T

SSa

b

c

d

e

f

g

a

ARRAA

KNMES

1

imndcwaIslad

m

sT

0d

Vaccine 30S (2012) B26– B36

Contents lists available at SciVerse ScienceDirect

Vaccine

j ourna l ho me pag e: www.elsev ier .com/ locate /vacc ine

he changing and dynamic epidemiology of meningococcal disease�

cott A. Halperina,∗, Julie A. Bettingerb, Brian Greenwoodc, Lee H. Harrisond, Jane Jelfse,hamez N. Ladhani f, Peter McIntyree, Mary E. Ramsayf, Marco A.P. Sáfadig

Canadian Center for Vaccinology, Dalhousie University, the IWK Health Centre, and Capital Health, Halifax, CanadaVaccine Evaluation Center, British Columbia Children’s Hospital and the University of British Columbia, Vancouver, CanadaLondon School of Hygiene & Tropical Medicine, London, UKInfectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, USANational Centre for Immunisation Research & Surveillance, Westmead, AustraliaHealth Protection Agency, London, UKFaculdade de Medicina da Santa Casa de São Paulo, São Paulo, Brazil

r t i c l e i n f o

rticle history:eceived 24 October 2011eceived in revised form 4 December 2011ccepted 5 December 2011vailable online 15 December 2011

eywords:

a b s t r a c t

The epidemiology of invasive meningococcal disease continues to change rapidly, even in the three yearssince the first Meningococcal Exchange Meeting in 2008. Control of disease caused by serogroup C hasbeen achieved in countries that have implemented meningococcal C or quadrivalent meningococcalACWY conjugate vaccines. Initiation of mass immunization programs with meningococcal A conjugatevaccines across the meningitis belt of Africa may lead to the interruption of cyclical meningococcal epi-demics. A meningococcal B vaccination program in New Zealand has led to a decreased incidence of high

eisseria meningitidiseningococcus

pidemiologyurveillance

rates of endemic serogroup B disease. Increases in serogroup Y disease have been observed in certainNordic countries which, if they persist, may require consideration of use of a multiple serogroup vac-cine. The imminent availability of recombinant broadly protective serogroup B vaccines may provide thetools for further control of invasive meningococcal disease in areas where serogroup B disease predom-inates. Continued surveillance of meningococcal disease is essential; ongoing global efforts to improvethe completeness of reporting are required.

. Introduction

In 2008, at the first Meningococcus Scientific Exchange Meetingn Siena, Italy, Harrison et al. reviewed the global epidemiology of

eningococcal disease [1]. In that review, it was stressed that theature and quality of the surveillance undertaken in a region has airect bearing on the reported incidence of invasive meningococ-al disease (IMD). The ideal of population-based, active surveillanceith clinical cases confirmed by laboratory testing and strain char-

cterization is still not attainable in most places in the world.nstead, combinations of syndromic surveillance, active and passiveurveillance, sentinel surveillance, and laboratory-based surveil-

ance are used, making comparison between jurisdictions difficultnd calculation of true incidence impossible. Changes in the epi-emiology of IMD over time can be described with some accuracy

� Presented in part at the Meningococcus Scientific Exchange Meeting “Towards aeningitis free world”, July 2–3, 2011, Siena Italy, sponsored by Novartis Vaccines.∗ Corresponding author at: Canadian Center for Vaccinology, Dalhousie Univer-

ity, IWK Health Centre, 5850/5980 University Avenue, Halifax NS B3K 6R8, Canada.el.: +1 902 470 8141; fax: +1 902 470 7232.

E-mail address: scott.halperin@dal.ca (S.A. Halperin).

264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved.oi:10.1016/j.vaccine.2011.12.032

© 2011 Elsevier Ltd. All rights reserved.

in regions where surveillance methodology has remained consis-tent. The purpose of this review is to provide an update on theglobal epidemiology of IMD in the 3 years since the first Meningoco-coccus Scientific Exchange Meeting. The effects of implementationof universal meningococcal C (MenC) or quadrivalent meningo-coccal ACWY (MenACWY) conjugate vaccines in various regionswill be described, as will the long-awaited implementation of themeningococcal A conjugate vaccine (MenA) program in the Africanmeningitis belt. Additional details related to the epidemiology ofmeningococcal B strains will also be provided in anticipation of thelicensure of meningococcal B vaccines (MenB) in the near future.

2. Description of the pathogen

Neisseria meningitidis is a gram-negative diplococcus whichcolonizes the pharynx and upper respiratory tract. Thirteenserogroups have been identified based on unique capsular polysac-charides; 6 serogroups cause virtually all human disease (A, B, C,W, X, Y) [2]. The reported incidence of IMD varies by region, rang-

ing from less than 0.5 cases per 100,000 in North America and justunder 1 case per 100,000 in Europe up to 10–1000 cases per 100,000during epidemic years in Africa (Table 1). The serogroups causingIMD also vary geographically, with serogroup A disease occurring

S.A. Halperin et al. / Vaccine 30S (2012) B26– B36 B27

iseas

im

3

3

3

aifs

3s([eta

TI

e

Fig. 1. Proportion of meningococcal d

n Africa and areas of Asia and B and C disease predominating inany other regions (Fig. 1).

. Meningococcal epidemiology, by region

.1. Africa and Asia

.1.1. AfricaThe geography of Africa varies from desert to tropical rain forest

nd so it is not surprising that the epidemiology of IMD, stronglynfluenced by climate, varies markedly across the continent. Dif-erent patterns of IMD are seen in North Africa, the Sahel andub-Sahel, and in Africa south of the sub-Sahel.

.1.1.1. North Africa. The epidemiology of IMD in North Africa wasystematically reviewed in 2005 by the Middle East & North AfricaMENA) Vaccine-Preventable Diseases Regional Advisory Group

3]. Few recent reports were found. However, it appears that thepidemiology of IMD in North Africa is similar to that seen inhe Middle East, with a low level of endemic infection punctu-ted by occasional outbreaks. There has been no report of a major

able 1nvasive meningococcal incidence by country or region.

Country/region Incidence/100,000 Year

African meningitis belt 10–1000 (during epidemics)a Not applicableNew Zealand 2.4 2010Australia 1.2 2009Europe 0.92 2009Chile 0.5 2010Argentina 0.6 2008Canada 0.47 2008United States 0.28 2009

a The annual incidence during serogroup A epidemics in the meningitis belt canxceed 1000 cases per 100,000 population.

e by serogroup by geographic region.

epidemic of meningococcal disease in North Africa since this reviewwas undertaken. The incidence of meningococcal disease in Egypt,where large epidemics of serogroup A disease occurred in thepast [4], is now low with an increased proportion of cases due toserogroup B infections, perhaps a consequence of the introductionof routine immunization of schoolchildren with serogroup A + Cpolysaccharide vaccines [5].

3.1.1.2. The Sahel and sub-Sahel. Information on the incidence ofmeningitis in 13 countries in the African meningitis belt is nowcollected on a weekly basis by the WHO Multi-Disease SurveillanceCentre (MDSC), Ougadougou, Burkina Faso [6]. Although etiology isknown for only a proportion of these cases and there is likely to bebias in the selection of the cases that are investigated, weekly MDSCreports provide a very valuable, up-to-date picture of the evolutionof meningococcal disease within the African meningitis belt. Therehas been sustained disease activity within the belt during the pastfive years (Fig. 2). Serogroup A meningococci were responsible forthe majority of cases in 2007–2009, including an outbreak with26,878 cases in Burkina Faso in 2007 (Table 2). In 2010 and 2011,serogroup W135 has predominated, especially in Niger, where theepidemic W135 strains isolated belonged to clonal complex ST-11[7]. Few serogroup A infections have been detected during the pasttwo years except in Chad and neighboring northern Cameroon [6]suggesting a low level of circulation of serogroup A meningococciwithin the African meningitis belt at the present time. This viewis supported by results from a series of carriage studies conductedacross the meningitis belt by partners in the African MeningococcalCarriage Consortium in 2010 which identified serogroup A carriageonly in Chad, while another study in Burkina Faso also found fewserogroup A carriers (Greenwood, personal communication).

The low level of circulation of serogroup A meningococci acrossthe meningitis belt has come at the time of the introduction of a newMenA conjugate vaccine (MenAfriVacTM) developed by the Menin-gitis Vaccine Project (MVP) with support from the Bill & Melinda

B28 S.A. Halperin et al. / Vaccine

Fig. 2. Number of cases (a) and deaths (b) from meningitis in the African meningitisb[s

G[oVtNtthwmi

TSm

y

o

elt, 2007–2011, based on data collected by the Multi-Disease Surveillance Centre6]. Figures for 2011 are for the first 26 weeks of the year, the peak meningococcaleason.

ates Foundation and produced by the Serum Institute of India8]. This vaccine was given to subjects aged 1–29 years through-ut Burkina Faso and in parts of Mali and Niger in December 2010.accination of the remaining populations of Mali and Niger and

he populations of Chad, northern Cameroon, and some states inigeria will be undertaken in the last quarter of 2011. Thereafter,

he vaccine will be rolled out progressively across the meningi-is belt. MenAfriVac was prequalified by WHO on the basis of itsigh level of immunogenicity and safety [9] and no efficacy trial

as done. Therefore, it essential that the impact of the vaccine iseasured carefully following its introduction. In Burkina Faso and

n the vaccinated areas of Mali and Niger there were few cases of

able 2erogroup distribution of cases of meningococcal meningitis identified in the Africaneningitis belt during the period 2007–2011 [6].

