Effect of a serogroup A meningococcal conjugate vaccine (PsA–TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study

Martin C J Maiden ,Odile B Harrison ,Olivier Manigart ,Mamoudou Harouna Djingarey ,Dominique A Caugant ,Matthew E Coldiron ,Maria Cláudia Nascimento ,Lodoum Mbainadji ,Caroline Trotter ,B Kodbesse,Florence Fermon ,Lisa S Rebbetts ,Arouna Woukeu ,C Ngadoua,Musa Hassan-King ,Yenenesh K Tekletsion ,Maxime Narbé ,James M Stuart ,Eleanor Watkins ,Doumagoum Moto Daugla ,Nathan Naïbeï ,Page A-L ,J Toralta,Daniel Chandramohan ,Jean Pierre Gami ,Dorothea M C Hill ,Kadidja Gamougam ,Brian Greenwood ,Stéphane Hugonnet

doi:10.1016/s0140-6736(13)61612-8

Abstract

SummaryBackgroundA serogroup A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA–TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic.MethodsWe obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA–TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1–29 years of a rural area roughly 13–15 and 2–4 months before and 4–6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods.FindingsRoughly 1·8 million individuals aged 1–29 years received one dose of PsA–TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100 000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100 000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046–0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2–4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4–6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002–0·138; p<0·0001).InterpretationPSA–TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established.FundingThe Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères.

Highlights

For more than 100 years, the Sahelian and sub-Sahelian regions of Africa have had periodic, large, and unpredictable epidemics of meningococcal meningitis.1 The first outbreaks in Chad were reported in 1916 and 1918,2 and major epidemics arose in 1924 and 1935–39, with a mortality rate of more than 75% in both epidemics.3 Another major cycle began in 1943, when more than 2000 cases were reported, and further epidemics arose in the 1950s and 1960s
Strains isolated from cases of meningitis were stored in brain infusion broth with glycerol at –80°C and sent to the Inter-Country Support Team, Ouagadougou, and to the WHO Collaborating Centre for Reference and Research on Meningococci in Oslo, Norway
CSF samples collected in trans-isolate medium from outbreak areas by a team from Médecins Sans Frontières (MSF) were analysed by genogrouping and PorA PCR in Oslo

Summary

Introduction

For more than 100 years, the Sahelian and sub-Sahelian regions of Africa have had periodic, large, and unpredictable epidemics of meningococcal meningitis. The first outbreaks in Chad were reported in 1916 and 1918,2 and major epidemics arose in 1924 and 1935–39, with a mortality rate of more than 75% in both epidemics. Another major cycle began in 1943, when more than 2000 cases were reported, and further epidemics arose in the 1950s and 1960s. The first outbreaks in Chad were reported in 1916 and 1918,2 and major epidemics arose in 1924 and 1935–39, with a mortality rate of more than 75% in both epidemics.. The first outbreaks in Chad were reported in 1916 and 1918,2 and major epidemics arose in 1924 and 1935–39, with a mortality rate of more than 75% in both epidemics.3 Another major cycle began in 1943, when more than 2000 cases were reported, and further epidemics arose in the 1950s and 1960s. A serogroup A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is being deployed across the African meningitis belt. We studied the effect of PsA–TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic

Methods

Results

Conclusion