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.

Improving Case-Based Meningitis Surveillance in 5 Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet consortium was established in 2014 to support implementation of case-based meningitis surveillance in 5 countries in the meningitis belt of sub-Saharan Africa: Burkina Faso, Chad, Mali, Niger, and Togo. Assessing surveillance performance is critical for interpretation of the collected data and implementation of future surveillance-strengthening initiatives. METHODS: Detailed epidemiologic and laboratory data were collected on suspected meningitis cases through case-based meningitis surveillance in participating districts in 5 countries. Performance of case-based surveillance was evaluated through sensitivity of case ascertainment in case-based versus aggregate meningitis surveillance and an analysis of surveillance indicators. RESULTS: From 2015 to 2017, 18 262 suspected meningitis cases were identified through case-based surveillance and 16 262 were identified through aggregate surveillance, for a case ascertainment sensitivity of 112.3%. Among suspected cases, 16 885 (92.5%) had a cerebrospinal fluid (CSF) specimen collected, 13 625 (80.7%) of which were received at a national reference laboratory. Among these, 13 439 (98.6%) underwent confirmatory testing, and, of those tested, 4371 (32.5%) were confirmed for a bacterial pathogen. CONCLUSIONS: Overall strong performance for case ascertainment, CSF collection, and laboratory confirmation provide evidence for the quality of MenAfriNet case-based surveillance in evaluating epidemiologic trends and informing future vaccination strategies.

Epidemiological changes in meningococcal meningitis in Niger from 2008 to 2011 and the impact of vaccination.

BACKGROUND: The epidemiology of bacterial meningitis in the African 'meningitis belt' changes periodically. In order to design an effective vaccination strategy, we have examined the epidemiological and microbiological patterns of bacterial meningitis, and especially that of meningococcal meningitis, in Niger during the period 2008-2011. During this period a mass vaccination campaign with the newly developed meningococcal A conjugate vaccine (MenAfriVac®) was undertaken. METHOD: Cerebrospinal fluid samples were collected from health facilities throughout Niger and analysed by culture, seroagglutination and/or speciation polymerase chain reaction, followed by genogrouping PCR for Neisseria meningitidis infections. A sample of strains were analysed by multi-locus sequence typing. RESULTS: N. meningitidis serogroup A cases were prevalent in 2008 and 2009 [98.6% and 97.5% of all N. meningitidis cases respectively]. The prevalence of serogroup A declined in 2010 [26.4%], with the emergence of serogroup W Sequence Type (ST) 11 [72.2% of cases], and the serogroup A meningococcus finally disappeared in 2011. The geographical distribution of cases N. meningitidis serogroups A and W within Niger is described. CONCLUSION: The substantial decline of serogroup A cases that has been observed from 2010 onwards in Niger seems to be due to several factors including a major polysaccharide A/C vaccination campaign in 2009, the introduction of MenAfriVac® in 10 districts at risk in December 2010, the natural dynamics of meningococcal infection and the persistence of serogroup A sequence-type 7 for about 10 years. The emergence of serogroup W strains suggests that there may be a need for serogroup W containing vaccines in Niger in the coming years.

First occurrence of Rift Valley fever outbreak in Niger, 2016.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis causing abortions and high mortality among animals, whereas in humans, the disease is usually mild or asymptomatic. In September 2016, the Republic of Niger declared the first RVF outbreak in the northern region of Tahoua near the Malian border. This study describes the outbreak and reports the results of serological and molecular investigations of the human and animal samples collected. Serum samples from both human and animal suspected cases have been confirmed at the Centre de Recherche Médicale et Sanitaire (CERMES) and the Laboratoire Centrale d'Elevage (LABOCEL) public health and animal reference laboratories, respectively. Techniques for biological confirmation were real time reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). Phylogenetic trees were established after genetic sequencing of the small and medium segments of the RVF virus (RVFV) genome. Out of the 399 human samples collected, 17 (4.3%) were confirmed positive for RVFV. Overall, 33 (8.3%) deaths occurred out of which five (29%) were among the 17 confirmed cases. Regarding animals, 45 samples were tested, three of which were RT-PCR positive and 24 were IgG positive. The phylogenetic analyses showed that the Niger strains clustered with Senegal 2013 and Mauritania 2015 RVFV strains. This first outbreak of RVF was very challenging for public and animal health laboratories in Niger. Besides resulting in human deaths, important loss of cattle has been reported. Therefore, vigilance has to be strengthened emphasising vector control strategies and active surveillance among animals.

Bacterial meningitis in Niger: an analysis of national surveillance data, 2003-2015.

INTRODUCTION: Bacterial meningitis (BM) is one of the most severe infectious disease in Niger republic. To best describe the trends of BM disease, meningitis surveillance data from the Centre de Recherche Medicale et Sanitaire (CERMES) and the Direction of Surveillance and Response to Epidemics (DSRE) were reviewed and analyzed. METHODS: Data on number of notified cases of BM and on pathogens were analyzed during 2003-2015. Excel 2013 was used for trend analysis on the etiology of BM prevalence and incidence. RESULTS: A total of 10051 cerebrospinal fluid (CSF) samples collected were confirmed by laboratory methods. The main etiologies of meningitis detected were N. meningitidis (82.1%), S. pneumonia (12.1%) and H. influenza (3.4%). N. meningitidis mostly affected children in the age groups of 5-9 years (32.9%) and 10-14 years (24.9%) with respective mean incidence of 14.9 and 11.3. The percentage estimate of N. meningitidis serogroup A (NmA) meningitis fell to 0% in 2015 while during the same year that of N. meningitidis serogroup C (NmC) and N. meningitidis serogroup W (NmW) reached 82.9% and 17% respectively. CONCLUSION: Overall, the epidemiological trends of the BM in Niger were dynamic. The emergence of NmC strains suggests that there may be an urgent need for serogroup C containing vaccines in Niger in the coming years.