Year Number of samplestesteda

Meningococcal serogroupb

SerogroupA

SerogroupW135

Otherserogroups

2007 2533 609 63 92008 3413 1062 7 65c

2009 5688 1966 167 472010 4132 439 726 752011d 4278 197 495 144

a The proportion of cases investigated varied between countries and from year toear but was usually about 10%.b In the remaining samples another bacterium was isolated or no isolate was

btained.c Mostly serogroup X.d Data up to week 26.

30S (2012) B26– B36

serogroup A meningococcal disease during the months followingvaccination despite enhanced surveillance, suggesting that the vac-cine was proving highly effective [10]. However, there were alsovery few cases in unvaccinated areas of Mali and Niger, or in neigh-boring Nigeria, so that these encouraging preliminary results needto be treated with caution.

If the new conjugate vaccine is to achieve maximum impact,it must be able to prevent carriage and thus induce herd immu-nity. The current low level of serogroup A meningococcal carriagein countries of the meningitis belt is making this difficult to assess.No serogroup A meningococci have been identified in oropharyn-geal swabs obtained from 12,000 subjects in Burkina Faso up to6 months after the mass vaccination campaign (Caugant, personalcommunication) but in Mali and Niger the prevaccination carriagerate has been too low to allow a vaccine effect to be measured. AsMenAfriVac is rolled out progressively across the meningitis belt,further evaluation of its impact on both IMD and carriage over aperiod of years will be needed before it has been proven definitivelyto prevent epidemics. Unanswered questions include the durabilityof protection provided by the vaccine and whether non-MenAfriVacserogroups, such as serogroups W-135 and X, will continue to beproblematic and require control through vaccination.

3.1.1.3. Africa south of the Sahel. Information on the pattern ofmeningococcal disease in areas south of the meningitis beltis scanty. Localized outbreaks occur from time to time in anunpredictable way; for example, an unexpected outbreak ofserogroup X disease occurred in the Pokot region of Kenya anda neighboring area of Uganda in 2005 [11,12]. Hospital surveysundertaken in Africa south of the meningitis belt usually haveshown the meningococcus well behind Streptococcus pneumoniaeand Haemophilus influenzae type b (Hib) as a cause of pediatricmeningitis [13–16]. However, this pattern is likely to change withwidespread deployment of Hib conjugate vaccines and increas-ing uptake of pneumococcal conjugate vaccines in Africa. It isimportant that surveillance of meningitis be intensified in thispart of Africa to measure the impact of these vaccines on Hib andpneumococcal meningitis and to assess whether the incidence ofmeningococcal meningitis is high enough in these countries towarrant introduction of routine vaccination with the new meningo-coccal conjugate vaccines that are now available.

In contrast to the situation in much of the rest of Africa south ofthe African meningitis belt, the epidemiology of meningococcal dis-ease in South Africa is monitored carefully by the National HealthLaboratory Service. During the period 2003–2007, an outbreakof serogroup W135 meningococcal disease with a high mortalityoccurred in Guateng Province [17]. The meningococcus responsi-ble for this outbreak belonged to the ST-11/ET-37 complex andwas closely related to the strain responsible for the W135 Hajjepidemic [17]. HIV infection was a strong risk factor for meningo-coccal disease during this outbreak, and HIV-infected individualshad an enhanced risk of death [18]. During 2009 and 2010, approx-imately 462 and 404 cases of IMD were recorded, respectively,with serogroups W135 and B predominating [19]. Serogroup W135is also the predominant serogroup causing IMD in neighboringMozambique [20].

3.1.2. AsiaThe epidemiology of meningococcal disease in large parts of Asia

and neighboring areas is poorly understood; there have been fewstudies and fewer publications. Two recent reviews have gatheredthe limited amount of information on meningococcal disease in

Asia that is available in the public domain. The first considers thewhole of Asia [21] while the second presents an in-depth reviewof meningococcal disease in India [22]. Both groups of authorspoint out that outbreaks are represented disproportionately in

ccine

patt

oideeisgoptsw[

VeBatKil

fifdbmiatmdnhaabiuWfiabpA

3

3

rgNinAcw

S.A. Halperin et al. / Va

ublications, most reports are based on limited hospital surveys,ntibiotics are given frequently in Asian countries prior to labora-ory investigation, and very few studies using modern diagnosticechniques such as PCR have been undertaken in Asia.

Vyse et al. review the little that is known about the epidemi-logy of meningococcal disease in 20 countries in Asia [21]. Theydentified reports of 14 epidemics during the past 50 years, pre-ominantly in China, Mongolia, India, or Nepal. All but one of thesepidemics was caused by a serogroup A meningococcus. The onexception was an epidemic of serogroup C disease in Vietnamn 1977–1979 [23] which occurred at about the same time thaterogroup C outbreaks were being reported in the African menin-itis belt [24,25]. The last major epidemic reported from Chinaccurred in 1984 [26] and since then there has been a switch inrevalence of the predominant meningococcal serogroup from Ao C [27], perhaps a consequence of widespread vaccination with aerogroup A polysaccharide vaccine. The last major Asian outbreaksere in India in 2005–2006 [28] and the Philippines in 2004–2005

29].Hospital records from Bangladesh, Indonesia, Myanmar, and

ietnam suggest a low level of endemic meningococcal dis-ase caused by a variety of serogroups including serogroup A inangladesh [30] and serogroup W135 in Malaysia and Singaporet the time of the Haj-related outbreak with this serogroup [31]. Inhe most developed countries of Asia such as Japan, Malaysia, Hongong, and Singapore, where diagnostic facilities are available, the

ncidence of endemic meningococcal disease appears to be veryow.

Epidemic meningococcal disease was described in India for therst time in the 1880s, about 20 years before it was first reported

rom sub-Saharan Africa [32]. Several large outbreaks with manyeaths were reported in the 1920s and 1930s; the most recent out-reak occurred in 2005–2006 [28]. Epidemics have been describedost frequently in the northern part of the country, especially

n New Delhi and its surroundings where they have occurred atpproximately 20-year intervals. These epidemics, extending overwo or three years, are seasonal with a peak during the driest

onths of the year [22]. Thus, they show some similarities to epi-emic meningococcal disease in Africa, although attack rates haveot been as high. As far as is known, all the major Indian epidemicsave been caused by serogroup A meningococci. Little is knownbout the incidence of endemic meningococcal disease in India orbout the situation in the southern part of the country or in neigh-oring Sri Lanka. A few hospital surveys suggest that the incidence

s low [22] but this may be a consequence of under diagnosis and/ornder-reporting. The Serum Institute of India is now producing aHO-prequalified serogroup A meningococcal conjugate vaccine

or Africa and is developing a polyvalent conjugate vaccine. It ismportant that the epidemiology of meningococcal disease in Indiand neighboring countries be defined more accurately so that it wille known if these vaccines could have an important role to play inrotecting the population of the subcontinent as well as that offrica.

.2. Australia and New Zealand

.2.1. AustraliaIn Australia, data on meningococcal disease are regularly

eported by both the Australian Meningococcal Surveillance Pro-ramme (laboratory-confirmed cases only) and the Nationalotifiable Diseases Surveillance System (NNDSS) which also

ncludes cases meeting clinical criteria [33–35]. There were 259

otifications of IMD or 1.2 cases notified per 100,000 population inustralia during 2009. Cases have declined since 2002 when 689ases were notified and were predominantly serogroups B and Cith low numbers of serogroups W135 and Y. Serogroup A has

30S (2012) B26– B36 B29

been very rare during the past 10 years, but during the late 1980sand early 1990s, serogroup A cases occurred among IndigenousAustralians residing in outback central Australia [36].

In response to several clusters and increasing notificationsof serogroup C meningococcal disease, a national serogroup Cmeningococcal immunization program was introduced in Australiain 2003, with a single dose administered to all children aged 12months. A catch-up program, targeting children and young adultsaged 2–19 years in 2003, continued until 2006 [35]. Since theinitiation of the national program, the number of notified casesof serogroup C meningococcal disease in Australia has declinedsteadily from a peak of 225 (1.15 cases per 100,000) in 2002to 13 in 2009 (0.07 per 100,000 population), a reduction of 94%[33,34]. Age-specific notification rates for serogroup C meningo-coccal disease fell across all age groups, and in the 15–19 year agegroup dropped from 2.6 notifications per 100,000 in 2003 to 0.2per 100,000 in 2008, a 92% decline [34]. There was a significantreduction in serogroup C disease among age groups not eligible forthe funded program, as reported from other countries that under-took large catch-up programs of MenC conjugate vaccination, e.g.,United Kingdom, Canada, and the Netherlands [37–40].

Australia is large and has a dispersed population, with signif-icant regional differences in proportion of meningococcal diseaseby serogroup. For example, New South Wales and Victoria experi-enced predominantly serogroup B disease but also high numbersof serogroup C disease, including several clusters of cases, fromthe late 1990s until the immunization program commenced in2003. Western Australia, on the other hand, reported predomi-nantly serogroup B disease with very few cases of serogroup Cmeningococcal disease over a similar time period [33,35].

To date, there have been very few MenC conjugate vaccine fail-ures, with only 6 identified between 2003 and 2009 (4 in <5 yearolds and 2 in 15–17 year olds) [34,35]. Serogroup C meningococcalvaccine coverage for one dose at 12 months of age, measured at 24months of age, has remained at ∼93% nationally since December2007 [35]. Based on these data, no booster doses for children whoreceived only one dose at 12 months of age are planned.

