Sickle Cell DiseaseInternational collaboration and global issues

Jacques Elion, MD, PhD National Reference Centers for Sickle Cell Disease

Department of Medical Genetics Robert Debré University Hospital, 75019 Paris, France

Inserm UMR 665National Institute for Blood Transfusion, 75015 ParisGuadeloupe University Hospital, 97139 Les Abymes (French West Indies)

Institut national de la santé et de la recherche médicale

La Havana20-24 May 2013

Map is from Piel FB et al: Nature Communications, Nov 2010

Independent origins of SCD in Africa and India

Spread by the slave trade

Royaume Uni Pays-Bas

Espagne

Portugal

Belgique

AllemagneFrance

Italie

Grèce

Irlande

Luxembourg

Danemark

Norvège

Suède

Finlande

ββββS

…or modern economical migrations

It is estimated that in excess of 300 000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries.

Major hemoglobin disorder No. of annual births

β thalassaemia major 22 989HbE β thalassaemia 19 128HbH disease 9 568Hb Bart hydrops (α°) 5 183SS disease 217 331S β thalassaemia 11 074SC disease 54 736

Sickle cell anaemia is by far the commonest and data suggests that close to 180 000 babies are born each year in sub-Saharan Africa with this condition

The burden of the haemoglobinopathies

Weatherall DJ. Blood. 2010

Affected newborns in subsaharan Africa

Modell, 2006Nigeria

(0-18%)(0-18%

(0-1%)

(0-2%)

(0-12%)

(0-35%)

(0-31%)

(0-33%)

(0-34%)

(0-23%)

(0-20%)

(0-31%)

(0-30%)

Sickle Cell Disease in IndiaBurden of Disease

Estimates births/year:

AS: 2,434,170

SCD-SS 121,375(Mohanty, ’02)

25-40% carriers

• African Union: Assembly decision/AU/ Dec. 81 July 2005

• UNESCO General Assembly September 2005

• WHO resolutions: WHA59.20 and EB 118 May 2006• UN General Assembly resolution: A/63/237

December 2008

• WHO-AFRO resolution: AFR/RC60/8 August 2010Sickle-cell disease: a strategy for the WHO African Region

SCD is recognized as a global public health issue

Still many issues remain unanswered

- based mainly on studies that were carried out before 1980 (in Africa)- obtained from a very limited number of centers in each of the countries - even in many richer countries, data of this kind are scarce

Epidemiological data must be interpreted with extreme caution

Thus, there is an urgent need of sound epidemiological data to estimate the health burden that will be encountered, particularly by the poorer countries as the haemoglobin disorders become even more frequent in the future.

unresolved issue 1

Weatherall DJ. Blood. 2010

- improved nutrition- better control of infectious disease

…childhood mortality rates are decreasing

Under these circumstances, the prevalence of genetic disorders like haemoglobinopathies tends to increase

The epidemiologic transition

Because of:

Furthermore, in many cases this affects countries with the highest rate of increase of their population.

But census data are uncertain

unresolved issue 2

SCD is apparently a simple disease- a single gene - a single mutation- a “simple” basic pathophysiological scheme

still it is highly variable in its clinical presentation

unresolved issue 3

- cell adhesion- inflammation- endothelial damage- altered hemorheology- NO bioavailability

Steinberg, N Engl J Med 1999

What is the problem?

- basic research has been done in the North, mostlyin the USA

- all the tools are there (pharmalogical labs, facilities for GWAS studies…)

but- we lack epidemiological data

- we know almost nothing about the natural history ofSCD in its natural environment

Worldwide disparity of resources

Hundreds of thousands SCD patients in sub-Saharan Africa AND India

Brazil is by far the country with the largest number of patients in the Americas, just followed by the Carribean countries

approx.

- 100,000 SCD patients in the US

- 50,000 SCD patients in Europe

Worldwide disparity of resources

Hundreds of thousands SCD patients in sub-Saharan Africa AND India

Brazil is by far the country with the largest number of patients in the Americas, just followed by the Carribean countries

approx.

- 100,000 SCD patients in the US

- 50,000 SCD patients in Europe

Global issue → clear necessity of coordinated efforts

- South-South sustainable collaboration- North-South equitable & sustainable collaboration- triangular partnerships

regional and international (global) networks

International collaboration is crucial

It is clear that research, training of doctors and health workers and education can be the driving force to improve clinical care globally

to the mutual benefit of both low- or middle-income countries and high-income countries and for the good of the patients.

Examples of fruitful collaborative networks- France – French-speaking African countries- UK - Tanzania- Portugal – Angola- Holland – Curaçao - USA – Ghana- Brazil – Ghana, Senegal, Benin, Angola

International collaboration

Within this frame, regional networks and international coordination are pivotal to promote:

- research- training and education- patients follow-up and management

Definition of the phenotype is crucial. Given the level of complexity of SCD it is is difficult to achieve an agreed classification of the different degrees of severity.

