NIDs were introduced in 1996.

Reported negative impacts of polio eradication activities include disruption of routine EPI work and of other health services, although there are few reliable quantifiable data on these matters. The effects could be reduced or avoided by better plan­ning in which the focus on routine immunization was renewed, by linking AFP surveillance to sur­veillance for other diseases, and by using training and supervision for the polio eradication initiative as an opportunity for other health services. Other recommendations from the WHO meeting includ­ed the following.

• A matrix framework of indicators developed for the country case studies should be distrib­uted as a simple planning and assessment tool for country managers.

• A state-of-the-art paper should be drafted, assembling documentation on the impact of polio eradication.

• Efforts should be initiated to document cur­rent gaps in knowledge of the impact of polio eradication.

Preparing for the post-eradication era

After 12 years the polio eradication initiative has reached every polio-endemic country, the burden of disease has been dramatically reduced, and wild poliovirus transmission has been restricted to a lim­ited number of countries. The progress achieved makes it likely that polio will be eradicated throughout the world in the near future. V&B is therefore expanding its focus to deal with the issues of post-eradication: containment,certification and stopping immunization.

Containment

Since there is no animal or environmental reservoir for polioviruses the only sources of the virus after human transmission ceases will be laboratories. To prevent the possibility of an inadvertent escape of wild poliovirus, stocks must be stored in secure

ANNUAL REPORT 1999

laboratory facilities. A plan for the containment of

polioviruses was prepared in 1998 and circulated

widely for comment in the scientific and biosafety communities. A final plan of action has been pre­

pared. It calls for national biosafety authorities to

inventory all stocks of poliovirus and potentially

infected materials. Poliovirus strains should no

longer be present in facilities where their use is not

essential. Strains of scientific value should be moved to secure repositories. One year after the last wild

poliovirus is identified all remaining stocks should

be placed in maximum containment laboratories where essential scientific work can continue. The procedures called for in the containment plan are

currently being field-tested in the Region of the

Americas, the European Region and the Western

Pacific Region.

Certification

The processes for certifying global polio eradication were defined in 1995 at the first meeting of the

Global Commission for the Certification of the

Eradication of Poliomyelitis. Certification requires

at least three years without polio cases under condi­tions of good surveillance. AFP surveillance is the

primary surveillance tool. The process calls for

national committees to prepare reports for review

by Regional Certification Commission, which, in

turn, will report to the Global Commission. By 1999 each Region had a certification commission

that had met to define Regional processes. The

Region of the Americas has been polio-free for eight years, and is increasingly focusing on the steps need to strengthen AFP surveillance at the country level

to meet certification criteria. The last indigenous

case in the Western Pacific Region having occurred

in March 1997, the Western Pacific Regional

Commission is preparing to receive reports from its Member States in the year 2000. The European

Regional Commission has begun reviewing prelim­

inary reports from its Member States in anticipation of certifying freedom from polio in 2001, three years after the last case in Turkey. Although it has begun to receive preliminary reports from some

countries, the Eastern Mediterranean Region has

affirmed that this Region must be certified as a whole and has emphasized the need to achieve rapid

progress in the countries where polio is still endem­

ic. The African Regional Commission and the

South-East Asia Regional Commission have met to

plan their work for the next years.

67

Stopping immunization

Stopping immunization against polio is the ulti­

mate objective of the eradication initiative and,

along with averted health care costs, will yield

annual global savings of $1.5 billion. A meeting was held in March 1998 to review- scientific data con­

cerning the stopping of immunization . A research

agenda was defined with a view to creating new data by means of modern techniques and to taking

advantage of opportunities presented by the

absence of circulating wild virus in developing countries. Three foci were outlined: the potential

for vaccine-derived viruses to continue circulating

after immunization is stopped; persistent shedding

of vaccine-derived polioviruses among some per­

sons with certain immunodeficiency disorders; and

the need for new polio vaccines in the post-eradica­

tion era. On this basis a number of research projects were initiated. A meeting was held in April 1999 to

review progress in these studies, and a meeting was

held in January 2000 to discuss new polio vaccines. Manufacturers will need a lead time of five to seven

years to ensure that sufficient quantities of any vac­

cine other than the current OPV will be available

when needed. It is therefore anticipated that a meet­

ing will be held later in 2000 to review new scien­

tific data and recommend a strategy for stopping immunization.

Partnership support and advocacy

The success of the polio eradication initiative hinges

on the successful partnership between the public and private sectors. The partnership is spearheaded

by \'\THO, Rotary International, CDC and

UNICEF. The coalition is made up of national gov­ernments, private foundations (e.g. Mr Ted Turner's

United Nations Foundation, the Bill and Melinda Gates Foundation), development banks (e.g. the

World Bank), donor governments (e.g. those of Australia, Belgium, Canada, Denmark, Finland,

Germany, Ital), Japan, the United Kingdom, and the USA), and corporate partners (e.g. Aventis

Pasteur, De Beers).

Rotary International

Through its Polio Plus programme, Rotary

International has been a key player in stimulating,

developing and maintaining the global polio eradi­

cation initiative. By the end of 2005, Rotary

DEPARTMENT DF VACCINES AND BIDLDGICALS

International estimates that its contribution to the initiative will total US$ 500 million, as well as mil­lions of volunteer hours given to the promotion of and participation in polio eradication activities. During 1999, Rotary International awarded grants totalling $32 million.

New partnership support

• The Bill & Melinda Gates Foundation provid­ed $50 million and Mr Ted Turner's United Nations Foundation granted $28 million to strengthen the vaccine delivery infrastructure and surveillance systems.

• De Beers made a multi-year donation of $2.7 million to fund six NIDs in Angola during 1999 and 2000, targeting 3.3 million children.

• Aventis Pasteur (formerly Pasteur Merieux Connaught) donated 50 million doses of vac­cine (worth approximately $5 million) for NIDs to be conducted during 2000-2002 in five countries currently affected by war (Angola, Liberia, Sierra Leone, Somalia, and Sudan).

• The World Bank joined with India to support the huge acceleration in polio eradication activities in that country by reprogramming $48 million in health sector loans.

Increased support from existing partners

• India received increases in bilateral support from the United Kingdom (US$ 62 million), the European Union (US$ 6 million), Germany (US$ 7.5 million), and Italy (US$ 1 million). India has larger resource require­ments than any other country, usually accounting for 35% of global external need in a given year.

• Canada pledged multi-year support to Nigeria in the amount of C$ 6 million (US$ 4.2 mil­lion). Nigeria is second to India in terms of resources required for polio eradication, usual­ly accounting for 15% of annual global costs.

• In addition to the support targeted on India, the United Kingdom's Department for International Development pledged support for six of the ten priority countries on the African continent (Angola, the Democratic Republic of Congo, Ethiopia, Nigeria, Somalia, and Sudan) with a grant of £20 mil­lion (US$ 32 million).

68

• The USA, through CDC, responded to the joint UNICEF/WHO appeal for OPV with an additional commitment of $15 million for 2000. Japan is planning to increase its com­mitment for OPV in 2000.

Partnership advocates tor polio eradication

During 1999, many partners in civil society joined the advocacy for polio eradication led by Rotary International.

