WHO Guideline on Meningitis Outbreak response in sub-Saharan Africa

Appendix A : Changing epidemiology in the meningitis belt

A. Overview

For over 100 years, major epidemics of meningococcal disease have occurred every few years within the African meningitis belt(1). These epidemics are very disruptive, requiring the establishment of emergency treatment centres and placing a severe strain on the routine health services. The reason for the susceptibility of this region of Africa to major epidemics of meningococcal disease is at least in part related to its climatic features, with outbreaks occurring mainly in the hot, dry season(2). Most epidemics have been due to Neisseria meningitidis serogroup A (Nm A), with some outbreaks caused by serogroup W, X and C, but with a conspicuous absence of outbreaks due to serogroup B .

In 2002, enhanced surveillance was established in the meningitis belt countries and coordinated by the WHO Inter-country Support Team (IST) in Ouagadougou, Burkina Faso. From then until 2013, the highest case load and number of epidemic districts occurred in 2009 (Figure 1). In this year >70% of the reported suspected cases from the belt were from Nigeria, as well as of epidemic districts. However only 18%% of confirmed cases were from Nigeria while 62% were from Niger, which experienced the second highest case load.

Fig 1: Suspected cases reported from the African Meningitis Belt 2002-2013

90,000 78,980 80,000 70,000 60,000 54,180 50,000 42,763 40,000 37,825 34,829 28,076 30,000 24,067 19,478 16,824 18,664 Cases 20,000 13,132 10,346 10,000 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

years

In 2006 and 2007, other years with a relatively high case load, the majority of cases and epidemic districts occurred in Burkina Faso. The lowest numbers of reported cases occurred in 2005 and 2013.

Since 2010 countries in sub-Saharan Africa have started to progressively introduce a new meningococcal A conjugate vaccine (MenAfriVac) through mass campaigns as a preventive measure that is expected to confer both long lasting individual protection and herd immunity (3-5). With the support of the Global Alliance for Vaccines and Immunization (GAVI), most countries in the meningitis belt have, since 2000, introduced Haemophilus influenzae type b (Hib) vaccines and some have already introduced Streptococcus pneumoniae (Spn) conjugate vaccines, such that the incidence of bacterial meningitis due to non-meningococcal pathogens is also evolving

The changing epidemiological pattern is well demonstrated in Tables 1 and 2, and Fig 2, with NmA declining to very low proportions of confrmed cases after 2010, and an accompanying rise in the % of NmW and to a lesser extent of NmX cases. It should be noted at the same time that the total numbers of reported cases have also been declining in the last three years (Fig 1 ).

Fig 2: Distribution of isolated pathogens, Enhanced meningitis surveillance, 2004-2013

100%

90%

80% Other pathogens 70% Hib

60% pneumo

50% other Men

MenC 40% MenX 30% W135

20% MenA

10%

0% 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 Tables 1 and 2. Suspected meningitis cases and pathogen distribution, Meningitis Belt 2003-2013. Total suspect Total + Men other Other Year cases samples MenC MenX Men A W135 Men pneumo Hib pathogens 2003 34,829 1674 892 221 94 319 86 62 2004 19,478 1372 1 3 664 111 30 439 124 2005 13,132 777 182 33 53 323 125 61 2006 42,763 2015 581 922 37 32 274 102 67 2007 54,180 1101 609 62 9 297 74 50 2008 28,076 1464 1062 7 65 243 48 39 2009 78,980 2683 17 1996 167 30 358 39 76 2010 24,067 1667 4 55 439 726 14 356 47 26 2011 16,824 1847 5 154 197 514 6 879 53 39 2012 18,664 1881 4 138 88 1009 33 539 45 25 2013 10,346 884 10 15 22 233 45 466 38 55 2004- 13 341,339 15,684 41 946 6181 2899 310 4174 695 438

