in the meningitis belt

Transcription

1 Biological aspects of meningitis epidemics in the meningitis belt Dr Pierre NICOLAS Meningococcus Unit, WHO collaborating centre IMTSSA, Allée du médecin colonel Jamot Parc du Pharo BP Marseille cédex 07 France

2 Introduction Neisseria meningitidis (Nm), is responsible for meningococcal disease that occurs worldwide In the meningitis belt epidemics are almost due to serogroup A meningococci Meningococcal meningitis epidemics need 3 factors to happen A susceptible population An hyperinvasive / hypervirulent strain Risk factors (environmental and climatological conditions as dryness, dust wind ) This presentation will focus on the bacteria meningococcus

3 Characterisation of meningococci : the group polysaccharidic capsule Polysaccharides group A, B, C, W135, Y, X useful for diagnosis using sera or PCR for prophylaxis PS vaccines A, C, W135, Y

4 Characterisation of meningococci : the group polysaccharidic capsule Polysaccharides group A, B, C, W135, Y, X group is not sufficient for epidemiology purposes Predominant serogroups In the African meningitis belt : group A In Europe: group B and group C In USA : group B, C and Y = 30% for each

5 Characterisation of meningococci Type and sub-type Outer membran protein (OMP) Por A, Por B using monoclonal antibodies or sequencing Por A=OMP1 sub-types Por B= OMP2/3 types these proteins induce protective bactericidal antibodies (subtype=pora) useful for prophylaxis Can help epidemiology but not sufficient A: 4: P1.9 W135: 2a: P1.5,2

6 Characterisation of meningococci the sequence type = ST DNA characterization of 7 loci from «housekeeping genes» Using «Multilocus sequence typing» Sequence Type or ST DNA Sequence Type ST A: 4: P1.9 ST-5 or ST-7 W135: 2a: P1.5,2 ST-11

7 MLST 7 loci ( bp), from 7 genes are sequenced, abcz adk aroe gdh pdhc pgm fumc putatif ABC transporter adenylate kinase shikimate dehydrogenase glucose 6 phosphate dehydrogenase pyruvate dehydrogenase sub unit phosphoglucomutase fumarase House keeping genes, low selective pressure

8 internet MLST site : MLST http: //pubmlst pubmlst.org org/neisseria neisseria/

9 MLST internet site allows exchanges

10 MLST technique Related sequence types are gathered in STcomplexes or clonal complexes (cc) < 40 ST complexes described, < ten are responsible for most of the meningococcal meningitis in the world ST-32 complex cc32 ST-41/44 complex cc41/44 cc269 cc35 ST-8 complex cc8 ST-11 complex cc11 in the African meningitis belt ST-5 complex cc5 MLST is used by reference laboratories all over the world, as it gives unambiguous results MLST has its internet site MLST is very convenient for long term epidemiology

11 Why to follow Neisseria meningitidis clones? Outbreaks, hyperendemic waves and pandemics = emergence of an unique strain characterized by its group, type/subtype, and genotype Sequencing and characterisation permit to know which is the responsible? and to follow it all over the world. the emergence of a new clone is often associated with new waves of epidemics Genotyping allowed the survey of capsule switches = a same genotype but a different capsule fine characterization + epidemiological features can help to understand epidemiology, predict what would happen in close countries to prepare adapted responses.

12 Epidemics of A:4:P1.9 ST-5 complex cc5 Senegal Gambia Mali Niger Nigeria Chad Guinea Burkina Faso Cameroon Ghana Togo Benin Sudan Ethiopia Djibouti Meningitis belt Sahelian Africa (Médecin général Lapeyssonnie) recurrent outbreaks each year each 5-10 years very large epidemics

13 Analysis of African isolates between 1988 and 2008 using MLST 778 isolates analyzed by MLST, most of them (746 / 96 %) belonged to 6 genotypes : 589 isolates group A (75%), 588 belonged to cc5 (99%) o 83 ST-5 10% o 290 ST-7 37% total 588 cc5 o 209 ST % o 6 other STs 0.9% o 1 ST isolates group W135 (15%) o 69 ST % o 51 ST-2881 total % 44 isolates group X (5.6%) o 43 ST %

14 Epidemics of A:4:P1.9 ST-5 complex responsible for 3 epidemic waves Meningococcus serogroup A, cc5 comprises 3 major STs: ST-5, ST-7, ST-2859 ST abcz adk aroe gdh fumc pdhc pgm

15 Global expansion of serogroup A meningococcus ST-5 ST-5 complex 1988 Saudi Arabia 1987 Nepal 1980s India China ST-5 The 2 first waves of ST-5 then ST-7 emerged out of Africa ST-5 emerged in the belt in 1988 and stayed until 2001.