• Martina Hingis, one of the world's leading tennis stars, and Dikembe Mutombo, the Atlantic Hawks star basketball player, gave prominent support. Mr Mutombo lent support in his country, the Democratic Republic of Congo, by visiting a hospital to immunize babies and making public service announcements on the Voice of America.

• World-renowned British photographer Lord Snowdon, a victim of polio in the past, travelled to war-torn Angola in May with the support of De Beers to prepare photographic records of the 1999 polio outbreak and share them with the world.

• The Federation Internationale de Football Association committed players and resources to the Kick Polio out of Africa campaign. During 2000, messages recorded by players will be broadcast across the continent, billboard advertisements will be displayed and leaflets will be distributed at football matches.

• Ms Mia Farrow agreed to serve as UNICEF Special Representative for Polio Eradication. She participated with her son, Thaddeus, who contracted polio in the past, in the launch of UNICEF's annual Progress of Nations report, highlighting the eradication initiative during 1999.

Requirements for financial resources, 2000-2005

During January 1999 the first detailed financial resource estimates were compiled for the mop-up and certification phase in 2000-2005. The final mop-up phase will be the most expensive because of the intensity of activities, particularly the house-to-house immunization of large groups of children.

ANNUAL REPORT 1999

Figure 33: External resources: projected contributions by partner agencies and shortfall, 2000-2005

U.S.CDC

External resorce required= US$ 1,000 million Received/projected= USS 700 million Shortfall = US$ 300 million

It is projected that external resources amounting to US$ 1.0 billion will be needed for polio eradication activities from 2000 to 2005. Donor contributions until 2005 are projected at $700 million, leaving a shortfall of $300 million (Fig. 34). The external resources required by the ten global priority coun­tries for polio eradication comprise approximately 70% of the global need of $300 million. Approximately two-thirds of the shortfall is required during the period 2000-2002. For every year that eradication is delayed, the total cost will increase by approximately $100 million.

Challenges and priorities during the "mop­up and certification phase", 2000-2005

Challenges

Ensuring adequate supplies of OPV for NIDs and Mop-Ups During 1999, an OPV shortfall occurred due to rapid implementation of accelerated activities (espe­cially the additional rounds of NIDs in large reservoir countries), interruption of production at one vaccine manufacturer, and rescheduling oflarge orders. To ensure the 2000 global OPV supply, UNICEF made available US$ 100 million to guar­antee purchase of the total OPV amount offered in global tender for 2000. WHO, UNICEF, and manufacturers further streamlined information

United Kingdom

Gates and UN Foundations

69

*Italy, Finland, Germany,Aventis-Pasteur, DeBeers

exchange, and strengthened vaccine forecasting, planning, and coordination among UN agencies, vaccine manufacturers, and donor governments. However, ongoing problems with delivery dates and possibly insufficient total supply are major risks to timely completion of eradication activities in 2000 and 2001.

Maintaining Political Commitment Sustaining political commitment is a major chal­lenge in the face of a disappearing disease, but is critical in polio endemic countries to support the acceleration of high-quality eradication activities, and to establish necessary multisectoral support. Some countries, particularly on the African conti­nent, have stopped NIDs, despite surveillance sen­sitivity chat remains well below certification stan­dards. Experience in other Regions has conclusively demonstrated that such actions may jeopardize progress because low-level polio transmission can continue undetected for more than 3 years in areas with sub-optimal surveillance. The longer that poliovirus transmission continues, the higher the risk of reinfecting polio-free areas.

Ensuring Access to All Children • In Conflict Countries: The success of the UN

Secretary-General and other partners in estab­lishing "Days ofTranquillity'' for NIDs during 1999 in DR Congo demonstrated again the

DEPARTMENT OF VACCINES AND BIOLOGICALS

feasibility of working successfully in conflict­affected areas. These efforts must be expanded during 2000, drawing upon the strengths of the UN Secretary-General, many UN agen­cies, and other important partners to promote for peace and to support logistically operations during a cessation of hostilities, particularly in Afghanistan, Angola, DR Congo, Sierra Leona, Somalia, and Sudan.

• In All Polio-Endemic Countries: The slogan "Every Child Counts" was adopted for the final push for polio eradication, and to empha­size that all must be reached and vaccinated. To do so, all immunization campaigns must be of the highest quality, and many must include a house-to-house vaccination strategy to reach all children.

Ensuring Adequate Financial Resources The projected $300 million shortfall through 2005 must be rapidly met to ensure that the acceleration strategy is not delayed. Delay in achieving the tar­get date will increase the total cost of eradication by as much as US$ 100 million per year. It will also be difficult to sustain current funding levels for more than 24-36 months, especially for polio-free coun­tries that need to continue NIDs to protect against importations.

Country Priorities

Overcoming obstacles and ensuring the highest quality of activities in the 30 remaining polio­endemic countries will be given highest priority. In particular, efforts will focus upon 17 of 30 coun­tries. 10 are "global" priorities because they face par­ticular challenges requiring multi-year intensified activities. These countries fall into two categories:

• "polio virus reservoirs" where transmission is particularly intense due to large dense popula­tions, low routine immunization coverage, and poor sanitation. The countries in this category are India, Pakistan, DR Congo, Bangladesh, Nigeria, and Ethiopia.

• countries affected by conflict, where imple­mentation of vaccination and surveillance activities is particularly challenging due to destroyed infrastructure. The countries in this category are DR Congo, Angola, Afghanistan, Somalia and Sudan. All have started accelerat­ed immunization activities.

70

DR Congo is a special case. As both a global reservoir and a country affected by conflict, it faces challenges inherent to both groups.

Central to the success of polio eradication is ensur­ing that extra rounds of high-quality NIDs are conducted in 2000 and 2001, particularly in 9 of the 10 global priority countries: Afghanistan, Angola, Bangladesh, DR Congo, India, Nigeria, Pakistan, Somalia, and the Sudan. In the 10th pri­ority country, Ethiopia, the critical priority 1s achieving certification standard surveillance.

Regional Priorities

In addition to the global priority countries, within each WHO region there are strategic priority coun­tries that evolve as the polio eradication programme progresses. At beginning 2000, seven particular priorities are:

• AFRO: Chad, Congo, Liberia, Niger, Sierra Leone

• EMRO: Iraq • SEARO: DPR Korea

Programmatic Priorities

Ensuring High-Quality NID Strategy Implementation A multi-sectoral approach is needed in many coun­tries to improve the quality of supplementary immunization activities to ensure that every child is reached. In PAHO countries, interruption of polio transmission required the collaborative efforts of all government agencies, including the armed forces, to reach and immunize all children. Although more children are now being vaccinated than ever before, some are still unreached due to poor microplan­ning, inadequate social mobilization, and lack of access due to conflict. During 2000, targeted efforts will seek to overcome these hurdles, including augmentation of country-level technical and administrative capacity.

High-quality AFP surveillance Late detection of polio-infected areas can be a con­sequence of non-certification standard surveillance. Particularly during the Mop-Up Phase of polio eradication, high-quality AFP surveillance is essen­tial to identify the remaining pockets of polio and to target immunization activities to break the final chains of transmission.