As in other countries, mortality data for meningococcal diseaseare problematic due to the number of data sources and differentcoding used in reporting jurisdictions [41]. In 2009, the NNDSSrecorded 10 deaths due to meningococcal disease of which 8 weredue to serogroup B, one from serogroup C in an unvaccinated per-son, and one from serogroup W135. The number of deaths due toserogroup C has declined from 24 in 2002. Serogroup B meningo-coccal notifications fluctuated from a high of 297 in 2002 to a lowof 221 notifications in 2008 [33,34]. Children aged 0–4 years stillhave the highest notification rates for serogroup B meningococ-cal disease, with 6.1 notifications per 100,000 population. Infants<12 months of age account for 52% of the serogroup B cases inthe 0–4 years age group, with 55% of those notifications in thoseaged <6 months of age [34,35]. The diverse serogroup B phe-notypes/genotypes reported by laboratories participating in theAustralian Meningococcal Surveillance Program suggest ongoingsporadic transmission, with no clustering of serogroup B meningo-coccal disease cases identified [33].

3.2.2. New ZealandThe epidemiology of IMD in New Zealand is quite distinct from

that in Australia. An ongoing strain-specific epidemic of serogroupB subtype B:4:P1.7-2,4, with notification rates as high as 17.4 per100,000 in 2000, resulted in a tailor-made vaccine, MeNZBTM beingdeveloped and introduced in 2004 [42–44]. Since the implemen-

tation of the vaccination program and its cessation in June 2008,meningococcal disease cases have steadily declined from 650 in2000–2001 to 123 in 2008 when the program ceased (3.1 casesper 100,000) and 96 cases in 2010 (2.4 cases per 100,000) [45]. Of

B ccine

to

d5ttbsvyi

ZfioW

ht

tpa(s

3

lsCCts[aatraattjtttihcl5wr

aissmEdps

100,000 in toddlers, and 0.17 vs. 0.29 per 100,000 in adolescents[49]. In the UK, a recent seroprevalence study showed rapidly

30 S.A. Halperin et al. / Va

hese 96 cases, 84 were laboratory-confirmed, and approximatelyne-third of the latter were P1.7-2,4 strains [45].

In two different studies, vaccine effectiveness following threeoses of the vaccine was estimated to be between 73% (95% CI2–85%) and 77% (95% CI 62–85%) [46,47]. Duration of protec-ion from MeNZBTM remains uncertain in infants who receivedhree doses, in particular those who did not receive the fourthooster dose. However, a recent study demonstrated persistence oferum bactericidal antibody titers (SBA above threshold) in olderaccinees; whether this might provide ongoing herd immunity toounger children in whom antibody waning was more pronounceds not known [48].

Serogroup C meningococcal disease notifications in Newealand have remained relatively constant, with 10–30 cases noti-ed annually over the past 10 years. In 2010, there were 22 casesf serogroup C (∼0.5 cases per 100,000) and very few of serogroups135 or Y [45].The burden of meningococcal disease in New Zealand remains

ighest in children aged <1 year (47.7 cases per 100,000) and con-inues to disproportionately affect Pacific Peoples and the Maori.

Deaths from confirmed meningococcal disease cases have fluc-uated between 26 deaths in 2001 to 6 deaths in 2010. During theast 10 years, the highest case fatality rate (CFR) was in personsged ≥40 years (9.1%, 29 deaths) and from serogroup C disease10.5%, 29 deaths) [45]. New Zealand continues to monitor closelyerogroup B meningococcal disease in the post-MenZBTM era.

.3. Europe

In Europe, most countries have established national surveil-ance for IMD, albeit with different case definitions and variedurveillance methodologies and, therefore, varied sensitivity [49].urrently, 29 countries provide annual reports to the Europeanentre for Disease Prevention and Control (ECDC), which took overhe role of collating national data from the European Union Inva-ive Bacterial Infections Surveillance (EU-IBIS) program in 200749]. In 2009, the latest year for which Europe-wide data arevailable, 29 countries reported 4637 cases of IMD, with an over-ll incidence of IMD of 0.92 per 100,000 population and withhe Republic of Ireland (3.4/100,000) and the UK (2.0/100,000)eporting the highest rates; only four other countries reportedn incidence greater than 1/100,000 (Lithuania, Spain, Denmark,nd Austria) [49]. IMD incidence in Europe has declined overhe past decade (from 1.9/100,000 in 1999); the main reason forhis decline has been the successful use of routine MenC con-ugate vaccination in several countries. Cases occur throughouthe year but are more common in the winter months. Overall,he highest incidence is in infants (15.9/100,000), followed byoddlers aged 1–4 years (5.4/100,000), and with a smaller peakn incidence among those aged 15–19 years (2.0/100,000). Thisigher incidence in younger infants is more pronounced in thoseountries that reported the highest burden of disease. In the Repub-ic of Ireland, for example, the incidence of IMD in 2009 was6/100,000 in infants, 15.1 in toddlers, and 7.9 in adolescents,hile in the United Kingdom, the incidence was 42.0, 12.0 and 3.3,

espectively [49].Capsular group data were provided by 26 countries and were

vailable for 88% of reported IMD cases, with serogroup B account-ng for 71% of cases (3010), followed by serogroup C (565, 13%) anderogroup Y (187, 4%); other capsular groups rarely caused inva-ive disease [49]. Although serotyping and subtyping of invasiveeningococcal isolates has been increasing among participating

uropean countries, complete multi locus sequence testing (MLST)ata were available for only 11% of isolates, limiting the inter-retation of data. However, combining data from 981 isolatesubjected to MLST from 2008 and 2009 showed a highly diverse

30S (2012) B26– B36

meningococcal population, with 26 different clonal complexes, themain ones belonging to ST-41/44 (256, 26.1%), ST-11 (207, 21.1%),and ST-32 (160, 16.3%) [49].

The overall CFR for IMD was 7.4%, but varied with the respon-sible meningococcal capsular group; the CFR was higher amongserogroup C (91/677, 13.4%) cases, followed by serogroup W135(10/80, 12.5%), serogroup Y (12/141, 8.5%), and serogroup B(249/3367, 7.4%) [49]. CFR also varied with clinical presentation,although this information was available for only half the cases.Overall, 45% presented with meningitis, 34% with septicemia only,18% with both meningitis and septicemia, and 3% with otherpresentations. CFR was highest among those presenting with sep-ticemia (138/836, 16.5%), followed by meningitis and septicemia(28/429, 6.8%), and lowest for meningitis (28/1093, 2.6%), a similarpicture to previous years [49].

3.3.1. Serogroup B diseaseA number of broad-spectrum meningococcal vaccines aimed

particularly against serogroup B disease are currently in late-phaseclinical trials and have been shown to be immunogenic in infants asyoung as 2 months of age [50]. Analysis of 4435 IMD cases reportedin England and Wales over 4 years between 2006 and 2010 showedthat 58% of serogroup B cases occurred among children aged <5years; this capsular group was responsible for 94% of cases in thisage group [51]. Infants aged <1 year accounted for 27% of all IMDcases; in this age group, the number of cases increased from birth tofive months of age, by which time 11% of all serogroup B cases hadalready occurred, before falling gradually in subsequent months.A similar distribution in the first few months of life has also beenobserved in a recent French study [52] and in the American ActiveBacterial Core surveillance (ABCs) program [53]. To have the biggestdirect impact on disease prevention, therefore, would require anyinfant vaccination program to commence as early as possible andvaccines that offer at least some protection after 1–2 doses. Afterinfancy, the number of IMD cases fell until 12 years of age and thenincreased to reach a peak at 18 years before falling again, suggest-ing that an effective adolescent MenB vaccination program couldalso have a significant direct impact on disease burden [51].

3.3.2. Serogroup C diseaseThe MenC conjugate vaccine was first licensed and introduced

into the UK immunization schedule in 1999. The vaccine wasoffered in stages to all individuals aged <18 years, and resulted in adramatic and sustained reduction in invasive serogroup C disease,with the lowest incidence of 0.02 cases per 100,000 reported in2008–2009 [54]. By 2009, twelve European countries had includedthe MenC vaccine in their national immunization program. Somecountries utilized the vaccines in the infant immunization pro-gram with a booster in the second year of life (UK, Ireland, Italy,Greece, Portugal, Spain and Iceland), while others recommendedthe vaccine in the second year of life (Belgium, Cyprus, Netherlands,Luxembourg, and Germany) [49]. None of the European countriescurrently routinely vaccinate with any of the recently licensedMenACWY conjugate vaccines. In countries with established MenCvaccination programs, the incidence of serogroup C disease issubstantially lower than in countries without MenC programs, par-ticularly in the age groups with the largest burden of serogroupC disease: 0.54 vs. 1.01 per 100,000 in infants, 0.22 vs. 0.45 per

declining protective serogroup C antibody levels in vaccinatedchildren, particularly among those who were immunized only ininfancy, and suggested that an adolescent MenC booster may berequired [55].

ccine

3

uoicc2lt2a2[1wacc

fifc2[2(8wiiclLariaYstiUsdthpytv

3

3

Uppml12ods

S.A. Halperin et al. / Va

.3.3. Serogroup Y diseaseUntil recently, invasive serogroup Y disease was rare in Europe,

nlike the United States where this capsular group accounts forne-third of all IMD cases [56]. In recent years, however, an increasen serogroup Y disease has been reported, particularly in the Nordicountries. In Sweden, for example, the proportion of serogroup Yases increased from 20% in 2008 to 34% in 2009 [49] and 38% in010, where it was responsible for 23 of the 60 serogrouped iso-

ates [57]. Characterization of the serogroup Y isolates showed thathe increase was mainly due to a specific clone (genosubtype P1.5-, 10-1, 36-2, ST 23, cc23, porB allele 3-36, fetA allele F4-1, fHbpllele 25, and penA allele 22), which increased from 1 case each in002 and 2004 to 12 cases in 2010, particularly in young adults58]. Norway has also reported an increase in serogroup Y from7% of all IMD cases in 2008 to 25% in 2009 and 31% in 2010. Casesere spread geographically, and were mainly in young adults, and

ll belonged to the ST-23 complex [49,59]. In Finland, serogroup Yases increased from an average of 4 cases (8%) in 1995–2009 to 13ases (38%) in 2010 [60].