Total suspect Total + Men other Other Year cases samples MenC MenX MenA W135 Men pneumo Hib pathogens total 2003 34,829 1674 53% 13% 6% 19% 5% 4% 100% 2004 19,478 1372 0% 0% 48% 8% 2% 32% 9% 100% 2005 13,132 777 23% 4% 7% 42% 16% 8% 100% 2006 42,763 2015 29% 46% 2% 2% 14% 5% 3% 100% 2007 54,180 1101 55% 6% 1% 27% 7% 5% 100% 2008 28,076 1464 73% 0% 4% 17% 3% 3% 100% 2009 78,980 2683 1% 74% 6% 1% 13% 1% 3% 100% 2010 24,067 1667 0% 3% 26% 44% 1% 21% 3% 2% 100% 2011 16,824 1847 0% 8% 11% 28% 0% 48% 3% 2% 100% 2012 18,664 1881 0% 7% 5% 54% 2% 29% 2% 1% 100% 2013 10,346 884 1% 2% 2% 26% 5% 53% 4% 6% 100% Total 341,339 15,684 0% 8% 39% 18% 2% 27% 4% 3% 100% Source: Enhanced surveillance data, IST-WA – number of reporting countries varies from year to year Footnote to Tables 1 and 2: The IST WA Bulletin only reported NmA, NmW and “other Nm” until 2009, inclusive . Therefore it is not possible to determine the distribution of Nm X, C or B until 2010. Information given on these pathogens before 2010 have been compiled from other sources (e.g. from Niger for Nm X in 2006).

The pathogen distribution partly reflects the laboratory sampling and confirmation capacity, which is higher in Burkina Faso and Niger. The proportion of suspect cases with laboratory confirmation across the Belt has been rising over the last ten years from 2-3% to 6-7% but is still at relatively low levels (Fig 3).

Fig 3: Suspected and confirmed meningitis cases reported to the enhanced surveillance network, 2004-2013 Lab positive Suspected cases 100000 3000 90000 2500 80000 70000 2000 60000 50000 1500 Suspected 40000 Confirmed 1000 30000 20000 500 10000 0 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

.

B. Neisseria meningitidis serogroups W and X

Neisseria meningitidis serogroup W (6-9)

For several decades, NmW has been known to have been associated with clinical cases, including epidemics, which, before 2002, had always been on a very small scale. Two outbreaks coinciding with pilgrimage seasons for Hajj/Umra in 2000 and 2001 were associated with NmW, with 98 and 152 confirmed cases respectively (the 2000 outbreak disseminated over the world with 400 cases). Table 3 shows reported outbreaks in the meningitis belt since 2002, the majority of which led to a vaccination response. The largest reported outbreak caused by serogroup W occurred in Burkina Faso in 2002 and comprised more than 13,000 suspected cases. Sporadic cases and outbreaks caused by serogroup W have continued to occur in several meningitis belt countries, with larger epidemics reported in Burkina Faso (2012), Niger (2010-11) and Chad (2009-10). During epidemics in Niger 2010, Burkina Faso 2002 and 2012, the proportion of infections among younger children (less than 5 years) was high. The dynamic of these Nm W outbreaks appears to differ from those due to Nm A, with lower peak and cumulative attack rates.

Neisseria meningitidis serogroup X (10-13)

NmX has been described to cause sporadic cases in Africa mainly since 1990. NmX epidemics were detected in 2006 (Niger, Uganda and Kenya), Togo 2007, Niger 2009 and Burkina Faso 2010. In Niger 2006 and Burkina 2010 several districts were affected by NmX epidemics with cumulative attack rates over 100cases /100,000 population. In Niger 2006 significant differences were observed for case fatality (12% for NmX cases vs 5 % for NmA) but age distribution was similar as also in Burkina Faso 2010 and Togo 2007 (the most affected age group was 5-14 years old). Case fatality was higher for NmX cases vs NmA cases in general, however in epidemic contexts no significant difference was observed, in general the epidemic CFR being lower than CFR for cases in non-epidemic cases.