ANNUAL REPORT 1999

Strengthening the Laboratory Network The laboratory network's workload will mcrease

dramatically once countries reach the standard level

of AFP performance, as demonstrated by Nigeria

and India. Laboratories in two important polio­

endemic countries (i.e. Bangladesh and Ethiopia)

have not yet been accredited. While specimens from these countries do get processed in accredited labo­

ratories elsewhere, it is important that these large

priority countries develop capacity to process stool

specimens. Laboratory accreditation in DPR Korea is critical.

8.2 Measles control

8.2.1 Global activities

Nearly a million deaths were attributed to measles

in 1998. The disease remains a major cause of vac­cine-preventable illness and death, despite the wide­

spread availability of an effective and safe vaccine for three decades. A failure to deliver at least one

dose of measles vaccine to all infants is the primary

reason for this preventable morbidity and mortality.

In 1989 the World Health Assembly adopted the

goal of reducing measles morbidity and mortality

by 90% and 95% respectively by 1995, relative to estimates of the disease burden in the pre-vaccine era. In 1990 the World Summit for Children adopt­

ed a goal of vaccinating 90% of children against

measles by 2000. In 1994, WHO's Region of the Americas set itself the target of achieving elimina­

tion by 2000; in 1997 the Eastern Mediterranean

Region decided on 2010 as its target date for elim­

ination, and in 1998 the European Region chose 2007 for this purpose.

Global reported measles vaccination coverage

declined from 79% in 1997 to 72% in 1998. In 1998, 16 countries reported measles coYerage belo,v

50%, ten of them in rhe African Region (Burundi, Cameroon, Central African Republic, Chad,

Democratic Republic of Congo, Ethiopia, Liberia,

Nigeria, Togo, and uganda), one in the Region of

the Americas (Haiti), two in the Eastern

Mediterranean Region (Afghanistan, Somalia), and

one in the South-East Asia Region (Democratic People's Republic of Korea).

71

Figure 37: Estimated global measles morbidity and mortality

Millions

120

Morbidity

100

80

60

40

20

0 Pre-vaccine era 1998

WHO unpublished data

Millions

7

6

s

4

3

2

0

Mortality

Pre-vaccine ero 1998

The African Region reported the highest number of

measles cases and the highest incidence rate. Of all

the cases reported globally, more than half were reported from countries in this region. Of the

regions with measles elimination goals, the Region

of the Americas reported the lowest incidence rate

(1.6 per 100 000 in 1998).

Supplementary vaccination campaigns have been conducted in several countries, targeting either

measles elimination or reductions in mortality and

morbidity. In 1998 and 1999, 15 countries in the African Region (Angola, Benin, Burkina Faso,

Central African Republic, Chad, Congo,

Democratic Republic of Congo, Ethiopia, Madagascar, lv1ali, Mauritania, Mozambique, Sierra

Leone, Uganda, United Republic ofTanzania), two

in the Eastern Mediterranean Region (Egypt, Sudan), and two in the Western Pacific Region

(Lao People's Democratic Republic, Viet Nam) conducted mass vaccination campaigns in high-risk areas to reduce morbidity and mortality among

children who were nor vaccinated through routine . . . . 1mmun1zanon services.

Based on experience in the Region of the Americas,

\VHO's measles elimination strategy comprises

three parts, two of which involve supplemental

vaccination: catch-up is defined as a one-time,

nationwide vaccination campaign usually targeting

all children aged 9 months to 14 years, regardless of history of measles disease or vaccination status;

DEPARTMENT DF VACCINES AND BIDLDGICALS

Figure 35: Regions with established measles elimination goals

keep-up is defined as routine services aimed at

vaccinating at least 95% of each successive birth cohort; and follow-up is defined as subsequent

nationwide vaccination campaigns conducted every

two to five years, usually targeting all children born after the catch-up campaign. All countries in the

Region of the Americas except French Guiana, the

USA, and several Caribbean islands had completed

catch-up campaigns by 1996. Since then most

countries in this Region have been conducting

follow-up campaigns.

In 9 of 15 countries in the Eastern Mediterranean

Region where measles elimination activities are in

progress, 13 million children have been vaccinated during catch-up measles vaccination campaigns

conducted since 1994. In the European Region, Romania implemented a catch-up campaign during

1998-1999 and vaccinated more than 2 million

children aged 7-18 years (girls aged 15-18 years received measles and rubella vaccine).

Since 1995, 23 million children have been vacci­

nated during catch-up campaigns in the six south­

ern African nations where initiatives on measles

elimination initiatives have been launched. In 1998

72

and 1999, catch-up campaigns were conducted in Australia, China (Hong Kong), New Zealand, the

Philippines and other Pacific island nations.

The global measles laboratory network, which is in

the early stages of development, needs to be strengthened, especially in those countries with

elimination goals, by recruiting additional laborato­

ries and compiling standard procedures for the

testing of samples. In 1998 and 1999, eight measles

laboratory workshops were conducted and 105 lab­

oratory staff from 42 countries in five Regions were trained in basic methods for measles diagnosis.

In 1997 and 1998 the number of countries report­ing vaccination coverage or measles cases decreased

in some regions. The European Region had the highest proportion of population from which data were not reported.

The strengthening of measles surveillance is

required in both developed and developing coun­

tries so that progress towards achieving morbidity and mortality reduction or regional elimination

goals can be monitored. All countries should

improve routine reporting of measles cases by month of occurrence and geopolitical unit.

ANNUAL REPORT 1999

Countries should use outbreak investigations to

obtain data on the age and vaccination status of

measles cases and should estimate population-based

case-fatality ratios. Case-based epidemiological and

virological data are needed when the incidence of

measles decreases to low levels after measures have

been taken to eliminate the disease.

The priorities for countries pursuing accelerated

measles control include:

• improving routine vaccination coverage levels

to at least 80% in all districts;

• conducting supplementary vaccination cam­

paigns together with the administration of vit­

amin A in high-risk areas;

• improving the completeness and promptness

with which measles cases are reported at

district level.

The priorities for countries and reg10ns with a

measles elimination goal include:

• improving routine vaccination coverage levels

to at least 90% in all districts;

• achieving coverage of more than 90% in catch­

up and follow-up campaigns or coverage of

more than 90% with a routine second dose of

measles vaccine;

• establishing case-based surveillance with labo­

ratory confirmation of suspected cases and

virus isolation from all chains of transmission.

Adherence to these priorities should ensure that the

measles morbidity and mortality burden will rapid­

ly decrease in 2000 and beyond, and that the

measles disease reduction targets will be reached.

8.2.2 African Region

Since the introduction of measles vaccine in Africa

there have been estimated reductions of 56% in

measles cases and of77% in deaths. WHO estimat­

ed that in 1997 there were over 11 million cases and

500 000 deaths from measles in the African Region,

representing 37% and 57% respectively of the glob­

al totals. In 1998 the region received reports of only

381 236 cases of measles, suggesting that routine

reporting underestimates disease incidence by at

least one order of magnitude.

The major burden of disease occurs in young chil­

dren in countries of West and Central Africa, the

majority of which have vaccine coverage below

50%. However, this is steadily increasing.