16 ST-5, ST-5 complex clonal expansion between 1988 and 2001 in Africa Senegal Guinea Bissau Burkina Faso Mali Niger Cameroon Nigéria 1996 Chad RCA 1992 Sudan 1988 Ethiopia SSSS aaaa uuuu dddd i i i i AAAA ra ra ra bbbb iiii aaaa oooo uuuu tb tb tb tb re aaaa kkkk Burundi Zaïre 1994 ST-5 was responsible for the most important epidemic ever seen in Africa in 1996 > 150,000 cas Nicolas P et al. J Clin Microbiol. 2005, IMTSSA - LE PHARO - MARSEILLE - FRANCE

17 pandemic due to meningococci A ST-7 ST-5 complex cc5 The second wave of ST-7 emerged also out of Africa ST-7 emerged in the belt in 1997 and was still present in Russia Mongolia 1994 India 2005? China 1992 Philippina 2005 ST-7

18 Emergence and expansion of ST-7 ST-5 complex between 1995 and 2008 in Africa Algeria Burkina Faso Togo Ghana Benin Niger 1999 Chad Mali Nigeria Cameroon Sudan Ethiopia ST-7 has totally replaced ST-5 Nicolas P et al. J Clin Microbiol. 2005, IMTSSA - LE PHARO - MARSEILLE - FRANCE

19 Emergence and expansion of ST-2859 ST-5 complex between 2003 and 2008 A third wave wave of ST-2859 (cc5) emerged first in Burkina Faso in 2003, was responsible for epidemics. ST-2859 was notified for the first time in Niger, Mali and Togo in Mali 2007 Burkina Faso Togo Niger ST-2859

20 Epidemics of group A cc5 in the future ST-5 has been responsible for very important epidemics, has disappeared after 13 years ST-7 has been responsible for important epidemics and is still present ( ) ST-2859 ( ) was responsible for 2 important epidemics in Burkina Faso in 2006 and Will it be responsible for important outbreaks next years, as it has begun its expansion to close countries?

21 Epidemics of W135:2a:P1.5,2 ST outbreak in Saudi Arabia Pilgrimage in Mecca in March 2000; 1,7 million pilgrims 253 meningitis cases were notified, confirmed by the laboratory, 161 serogrouped: Serogroup A 37% Serogroup W135 57% Lingappa JR et al. Emerg. Infect.Dis. 2003, 9,(6)

22 Epidemics of W135:2a:P1.5,2 ST-11 W135 global epidemic in cases in Europe notified by 9 countries between March and July 14 deaths (15,5%) among returning pilgrims and their close contacts Epidemic in England and Wales in cases Outbreak in France in 2000 : 27 cases between March 22nd and November 20th Hahné SJM et al. Lancet 2002, 359, Matsika-Claquin MD et al. Presse Médicale 2001, 30,

23 Epidemics of W135:2a:P1.5,2 ST-11 W135 ST-11 after 2000 in Africa Senegal Niger Chad RCA 2001 Sudan 2000 Outbreak in Saudi Arabia 2000 Burkina Faso Cameroon Bukina Faso outbreak in 2002, The first ever notified in Africa 12,617 cases and 1,447 deaths

24 Epidemics of W135:2a:P1.5,2 ST-11 How explain the emergence of this W135 clone? capsule switch between C, B and W135? is probable but not recently Vaccine pressure using A et C vaccination campaigns favouring switch and emergence of W135? In 2004 in Burkina Faso, AC vaccine is not a risk factor for W135 meningitis Emergence of W135 clone that has already circulated in France, USA, Canada, Indonesia, Saudi Arabia, Algeria, Mali, Ghana and Gambia, the annual Hajj amplifying the spread of this clone

25 Epidemics of W135:2a:P1.5,2 ST-11 Serogroup W135 meningococci in the future? in all the countries of the African belt. Last years, outbreaks associated A+W135 Difficulties to choose the right vaccine In , W135 cases have dramatically decreased W135 was responsible for sporadic cases in few countries in Cameroon, Benin, Niger, most of the strains belonged to the less invasive, less virulent, less epidemic clone ST In Chad the 2 ST-11 and ST-2881 were found equally

26 Conclusion Epidemiological and laboratory surveillances are crucial as Neisseria meningitidis is always evolving. Meningococci serogroup X:NT:P1.5 ST-181 were responsible for the first important outbreak ever described in 2006 in Niger (800 cases notified). was responsible for many cases in 2007 in Central Togo Reference laboratories of the meningitis belt are recommended to send meningococcal isolates to WHO collaborating centres, to reference laboratories Marseille Oslo Atlanta Orebro

27 We thank the following colleagues for bacterial strains / data Djibo, Chippaux, Chanteaux, Boisier, Niger Lafourcade, Mueller, Gessner, Da Silva, Agence de Médecine Préventive Ouedraogo, Sangaré, Traoré, Niamba, Drabo, Yaro Burkina Faso Agbenoko, Badziklou, Tamekloe, Sitti Hlomashi Ayoko, Togo Caugant, Norway Olcen, Sweden Popovic, USA Alonso, Taha, France Hounsou, Bankole, Benin Guérin, Gerstl, Epicentre Cherif Baharadine, Koyange, Laboratoire Epervier, Chad Médecins Sans Frontières Fonkoua, Massenet, Cameroon Nageeb Sulaiman Saed Sudan