In England and Wales, enhanced national surveillance identi-ed an increase in laboratory-confirmed serogroup Y disease from

ewer than 30 annual cases (≤2% of all IMD) before 2006 to 34ases (3%) in 2007, 44 (4%) in 2008, 65 (6%) in 2009, and 68 in010. Cases were seen particularly in adolescents and the elderly61,62]. Serogroup Y isolates causing invasive disease between007 and 2009 belonged mainly to one of four clonal complexescc): cc23 (64, 56%), cc174 (24, 21%), cc167 (12, 11%), and cc22 (9,%). The 2009 increase was primarily due to ST-1655 (cc23), whichas responsible for 22 cases in 2009 compared to 4 cases each

n 2007 and 2008. This clone was more likely to harbor inactivat-ng mutations in the meningococcal acyltransferase lpxL1 gene andause meningitis in younger age groups (<25 years). InactivatingpxL1 mutations has been shown to result in underacylation of theipid A moiety of meningococcal lipopolysaccharide (LPS), whichllows the organism to evade the host innate immune system, thuseducing the risk of septic shock and coagulopathy but, in turn,ncreasing the risk of meningitis, particularly in children and youngdults [63,64]. In keeping with the increase in invasive serogroup

disease, a recent meningococcal carriage study among univer-ity students in England that found high levels of carriage reportedhat up to one-third of strains belonged to serogroup Y, includ-ng strains belonging to cc23 (ST-1655) [65,66]. Moreover, a recentK seroprevalence study reported that natural immunity against

erogroup Y was low across all age groups [67]. While serogroup Yisease in the elderly usually occurs among those with comorbidi-ies and presents with pneumonia, children and adults are usuallyealthy and often present with meningitis or septicemia [61]. Theropensity for the emerging serogroup Y strains to cause disease inoung adults, therefore, is concerning and will require close moni-oring and future consideration of the use of MenACWY conjugateaccines [68].

.4. North America

.4.1. United StatesOver the past several decades, the incidence of IMD in the

nited States has fluctuated between 0.5 and 1.5 cases per 100,000opulation in approximately 10-year cycles, with the most recenteak occurring in 1997 [69]. Since then, the annual incidence ofeningococcal disease has declined steadily to historically low

evels, with an incidence of culture-confirmed cases of 0.28 per00,000 in 2009 [56,70]. During the same year, the incidence was

.50, 0.38, and 0.32 per 100,000 among children <1, 1, and 2–4 yearsld, respectively. This major decline began well before the intro-uction of meningococcal conjugate vaccines and also includeserogroup B, which is not covered by available vaccines. Whether

30S (2012) B26– B36 B31

this decline represents a permanent change in meningococcal dis-ease epidemiology in the US is not known.

Since 2005, two MenACWY conjugate vaccines have beenlicensed in the US. The first vaccine, which uses diphtheria toxoidas the protein carrier (MCV4-DT), was licensed in 2005. The sec-ond vaccine uses the non toxic CRM197 diphtheria toxin derivativeas the protein carrier (MCV4-CRM) and was licensed in 2010. TheAdvisory Committee on Immunization Practices recommends thatall adolescents 11–18 years old and other persons at high risk bevaccinated with MenACWY [71,72].

Data are beginning to emerge on the effectiveness of MCV4-DT; no data are available for MCV4-CRM because of its relativelyrecent licensure [69]. In one study, vaccine effectiveness was esti-mated based on the number of reported MCV4-DT vaccine failuresand estimates of vaccine coverage [73]. That study suggested thatMCV4-DT had an effectiveness of 80–85% in the 3–4 years sinceimmunization. In a case–control study that is still in progress, vac-cine effectiveness for all serogroups was estimated to be 78% (95%CI, 29–93%). For serogroups C and Y, vaccine effectiveness was esti-mated to be 77% and 88%, respectively, with very wide confidenceintervals for both ((14–94%) and (−23–99%), respectively). Therewas also evidence of waning effectiveness over time: 94% (14–99%)in the first year, 83% (1–97%) for 1 to <2 years, and 56% (−74–89%)for 2 and <5 years since immunization. These data are in line withobserved declines in serum bactericidal antibody titers [69].

Finally, the incidence of serogroup C, Y, or W-135 meningococcaldisease (there is virtually no serogroup A disease in the US) among11–19 year olds decreased from 0.27 to 0.14 per 100,000 populationfrom 2006–2007 to 2008–2009. There was also a 74% decline in thenumber of cases in 11–14 year olds from 2000–2004 to 2005–2009.Although this before–after analysis cannot determine definitivelywhether these declines were caused by MCV4-DT, it does suggesta selective impact of the vaccine on the immunized population.

A concern about use of meningococcal vaccines that do not coverall major serogroups is the emergence of strains not covered bythe vaccines, primarily through the mechanism of polysaccharidecapsular switching and clonal expansion of a vaccine-serogroupstrain to a serogroup B strain. This is particularly relevant becausethis phenomenon has been described in other settings [74–76]and because capsular switching appears to be common, even inthe absence of universal immunization [77]. However, surveillancein the UK, the country with the longest experience, has shownno evidence of capsular switching [78]. In addition, surveillanceundertaken by EU-IBIS showed that, although short-term changesin strain diversity occurred in all countries, there was no evidenceof any increase in serogroup B strains with serotyping consistentwith serogroup C strains in those countries with MenC vaccination[49]. Molecular surveillance in the US is ongoing to monitor changesin meningococcal population structure that occur following intro-duction of MCV4-DT and MCV4-CRM.

3.4.2. CanadaN. meningitidis in Canada is a disease of low endemicity with

periodic outbreaks. It affects approximately one person per 100,000each year [79]. Although fluctuations in disease incidence haveoccurred over time, since 1941 when incidence peaked at 12.8 per100,000 [80], the reported national rates have remained below 2per 100,000 for most of the last 60 years [81–84], with a record lowof 0.43 per 100,000 in 1965 [81]. The age-related incidence patternis similar to that in the US and Europe. The highest incidence ratesare seen in infants <1 year of age, followed by children 1–4 years ofage and adolescents 15–19 years of age.

3.4.2.1. Surveillance. Three surveillance systems exist to monitorIMD in Canada: the National Notifiable Disease Surveillance Sys-tem; the Canadian Immunization Monitoring Program Active, and

B ccine

tNtNraAtIjiltse

3tiacNnaawmMoaprd

3vCdmeoniros

0madas

tpitsrs[

3

i

32 S.A. Halperin et al. / Va

he International Circumpolar Surveillance System. The Nationalotifiable Disease Surveillance System is a passive surveillance sys-

em that includes confirmed and suspected cases of IMD caused by. meningitidis [85]. Data are collected at the provincial and territo-

ial level, and forwarded to the federal government for assemblynd analysis. The Canadian Immunization Monitoring Programctive (IMPACT) is an active, sentinel surveillance system that cap-

ures laboratory-confirmed cases of IMD in adults and children.MPACT meningococcal surveillance covers 17 million Canadians,ust over 50% of the population [86]. Finally, Canada participatesn the International Circumpolar Surveillance, a passive surveil-ance system that captures confirmed and suspected cases of IMDhat occur north of 60◦ latitude [87]. These systems provide a rea-onable estimate of disease burden and monitor for shifts in thepidemiology of IMD.

.4.2.2. Immunization programs. Canada was one of the first coun-ries to implement universal vaccination with MenC vaccines innfants, toddlers, and adolescents. From 2002 to 2005 all provincesnd territories initiated programs using one of three licensed vac-ines: MenC-TT (NeisVac-C®, Baxter) or MenC-CRM (Menjugate®,ovartis, or Meningitec®, Pfizer). Because meningococcal immu-ization policy and decisions in Canada are made at a provincialnd territorial level, rather than federal level, a variety of 1-, 2-,nd 3- dose immunization schedules were implemented in infants,ith the most common option being one dose provided at 12onths of age with catch-up programs in early adolescence. As ofarch 2011, five out of 13 provinces and territories were using one

f the two MenACWY conjugate vaccines in adolescents as theirdolescent catch-up vaccine [88]. The MenACWY vaccines are alsorovided in the public program for some groups with increasedisk of invasive disease, such as individuals with primary antibodyeficiencies [82].

.4.2.3. Incidence of disease. Among countries that initiated uni-ersal MenC conjugate immunization programs (e.g., Spain, UK),anada started with the lowest incidence (6.4 per 100,000 in chil-ren <1 year of age and 0.74 overall) [80] and has been able toeasure the effects of universal immunization in a setting of low

ndemicity [39,89]. In spite of a lower starting point, the incidencef serogroup C disease declined in provinces with universal immu-ization programs (0.41 per 100,000 in 2002 to 0.07 per 100,000

n 2006) when compared to provinces without programs [88]. Inecent years (2008), Canada has experienced a very low incidencef 0.47 per 100,000 for all serogroups and 0.08 per 100,000 forerogroup C disease [90,91].

With an average annual incidence of 0.23 per 100,000 (range.20–0.35) from 2006 to 2009, serogroup B now accounts for theajority (53%) of infections in Canada, with the highest average

nnual incidence of 2.2 per 100,000 (range 2.2–2.6) seen in chil-ren 0–4 years of age [90,91]. Starting in 2003 and peaking in 2007,n emerging clone of ST-269 was responsible for an increase inerogroup B disease [90,92].