Outbreaks continue to occur. Several countries have

implemented or are planning rotating measles cam­

paigns covering most of their territory.

Countries in East Africa have a significant burden

of measles: Kenya, Tanzania, and Uganda each

report over 20 000 cases per year even though

reporting is known to be insensitive. Outbreaks are

Figure 36: Reported global measles cases and measles vaccine coverage, 1983-1998

■ Cases - Coverage

4 100

90

3 -;;,-,::

§ .§.

80 ~

70 i;l ~

:() 2 ~

s lil ...

8

60 ~ ol ~

~ ,ls 50

40

30 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

Reported at WHO Headquarters as of 8 August 1999

73

DEPARTMENT DF VACCINES AND BIOLOGICALS

Figure 37: Countries implementing strategies for measles elimination, 1999

j

Measles elimination

Figure 38: Global measles laboratory network training, 1998-2000

Laboratories with measle isolation

capabilities

74

o Reference Polio Lab 0 National Polio Lab J:i!j)Trained

Includes rubella training

II Training planned in 2000

'• -,a '

\ .... ~_Jo

-- G \,

Ill

~ )I

ANNUAL REPORT 1999

Table 6: Reported routine measles vaccination coverage among children aged 1 year by WHO Region and worldwide, 1997 and 1998

;•.",;',,!

fl !;~Jes elimination goal: ::; 'Afuericas i},f t:"lterranean

',,•·,,,•'''',:,,, '

·~;~~contrr,I goal: '. r11llippl11ti · :)~et .tfiinf .··•• • ·.

• Rtporttd to WHO as of August, 1999

1997

75%

80% 76%

56%

84% 93%

79%

Reported coverage

%change from

1997to 1998 1998

nro 2 78% -2 71% -5

49% -7

67% -17 93% 0

72'6 -7

.. 1998 estimates of surviving infanll by country (source: UN Population Dirision)

75

Completeness of reporting by countries

WHO Member States 96 of Region's infants""

Number of countries residing in countries that

have reported MCV coverage reporting to WHO

Total 1997 1998 1997 1998

47 40 38 74% 75%

24 23 30 97% 94%

53 35 30 64% 57%

48 41 36 92% 89% 10 8 9 96% 97% 35 34 30 100% 95%

217 181 163 91% 89%

DEPARTMENT DF VACCINES AND BIOLOGICALS

typically among children of preschool age,

although some districts, particularly in Tanzania, report that more than half their cases are in chil­

dren aged over five years. These countries have

adopted a strategy for improving routine coverage,

implementing case-based surveillance, and con­

ducting supplemental vaccination strategies.

Measles campaigns will be implemented over two

to three years in the age groups and districts where

measles cases are occurring.

The countries of southern Africa have embarked on a measles elimination programme, the first

stage of which has comprised mass campaigns to

immunize children aged 9 months to 14 years. Botswana, Malawi, Namibia, South Africa,

Swaziland, and Zimbabwe have implemented such

campaigns and have achieved coverage of at least

80%. The number of reported measles cases has

dropped from over 50 000 a year before the cam­

paigns to less than 2000 in 1999. In Mozambique a strategy for vaccinating in high-risk urban areas

was adopted but initial results suggest that this has not had the desired result of decreasing the inci­

dence of measles in either urban or surrounding

rural areas.

The following challenges for measles control in the

next five years have been identified.

• The 1995 goals for reducing measles mortality and morbidity have. not been achieved. However, there is a high

birth rates favour measles transm1ss10n, 1t 1s

necessary to have both high routine coverage and supplemental vaccination activities m

order to achieve high levels of control.

• Accelerated measles control requires improved surveillance. Data on age and vaccination status

are needed for nearly all reported measles cases.

• There is a crisis in the cold chain and in the quality of vaccination in many countries, par­

ticularly the poorest ones in the region. This means that immunization safety may not be

guaranteed. Furthermore, logistical problems, including interruptions in supplies of vaccines,

have reduced coverage during campaigns in

some countries. The monitoring of adherence

to safe injection practices and of AEFls is not

routinely done or reported.

8.2.2 Region of the Americas

This region continues to make substantial progress towards the goal of eradicating indigenous measles

transmission by the end of 2000. During 1999 there were 2874 confirmed cases, a decline of 95% from the peak of 53 661 in 1997. They occurred in 11 countries, of which only Argentina, Bolivia,

Brazil, and the Dominican Republic experienced

indigenous transmission: Bolivia reported 1420 cases (49% of the total for the Region), Brazil

reported 762 (27%), Argentina reported 247 (9%),

demand for accelerated measles control actlvltles

throughout the region, and countries have reiterated their

commitment to the goals set at the World Summit for

Children. At least 25 coun­

tries in the region have imple­

ment.ed mass campaigns

against measles as a means of either eliminating the disease

(in the southern block) or

reducing the mortality attrib­

utable to it.

Figure 43: Reported measles cases in 7 countries with measles elimination goals in Southern Africa, 1987-1999

• In areas where extremely high routine coverage has not been

achieved and where high pµp­ulation densities and high

76

ANNUAL REPORT 1999

and the Dominican Republic reported 206 (7%).

AMRO has emphasized the importance of height­ened national and international coordination in

these priority countries in order to prevent the

spread of measles into other areas. The health

authorities have pledged their full support for the

goal set for measles eradication.

Attention is centred on progress achieved towards measles eradication in the four priority countries,

which are implementing a dual strategy involving intensive mop-up vaccination in municipalities that fail to reach 95% coverage, together with a

bimonthly active search for measles cases. Bolivia

has been the country most affected by measles, with

1420 confirmed cases during 1999, i.e. approxi­mately 49% of those in the Region. Large areas of

under-immunized populations largely explain this

result. A majority of the confirmed cases occurred in children under 5 years of age; they were followed

by individuals aged 5 to 19 years and young adults

aged 20-29 years. The transmission of measles virus was initially clustered in urban centres, later moving

to certain forested areas. An aggressive plan of

action was launched by health authorities to stop

the outbreak and interrupt virus transmission, with

technical and financial support from AMRO and financial assistance from the World Bank, the Inter­

American Development Bank, UNICEF and local nongovernmental organizations. The Ministry of Health issued a Ministerial Resolution supporting

the implementation of a comprehensive national

vaccination campaign, and this was held in

December 1999.

Figure 40: Immunization coverage and reported numbers of measles cases, Region of the Americas, 1980-2000* **

300000

250000

200000 el s ~ 1S0 000 ~ ;§

100000

soooo

Source: PAH0/WH0

■ Cases - Coverage

• Data as of 23 February- 52 confirmed cases •• 1999 provisional coverage data

Catch-upcampaigns

Priority activities for measles eradication in the Region of the Americas

100

follow-upcampaigns

■ Timely follow-up measles campaigns when the pool of susceptibles nears the number of children born in an average birth cohort. ■ Attainment of the goal of at least 95% vaccination coverage in all municipalities. ■ Proper investigation of all reported cases of suspected measles and obtainment of the appropriate blood and urine samples. ■ Avoidance of missed opportunities: when appropriate, contacts between children and health care workers should be used as

opportunities to vaccinate. ■ Assuring availability of the necessary vaccine supply at the central, regional and local level at all times. ■ -Identification of hard-to-reach population groups and implementation of social mobilization activities that will enhance compliance

with vaccination efforts. ■ Alerting health care workers about the Regional eradication initiative and stressing the importance of their cooperation in it.

