Defining seroprevalence and correlates of protection for Neisseria meningitidis group A in the African meningitis belt

Lead Research Organisation: University of Bristol
Department Name: Social Medicine

Abstract

We are trying to find out more about the factors that protect people against meningitis caused by bacteria known as ‘group A meningococcus’. Large, devastating epidemics of this disease occur in Africa in a sub-Saharan region called the ‘meningitis belt’. A vaccine is being developed against this disease, and will be first used in Burkina Faso in 2009.

People who are vaccinated produce antibodies in their blood that protect them from this form of meningitis. We also know that some individuals can develop antibodies naturally if they are exposed to the bacteria during the course of their life. Although we can measure these antibodies we do not know what levels are needed for protection. To study this, we are going to take blood samples from unvaccinated individuals in Burkina Faso and compare the proportion of people in different age groups who have antibodies above a certain threshold with their chances of getting meningitis.

If we can define this marker of protection, we will help scientists address other important questions, such as how often populations should be vaccinated to maintain protection against the disease. In addition, we will create a collection of blood samples that can be used by other researchers to study other types of meningitis in Africa.

Technical Summary

Background:
The meningitis belt of sub-Saharan Africa is characterised by the periodic occurrence of devastating epidemics of meningococcal meningitis. New conjugate vaccines are being developed to prevent epidemics due to Neisseria meningitidis group A (NmA). Correlates of protection have not been defined for group A in the African meningitis belt, but would be of great value given the imminent introduction of group A conjugate vaccines to the region. We will study the association between seroprevalence against NmA and concurrent age-specific incidence of NmA disease, to assist with development of correlates of protection against NmA disease.

Research objectives:
? To measure the age-specific prevalence of serum bactericidal and IgG antibodies to NmA in a randomly sampled population of around 1000 individuals in Bobo-Dioulasso, Burkina Faso
? To analyse the association between age-specific seroprevalence and age-specific disease incidence measured concurrently in the same setting
? To measure the prevalence of pharyngeal NmA carriage in a subset of 500 individuals
? To create a serum collection for use in further studies of bacterial meningitis in Africa

Methods:
Fieldwork will be conducted in Burkina Faso in partnership with Agence de Medecine Preventive and Centre Muraz. Serum samples collected from study participants will be processed locally and sent to the Health Protection Agency, Manchester for antibody testing. Pharyngeal swabs will be analysed by standard bacteriological methods at Centre Muraz, including culture for carriage strain isolation and identification and PCR for Nm confirmation and genogrouping. The age-specific prevalence of bactericidal and anti-capsular antibodies to group A will be described and 95% confidence intervals for the point prevalence estimates will be compared. Seroprevalence data will be analysed in relation to the age-specific disease data, and the plausibility of a range of putatively protective titres will be explored. Simple mathematical models will be constructed to explore the relationship between carriage, immunity and disease.

Exploitation of research results:
In the near-term this study will lead to the improved definition of correlates of protection for group A meningococcal disease in the African meningitis belt. Valid correlates of protection will assist further vaccine development by public and private initiatives, the interpretation of vaccine impact observed after introduction on the population level, and definition of immunisation strategy, notably the interval between vaccine campaigns. The sera obtained during this study will be stored and the collection will be made available for appropriate further studies of serological correlates for bacterial meningitis.

Publications

10 25 50
 
Description Meningitis Research Foundation Annual Grant Round 2009/10
Amount £332,668 (GBP)
Organisation Meningitis Research Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2011 
End 12/2015
 
Title Burkina Serum Collection 
Description Approximately 1000 serum samples collected in urban Burkina Faso that can be used for other investigations related to meningitis. 
Type Of Material Biological samples 
Provided To Others? No  
Impact The sample collection is available for other researchers to use, but we have not yet recieved any requests. 
 
Description MRF persistence study 
Organisation MURAZ Center
Country Burkina Faso 
Sector Academic/University 
PI Contribution Co-investigator on project to evaluate the persistence of vaccine-induded antibodies against group A meningococci. I take the lead in data analysis and modelling
Collaborator Contribution Co-investigators on project. HPA lead on laboratory analyses. AMP and Centre Muraz lead on fieldwork.
Impact Successful grant application to Meningitis Research Foundation. The first round of fieldwork has been completed and laboaratory analyses are ongoing. This is a multidisciplinary project involving epidemiologists and laboratory scientists
Start Year 2010
 
Description MRF persistence study 
Organisation Preventive Medicine Agency
Country France 
Sector Charity/Non Profit 
PI Contribution Co-investigator on project to evaluate the persistence of vaccine-induded antibodies against group A meningococci. I take the lead in data analysis and modelling
Collaborator Contribution Co-investigators on project. HPA lead on laboratory analyses. AMP and Centre Muraz lead on fieldwork.
Impact Successful grant application to Meningitis Research Foundation. The first round of fieldwork has been completed and laboaratory analyses are ongoing. This is a multidisciplinary project involving epidemiologists and laboratory scientists
Start Year 2010
 
Description MRF persistence study 
Organisation Public Health England
Department Vaccine Evaluation Unit
Country United Kingdom 
Sector Public 
PI Contribution Co-investigator on project to evaluate the persistence of vaccine-induded antibodies against group A meningococci. I take the lead in data analysis and modelling
Collaborator Contribution Co-investigators on project. HPA lead on laboratory analyses. AMP and Centre Muraz lead on fieldwork.
Impact Successful grant application to Meningitis Research Foundation. The first round of fieldwork has been completed and laboaratory analyses are ongoing. This is a multidisciplinary project involving epidemiologists and laboratory scientists
Start Year 2010