The incidence of serogroup Y disease has remained stable overime, with an annual average incidence of approximately 0.09er 100,000 [83,91]. About one-third of serogroup Y cases occur

n adults 60 years of age and older [93,94]. Two genetic popula-ions (clonal complex ST-23 and ST-167) represent the majority oferogroups Y isolates [95]. The annual incidence of W-135 diseaseemains steady at 0.01–0.05 per 100,000, and one or two cases oferogroup A disease occur each year and are usually travel-related83,89].

.5. Latin America

Although progress has been made in improving and coordinat-ng the surveillance of IMD in Latin America, under-reporting is

30S (2012) B26– B36

prevalent and limited published data are available on N. menin-gitidis disease and carriage in the region. Incidence varies widely,from fewer than 0.05 cases per 100,000 in Mexico to almost 1.8cases per 100,000 in Brazil. The highest incidence of IMD is con-sistently observed in infants. Most cases of IMD are sporadic, withseasonal variations and outbreaks occurring at irregular intervals.During outbreaks recently reported in the region, the majoritywith serogroup C, a shift in the age distribution of IMD has beenobserved, with increased numbers of cases among adolescents andyoung adults [96].

The exceedingly low rates of meningococcal disease reportedby some countries and the high proportion of meningitis reportedwithout a determined bacterial etiology suggests that the true bur-den of IMD is underestimated in the region. In part, this is the resultof difficulty in recovering the organism because of obtaining inad-equate samples for culture and the widespread use of antibioticsprior to sample collection.

Information on IMD in Latin America is based on a surveil-lance network (SIREVA II, PAHO/WHO) that performs a systematicanalysis of isolates recovered from several countries in the region[97]. Serogroups B and C are responsible for the majority of casesreported. Emergence of serogroups W135 and Y has been recentlyreported in some countries, whereas serogroup A disease has dis-appeared from Latin America.

3.5.1. Argentina, Brazil, Chile, and UruguayNotably, higher incidence rates of IMD in the region are reported

in countries with a well-established surveillance system.IMD is endemic in Brazil, with periodic outbreaks and marked

differences from region to region. In recent years, IMD incidencehas been approximately 1.8 cases per 100,000 population, varyingfrom less than 1 case per 100,000 in the Northern region to 3.5cases per 100,000 in the State of São Paulo in 2010. The highestage-specific incidence of IMD occurs in infants <1 year of age andthe overall CFR (approximately 20%) was consistently high in thelast decade [98,99].

During the 1970s Brazil suffered its largest recorded epidemicof IMD, with its epicenter in São Paulo. There were two overlappingepidemic waves, the first with serogroup C, starting in April 1971,and the second with serogroup A, beginning in April 1974, withpersistent high rates of serogroup C. The incidence rate reached apeak of 179 cases per 100,000 inhabitants in 1974. This epidemicprovided the first major experience in the world in which polysac-charide A and C vaccines were used on a large scale, resulting incontrol of the epidemic in 1975 [100].

During the 1980s there was a period of reduced diseaseincidence (1 case/100,000 population), with serogroup B becom-ing more prevalent than C and practically no reported cases ofserogroup A. From 1987 onwards, there was an increase in thenumber of cases of serogroup B, phenotype B:4,7:P1.19,15, in sev-eral locations around the country. This increase reached its peakin 1996, with 7104 cases recorded (4.5 cases/100,000 population),to a great extent resulting from outbreaks in large cities such asSão Paulo and Rio de Janeiro. The other prevailing phenotypesidentified were B:4,7:P1.7,1 and the “Norwegian” epidemic phe-notype B:15:P1.7,16 (mostly confined to the southern states of thecountry). These three prevalent serosubtypes belong to the sameelectrophoretic type, ET-5 [101].

From 2002 onwards a significant increase in the proportion ofcases attributed to serogroup C, associated with the ST-103 com-plex, was observed and nowadays serogroup C is the most frequent

serogroup causing IMD in Brazil [98,99]. Emergence of serogroupW135, associated with the ST-11 complex, was recently reported inthe States of São Paulo, Rio de Janeiro, and Rio Grande do Sul [96]. In2010, serogroup C was responsible for 75% of the cases identified,

ccine

s2

rSob

srAmp<g

tn3bTg

oisDSnwoaibs

ilwoBMcadiyo

miCaB

3

sUcsiip5f

S.A. Halperin et al. / Va

erogroup B for 17%, serogroup W135 for 6%, and serogroup Y for% [96].

The incorporation of non culture methods such as RT-PCR intooutine public health surveillance, as recently demonstrated in thetate of São Paulo, provided an additional yield of 85% for RT-PCRver culture-based results, adding to estimates of the true IMDurden [102].

Several outbreaks of meningococcal disease caused byerogroup C, associated with the ST-103 complex, have beeneported in Brazil in recent years, affecting different cities [96,103].s a strategy to control these outbreaks, vaccination was recom-ended for the population age groups at highest risk. In these

rograms, MenC conjugate vaccines were administered to children2 years of age and meningococcal A/C polysaccharide vaccinesiven to those >2 years of age [96,98].

In September 2010, Brazil was the first Latin-American countryo incorporate the MenC conjugate vaccine into the routine immu-ization program, with two doses being given in the first year, at

and 5 months of age, and a booster dose at 12 months. Toddlersetween 12 and 23 months receive one dose of the vaccine [99].he MenC conjugate vaccine is also provided to selected high-riskroups [96].

In Argentina, a decrease in the incidence of IMD has beenbserved in the last years (from 2.4 cases per 100,000 populationn 1994 to 0.6 cases per 100,000 inhabitants in 2008), without anypecific vaccination intervention except for control of outbreaks.uring this period, CFR was stable, between 8% and 10% [96,104].erogroup B was prevalent in the last decade until 2008, when a sig-ificant increase in the proportion of cases due to serogroup W135as observed [105]. In 2010, serogroup B was responsible for 42%

f all cases identified, serogroup C for 5%, serogroup W135 for 50%,nd serogroup Y for 3% [96]. The emergence of serogroup W135n Argentina was associated with the Hajj-associated W135 strain,elonging to the ST-11 complex, which has spread internationallyince 2000 [97].

Uruguay observed a peak in the incidence of IMD in some regionsn 2001, when the incidence reached 30 cases per 100,000 popu-ation. A shift in the age distribution of the disease was observed,

ith detection of disease in older age groups and a predominancef one strain (B:4,7:P1.15,19) over a combination of other group

strains [106]. A mass campaign with the Cuban-produced Outerembrane Vesicle (OMV) vaccine was initiated and included all

hildren and adolescents 4–19 years old. It was estimated thatt least 70% of the target population had been vaccinated and aecrease in incidence was observed. In the following years, IMD

ncidence remained stable, with higher incidence in children <5ears of age and predominance of serogroup B. In 2010, almost 85%f all cases identified were caused by serogroup B [97].

From 1994 to 2001, Chile reported stable rates of IMD, approxi-ately 3 cases per 100,000 population, with a decreasing incidence

n the last years (0.5 cases per 100,000 population in 2010) and aFR of 14%, with 64% of the deaths occurring in children <5 years ofge [107]. In 2010, 67% of the isolates characterized were serogroup, 13% serogroup C, 11% serogroup W135, and 7% serogroup Y [97].

.5.2. Colombia, Venezuela, Ecuador, Peru, Paraguay, and BoliviaSince 1994, the Instituto Nacional de Salud has maintained a

urveillance network for acute bacterial meningitis in Colombia.ntil 2005, serogroup B was the most frequently isolated serogroupausing IMD in Colombia. In 2003, an unexpected increase inerogroup Y was identified, and by 2006 this serogroup becamencreasingly prevalent, representing almost 50% of the isolates

dentified [108]. Venezuela also reported an increase in the pro-ortion of cases due to serogroup Y in 2006, when it represented0% of all cases identified; serogroup B and serogroup C accountedor 36% and 14% of cases, respectively [109]. In 2010, serogroup Y

30S (2012) B26– B36 B33

was responsible for 18% and 22% of all cases identified in Colombiaand Venezuela, respectively [97].

The other countries reported a very small number of cases eachyear, making serogroup distribution of cases unreliable.

3.5.3. Mexico, Central America, and the CaribbeanLow rates of IMD are reported consistently in Mexico, Central

America, and the Caribbean [96]. However, a prospective surveil-lance study performed recently along the border of Mexico and theUS found that the overall incidence and fatality rate observed inTijuana were similar to those found in the US, suggesting that theincidence of IMD in Mexico may be substantially higher than therate which is reported currently [110].

Among isolates submitted in 2010 to characterization by SIREVAII [97] from Panama, Costa Rica, and the Dominican Republic,serogroups B and C were responsible for the majority of cases.

In 1982, Cuba implemented a vaccination program, initiallyin high-risk groups and subsequently involving infants, children,and young adults up to 24 years of age, using a locally producedserogroup B OMV plus a serogroup C polysaccharide vaccine. Since1991, this vaccine has been used routinely in the childhood immu-nization schedule, given at 3 and 5 months of age. Deployment ofthis vaccine has been associated with a decrease in disease inci-dence of IMD from 6.5 cases per 100,000 population per year in1989 to 0.8 per 100,000 population per year in 1993 [111]. Virtuallyall cases reported in the last years were serogroup B [97].