77

DEPARTMENT OF VACCINES AND BIOLOGICALS

Figure 4S: Confirmed measles cases by state or province, Region of the Americas

.... -

Total Americas 2 826 cases

1 dot = 2 cases

Source: Country reports

A similar situation arose in the Dominican Republic. In conjunction with the country's health authorities, AMRO organized a task force to ensure the effective control of measles virus transmission. The outbreak began as a consequence of an impor­tation to a tourist area from Argentina in 1997. Despite two vaccination efforts in 1998 the virus continued to circulate and subsequently spread throughout the country in 1999. Over 50% of the cases were reported from the Santo Domingo met­ropolitan area, where pockets of unimmunized children, overcrowding and low coverage rates from previous follow-up campaigns helped to spread the disease. As happened in Bolivia, a major­ity of cases were found in young children. In February 2000, a five-year plan of action for immunization, developed by the Ministry of Health with technical input from AMRO, received US$ 13 million from AMRO, the World Bank and the Japanese International Cooperation Agency.

In Brazil, most states are reporting a decrease in transmission, notwithstanding intense surveillance

by 27 additional epidemiologists engaged as part of the special task force. The remaining cases are pri­marily clustered in the north-east of the country, the

78

state of Pernambuco being the most affected. A fol­low-up campaign will be carried out in June 2000, targeting children aged from 5 to 15 years in some states. The government has undertaken to renew financing for the task force. Progress is also evident in Argentina, which reported a majority of the cases in 1998. A provisional total of762 measles cases has been confirmed in 1999, a decline from the 2930 confirmed cases in 1998. Unlike the 1997 outbreak in Sao Paulo, the age group most affected in 1999 was that of children aged under 1 year, , followed by children aged 1 year and children aged 2-5 years. An emergency plan was developed and four national epidemiologists were engaged to assist the country's health authorities with eradication efforts.

AMRO has intensified its collaboration with all countries to ensure that sufficient resources are allo­cated to maintain adequate stocks of measles vac­cines and other vaccines, as well as supplies. These measures are critical for routine immunization ser­vices, mop-up vaccination activities, and the rapid execution of control measures in the event of an outbreak. Efforts are also being made to strengthen

surveillance systems and improve capabilities for case investigation.

ANNUAL REPORT 1999

8.2.4 Eastern Mediterranean Region

During 1998, 88 941 measles cases were reported, significantly more than the 22 941 reported in

1997. This was mainly attributable to an outbreak in Iraq in which more than 43 000 cases were

reported, and also to an improvement in measles

surveillance in other Member States. However, sur­

veillance is weak in many countries, measles is

accepted as a natural event, and the great majority of mild cases do not present at health facilities.

Consequently, the reported cases represent only a small fraction of the total. Furthermore, reported

cases are usually severe ones that are admitted to

hospitals, while cases that are treated as outpatients

in basic health facilities, i.e. health units and health

centres, are not reported. In addition, few reports are received from the private sector, even though it is very active in most Member States.

8.2.5 European Region

The strategic plan for measles elimination in the

European Region was considered at the Thirteenth

European Advisory Group on Immunization (EAG). The EAG was convinced that the elimina­

tion strategy, which is based on the identification of

susceptibility, was the most appropriate approach

for the region. It was agreed that the target date for elimination should be set at 2007.

To date, three intercountry workshops on measles

elimination have been conducted. The aim of these workshops was to review the epidemiological situa­

tion in the participating countries. So far, 8 of the

CEE countries, the 5 Central Asian Republics and 10

of the Western countries have developed their

national plan based on the European strategy. One of

the greatest challenges is to get a strong political com­mitment and therefore every possible opportunity

should be sought to recruit the support of national and international agencies as soon as possible.

8.2.6 South East Asia Region

Measles continues to be a major cause of morbidity

and mortality in the region, 65 208 cases having

been reported in 1998. The true incidence, howev­

er, is likely to be several million cases. In the absence

79

of a regional resolution calling for measles

elimination, countries are implementing strategies

aimed at disease control and at outbreak preven­tion. Improved surveillance is an essential prerequi­

site for better-targeted immunization activities, and

countries are building on the experiences gained from AFP surveillance to establish NT and measles

surveillance. Indonesia, Sri Lanka, and Thailand

have established laboratory confirmation of measles

outbreaks.

The provision of technical support to Member States in relation to injection safety and waste dis­

posal is a top priority for V&B/SEARO, and an excellent opportunity to promote sustainability in

systems development. To that end, a Regional plan

of action is being developed to revive interest in a

public health problem that requires inputs from several curative and preventive disease strategies. In the meantime, SEARO promotes the bundling of

vaccines with equipment that helps to ensure safe

injection and waste disposal. A priority activity for

2000 will be an intercountry planning workshop to

be held in collaboration with WHO Headquarters.

Other opportunities for systems development arise in connection with the strengthening of manage­

ment and the replacement of the cold chain.

SEARO has employed a full-time cold chain con­

sultant. None of the countries has an adequate plan for conversion to a CFC-free cold chain system, and

this presents a major challenge.

8.2. 7 Western Pacific Region

Pilot measles campaigns were conducted in Cambodia, the Lao People's Democratic Republic,

and Viet Nam,. In November and December 1999, Viet Nam conducted a campaign in Hai Phong

Province, targeting over 320 000 children aged from 9 months to 10 years, and reportedcoverage of

99.6%. In January and February 2000, Cambodia

conducted a campaign in six provinces and in March and April 2000 the Lao People's Democratic Republic conducted a campaign in Phongsaly and

Khammoune Provinces. A database for measles sur­veillance was installed in all three countries. Work

began on the establishment of a Regional laborato­

ry network for measles, and Regional and national laboratories have been identified for most countries.

DEPARTMENT DF VACCINES AND BIDLDGICALS

8.3 Neonatal tetanus

8.3.1 Global activities

The goal of NT elimination has been achieved in

104 of 161 countries. However, in 1998 it was esti­mated that there were 289 000 cases of NT, resulting

in 215 000 deaths, and that there were 30 000 mater­

nal tetanus (MT) deaths. Twenty-seven countries, 18

of them in the African Region, account for 90% of

the global burden of NT. The recommended strategy

for eliminating maternal and neonatal tetanus (MNT) focuses on the high-risk approach because NT and MT cases occur in areas with limited access

to antenatal care and clean delivery services.

The estimated cost over five years for eliminating MNT in the remaining countries is US$ 130 mil­

lion., and it is estimated that the average contribu­

tion from the targeted countries will amount to

approximately 25%. The requirement from external sources is thus $100 million, of which nearly

$45 million have already been raised. The US

Fund for UNICEF would like to secure funding commitments for all MNT activities by the year

2001.

Many issues still have to be addressed in order to

determine NT elimination accurately by district.

