Elsevier

Vaccine

Volume 31, Issue 11, 1 March 2013, Pages 1453-1457
Vaccine

Conference report
Priorities for research on meningococcal disease and the impact of serogroup A vaccination in the African meningitis belt

https://doi.org/10.1016/j.vaccine.2012.12.035Get rights and content

Abstract

For over 100 years, large epidemics of meningococcal meningitis have occurred every few years in areas of the African Sahel and sub-Sahel known as the African meningitis belt. Until recently, the main approach to the control of these epidemics has been reactive vaccination with a polysaccharide vaccine after an outbreak has reached a defined threshold and provision of easy access to effective treatment but this approach has not prevented the occurrence of new epidemics. Meningococcal conjugate vaccines, which can prevent meningococcal carriage and thus interrupt transmission, may be more effective than polysaccharide vaccines at preventing epidemics. Because the majority of African epidemics have been caused by serogroup A meningococci, a serogroup A polysaccharide/tetanus toxoid protein conjugate vaccine (PsA–TT) has recently been developed. Results from an initial evaluation of the impact of this vaccine on meningococcal disease and meningococcal carriage in Burkina Faso have been encouraging.

To review how the research agenda for meningococcal disease in Africa has been changed by the advent of PsA–TT and to define a new set of research priorities for study of meningococcal infection in Africa, a meeting of 41 scientists was held in Dakar, Senegal on April 24th and 25th 2012. The research recommendations developed during the course of this meeting are presented in this paper.

The need for enhanced surveillance for meningitis in defined populations with good diagnostic facilities in African countries at risk of epidemics was identified as the highest priority. This is needed to determine the duration of protection against serogroup A meningococcal disease provided by PsA–TT and to determine the risk of disease and carriage caused by meningococci of other serogroups. Other research areas given high priority included identification and validation of serological correlates of protection against meningococcal disease and carriage, development of improved methods for detecting carriage and epidemiological studies aimed at determining the reasons underlying the peculiar epidemiology of meningococcal disease in the African meningitis belt. Minutes and working papers from the meeting are provided in supplementary tables and some of the presentations made at the meeting are available on the MenAfriCar consortium website (www.menafricar.org) and on the web site of the Centers for Disease Control (www.cdc.gov).

Introduction

For over 100 years, large epidemics of meningococcal meningitis have occurred every few years in countries of the Sahel and sub-Sahel, an area known as the African meningitis belt [1]. The unique epidemiology of meningococcal infection in this part of Africa includes the occurrence of epidemics every few years, which may result in tens of thousands of cases and thousands of deaths, severely disrupting routine health services. Subjects of all age may be affected but older children and young adults are the groups most at risk. Epidemics occur during the dry season, subsiding during the rainy season but sometimes recur in neighboring areas in the following dry season [2], [3], [4]. The majority of African epidemics have been caused by meningococci belonging to serogroup A but substantial outbreaks caused by meningococci belonging to serogroup C, W135 or X have also occurred [5], [6], [7].

Since the late 1970s, the main approach to epidemic control in the African meningitis belt has been reactive vaccination with a serogroup A + C or serogroup A + C + W135 polysaccharide vaccine after an outbreak has reached the World Health Organization (WHO) defined threshold [8]. When reactive vaccination is initiated early in the course of an epidemic, it can be effective in reducing morbidity and mortality but despite the administration of many millions of doses of polysaccharide vaccine over four decades, the frequency of epidemics in meningitis belt countries has not declined. This is because meningococcal polysaccharide vaccines induce only short lasting immunity, especially in infants and young children, do not induce immunological memory, may induce hyporesponsiveness when given repeatedly and, most importantly, have little or no impact on pharyngeal carriage and thus they are unable to prevent transmission [9]. Conjugate vaccines overcome many of these limitations as they are immunogenic in infants, induce immune memory and prevent transmission. Consequently conjugate vaccines are a more appropriate tool for effective prevention strategies than polysaccharide vaccines in sub-Saharan Africa as well as in other parts of the world.