It is vital to attempt to produce a workable description of severity as a prelude to the potential international collaborations and to normalise clinical and biological data collection.

Comparative cohort studies are badlyneeded

Results of projects such as the Jamaican Cohort Study or the USA Cooperative Study of Sickle Cell Disease are clear indications that such initiatives should be pursued in a comparative manner.

Weatherall et al. Blood. 2005

The Central AfricanSCD network

- Cameroon Angola- DRC Ouganda- Congo Zambia- CAR Kenya- Gabon Burundi- Tanzania Ruanda- South Sudan

REDAC

Africa (1)

Examples of successful regional networks

CADRE studySCD cardiovascular aspectsBrigitte Ranque, Xavier Jouven et al

Laboratoire d’Excellence GR-Ex

Coordonnation: Olivier Hermine

ResearchNetworks

Cohort of 5.000 patients

Examples of successful regional networks

Africa (2)

SickleCHARTA

NIH

Sanger Institute

PI: Julie MakaniTanzania

Establish a network of Excellence SCD Centres in Africa

- Epidemiological geneticsGWAS studies

- Healthcare- Training

Cohort: 10.000 SCD patients

Examples of successful regional networks

CAribbean network of REsearchers on

Sickle cell disease and Thalassemia

Caribbean Network

11 Caribbean countries

- Newborn screening- Follow-up- Education- Research

Relationship between Acute Chest Syndrome and the sympatho-vagal balance in adults with hemoglobin SS disease; a case control study Knight-Madden JM,

Connes P, Bowers A, Nebor D, Hardy-

Dessources MD, Romana M, Reid H,

Pichon AP, Barthélémy JC, Cumming VB,

Elion J, Reid M. 2012, sous presse.

President : MD Hardy-Dessources

Examples of successful regional networks

The Global SCD Network

• Mission

– Furthering research and advancing clinical care globally

• Goals

– Facilitate North-South, South-South and triangular partnerships

• Research

• Training

• Education

• Clinical programs

Medical Director: Isaac OdameSickKids Hospital, Toronto

International Advisory Board:

Jacques Elion, Chairman

Foundational and Transformative GSCDN

NINGSite

GSCDN Website

Foundational Transformative Visionary

Establish Int’l Advisory

Council

HIGH

HIGH

LOW

Level of Effort to Implement

IMMEDIATE PRIORITIES SHORT /MEDIUM TERM

PRIORITIES

LONG TERM PRIORITIES

* Red line indicates maturity curve

GSCDN Conference at CDC

Published data of SCD

related mortality

Foster Partnerships; start with CDC, UNESCO

SCD Centre Planning

1 SCD Model CentreImplement Programs

In 3 or 4 LICs

Standard SC Centre

Model RolloutsSCD Leader, WHO

Partner , Continued

SC Centre Expansion

www.globalsicklecelldisease.org

GSCDN Website

http://www.globalsicklecelldisease.org/

Interactive Treatment Centres Map

http://globalscd.ning.com

GSCDN ‘Ning’ Online Community

Foundational and Transformative GSCDN

NINGSite

GSCDN Website

Foundational Transformative Visionary

Establish Int’l Advisory

Council

HIGH

HIGH

LOW

Level of Effort to Implement

IMMEDIATE PRIORITIES SHORT /MEDIUM TERM

PRIORITIES

LONG TERM PRIORITIES

* Red line indicates maturity curve

GSCDN Conference at CDC

Published data of SCD

related mortality

Foster Partnerships; start with CDC, UNESCO

SCD Centre Planning

1 SCD Model CentreImplement Programs

In 3 or 4 LICs

Standard SC Centre

Model RolloutsSCD Leader, WHO

Partner , Continued

SC Centre Expansion

Sickle cell disease in Africa: a neglected cause of early childhood mortality.Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN.Am J Prev Med. 2011

Foundational and Transformative GSCDN

NINGSite

GSCDN Website

Foundational Transformative Visionary

Establish Int’l Advisory

Council

HIGH

HIGH

LOW

Level of Effort to Implement

IMMEDIATE PRIORITIES SHORT /MEDIUM TERM

PRIORITIES

LONG TERM PRIORITIES

* Red line indicates maturity curve

GSCDN Conference at CDC

Published data of SCD

related mortality

Foster Partnerships; start with CDC, UNESCO

SCD Centre Planning

1 SCD Model CentreImplement Programs

In 3 or 4 LICs

Standard SC Centre

Model RolloutsSCD Leader, WHO

Partner , Continued

SC Centre Expansion

Sickle cell disease in Africa: a neglected cause of early childhood mortality.Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN.Am J Prev Med. 2011

The importance of local management in reinforcing the whole

GSCDN and the regional SCD Networks

CAREST

REDAC

GLOBAL SICKLE CELL

DISEASENETWORK

Juntos mas fuertes

Together we will be stronger

Ensemble nous serons plus forts

Ansanm nou ké pli fô

Organize / Join SCD Networks!