4. The next five years

In view of the dynamic nature of IMD epidemiology, globalsurveillance will continue to be a priority over the next 5 years.In Africa, as the MenA vaccination programs are fully implementedacross the meningitis belt, there will be an ongoing need for surveil-lance and other observational approaches such as case controlstudies to measure the vaccine’s effectiveness. MenC vaccinationprograms will continue to be implemented in jurisdictions whererates of serogroup C disease remain high. The future for MenACWYuniversal immunization programs will evolve as local epidemiol-ogy changes and as MenACWY vaccines that are immunogenic inyoung infants become available. Whether the apparent increasein serogroup Y disease in some European countries will con-tinue and necessitate expansion of coverage beyond serogroup Cremains to be seen. The imminent licensure of recombinant pro-tein MenB vaccines with broad strain coverage will also affect theepidemiology of IMD in jurisdictions that choose to implementuniversal vaccination programs. Where meningococcal conjugatevaccines are used widely, monitoring whether capsular switchingand serogroup replacement become epidemiologically importantphenomena and whether serogroup B strains not covered by therecombinant protein MenB vaccines emerge will be a high priorityfor IMD surveillance systems.

Conflict of interest statement

The authors have received grant and contract funding fromNovartis Vaccines, sponsor of the Meningococcus ScientificExchange Meeting, but have no financial interest in the company.

References

[1] Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal

disease. Vaccine 2009;27(Suppl. 2):B51–63.

[2] Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. NEngl J Med 2001;344:1378–88.

[3] Hausdorff WP, Hajjeh R, Al-Mazrou A, Shibl A, Soriano-Gabarro M. The epi-demiology of pneumococcal, meningococcal, and Haemophilus disease in the

B ccine

34 S.A. Halperin et al. / Va

Middle East and North Africa (MENA) Region—Current status and needs. Vac-cine 2007;25(11):1935–44.

[4] el-Akkad AM. Epidemiology of cerebrospinal meningitis in Egypt during thelast 50 years. J Egypt Public Health Assoc 1969;44(4):260–79.

[5] Nakhla I, Frenck Jr RW, Teleb NA, El Oun S, Sultan Y, Mansour H, et al. Thechanging epidemiology of meningococcal meningitis after introduction ofbivalent A/C polysaccharide vaccine into school-based vaccination programsin Egypt. Vaccine 2005;23(25):3288–93.

[6] World Health Organization. WHO-Multi-Disease Surveillance Centre Oua-gadougou, Regional Meningitis Surveillance, <http://www.who.int/csr/disease/meningococcal/epidemiological/en/index.html> [accessed 20.10.11].

[7] Collard J-M, Maman Z, Yacouba H, Djibo S, Nicolas P, Jusot J-F, et al. Increasein Neisseria meningitidis serogroup W135, Niger, 2010 [letter]. Emerg InfectDis 2010;16(9):1496–8.

[8] LaForce FM, Ravenscroft N, Djingarey M, Viviani S. Epidemic meningitis dueto Group A Neisseria meningitidis in the African meningitis belt: a persistentproblem with an imminent solution. Vaccine 2009;27(Suppl. 2):B13–9.

[9] Sow SO, Okoko BJ, Diallo A, Viviani S, Borrow R, Carlone G, et al. Immuno-genicity and safety of a meningococcal A conjugate vaccine in Africans. NEngl J Med 2011;364(24):2293–304.

[10] Meningitis Vaccine Project. Dramatic fall in cases of meningitis A in three WestAfrican nations after new vaccine introduction, <http://www.meningvax.org/files/PR MenAfriVacimpact 9June2011 EN.pdf> [accessed 20.10.11].

[11] Mutonga DM, Pimentel G, Muindi J, Nzioka C, Mutiso J, Klena JD, et al.Epidemiology and risk factors for serogroup X meningococcal meningitisduring an outbreak in western Kenya, 2005–2006. Am J Trop Med Hyg2009;80(4):619–24.

[12] WHO. Meningococcal disease, Uganda – update. Wkly Epidemiol Rec2006;81:62.

[13] Pelkonen T, Roine I, Monteiro L, Joao Simoes M, Anjos E, Pelerito A, et al.Acute childhood bacterial meningitis in Luanda, Angola. Scand J Infect Dis2008;40(11-12):859–66.

[14] Roca A, Bassat Q, Morais L, Machevo S, Sigaúque B, O’Callaghan C, et al.Surveillance for acute bacterial meningitis among children admitted to adistrict hospital in rural Mozambique. Clin Infect Dis 2009;48(Suppl. 2):S172–80.

[15] McCormick DW, Molyneux EM. Bacterial meningitis and Haemophilus influen-zae type b conjugate vaccine, Malawi. Emerg Infect Dis 2011;17(4):688–90.

[16] Bercion R, Bobossi-Serengbe G, Gody JC, Beyam EN, Manirakiza A, Le Faou A.Acute bacterial meningitis at the ‘Complexe Pédiatrique’ of Bangui, CentralAfrican Republic. J Trop Pediatr 2008;54(2):125–8.

[17] Von Gottberg A, du Plessis M, Cohen C, Prentice E, Schrag S, de Gouveia L,et al. Emergence of endemic serogroup W135 meningococcal disease asso-ciated with a high mortality rate in South Africa. Clin Infect Dis 2008;46(3):377–86.

[18] Cohen C, Singh E, Wu HM, Martin S, de Gouveia L, Klugman KP, et al. Increasedincidence of meningococcal disease in HIV-infected individuals associatedwith higher case-fatality ratios in South Africa. AIDS 2010;24(9):1351–60.

[19] de Gouveia L, von Gottberg A. Neisseria meningitidis. Commun Dis Surveill Bull2011;9(2):45–7.

[20] Ibarz-Pavón AB, Morais L, Sigaúque B, Mandomando I, Bassat Q, Nhacolo A,et al. Epidemiology, molecular characterisation and antibiotic resistance ofNeisseria meningitidis from patients ≤15 years in Manhic a, rural Mozambique.PloS One 2011;6(6):e19717.

[21] Vyse A, Wolter JM, Chen J, Ng T, Soriano-Gabarro M. Meningococcal dis-ease in Asia: an under-recognised public health burden. Epidemiol Infect2011;139:967–85.

[22] Sinclair D, Preziosi M-P, Jacob John T, Greenwood B. The epidemiol-ogy of meningocccal disease in India. Trop Med Int Health 2010;15(12):1421–35.

[23] Oberti J, Hoi NT, Caravano R, Tan CM, Roux J. Etude d’une épidémie deméningococcie au Viet Nam (provinces du sud). Bull World Health Org1981;59(4):585–90.

[24] Whittle HC, Evans-Jones LG, Onyewotu I, Adjukiewicz A, Turunen U, CrockfordJ, et al. Group-C meningococcal meningitis in the northern savanna of Africa.Lancet 1975;1(7921):1377.

[25] Broome CV, Rugh MA, Yada AA, Giat L, Giat H, Zeltner JM, et al. Epidemicgroup C meningococcal meningitis in Upper Volta, 1979. Bull World HealthOrg 1983;61(2):325–30.

[26] Hu XJ. Study on periodically prevalent feature for epidemic cerebrospinalmeningitis in China. Chin J Epidemiol 1991;12:136–9 [in Chinese].

[27] Ni JD, Jin YH, Dai B, Wang XP, Liu DQ, Chen X, et al. Recent epidemiologicalchanges in meningocccal disease may be due to the dispalacment of serogroupA by serogroup C in Hefei city, China. Postgrad Med J 2008;84(988):87–92.

[28] Nair D, Dawar R, Deb N, Capoor MR, Singal S, Upadhayay DJ, et al. Outbreak ofmeningococcal disease in and around New Delhi, India, 2005–2006: a reportfrom a tertiary care hospital. Epidemiol Infect 2009;137(4):570–6.

[29] World Health Organization. Epidemic and pandemic alert and response (EPR).Meningococcal disease in the Philippines – update <http://www.who.int/csr/don/2005 01 28a/en/index.html>; 2005.

[30] Hossain MA, Ahmed DA, Ahmed T, Islam N, Breiman RF. Short report:

increasing isolations of Neisseria meningitidis serogroup A from blood andcerebrospinal fluid in Dhaka, Bangladesh, 1999–2006. Am J Trop Med Hyg2009;80(4):615–8.

[31] Wilder-Smith A, Chow A, Goh KT. Emerence and disapapearance of W135meningococcal disease. Epidemiol Infect 2010;138(7):976–8.

30S (2012) B26– B36

[32] Patel PT. Cerebrospinal fever in Bombay. A study of 170 consecutive casesduring the years 1921–1924. Lancet 1926;11:539–41.

[33] Australian Meningococcal Surveillance Programme. Annual report of the Aus-tralian Meningococcal Surveillance Programme, 2009. Commun Dis Intell2010;34(3):291–302.

[34] Australian Government Department of Health and Ageing. Communica-ble Diseases Surveillance: National Notifiable Diseases Surveillance System.Commun Dis Intell 2010;34(3):214–6.

[35] Chiu C, Dey A, Wang H, Menzies R, Deeks S, Mahajan D, et al. Vac-cine preventable diseases in Australia, 2005 to 2007. Commun Dis Intell2010;34(Suppl):S81–3.

[36] Patel MS, Merianos A, Hanna JN, Vartto K, Tait P, Morey F, et al. Epi-demic meningococcal meningitis in central Australia, 1987–1991. Med J Aust1993;158:336–40.

[37] Trotter C, Gay N, Edmunds W. Dynamic models of meningococcal car-riage and the impact of serogroup C conjugate vaccination. Am J Epidemiol2005;162:89–100.

[38] de Greeff SC, de Melker HE, Spanjaard L, Schouls LM, van Der Ende A.Protection from routine vaccination at the age of 14 months with meningo-coccal serogroup C conjugate vaccine in the Netherlands. Pediatr Infect Dis J2006;25(1):79–80.

[39] Kinlin LM, Jamieson F, Brown EM, Brown ES, Rawte P, Dolman S, et al.Rapid identification of herd effects with the introduction of serogroup Cmeningococcal conjugate vaccine in Ontario, Canada, 2000–2006. Vaccine2009;27:1735–40.