They include: the validity of methods in use; the

Figure 42: Neonatal tetanus in Latin America, 1985-1999*

Source: HVP/PAHO * Provisional data

80

improvement of information systems for district­

level monitoring; the need to develop monitoring

standards and policies; and the need for consensus

on monitoring issues.

8.3.2 African Region

Neonatal tetanus remains an important public health problem in the African Region, causing

approximately 164 000 cases and llO 000 deaths a

year. Reported coverage with at least two doses of

tetanus toxoid (TT2+) has remained stable in the range of about 30-35% for the past five years

(35% in 1998). The reported numbers of NT cases

have not declined in the past seven years: there were

4517 cases in 1992 and 4838 in 1998.

Notwithstanding the lack of progress in NT control over the Region as a whole, several countries have

made progress. In Malawi, Mozambique (Maputo),

certain districts in Nigeria, and Tanzania, the sys­

tematic vaccination of women of childbearing age has resulted in substantial reductions in the num­

bers of cases. Case-based surveillance for MNT cases has been instituted in several West African

countries: Benin, Cote d'Ivoire, Liberia, Mali, and

Senegal.

Several issues associated with assessment, surveil­

lance and certification are constraining NT control.

ANNUAL REPORT 1999

Underreporting of NT is estimated to amount to

96%, only 4838 cases having been reported in 1998.TT2+ coverage is not accurately reflecting the

immunity levels in women of childbearing age.

During the past five years, two studies indicated that immunity levels were underestimated by 20-

30% and one indicated an immunity level similar

to TT2+ coverage.

8.3.3 Region of the Americas

The number of NT cases continues to decline (Fig. 42), 157 having been reported during

1999.The strategy has been to vaccinate women in

areas and population groups at highest risk within the high-risk municipalities where there are still iso­

lated cases. AMRO has therefore recommended that countries carry out national evaluations to

determine which municipalities remain in the

attack phase, requiring intensive vaccination, and

which have advanced to the maintenance phase,

involving vaccination through routine programmes.

Furthermore, countries should look into the epi­

demiological and social conditions associated with

these cases, e.g. migration, lack of vaccination, and marginality, in order to target vaccination on those

groups or areas at highest risk within high-risk municipalities.

8.3.4 Eastern Mediterranean Region

The goal of less than one case of NT per 1000 live

births in each administrative district was achieved

in 15 of the 23 Member States, namely Bahrain,

Cyprus, Islamic Republic of Iran, Jordan, Kuwait, Lebanon, Libyan Arab Jamahiriya, Morocco,

Oman, the Self-Ruled Areas in Palestine and the

population served by UNRWA, Qatar, Saudi

Arabia, Syrian Arab Republic, Tunisia, and the United Arab Emirates. The elimination goal has not

yet been achieved in eight countries: Afghanistan,

Djibouti, Egypt, Iraq, Pakistan, Somalia, Sudan,

and Yemen. Among these countries, Djibouti, Egypt, and Iraq are very close to the goal, few

districts having higher rates than the target.

The total number of reported cases of NT in 1998

was 2955, which was similar to the numbers report­ed in previous years. However, NT is still seriously

underreported, the degree of under-reponing vary­

ing between _Member States. In some countries,

such as Afghanistan and Somalia, the sun-eillance

81

Figure 43: Distribution of neonatal tetanus cases by country, 1999 Women of childbearing who live in districts classified as being at high risk for the disease.

system is extremely weak or almost non-existent.

Other countries, such as Egypt, have sensitive sur­

veillance systems, whereby more than 70% of cases

are detected and reported. Because the disease occurs early in life its victims' deaths, and even their

births, may not be officially recorded. Moreover,

NT is most prevalent in poor rural areas with inef­

ficient or non-existent health services, where it is

perceived by the people as having an inevitably

fatal outcome. Consequently, they tend not to seek medical advice and are inclined to delay the

regisuation of births.

8.3.5 South-East Asia Region

Five countries are considered as having eliminated

NT. In 1999, Myanmar implemented its elimina­

tion plan based on the high-risk approach and has completed two of the three rounds of TT immu­nization in 54 targeted townships, administering

nvo doses rn 1.4 million women of childbearing

age. Bangladesh, India, Indonesia, Myanmar, and

~epal are developing plans to reach the target of less than one NT case per 1000 live births by 2000,

on i:he basis of the high-risk approach, whereby it is

intended to immunize all women of childbearing

age in high-risk areas ,vith at least three doses ofTT

vaccine. Bangladesh conducted an NT and measles

DEPARTMENT OF VACCINES ANO BIOLOGICALS

campaign in 1999, targeting approximately 10% of the population. Indonesia introduced school-based TT immunization. In Rajasthan (India) over 4 mil­lion women received two doses of TT during a UNICEF-sponsored campaign in 1998.

8.3.6 Western Pacific Region

Excluding China, reported coverage during 1998 with two doses ofTT in pregnant women was 71 %. China, the Philippines, and Viet Nam have achieved the elimination goal at the province/pre­fecture level and are progressing towards elimina­tion at the district level. Cambodia, the Lao People's Democratic Republic, and Papua New Guinea have made progress but NT is still widespread in these countries.

8.4 Vitamin A supplementation

8.4.1 Global situation

In countries where vitamin A deficiency occurs the integration of vitamin A supplementation into

immunization services is increasingly common. The provision of a high dose of vitamin A every four to six months not only protects against blindness but also has a dramatic impact on the health of children aged 6-59 months, reducing the risks of all-cause, measles and diarrhoeal disease mortality by 23%, 50% and about 33% respectively.

Vitamin A deficiency is a public health problem in 118 countries, all of them in the developing world. The worst effects occur in Africa and Asia. Globally, between 100 million and 256 million children under 5 years of age are at risk. These children suf­fer a dramatically increased risk of death, blindness and illness, especially measles and diarrhoea. Annually, vitamin A deficiency causes blindness in 250 000 to 500 000 children and is a major factor contributing to between 1 million and 3 million child deaths. In 1990 the World Summit for Children set the goal of eliminating vitamin A deficiency by 2000.

Food fortification and dietary diversity are essential for the control of vitamin A deficiency, but are often difficult to achieve quickly or widely in those

Figure 48: Countries administering vitamin A supplementation during NIDs, 1999

lflj Vitamin A with NIDs (national or sub-national) (56 countries; indudes both polio and measles campaigns)

Vitamin A with routine EPI (26 countries; induding Samoa, Micronesia, Kirbati)

82

ANNUAL REPORT 1999

developing countries where the condition is most

severe. Consequently, supplementation has been

introduced as a low-cost, highly effective and

sustainable means of rapidly improving the vitamin

A status and health of children. Immunization ser­

vices, particularly polio NIDs, provide a ready­

made infrastructure for this purpose. Furthermore,

cost-effectiveness and impact can be increased by

combining these two interventions.

In 1999, 53 countries introduced vitamin A sup­

plementation into their polio NIDs, and three addi­tional countries introduced it into their measles

vaccination campaigns. Over 60 million children received vitamin A and benefited from its protective

effects. Moreover, 26 countries provided vitamin A

supplementation together with their routine immu­

nization services. Fig. 44 is a summary of global vit­amin A supplementation in conjunction with

immunization during 1999.