Outbreak of Hepatitis E Virus Infection in Displaced Persons Camps in Diffa Region, Niger, 2017.

Hepatitis E virus (HEV) infection in developing countries is associated with poor hygiene, lack of clean drinking water, and inadequate sanitation. In this study, we report the first case investigation and describe the present situation of HEV outbreak within displaced persons camps in the Diffa region, Republic of Niger. The investigation showed the outbreak to be closely linked to unclean water supply, low hygiene, and sanitation facility standards. Between January and September 2017, a total of 1,917 HEV suspect cases were recorded from which 736 (38.4%) have been confirmed positive for HEV by reverse transcription polymerase chain reaction and enzyme linked immunosorbent assay. Overall, 38 (1.9%) deaths were recorded, including 17 (44.7%) pregnant women. The ongoing outbreak highlights poor drinking water quality and sanitation conditions in displaced persons camps in the Diffa region. Disease containment and patient care activities, particularly for pregnant women, may have resulted in decreased transmission of infection and deaths.

Case-fatality rate during a measles outbreak in eastern Niger in 2003.

BACKGROUND: The World Health Organization (WHO) estimates that the case-fatality rate (CFR) for measles in West Africa is 4%-6%. In Niger, 50,138 measles cases and 201 deaths (CFR, 0.4%) were reported in 2003. We conducted an investigation to determine the epidemiology and the true CFR of measles in the Mirriah district in Niger. METHODS: Twenty-two villages from the Mirriah district that reported measles cases in 2003 were included in the investigation. A comprehensive household search for measles cases and deaths was conducted, and serum samples from 12 villages were collected for laboratory confirmation. A measles case was defined as illness characterized by fever, rash, and either cough, coryza, or conjunctivitis, with rash onset during the period from 1 January 2003 to 15 April 2003. Deaths occurring within 30 days after rash onset were attributed to measles unless they were obviously due to other causes. RESULTS: Measles was confirmed serologically in all villages from which samples were collected. Of 945 case patients identified, 900 (95.2%) were aged <15 years, 114 (12.3%) were vaccinated, and 789 (83.5%) sought treatment at a health care facility. A total of 92 deaths were attributed to measles (CFR, 9.7%; 95% confidence interval, 7.9%-11.5%). The CFR was highest in infants aged <1 year (15.6%). Households with >or=2 case patients had a higher CFR (10.8%) than that of households with only 1 case patient (6.0%). Households consisting of >or=8 members had a CFR of 12.8%, whereas the CFR of smaller households was 7.1%. CONCLUSIONS: This investigation suggests that the measles CFR in the Mirriah district may be 2-fold higher than the WHO regional estimate and 20-fold higher than the estimate derived from routine surveillance. Reducing measles mortality in Niger will require wide-age-range vaccination campaigns, improvement in routine immunization services, and periodic "follow-up" campaigns.

Emergence of epidemic Neisseria meningitidis serogroup C in Niger, 2015: an analysis of national surveillance data.

BACKGROUND: To combat Neisseria meningitidis serogroup A epidemics in the meningitis belt of sub-Saharan Africa, a meningococcal serogroup A conjugate vaccine (MACV) has been progressively rolled out since 2010. We report the first meningitis epidemic in Niger since the nationwide introduction of MACV. METHODS: We compiled and analysed nationwide case-based meningitis surveillance data in Niger. Cases were confirmed by culture or direct real-time PCR, or both, of cerebrospinal fluid specimens, and whole-genome sequencing was used to characterise isolates. Information on vaccination campaigns was collected by the Niger Ministry of Health and WHO. FINDINGS: From Jan 1 to June 30, 2015, 9367 suspected meningitis cases and 549 deaths were reported in Niger. Among 4301 cerebrospinal fluid specimens tested, 1603 (37·3%) were positive for a bacterial pathogen, including 1147 (71·5%) that were positive for N meningitidis serogroup C (NmC). Whole-genome sequencing of 77 NmC isolates revealed the strain to be ST-10217. Although vaccination campaigns were limited in scope because of a global vaccine shortage, 1·4 million people were vaccinated from March to June, 2015. INTERPRETATION: This epidemic represents the largest global NmC outbreak so far and shows the continued threat of N meningitidis in sub-Saharan Africa. The risk of further regional expansion of this novel clone highlights the need for continued strengthening of case-based surveillance. The availability of an affordable, multivalent conjugate vaccine may be important in future epidemic response. FUNDING: MenAfriNet consortium, a partnership between the US Centers for Disease Control and Prevention, WHO, and Agence de Médecine Preventive, through a grant from the Bill & Melinda Gates Foundation.