[40] De Wals P, Deceuninck G, Lefebvre B, Boulianne N, De Serres G. Effectiveness ofserogroup C meningococcal conjugate vaccine: A 7-year follow-up in Quebec,Canada. Pediatr Infect Dis J 2011;30(7):566–9.

[41] Simpkins D, Wood N, Jelfs J, McIntyre PB, Menzies R, Lawrence G, et al. Moderntrends in mortality from meningococcal disease in Australia. Pediatr Infect DisJ 2009;28(12):1119–20.

[42] Martin DR, Walker SJ, Baker MG, Lennon D. New Zealand epidemic ofmeningococcal disease identified by a strain with phenotype B:4:P1.4. J InfDis 1998;177:497–500.

[43] Oster P, Lennon D, O’Hallahan J, Mulholland K, Reid S, Martin D. MeNZB:a safe and highly immunogenic tailor-made vaccine against the NewZealand Neisseria meningitidis serogroup B disease epidemic strain. Vaccine2005;23:2191–6.

[44] Oster P, O’Hallahan J, Aaberge I, Tilman S, Ypma E, Martin D. Immunogenicityand safety of a strain-specific MenB OMV vaccine delivered to under 5-yearolds in New Zealand. Vaccine 2007;25:3075–9.

[45] Lopez L, Sexton K, Carter P. The epidemiology of meningococcal disease inNew Zealand in 2010. Wellington, New Zealand: Institute of Environmen-tal Science and Research Ltd. (ESR); 2011. Available at: www.surv.esr.cri.nz/PDF surveillance/MeningococcalDisease/2010/2010AnnualRpt.pdf [accessedSeptember 2011].

[46] Kelly C, Arnold R, Galloway Y, O’Hallahan J. A prospective study of theeffectiveness of New Zealand meningococcal B vaccine. Am J Epidemiol2007;166:817–23.

[47] Arnold R, Galloway Y, McNicholas A, O’Hallahan J. Effectiveness of a vacci-nation programme for and epidemic of meningococcal B in New Zealand.Vaccine 2011;29(40):7100–6.

[48] Jackson C, Lennon D, Wong S, Yan J, Stewart J, Reid S, et al. Antibody persis-tence following MeNZB vaccination of adults and children and response to afourth dose in toddlers. Arch Dis Child 2011;96:744–51.

[49] European Centre for Disease Prevention and Control Surveillance of invasivebacterial diseases in Europe 2008/2009, Stockholm: ECDC; 2011. Avail-able at: <http://ecdc.europa.eu/en/activities/diseaseprogrammes/vpd/Pages/index.aspx> [accessed 04.10.11].

[50] Granoff DM. Review of meningococcal group B vaccines. Clin Infect Dis2010;50(Suppl. 2):S54–65.

[51] Flood J, Ladhani S, Campbell H, Borrow R, Gray SJ, Marsh WJ, et al. P 043.The epidemiology of invasive meningococcal disease in England and Wales:implications for potential infant immunisation schedules (page 124–5).

[52] Levy C, Taha MK, Weil OC, Quinet B, Lecuyer A, Alonso JM, et al. Associationof meningococcal phenotypes and genotypes with clinical characteristics andmortality of meningitis in children. Pediatr Infect Dis J 2010;29:618–23.

[53] Hershey JH, Hitchcock W. Epidemiology and meningococcal serogroup dis-tribution in the United States. Clin Pediatr (Phila) 2010;49:519–24.

[54] Campbell H, Andrews N, Borrow R, Trotter C, Miller E. Updated postlicen-sure surveillance of the meningococcal C conjugate vaccine in England andWales: effectiveness, validation of serological correlates of protection, andmodeling predictions of the duration of herd immunity. Clin Vaccine Immunol2010;17(May (5)):840–7.

[55] Ishola D, Borrow R, Findlow H, Trotter C, Ramsay M. P 068. Prevalence ofserum bactericidal antibody to serogroup C Neisseria meningitidis in Eng-land, a decade after vaccine introduction (pages 174–5). The 11th EuropeanMeningococcal Group Meeting (EMGM) Congress 2011: Ljubljana, Slovenia,Abstract available at: <http://emgm.eu/meetings/emgm2011/abstracts.pdf>[accessed 04.10.11].

[56] Centers for Disease Control and Prevention. Active Bacterial Core

Surveillance (ABCs) report, Emerging Infections Program Network, Neis-seria meningitidis, 2009. Available at: <http://www.cdc.gov/abcs/reports-findings/survreports/mening09.pdf>; 2010 [accessed 04.10.11].

[57] Jacobsson S, Mölling P, Thulin Hedberg S, Lepp T, Unemo M, Fred-lund H, et al. P006. Invasive meningococcal disease in Sweden, 2010

ccine

S.A. Halperin et al. / Va

(Page 45–6). The 11th European Meningococcal Group Meeting (EMGM)Congress 2011: Ljubljana, Slovenia, Abstract available at: <http://emgm.eu/meetings/emgm2011/abstracts.pdf> [accessed 04.10.11].

[58] Thulin Hedberg S, Törös B, Fredlund H, Olcén P, Mölling P. Genetic characteri-sation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden,2000 to 2010. Euro Surveill 2011;16(23):8–14.

[59] Caugant DA, Løvoll Ø, Blystad H. P040. Meningococcal disease in Norway,2009–2010: emergence of serogroup Y. EMGM (Pages 117–8). The 11thEuropean Meningococcal Group Meeting (EMGM) Congress 2011: Ljubl-jana, Slovenia. Abstract available at: <http://emgm.eu/meetings/emgm2011/abstracts.pdf> [accessed 04.10.11].

[60] Vainio A, Toropainen M, Kuusi M, Virolaine A. P 037. Characteristicsof invasive meningococcal serogroup Y isolates in Finland, 1995-2010(Pages 111–2). The 11th European Meningococcal Group Meeting (EMGM)Congress 2011: Ljubljana, Slovenia. Abstract available at: <http://emgm.eu/meetings/emgm2011/abstracts.pdf> [accessed 04.11.11].

[61] Ladhani SN, Lucidarme J, Newbold LS, Gray SJ, Carr AD, Findlow J, et al. Invasivemeningococcal capsular Y disease, England and Wales, 2007–2009. EmergInfect Dis, 2012 Jan. doi:10.3201/eid/1801.110901.

[62] Gray SJ, Campbell H, Marsh WJ, Carr AD, Newbold LS, Mallard RH, et al.EB. P 004. The epidemiology and surveillance of meningococcal disease inEngland and Wales (Page 41). The 11th European Meningococcal GroupMeeting (EMGM) Congress 2011: Ljubljana, Slovenia, Abstract available at:<http://emgm.eu/meetings/emgm2011/abstracts.pdf> [accessed 04.11.11].

[63] Fransen F, Heckenberg SGB, Hamstra HJ, Feller M, Boog CJP, van Putten JPM,et al. Naturally occurring lipid A mutants in Neisseria meningitidis frompatients with invasive meningococcal disease are associated with reducedcoagulopathy. PLoS Pathog 2009;5(4):e1000396.

[64] Fransen F, Hamstra HJ, Boog CJ, van Putten JP, van den Dobbelsteen GP, vander Ley P. The structure of Neisseria meningitidis lipid A determines outcomein experimental meningococcal disease. Infect Immun 2010;78(7):3177–86.

[65] Ala’aldeen DA, Oldfield NJ, Bidmos FA, Abouseada NM, Ahmed NW, TurnerDP, et al. Carriage of meningococci by university students, United Kingdom.Emerg Infect Dis 2011;17(9):1762–3.

[66] Bidmos FA, Neal KR, Oldfield NJ, Turner DP, Ala’Aldeen DA, Bayliss CD.Persistence, replacement, and rapid clonal expansion of meningococcalcarriage isolates in a 2008 university student cohort. J Clin Microbiol2011;49(2):506–12.

[67] Trotter C, Findlow H, Chadha H, Townsend K, Thompson D, Mabey L, et al.P 036. Seroprevalence of serum bactericidal antibodies against group W135and Y meningococci in England in 2009 (pages 109–10). The 11th EuropeanMeningococcal Group Meeting (EMGM) Congress 2011: Ljubljana, Slovenia,Abstract available at: <http://emgm.eu/meetings/emgm2011/abstracts.pdf>[accessed 04.11.11].

[68] Gasparini R, Panatto D. Meningococcal glycoconjugate vaccines. Hum Vaccine2011;7(2):170–82.

[69] Granoff D, Pelton SI, Harrison LH. Meningococcal vaccines. In: Plotkin SA,Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: W.B. SaundersCompany, in press.

[70] Cohn AC, MacNeil JR, Harrison LH, Hatcher C, Theodore J, Schmidt M, et al.Changes in Neisseria meningitidis disease epidemiology in the United States,1998-2007: implications for prevention of meningococcal disease. Clin InfectDis 2010;50(2):184–91.

[71] Advisory Committee on Immunization Practices (ACIP). Updated recommen-dations for use of meningococcal conjugate vaccines, 2010. MMWR MorbMortal Wkly Rep 2011;60:72–6.

[72] Advisory Committee on Immunization Practices (ACIP). Licensure of ameningococcal conjugate vaccine for children aged 2 through 10 yearsand updated booster dose guidance for adolescents and other persons atincreased risk for meningococcal disease, 2011. MMWR Morb Mortal WklyRep 2011;60:1018–9.

[73] MacNeil JR, Cohn AC, Zell ER, Schmink S, Miller E, Clark T, et al. Early estimateof the effectiveness of quadrivalent meningococcal conjugate vaccine. PediatrInfect Dis J 2011;30(6):451–5.