The integration of vitamin A with immunization

campaigns is building a platform for the longer­term strategy of adding vitamin A to routine immu­

nization contacts (for postpartum mothers at the

first EPI contact and for children receiving measles

immunization at 9 months of age). For example,

NIDs with vitamin A supplementation have:

increased awareness and advocacy of vitamin A

deficiency among the highest levels of decision­makers; strengthened the technical capacity of

health workers to administer vitamin A; and result­

ed in an integrated reporting system. Furthermore, vitamin A supplementation is helping to increase

participation in NIDs and routine immunization

services because vitamins are highly valued by

mothers.

With continued funding from the Micronutrient

Initiative (Canada), during 1999, V&B has worked in dose partnership with WHO's Department of

Nutrition for Health and Development and

UNICEF to: • promote the policy of integrating vitamin A

supplementation into immunization services;

• develop guidelines and training materials (including a new CD-ROM Training and

Information Package on Immunization and

Vitamin A, produced jointly with Helen Keller

International);

• provide technical training and operational sup­

port to countries;

83

• undertake research on simplifying the delivery method, confirming the seroconversion effect,

and assessing impact;

• adapt WHO's monitoring and surveillance

system to include linked vitamin A and EPI

activities and results.

Building on the momentum already generated,

efforts in 2000 will focus on promoting and strengthening the delivery of vitamin A with rou­tine immunization services. This will include

expanding the opportunities to give vitamin A dur­ing early immunization contacts (i.e. DTP vaccina­

tion), thereby making the most of the immuniza­

tion-linked delivery schedule for children during

their first year of life.

8.4.2 Region of the Americas

The 12 countries in which subdinical vitamin A

deficiency is of severe to moderate public health sig­nificance (based on % prevalence of serum retinal

less than 20µg/ dl) are currently providing vitamin A

supplementation to targeted children, particularly through EPI contacts. Six of these countries

(Bolivia, Brazil, Dominican Republic, Ecuador,

Nicaragua and Peru) are participating in a two-year

project to provide vitamin A supplementation twice a year to children aged 6-24 months and once to

mothers up to six weeks postpartum. The purpose

of maternal supplementation is to increase the vita­min A content of breast milk so as to benefit lactat­

ing infants aged under six months. This project,

coordinated by AMRO's Food and Nutrition

Programme and the Division of Vaccines and Immunization, is designed to review and imple­

ment or reinforce vitamin A supplementation pro­

grammes that are linked to immunization cam­

paigns as well as to routine immunization and other maternal and child health contacts.

For children aged 6-11 months, coverage rates

are relatively high (>60%). However, they are somewhat lmver for children over 1 year of age and

even lower for the second dose per year. Attention is

being given to means of improving the level of vit­

amin A supplementation through immunization

contacts, with particular reference to the manage­ment of the logistics of this intervention in the

field. Lines of coordination between EPI and nutri­

tion programmes need to be dearly identified in the

areas of training, capsule distribution, data collec-

DEPARTMENT DF VACCINES AND BIOLOGICALS

tion, monitoring and supervision. In addition, sup­plies of vitamin A capsules could be handled togeth­er with vaccines for the purposes of stock checks, local transport and dissemination. These issues and others should be carefully dealt with in order to achieve an effective integrated programme.

8.4.3 South-East Asia Region

Vitamin A deficiency has been raised by WHO as a priority project at the Region's last three TCG meetings on immunization and polio eradication and at several meetings of the lnteragency Coordinating Committee at country level. Since immunization workers are likely to remain the most important means of getting vitamin A to children,

84

WHO will continue to encourage countries with adequate trained manpower to provide vitamin A during NIDs, on condition that there is a minimal risk of adversely affecting the performance of polio immunization. Bangladesh and the Democratic People's Republic of Korea aredistributing vitamin A during NIDs. Nepal distributes vitamin A during one round of its NIDs. Myanmar began the distri­bution of vitamin A during its NIDs in January 2000. In India's state of Orissa, vitamin A supple­mentation was introduced during an NID in October 1999 and an assessment and impact study, now in progress, is expected to influence the country's policy on vitamin A supplementation campaigns. D

ANNUAL REPORT 1999

[j] Annexes

Annex 1: Documents produced by the V&B Document Centre during 1999

Over the year the Document Centre produced 74 documents, 38 of them in English, 23 in French, 5 in Spanish and 4 in Russian. These documents are available on the Internet at: www.vaccines.who.int/vaccines-documents.

General V&B documents

WHO/V&B/99.01

WHO/V&B/99.02

WHO/V&B/99.03

WHO/V&B/99.04

WHO/V&B/99.05

WHO/V&B/99.06

WHO/V&B/99.07

WHO/V&B/99.08

WHO/V&B/99.09

V&B Annual Report, 1998 English only

V&B Catalogue '99 - Listing of materials currently available from V&B Document Centre English only

Informal consultation on the control of pertussis with whole cell and acellular vaccines, Geneva, 18-19 May 1998 English only

The current status of development of prohphylactic vaccines against human papillomavirus infection - Report of a technical meeting, Geneva, 16-18 February 1999 English only

Fourth informal consultation on the polio laboratory network, Geneva, 1-2 October 1998 English only

Informal meeting on issues of immunization data and monitoring/management of adverse events, Geneva, 17-20 November 1998 English only

Fourth annual meeting of the Advisory Committee on Training (ACT), Geneva, 23-24 February 1999 English onJ;,

Informal consultation of experts on national regulation of vaccines, Geneva, 21-22 January 1999 English only

Review of existing documents on planning, performance and assessment of clinical studies on vaccines English, French, Spanish

85

WHO/V&B/99.10

WHO/V&B/99.11

WHO/V&B/99.12

WHO/V&B/99.13

WHO/V&B/99.14

WHO/V&B/99.15

WHO/V&B/99.16

WHO/V&B/99.17

WHO/V&B/99.18

WHO/V&B/99.19

WHO/V&B/99.20

WHO/V&B/99.21

WHO/V&B/99.22

WHO/V&B/99.23

WHO/V&B/99.24

DEPARTMENT OF VACCINES AND BIOLOGICALS

Regulation of vaccines: Building on existing drug regulatory authorities English, French, Spanish

Testing the correlation between vaccine vial monitors and vaccine potency English, French

Procurement of vaccines for public-sector programmes. A reference manual English only

Options for a global fund for new vaccines English only

Field manual for neonatal tetanus elimination English, French

Temperature monitors for vaccines and the cold chain (Revises and replaces WHO/EPI/CCIS/85.02 Rev.5) English, French

Report of the first meeting of interested partners to the Health Technology and Pharmaceuticals Cluster, Geneva, 16-19 March 1999 English only

WHO vaccine-preventable diseases monitoring system, 1999 global summary (Revises and replaces WHO/EPI/GEN/98.10) English only

Quality of the cold chain - WHO/UNICEF policy statement on the use of vaccine vial monitors in immunization services English, French

Standardization and validation of serologic assays for the evaluation of immune responses to Neisseria meningitidis serogroup NC vaccines, Geneva, 8-9 March 1999 English only

