During this Nm meningitis epidemic in western Burkina Faso, we found high incidences with up to 10% of children undergoing lumbar puncture for suspected meningitis. Cumulative incidence of Nm meningitis was up to 0.9%, which is an underestimate, because our surveillance started just before the peak of the epidemic, CSF specimens were tested for only about half of suspected cases, and culture and multiplex PCR testing in Burkina Faso has been reported to have only 31% sensitivity compared with nested PCR testing in a European reference laboratory [9
]. Taking into account these elements, the cumulative incidence of Nm meningitis during this epidemic may have been around 4%. Incidences varied substantially among the health centers and study villages. This observation underlines the importance of analyzing surveillance data at the health center level to fully understand the epidemic process and even to target epidemic control activities.
As a hypothetical interpretation, the difference in incidence, carriage, and seroprevalence among the 3 villages may be explained as follows: in the early phase of the epidemic, Kofila (the village with lowest incidence, situated in the middle) was protected by some unkown factor, which kept NmA carriage and transmission, and in consequence incidence, low. NmA seroprevalence in this village also remained relatively low, as the stimulus from NmA carriage lacked. Later on, this protective factor waned, NmA transmission increased, and Kofila would have become epidemic (as the slightly rising incidence of suspected cases suggests), when vaccination became effective in time to stop the process. This explanation is hypothetical, but our observation suggests in any case that high carriage prevalence is needed for an epidemic to occur. The epidemic strain had been isolated from meningitis cases throughout the Bobo-Dioulasso region since 2003 during nonepidemic conditions [10
] while being rarely found in carriage ([11, 12
]). The possibility cannot be excluded that the epidemic strain differed from the hyperendemic strain below pheno- and genotype. The great instability of meningococci is demonstrated by the finding of 4 different PFGE profiles in NmA isolates from the same carrier. These mutations may have occurred during carriage or, less likely, during culture.
To explain the surge in NmA carriage during epidemics, we previously hypothesized that some additional highly localized factor could be involved—we suggested viral respiratory tract infections [14
]. This hypothesis was based on the association of NmA carriage with upper respiratory tract infection (URTI) symptoms reported earlier from this study [15
]. The presented additional finding of a strong prospective association between flulike symptoms and visibly purulent/Nm meningitis provides new force to this hypothesis. URTI symptoms did not predict disease, but their prevalence correlated with disease incidence across villages. Flulike symptoms did not predict carriage, and their prevalence did not correlate with incidence across villages. In combination, this could indicate that widespread URTI increases NmA circulation in the population, whereas flulike disease puts individuals at risk for meningitis. The surprisingly high prevalence of URTI symptoms in our study requires additional evaluation with regard to seasonality and health impact.
Exposure to kitchen fire smoke already has been described as a risk factor for meningitis in Ghana [16
]. This possibly corresponds to facilitated invasion of meningococci via smoke-damaged mucosa, reinforcing the noxious effect of dry climate [14
Although limited by small sample size, subsequent vaccination, and probable impact of intensive NmA circulation on rSBA titers, our serological data provide some evidence for a correlate of protection in the epidemic context. The cutoff NmA rSBA titer of ≥1024 would be substantially higher than established correlates of protection, for example, against NmC in the UK population (rSBA titer ≥8) [17
]. Hypothetical explanations include differences between serogroups, avidity of natural versus vaccine-induced antibody, and population or environmental characteristics influencing effective protection by serum antibodies (hypothesis of direct nasomeningeal invasion of meningococci during the dry season in the African meningitis belt [14
]). To increase the number of observed cases, we used visibly purulent/Nm meningitis as outcome, which appears justified as all but 1 confirmed cases were due to NmA. Individuals could have acquired NmA carriage or been vaccinated after the study visit, which may have altered their rSBA titers. However, all cases but 1 occurred within 1 week after the blood draw; therefore, vaccination following the visit unlikely would have provided protection.
In high-carriage villages, NmA carriage was strongly associated with NmA rSBA titers ≥8 and to a lesser degree with titers ≥1024, suggesting that NmA carriage induces some serogroup-specific immunity, whereas high titers are determined in addition by other factors. As both NmA and NmY carriage were associated with rSBA titers ≥1024 to a similar extent in all 3 villages (NmY carriage not significantly, possibly due to fewer carriage events), carriage of other meningococcal serogroups could contribute to high titers via noncapsular elements of the bacterium.
Seroprevalence against W135 was similar to findings in Bobo-Dioulasso in 2003 [12
]. This is surprising, as in contrast to 2003, we did not find any NmW135 carriage, which may have been absent from the population for several years. The high NmY carriage prevalence in this study possibly contributed to NmW135 immunity, as suggested by the positive association between NmY carriage and NmW135 rSBA titers. The capsular sero(sub)type of the NmY carriage strains (14:P1.5,2) differed from that of the NmW135 strain used for rSBA (NT:P1.18–1,3), such that other minor antigens would play a role in this cross-reacting immunity.
Some findings are relevant for vaccine prevention. First, the observed age distribution of NmA carriage and incidence argues for conjugate vaccination during the first year of life and up to at least 29 years, to optimize indirect protection from the vaccine strategy. However, despite the NmA conjugate vaccine introduction targeting the 1- to 29-year-old population, substantial NmA transmission among older age groups may occur as soon as epidemiogenic factors are present.
As previously described for H. influenzae
type b vaccines [19
], meningococcal polysaccharide vaccine seems to diminish NmA rSBA titers during the first days following vaccination. This effect could be caused by an initial decrease in free immunoglobulin G antibody in response to antigen presentation. Interestingly, the difference between vaccinated and unvaccinated persons in our study was only seen in the 2 villages with intense NmA circulation and high rSBA seroprevalence. The clinical relevance of this rSBA reduction is not clear. An incidence reduction, not increase, was observed during the week following the mass campaign, but the small sample size does not allow this question to be evaluated.
The reported data do not show any impact of polysaccharide vaccine on NmA carriage during the first days after vaccination, which is in concordance with a recent systematic review [22
]. Finally, the high vaccine coverage among age groups outside the vaccination target is of importance for vaccination operations, as additional doses are required to achieve high coverage in the target population.
In summary, this evaluation of an NmA epidemic documented a high burden of disease in individual health centers and villages, showed high carriage prevalence of the outbreak strain in all age groups, demonstrated great variability of carriage and immunity within a small geographical zone during the epidemic, provided some evidence for an implication of URTI and flulike disease in the epidemic process, and suggested rSBA titers ≥1024 as correlate of protection against epidemic NmA disease. Other serogroups, particularly NmW135 and NmX, have epidemic potential in sub-Saharan Africa ([23
]), and the observations from an NmA epidemic will increase our understanding of meningococcal epidemiology after the introduction of NmA conjugate vaccine.