It should be noted that the occurrence of NmX has been and still is difficult to detect. Only in the recent 10 years some countries’ laboratories have started to test for NmX. It cannot be detected by current rapid diagnostic tests and many laboratories did not have specific antisera for culture or an appropriate PCR protocol. Table 3: Outbreaks of serogroup W meningococcal meningitis in the meningitis belt 2002-2014

Year #cases # deaths # districts % confirmed Age group Vaccination Treatment Source (letality) in W135 epidemic W135 Burkina 2002 13 124 1510 30 203 culture 16% <1 year, Tetravalent Chloramphe Bertherat et Faso (11.5%) pos. 28% 1–4, 25000 doses nicol – al W135=83%, 31% 5–9, Ampicilllin A=7% 8% 10–14 17% >15 attack rate highest in patients <5 years Burkina 2003 3 For the year: Tri and IST bulletin Faso 264 MenA and tetravalent 104 W135 Burkina 2004 2 For the year: Tri and IST bulletin Faso 128 MenA and tetravalent 66 W135 Chad 2005 14 6 W135; Trivalent IST bulletin 9 MenA 178000 d. WER Sudan 2005 24 Displaced 10 W135 Trivalent ICG request 1 MenA 161000 DON Kenya 2006 74 15 (20%) 4 divisions Trivalent Chloramphe WER 200 000 d. nicol Uganda 2006 37 5 4 W135; Trivalent Chloramphe ICG 3 MenA nicol Sudan 2006 28 1 15 MenA 25000 d. Chloramphe ICG 5 W135 trivalent nicol Sudan 2007 1 1 MenA Trivalent Chloramphe ICG 4 W135 nicol Togo 2007 246 15 79 MenA W ICG request 25 W135 containing Chad 2009 1299 140 W135=58% of 3 requests – Chloramphe ICG (11%) all samples trivalent nicol tested (288 CSF) Cameroon 2009 5 W135=77; No vacc. IST Bulletin NmA=2 Ghana 2010 52 1 6 MenA Trivalent ICG request 9 W135 131576 d. Chad 2010 3058 231 11 76 positive Trivalent WER MenA 63% 156615 d. W135 18% Niger 2010 1188 103 4 248 confirmed 1–4 years of Tetravalent Collard et al (8.7%) Men age: and trivalent W135=49%, more disease (678626 d.) A=47% caused by W135 Nigeria 2010 4699 322 5 43 MenA Trivalent WER 58 W135 191200 d. Sudan 2010 55 5 1 4 W135 Trivalent WER 1 MenA 87983 d. ICG request Niger 2011 1 28 confirmed Trivalent Ceftriaxone ICG Men, 110000 d. 27 W135 Burkina 2012 5300 553 13 1’030 11% <1 year, MacNeil et Faso (10.4%) confirmed; 29% 1–4 years, al Nm (77%) 29% 5–9 years, Nm W135= 16% 10–14 years, 68% 15% >15 years Nm X=8% Sp=22% , Hib=2% Benin 2012 4 100000 ICG quadrivalent Côte 2012 2 163000 ICG d’Ivoire trivalent Ghana 2012 3 195000 ICG trivelent Gambia 2012 469 8% 138 positive; 67% were <5 Tetravalent Prophylaxis Hossain et al W135=83% years cipro to Sp=13% close contacts Guinea 2013 102 10% 1 W135 >50% Trivalent WER Uganda 2014 155 1 Most affected Trivalent Ceftriaxone ICG age group 5-14y.

Table 4: Outbreaks of serogroup X meningococcal meningitis in the meningitis belt 2006-2014