Most African epidemics of meningococcal disease have been caused by meningococci belonging to serogroup A but, until recently, there was no serogroup A conjugate vaccine available for use in Africa as the quadrivalent vaccines containing a serogroup A conjugate produced by major pharmaceutical companies are too expensive for use in the poorest countries in Africa. However, in 2009, a serogroup A polysaccharide/tetanus toxoid conjugate vaccine (PsA–TT) (MenAfriVac™) was licensed in India. This vaccine was developed by the Meningitis Vaccine Project (MVP) (www.meningvax.org), a partnership between WHO and PATH working in close collaboration with the Serum Institute of India, the vaccine manufacturer [10]. In 2010, the vaccine was pre-qualified by WHO on the basis of its safety and immunogenicity and non-inferiority to a reference polysaccharide vaccine [11], a similar approach to the one adopted in Europe and North America for the licensure of other monovalent or multivalent meningococcal conjugate vaccines. At the end of 2010, immunization of the whole 1- to 29-year-old population of Burkina Faso was undertaken during a ten-day period to achieve a reduction in the circulation of the serogroup A meningococcus nationwide as quickly as possible and to directly protect the age group at highest risk of meningococcal disease [12]. Vaccination of a proportion of the 1- to 29-year-old populations of Mali and Niger was also accomplished in 2010. In 2011–2012, the remaining 1- to 29-year-old populations of Mali and Niger were vaccinated and vaccination commenced in Chad, northern Cameroon and in six states in northern Nigeria. PsA–TT will be rolled out progressively across the meningitis belt during the next four years. PsA–TT is also being evaluated in infants and, if it receives regulatory approval for use in this age group, it will be used to vaccinate new birth cohorts in meningitis belt countries and/or in catch-up campaigns.

Initial results from Burkina Faso suggest that PsA–TT has been highly effective at preventing invasive serogroup A meningococcal disease, reducing serogroup A disease by nearly 100%, eliminating district level serogroup A outbreaks [13] and causing a rapid reduction in serogroup A meningococcal carriage [14]. During the 2011 meningitis season, a few months after the 2010 PsA–TT vaccination campaign, the incidence of suspected bacterial meningitis in Burkina Faso was reduced in all age groups, including those too young or too old to have been vaccinated, suggesting an additional indirect herd effect. In the two years following the introduction of PsA–TT there have been no cases of serogroup A meningococcal disease in vaccinated subjects. The results of these studies in Burkina Faso suggest that if a high level of vaccine coverage can be achieved across the meningitis belt, PsA–TT will prevent or greatly attenuate serogroup A meningococcal epidemics in the Africa and this view is supported by preliminary data from the 2012 meningitis season with no cases of serogroup A meningococcal disease being reported from Burkina Faso, Mali or Niger where PsA–TT has been deployed. However, it should be noted that the vaccine was introduced at a time of low natural transmission of serogroup A meningococci in the central part of the meningitis belt. Despite this initial success of PsA–TT, a number of important challenges to the control of epidemic meningitis in Africa remain. These include:

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    The need for high quality data on the long term impact of PsA–TT to ensure continuing political willingness to build an effective, sustainable meningococcal vaccination strategy for Africa.

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    Determination of the mechanisms of indirect protection produced by PsA–TT.

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    Assessment of the burden of disease due to other meningococcal serogroups, as a result of serogroup replacement or natural fluctuations in the prevalence of different serogroups, and hence the potential need for a more complex conjugate vaccine for the African meningitis belt.

To develop a plan to address these challenges, a meeting of experts was held in Dakar, Senegal on April 24th and 25th 2012. This report summarizes the key conclusions from this meeting.

Section snippets

Format of the meeting

Over forty delegates, including epidemiologists, clinicians, microbiologists, immunologists, vaccinologists, molecular biologists and public health specialists attended the meeting together with representatives of the World Health Organization, research donors and non-government agencies (Supplementary Table 1). Participants were invited so as to provide representatives from the main groups concerned with the control of meningococcal disease in Africa. The meeting was supported by the Bill &

Presentations and working group discussions

A list of the speakers at the meeting and the topics of their presentations is shown in Supplementary Table 2. Minutes of the meeting, which summarize the presentations and the outcome of the discussion groups, are provided in Supplementary Table 3. Reports of the two working groups are presented in Supplementary Tables 4a and 4b. Powerpoint of presentations by some of the key speakers are available on the MenAfricar website (www.menafricar.org) and on the Centers for Disease Control website (//www.cdc.gov/

Research priorities

Based on the output of the meeting, and subsequent work by the delegates, the following research priorities were identified as key to a better understanding of meningococcal disease in the African meningitis at a time when a conjugate vaccine is being deployed.

Conclusions

Although the development and successful deployment of PsA–TT is a major achievement that is likely to have a dramatic impact on epidemic serogroup A meningococcal disease in countries of the African meningitis belt, the ways in which the meningococcus will adapt to this changing situation are uncertain. It is, therefore, important that the health authorities of affected countries and WHO (both AFRO and Geneva) recognize that despite the successful introduction of PsAA-TT, the battle against

Acknowledgments

Amit Bhasin, Karen Slater, Karen Thurley and the staff of the Lagon 1 Hotel, Dakar, Senegal are thanked for their help with the organization of the meeting which was supported by a grant from the Bill & Melinda Gates Foundation.
Authors

The following contributed to the ideas presented in this paper: Danny Altmann, Abraham Aseffa, Margaret Bash, Nicole Basta, Ray Borrow, Claire Broome, Dominique Caugant, Tom Clark, Jean-Marc Collard, Mamoudou Djingarey, David Goldblatt, Brian Greenwood, Ulla

References (16)

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