Background

Causative agent. Meningococcal meningitis is a severe acute infection of the meninges caused by the Gram-negative bacterium Neisseria meningitidis. The meningococcus is a commensal of the human nasopharyngeal mucosa that is carried by at least 10% of the population and is transmitted from person to person by upper-respiratory tract secretions. Occasionally, N. meningitidis will cross the mucosal membrane and enter the bloodstream, causing various clinical syndromes — acute meningitis is the most common. Meningitis is characterized by a sudden onset of headache, fever and neck stiffness. Despite treatment, at least 10% of patients die within 1 or 2 days of onset and 10–20% of survivors develop significant neurological sequelae. Meningococci remain highly susceptible to penicillin, which is the drug of choice for treatment, although a single dose of oily chloramphenicol is often a preferred alternative in outbreaks. Although 13 serogroups of meningococcus have been identified, only five (A, B, C, W135 and Y) account for nearly all reported disease1,2,3.

Distribution. More than 700,000 meningitis cases were reported to the WHO between 1995 and 2003. Ninety percent of cases occurred in sub-Saharan Africa's 'meningitis belt' (Fig. 1), a savannah region extending from Senegal to Ethiopia with a total population of 400 million. Epidemic disease occurs in the dry season, when the nasopharynx is exposed to extreme heat, dryness and dust. Annual incidence rates can reach 1,000 cases per 100,000 population (1%). During 1996–1997 more than 250,000 cases and 25,000 deaths were reported in this area. In comparison, annual reported incidence in developed countries ranges from 1 to 3 cases per 100,000 population2,4,5,6.

Figure 1
figure 1

Incidence of reported meningitis among total population, 1995–2003.

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Current global status. Serogroup A meningococcus is the main cause of epidemic meningitis in sub-Saharan Africa. However, serogroup C meningococcus has been isolated from some epidemics and serogroup W135 was recently identified as the main pathogen during a 2002 outbreak in Burkina Faso. This epidemic followed cases of W135 meningitis among Hajj pilgrims and their contacts in 2001–2002 (Refs 4,5, 7–9).

Although serogroups A and C predominate in Asia and Africa, serogroups B and C are responsible for most cases in Europe and the Americas. Serogroup B epidemics have developed gradually and persisted for a decade or more in Europe, the United States, Central and South America, and New Zealand. Since the mid-1990s, there has been an increase in serogroup Y meningitis in the United States and Europe. Recently, several outbreaks of serogroup C have been reported in Canada, the United States, Spain and the United Kingdom.

Recent developments

New basic knowledge. Serological methods have been used to classify meningococci according to antigenic variation of the capsular polysaccharide (serogroup) and of the outer membrane proteins (serotypes and subtypes). Recently, analytical tools have been developed that allow more accurate global monitoring of strains. Among them, multilocus enzyme electrophoresis (MLEE) and multilocus sequence typing (MLST) enable genetic grouping of meningococci into clone complexes that are associated with different epidemiological patterns. In the future, DNA microarray technology might become the standard for molecular typing3,7,8.

New tools and interventions. Current meningococcal polysaccharide vaccines are poorly immunogenic in infants, fail to induce immunological memory and have little effect on colonization1,10,11. Consequently, the recommended WHO strategy for epidemic control in hyperendemic countries is based on detecting, confirming and vaccinating at-risk populations, while improving case management. The development of conjugate vaccines (capsular polysaccharides conjugated to protein antigens) offers hope for a more effective prevention strategy. Effective conjugate C vaccines have been introduced in Europe for the prevention of serogroup C disease. These vaccines were found to be immunogenic in infants, to induce immunological memory and to decrease carriage such that non-vaccinees were protected (herd immunity)12. Several vaccine manufacturers are developing multivalent A/C/W135/Y meningococcal conjugate vaccines. Hopefully, when delivered in early infancy, these polyvalent conjugate vaccines will not need additional booster doses12. Design of a vaccine against serogroup B meningococci has proven difficult, but vaccines based on outer membrane vesicles (OMV) have been successfully used to control outbreaks in Cuba, Brazil, Chile and Norway, and are currently under trial in New Zealand13.

New strategies, policies and partnerships. New initiatives aim at improving access to vaccines. The Meningitis Vaccine Project (MVP), a partnership between the WHO and PATH, was created in 2001 with support from the Bill & Melinda Gates Foundation with the goal of eliminating meningococcal epidemics in sub-Saharan Africa through the development and use of conjugate vaccines14. MVP is developing a meningococcal A conjugate vaccine at a target price of US$0.40 per dose. Clinical trials will begin in 2005 and it is expected to be licensed in 2008–2009 for use in routine infant immunization and 'catch-up' campaigns. Until then, countries must optimize their use of current vaccines. Emergency access to vaccines is coordinated by an international group that was established after the 1996–1997 African epidemics. More recently, the WHO initiated a public–private partnership to produce an affordable A/C/W135 meningococcal polysaccharide vaccine for use in epidemic response and established an emergency vaccine stockpile for use in future epidemics. Similarly, the current OMV group B vaccine being tested in New Zealand was developed as a public–private partnership13.

Conclusions and future outlook

The successful introduction of a meningococcal C conjugate vaccine in the United Kingdom has given new hope that epidemic meningitis in Africa can be prevented with the use of appropriate conjugate vaccines. The creation of innovative partnerships has facilitated the development of new products that will result in more effective preventive strategies.