[74] Castilla J, Vázquez JA, Salcedo C, García Cenoz M, García Irure JJ, Torroba L,et al. B:2a:P1.5 meningococcal strains likely arisen from capsular switchingevent still spreading in Spain. J Clin Microbiol 2009;47(2):463–5.

[75] Mayer LW, Reeves MW, Al-Hamdan N, Sacchi CT, Taha MK, Ajello GW, et al.Outbreak of W135 meningococcal disease in 2000: not emergence of a newW135 strain but clonal expansion within the electophoretic type-37 complex.J Infect Dis 2002;185(11):1596–605.

[76] Decosas J, Koama JB. Chronicle of an outbreak foretold: meningococcal menin-gitis W135 in Burkina Faso. Lancet Infect Dis 2002;2:763–5.

[77] Harrison LH, Shutt KA, Schmink SE, Marsh JW, Harcourt BH, Wang X, et al.Population structure and capsular switching of invasive Neisseria meningi-tidis isolates in the pre-meningococcal conjugate vaccine era–United States,2000–2005. J Infect Dis 2010;201(8):1208–24.

[78] Trotter CL, Ramsay ME, Gray S, Fox A, Kaczmarski E. No evidence for capsulereplacement following mass immunisation with meningococcal serogroup Cconjugate vaccines in England and Wales. Lancet Infect Dis 2006;6(10):616–7[author reply 617–8].

[79] Pollard AJ, Scheifele D. Meningococcal disease and vaccination in North Amer-ica. J Paediatr Child Health 2001;37(5):S20–7.

[80] Varughese P, Acres S. Meningococcal disease in Canada. In: Vedros N, edi-tor. Evolution of meningococcal disease. Boca Raton: CRC Press, Inc.; 1987.p. 47–63.

30S (2012) B26– B36 B35

[81] Watkins KM, Deeks SL, Medaglia A, Tsang RSW. Enhanced surveillance of inva-sive meningococcal disease in Canada: 1 January, 2002, through 31 December,2003. Can Commun Dis Rep 2006;32(8):97–107.

[82] Varughese PV, Carter AO. Meningococcal disease in Canada. Surveillance sum-mary to 1987. Can Dis Wkly Rep 1989;15(17):89–96.

[83] National Advisory Committee on Immunization. Update on the invasivemeningococcal disease and meningococcal vaccine conjugate recommen-dations. An Advisory Committee Statement (ACS). Can Commun Dis Rep2009;36(ACS-3):1–40.

[84] Deeks S, et al. Surveillance of invasive meningococcal disease in Canada:1995–1996. Can Commun Dis Rep 1997;23(16):121–5.

[85] Case definitions for communicable diseases under national surveillance. CanCommun Dis Rep 2009;35(S2):1–128.

[86] Scheifele DW. IMPACT after 17 years: lessons learned about successful net-working. Paediatr Child Health 2009;14(1):33–5.

[87] Parkinson AJ, Bruce MG, Zulz T. International Circumpolar Surveillance: anArctic network for the surveillance of infectious diseases. Emerg Infect Dis2008;14(1):18–24.

[88] Publicly funded immunization programs in Canada - Routine schedule forinfants and children including special programs and catch-up programs.2011 July 7, 2011 [cited 2011 August 10]; Available at: <http://www.phac-aspc.gc.ca/im/ptimprog-progimpt/table-1-eng.php>.

[89] Bettinger JA, Scheifele DW, Le Saux N, Halperin SA, Vaudry W, Tsang R, et al.The impact of childhood meningococcal serogroup C conjugate vaccine pro-grams in Canada. Pediatr Infect Dis J 2009;28(3):220–4.

[90] Bettinger JA, Le Saux N, Scheifele DW, Vaudry W, Halperin SA, Bortolussi R,et al. The epidemiology of serogroup B meningococcal infections in Canada:IMPACT 2002–2009 [abstract]. Can J Infect Dis Med Microbiol 2010;21(4):179.Abstract O10.

[91] Bettinger J, Scheifele D, Le Saux N, Halperin S, Vaudry W, Bortolussi R, et al.Update on the incidence of meningococcal infections in Canada, IMPACT2002–2009 [abstract]. In: Program and abstract guide of the 17th Interna-tional Pathogenic Neisseria Conference. 2010; Sep 11–16; Banff, AB. p. 95.Abstract P036.

[92] Law DK, Lorange M, Ringuette L, Dion R, Giguère M, Henderson AM, et al. Inva-sive meningococcal disease in Quebec, Canada, due to an emerging clone ofST-269 serogroup B meningococci with serotype antigen 17 and serosubtypeantigen P1.19 (B:17:P1.19). J Clin Microbiol 2006;44(8):2743–9.

[93] Le Saux N, Bettinger JA, Wootton S, Halperin SA, Vaudry W, Scheifele DW, et al.Profile of serogroup Y meningococcal infections in Canada: implications forvaccine selection. For the members of the Canadian Immunization MonitoringProgram, Active (IMPACT). Can J Infect Dis Med Microbiol 2009;20(4):e130–4.

[94] Tsang RSW, Squires SG, Zollinger WD, Ashton FE. Distribution of serogroupsof Neisseria meningitidis and antigenic characterization of serogroup Ymeningococci in Canada: January 1, 1999 to June 30, 2001. Can J Infect Dis2002;13(6):391–6.

[95] Tsang RS, Henderson AM, Cameron ML, Tyler SD, Tyson S, Law DK, et al.Genetic and antigenic analysis of invasive serogroup Y Neisseria menin-gitidis isolates collected from 1999 to 2003 in Canada. J Clin Microbiol2007;45(6):1753–8.

[96] Safadi MA, Cintra O. Epidemiology of meningococcal disease in LatinAmerica: current situation and opportunities for prevention. Neurol Res2010;32(3):263–71.

[97] Pan American Health Organization. Informe Regional de SIREVA II: Datospor país y por grupos de edad sobre las características de los ais-lamientos de Streptococcus pneumoniae, Haemophilus influenzae y Neisseriameningitidis, en procesos invasores, 2010. OPS. Documentos Técnicos,Tecnologías Esenciales de Salud. Washington, DC, 2011: Pan Ameri-can Health Organization, Available at: <http://new.paho.org/hq/index.php?option=com content&task=blogcategory&id=3609&Itemid=3953>; 2011.

[98] Epidemiologic Surveillance Center (Brazil). Respiratory transmitted diseases,Available at: <http://www.cve.saude.sp.gov.br>.

[99] Ministry of Health. Meningococcal disease in Brazil, Available at: <http://portal.saude.gov.br/portal/saude/area.cfm?id area=962>.

[100] Moraes JC, Barata RB. Meningococcal disease in São Paulo, Brazil, inthe 20th century XX: epidemiological characteristics. Cad Saude Publica2005;21(5):1458–71 [in Portuguese].

[101] Lemos AP, Brandaõ AP, Gorla MC, Paiva MV, Simonsen V, Melles CE,et al. Phenotypic characterization of Neisseria meningitidis strains iso-lated from invasive disease in Brazil from 1990 to 2001. J Med Microbiol2006;55(6):751–7.

[102] Sacchi CT, Fukasawa LO, Gonc alves MG, Salgado MM, Shutt KA, CarvalhanasTR, et al. Incorporation of real-time PCR into routine public health surveil-lance of culture negative bacterial meningitis in São Paulo, Brazil. PLoS ONE2011;6(6):e20675.

[103] Iser BP, Lima HC, De Moraes C, De Almeida RP, Watanabe LT, Alves SL,et al. Outbreak of Neisseria meningitidis C in workers at a large food-processing plant in Brazil: challenges of controlling disease spread tothe larger community. Epidemiol Infect 2011:1–10 [Epub ahead of print]DOI:10.1017/S0950268811001610.

[104] Argentinean Society of Pediatrics. Bacterial meningitis and meningococcal

disease. Infectious Diseases National Committee, Available at: <http://www.sap.org.ar/staticfiles/comunicaciones/menin2008.pdf>; 2011.

[105] Efron AM, Sorhouet C, Salcedo C, Abad R, Regueira M, Vázquez JA. W135 inva-sive meningococcal strains spreading in South America: significant increasein incidence rate in Argentina. J Clin Microbiol 2009;47(6):1979–80.

B ccine

[

[

[

36 S.A. Halperin et al. / Va

106] Pírez MC, Picón T, Galazka J, Rubio I, Montano A, Ferrari AM, et al. Control de unbrote epidémico de enfermedad meningocócica por N. meningitidis serogrupoB. Rev Med Uruguay 2004;20(2):92–101.

107] Chile Ministry of Health. Epidemiologic Surveillance Department. Meningo-coccal disease situation, Available at: <http://epi.minsal.cl/epi/html/bolets/reportes/Meningitis/meningitis.pdf>; 2011.

108] Agudelo CI, Sanabria OM, Ovalle MV. Serogroup Y meningococcal disease,Colombia. Emerg Infect Dis 2008;14:990–1.

30S (2012) B26– B36

[109] Ministry of Health, Venezuela. Epidemiology, Available at: <http://www.mpps.gob.ve/ms/index.php> [July 2008].

[110] Chacon-Cruz E, Sugerman DE, Ginsberg MM, Hopkins J, Hurtado-Montalvo

JA, Lopez-Viera JL, et al. Surveillance for invasive meningococcal disease inchildren, US-Mexico border, 2005–2008. Emerg Infect Dis 2011;17(3):543–6.

[111] Pérez Rodríguez A, Dickinson F, Baly A, Martin R. The epidemiological impactof antimeningococcal B vaccination in Cuba. Mem Inst Oswaldo Cruz, Rio deJaneiro 1999;94:433–40.