Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010-2018.

Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger. As a national reference laboratory for meningitis, Centre de Recherche Médicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010-2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010-2012) and after (2016-2018) PCV13 introduction. During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010-12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016-18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged ≥ 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged ≥ 5 years, but not among those < 5 years. VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance.

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.

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.

Development of Real-Time PCR Methods for the Detection of Bacterial Meningitis Pathogens without DNA Extraction.

Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are the lead causes of bacterial meningitis. Detection of these pathogens from clinical specimens using traditional real-time PCR (rt-PCR) requires DNA extraction to remove the PCR inhibitors prior to testing, which is time consuming and labor intensive. In this study, five species-specific (Nm-sodC and -ctrA, Hi-hpd#1 and -hpd#3 and Sp-lytA) and six serogroup-specific rt-PCR tests (A, B, C, W, X, Y) targeting Nm capsular genes were evaluated in the two direct rt-PCR methods using PerfeCTa and 5x Omni that do not require DNA extraction. The sensitivity and specify of the two direct rt-PCR methods were compared to TaqMan traditional rt-PCR, the current standard rt-PCR method for the detection of meningitis pathogens. The LLD for all 11 rt-PCR tests ranged from 6,227 to 272,229 CFU/ml for TaqMan, 1,824-135,982 for 5x Omni, and 168-6,836 CFU/ml for PerfeCTa. The diagnostic sensitivity using TaqMan ranged from 89.2%-99.6%, except for NmB-csb, which was 69.7%. For 5x Omni, the sensitivity varied from 67.1% to 99.8%, with three tests below 90%. The sensitivity of these tests using PerfeCTa varied from 89.4% to 99.8%. The specificity ranges of the 11 tests were 98.0-99.9%, 97.5-99.9%, and 92.9-99.9% for TaqMan, 5x Omni, and PerfeCTa, respectively. PerfeCTa direct rt-PCR demonstrated similar or better sensitivity compared to 5x Omni direct rt-PCR or TaqMan traditional rt-PCR. Since the direct rt-PCR method does not require DNA extraction, it reduces the time and cost for processing CSF specimens, increases testing throughput, decreases the risk of cross-contamination, and conserves precious CSF. The direct rt-PCR method will be beneficial to laboratories with high testing volume.