Advocacy - A practical guide: with polio eradication as a case study English only

Study of donor inputs to vaccine production English only

Guidelines for surveillance of congenital rubella syndrome (CRS) and rubella - Field test version, May 1999 English (French in preparation)

Issues relating to the use of BCG in immunization programmes - A discussion document English (French in preparation)

Strategies, policies and practices for immunization of adolescents: A review English (French in preparation)

86

WHO/V&B/99 .25

WHO/V&B/99.26

WHO/V&B/99.27

WHO/V&B/99.28

WHO/V&B/99.29

WHO/V&B/99.30

WHO/V&B/99.31

WHO/V&B/99 .32

WHO/V&B/99.33

WHO/V&B/99.35

WHO/EPI/GEN/98.17

Newsletters

WHO/EPI/Measles/99.01

WHO/EPI/PN/99.01

WHO/EPI/PN/99 .02

ANNUAL REPORT 1999

Safety of injections - WHO/UNICEF joint statement on the use of auto-disable syringes in immunization services (Revises and replaces WHO/EPI/LHIS/98.04) English, Russian (French and Spanish in preparation)

Generic protocol to estimate the burden of Shigella diarrhoea and dysenteric mortality - Field resr version, May 1999 English only

Towards a CFC-free world - Training for refrigerator technicians. Module A: R12 - Recovery, recycling and repair English (French to follow)

Towards a CFC-free world - Training for refrigerator technicians. Module B: Working with R134a English (French to follow)

Towards a CFC-free world - Training for refrigerator technicians. Module C: Working with Lokring technology English (French to follow)

Towards a CFC-free world - Training for refrigerator technicians. Module D: Guidelines for the introduction of CFC-free equipment to national Expanded Programmes on Immunization English (French to follow)

Report of the fourth meeting of the Global Technical Consultative Group for poliomyelitis eradication, Geneva, 1-2 June 1999 English only

Global action plan for laboratory containment of wild poliovirus English (French and Spanish in preparation)

Immunization and health sector reform in the Kyrgyz Republic, March 1999 English (Russian in preparation)

Report on the overview of vaccine research in WHO and UNAIDS English on{y

Global eradication of poliomyelitis: Report of the third meeting of the Global Commission for the Certification of the Eradication of Polio, Geneva, 9 July 1998 English only

Measles Bulletin, Issue 1, September 1999 English, French

Polio News, Issue 3, March 1999 (English only)

Polio News, Issue 4, June 1999 (English only)

87

WHO/EPI/PN/99.03

WHO/EPI/PN/99.04

DEPARTMENT OF VACCINES AND BIOLOGICALS

Polio News, Issue 5, September 1999 (English only)

Polio News, Issue 6, December 1999 (English only)

Translations of previous years' documents

French WHO/EPI/GEN/98.08

WHO/EPI/GEN/98.09

WHO/EPI/GEN/98.11

WHO/EPI/TRAM/98.01 11

WHO/EPI/TRAM/98.12

WHO/EPI/TRAM/98.13

WHO/EPI/TRAM/97.06

WHO/EPI/TRAM/97.07

Russian WHO/EPI/GEN/97.03

Spanish WHO/VSQ/97.03

GAV/ documents

GAVl/99.01

GAVI/99.02

Fievre jaune - Reunion technique de consensus, Geneve, 2-3 Mars 1998

Fievre jaune - Surveillance de la fievre jaune: lignes directrices a l' echelon du district

Fievre jaune

Vaccination pratique: Modules 1-11

Vaccination pratique: Module d' activites pedagogiques

Vaccination pratique: Guide a !'usage du formateur

Cours a !'usage des agents de sante: Reperer et surmonter les obstacles a I' amelioration de la couverture vaccinale - Modules du stagiaire: Introduction au cours Module 1: Recueillir des informations dans la communaute et les exploiter Module 2: Communiquer avec les meres au sujet des vaccinations

Cours a !'usage des agents de same: Reperer et surmonter les obstacles a l' amelioration de la couverture vaccinale - Lignes directrices a l'usage de I' animateur: Introduction, Module 1, Module 2

Polio: The beginning of the end

Gufa para la inspecci6n de fabricantes de productos biol6gicos

Global Alliance for Vaccines and Immunization, Seattle, Washington, 12-15 July 1999 English, French

Global Alliance for Vaccines and Immunization - First Board Meeting, UNICEF House, New York, 28 October 1999 English, French

88

ANNUAL REPORT 1999

Annex 2: Internet information

The world wide web (www) pages of the Department of Vaccines and Biologicals (V&B) are part of the material on the web under the WHO home page and the HTP duster. The address for the home page for

vaccines and immunization is now ·www.vaccines.who.int. This is very easy to remember and to find via search

engines. A large amount of basic information about vaccines and immunization is posted on this site, together

with regularly revised data. Each unit is placing increasing emphasis on developing the site as a way of

disseminating technical information. Most publications are now posted on the V&B Document Centre web

site in pdf format as soon as they are sent to the printer. They are thus on the web before the printed material

is available.

Figure 45: Polio Eradication lnitiaitive web pages

ii :3 :;i ~ ~ iJt QJ r-' Iii :1 Forward Reload Home Search Guide Images Print Security Stop

ii L~cation:{ ht! ://www.olioeradication.org/ ·-- ~~--·"' " - --~-··- -.-•-

We,corne to the WHO official s;te cf \r·e /aroest ever disease eradical'on :r·JLative ...

Global

Polio Eradication lnHiatiYe

Find out the latest an:

PJdkt.lkWL Initiative. .. the latest news from the Global Polio Eradication

,· r. E,c}i:J,2,,;cr,--·:/c,/c5' f;_·se-c:,:r-d.~. -- Progress towards poliomyelitis eradic:ation.

Hor:1e ?age • Ba:i::kgri:iund • ·31':rba! ~:t2I1Js • N3!ional tmmunfa:ation Oay'S Oo~1.nb2:Js • Pdi,:i in th~ Ne:.1r.; • Phi::to Ga1le.f:/ • Partne.r.; ■ Ci:intact Us ■ Links

R°.JF ~I,:; and ~ pi,,a-sr, elk/,· i>s,,,, h g:, h oor ~ page or d,d,- i>s,,,, ;,, e--<mil u':S .

.ACROBAT Reader is needed to view many documents available in PDF format. ~:1ici: r.e,eto do unload from Afobe .com

World Health OC9ani,ation, Di>,ision for Vaooines and other Biologicals, E:apande.d Programme on Immunization, Geneva, Suitzer1and

89

DEPARTMENT DF VACCINES AND BIOLOGICALS

The Polio Eradication Initiative has an extensive site, much of the information on which is also available as a CD-Rom. Another priority project, Safety of Immunization, has a well-developed site entitled "Vaccines are safe". Large amounts of useful material are also posted under the ATT and VAM pages.

Figure 46: "Vaccines are safe''web pages

clot Topics 0 Vaccine safety current affairs of immediate interest to the public

90

• Rolavirus and intussusception (15 July 1999)

• Thiometsal (9 July 1999)

• SV40 virus and polio vaccine

• Hepatitis B vaccine and MS