Year #cases # deaths # districts % confirmed Age group Vaccination Treatment Source Cum comments (letality) in Nm X attack epidemic rate NmX Whole country : article looked at all suspect cases and 44 Hib, 118 Nm X 12.7% Spn,1139 Nm, (avg 7.9 ys, confirmation, not for NmX 581 Nm X younger than only those from cases (vs (51% of Nm), Nm A) 5-9 epid distr 5.1 % for 512 Nm A years, highest timing: outbreak A, stat 3(Niamey, (45% of Nm), Nm X later than Nm A, significa D.Doutchi 24 NmW (2% incidence, Boisier et al, Nm X peak around Niger 2006 4185 nt and Say) of Nm) then 1-4 CID 2007 wk 16 only Nm WHO CO distribution for the enh surv region available (i.e 249 Nm, 240 wk1-22 and for all of Niamey, NmX, 3 NmA, MOH PPT but 80% cases and 1 NmY, 5 Nm men annual epid in Niamey I) ind (non Nm meeting epidemio data up to Niger 2006 551 74 (13%) Niamey not know) 2006 136.57 wk 22 only Nm WHO CO distribution for the enh surv region available (i.e 178 Nm, 51 wk1-22 and Tillaberi but 70% NmA, 4 MOH PPT cases and therefore NmW, 120 men annual CSF from Say distr) 53 NmX, 3 Nm meeting epidemio data up to Niger 2006 626 (8.5%) Dosso ind, 2006 106.6 wk 22 only Nm WHO CO distribution for the enh surv region available (i.e wk1-22 and Dosso, but 70% 96 Nm, 89 Nm MOH PPT cases and CSF from X, 3 Nm W, 3 men annual D. Doutchi) Nm A, 1 Nm meeting epidemio data up to Niger 2006 258 15 (6%) Say ind 2006 97.14 wk 22 vaccination with ACW Mutonga et 16 (21% Kacheliba same for Nm (concomitant al, Am J of 76 and Alale X as controls with A/W Trop Med border with cases divisions 9 CSF +, (median 14 ys, outbreaks 2009, EID Uganda, can be known in West 9Nm, 5NmX, 58% cases 5- Kenya/ 2007 letter considered same Kenya 2006 82 outcome Pokot distr 1 W, 1Y, 1C 24 ys) Uganda) to the editor outbreak weak confirmation (little info), X cases detected later, first "Nm A outbreak" and then detected ICG Request NmX after and WHO campaign. 2 Nm A, 4 Nm vaccination CO/MOH Epidemio data up to Uganda 2006 91 3 (4%) Moroto X with AC data wk 16 weak confirmation (little info), X cases detected later, seems first "Nm A ICG Request outbreak" and then and WHO detected NmX after no CO/MOH campaign, epidemio Uganda 2006 178 2 (1%) Kotido 2 Nm X vaccination data data up to wk 17 ICG Request and WHO CO/MOH Nm X confirmed by Uganda 2007 147 11 (7%) Kotido 6 NmX data 94 WHOCC Oslo (7.2% 97 CSF+, 75 Delrieu et al, sur 139 NmX, 8 PLOS 2011 cas in wk W135, 5 NG 5-14 ys (77% and Togo Togo 2007 172 17 surv Kozah Nm, 7 Spn, 2 of cases) CO 61.9 data up to wk 17 table) Hib Burkina 6 districts for MOH PPT 863 Nm X(each (through cases and deaths, Burkina 2010 6145 (14%) below) WHO CO) whole country Burkina MOH PPT 3CSF+, 3 (through Burkina 2010 120 12 (10%) Barsalogho NmX WHO CO) 73.5 21 CSF+, 19 Burkina Nm X (24 X MOH PPT PCR), 1 Nm (through Burkina 2010 197 17 (9%) Gourcy A, 1 Spn WHO CO) 106.4 Burkina MOH PPT Ouaghigou 19 CSF+, 19 (through Burkina 2010 248 34 (14%) ya Nm X WHO CO) 57.6 5 CSF+, 4 Burkina NmX (10 MOH PPT NmX PCR), 1 (through Burkina 2010 219 26 (12%) Pouytenga Spn WHO CO) 127.6 42 CSF+, 39 Burkina Nm X (50 MOH PPT NmX PCR), 1 (through Burkina 2010 301 30 (10%) Séguenaga W135, 1 Spn WHO CO) 167.9 37 CSF+, 21 Burkina Nm X, 5 MOH PPT NmA, 1 Hib, (through Burkina 2010 144 23 (16%) Toma 11 Spn WHO CO) 79.9

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