Modeling Optimal Laboratory Testing Strategies for Bacterial Meningitis Surveillance in Africa.

Since 2010, the introduction of an effective serogroup A meningococcal conjugate vaccine has led to the near-elimination of invasive Neisseria meningitidis serogroup A disease in Africa's meningitis belt. However, a significant burden of disease and epidemics due to other bacterial meningitis pathogens remain in the region. High-quality surveillance data with laboratory confirmation is important to monitor circulating bacterial meningitis pathogens and design appropriate interventions, but complete testing of all reported cases is often infeasible. Here, we use case-based surveillance data from 5 countries in the meningitis belt to determine how accurately estimates of the distribution of causative pathogens would represent the true distribution under different laboratory testing strategies. Detailed case-based surveillance data was collected by the MenAfriNet surveillance consortium in up to 3 seasons from participating districts in 5 countries. For each unique country-season pair, we simulated the accuracy of laboratory surveillance by repeatedly drawing subsets of tested cases and calculating the margin of error of the estimated proportion of cases caused by each pathogen (the greatest pathogen-specific absolute error in proportions between the subset and the full set of cases). Across the 12 country-season pairs analyzed, the 95% credible intervals around estimates of the proportion of cases caused by each pathogen had median widths of ±0.13, ±0.07, and ±0.05, respectively, when random samples of 25%, 50%, and 75% of cases were selected for testing. The level of geographic stratification in the sampling process did not meaningfully affect accuracy estimates. These findings can inform testing thresholds for laboratory surveillance programs in the meningitis belt.

Epidemiology of Bacterial Meningitis in the Nine Years Since Meningococcal Serogroup A Conjugate Vaccine Introduction, Niger, 2010-2018.

BACKGROUND: In 2010, Niger and other meningitis belt countries introduced a meningococcal serogroup A conjugate vaccine (MACV). We describe the epidemiology of bacterial meningitis in Niger from 2010 to 2018. METHODS: Suspected and confirmed meningitis cases from January 1, 2010 to July 15, 2018 were obtained from national aggregate and laboratory surveillance. Cerebrospinal fluid specimens were analyzed by culture and/or polymerase chain reaction. Annual incidence was calculated as cases per 100 000 population. Selected isolates obtained during 2016-2017 were characterized by whole-genome sequencing. RESULTS: Of the 21 142 suspected cases of meningitis, 5590 were confirmed: Neisseria meningitidis ([Nm] 85%), Streptococcus pneumoniae ([Sp] 13%), and Haemophilus influenzae ([Hi] 2%). No NmA cases occurred after 2011. Annual incidence per 100 000 population was more dynamic for Nm (0.06-7.71) than for Sp (0.18-0.70) and Hi (0.01-0.23). The predominant Nm serogroups varied over time (NmW in 2010-2011, NmC in 2015-2018, and both NmC and NmX in 2017-2018). Meningococcal meningitis incidence was highest in the regions of Niamey, Tillabery, Dosso, Tahoua, and Maradi. The NmW isolates were clonal complex (CC)11, NmX were CC181, and NmC were CC10217. CONCLUSIONS: After MACV introduction, we observed an absence of NmA, the emergence and continuing burden of NmC, and an increase in NmX. Niger's dynamic Nm serogroup distribution highlights the need for strong surveillance programs to inform vaccine policy.

Vaccine Effectiveness of Polysaccharide Vaccines Against Clinical Meningitis - Niamey, Niger, June 2015.

INTRODUCTION: In 2015, a large outbreak of serogroup C meningococcal meningitis hit Niamey, Niger, in response to which a vaccination campaign was conducted late April. Using a case-control study we measured the vaccine effectiveness (VE) of tri - (ACW) and quadrivalent (ACYW) polysaccharide meningococcal vaccines against clinical meningitis among 2-15 year olds in Niamey II district between April 28th and June 30th 2015. METHODS: We selected all clinical cases registered in health centers and conducted a household- vaccination coverage cluster survey (control group).  We ascertained vaccination from children/parent reports. Using odds of vaccination among controls and cases, we computed VE as 1-(Odds Ratio). To compute VE by day since vaccination, we simulated a density case control design randomly attributing recruitment dates to controls based on case dates of onset (3 controls per case). We calculated the number of days between vaccination and the date of onset/recruitment and computed VE by number of days since vaccination using a cubic-spline model. We repeated this simulated analysis 500 times and calculated the mean VE and the mean lower and upper bound of the 95% confidence interval (CI). RESULTS: Among 523 cases and 1800 controls, 57% and 92% were vaccinated respectively. Overall, VE at more than 10 days following vaccination was 84% (95%CI: 75-89) and 97% (94-99) for the tri- and quadrivalent vaccines respectively. VE at days 5 and 10 after trivalent vaccination was 84% (95% CI: 74-91) and 89% (95% CI: 83-93) respectively. It was 88% (95% CI: 75-94) and 95.8% (95% CI: 92 -98) respectively for the quadrivalent vaccine. CONCLUSION: Results suggest a high VE of the polysaccharide vaccines against clinical meningitis, an outcome of low specificity, and a rapid protection after vaccination. We identified no potential biases leading to VE overestimation. Measuring VE and rapidity of protection against laboratory confirmed meningococcal meningitis is needed.