Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Haemophilus influenzae Type b.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Meningitis and Pneumonia Hospitalizations in Children aged <5 Years in Senegal, 2010-2016.

BACKGROUND: Senegal introduced a 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, given at 6, 10, and 14 weeks of age. We document trends of meningitis and pneumonia after the PCV13 introduction. METHODS: From October 2010-October 2016, hospitalization data for clinical meningitis and pneumonia in children aged <5 years were collected from logbooks at a large, tertiary, pediatric hospital in Dakar. We used a set of predetermined keywords to define hospitalizations for extraction from hospital registers. We conducted a time-series analysis and compared hospitalizations before and after the PCV13 introduction, accounting for seasonality. The initial PCV13 uptake period (October 2013-September 2014) was considered to be transitional and was excluded. RESULTS: Over the 7-year period, 1836 and 889 hospitalizations with a discharge diagnosis of pneumonia and meningitis, respectively, occurred in children aged <5 years. In children aged <12 months, a small, significant reduction in pneumonia was observed post-PCV13 (-3.8%, 95% confidence interval [CI] -1.5 to -5.9%). No decline was observed among children aged 12-59 months (-0.7%, 95% CI -0.8 to 2.2%). Meningitis hospitalizations remained stable for children aged <12 months (1.8%, 95% CI -0.9 to 4.4%) and 12-59 months (-0.5%, 95% CI -3.6 to 2.6%). CONCLUSIONS: We used data from 1 hospital to detect a small, significant reduction in all-cause pneumonia hospitalizations 2 years post-PCV13 introduction in infants; the same trend was not measurable in children aged 12-59 months or in meningitis cases. There is a need for continued surveillance to assess the long-term impact of sustained PCV13 use and to monitor how pneumococcus is causing disease in the meningitis belt.

Changes in the Molecular Epidemiology of Pediatric Bacterial Meningitis in Senegal After Pneumococcal Conjugate Vaccine Introduction.

BACKGROUND: Bacterial meningitis is a major cause of mortality among children under 5 years of age. Senegal is part of World Health Organization-coordinated sentinel site surveillance for pediatric bacterial meningitis surveillance. We conducted this analysis to describe the epidemiology and etiology of bacterial meningitis among children less than 5 years in Senegal from 2010 and to 2016. METHODS: Children who met the inclusion criteria for suspected meningitis at the Centre Hospitalier National d'Enfants Albert Royer, Senegal, from 2010 to 2016 were included. Cerebrospinal fluid specimens were collected from suspected cases examined by routine bacteriology and molecular assays. Serotyping, antimicrobial susceptibility testing, and whole-genome sequencing were performed. RESULTS: A total of 1013 children were admitted with suspected meningitis during the surveillance period. Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus accounted for 66% (76/115), 25% (29/115), and 9% (10/115) of all confirmed cases, respectively. Most of the suspected cases (63%; 639/1013) and laboratory-confirmed (57%; 66/115) cases occurred during the first year of life. Pneumococcal meningitis case fatality rate was 6-fold higher than that of meningococcal meningitis (28% vs 5%). The predominant pneumococcal lineage causing meningitis was sequence type 618 (n = 7), commonly found among serotype 1 isolates. An ST 2174 lineage that included serotypes 19A and 23F was resistant to trimethoprim-sulfamethoxazole. CONCLUSIONS: There has been a decline in pneumococcal meningitis post-pneumococcal conjugate vaccine introduction in Senegal. However, disease caused by pathogens covered by vaccines in widespread use still persists. There is need for continued effective monitoring of vaccine-preventable meningitis.

Impact of rotavirus vaccine on acute gastroenteritis in children under 5 years in Senegal: Experience of sentinel site of the Albert Royer Children's Hospital in Dakar.

BACKGROUND: Acute gastroenteritis (AGE) is a leading cause of morbidity and mortality among children <5 years of age in developing countries, with rotavirus being the most common infectious etiology. In November 2014, monovalent rotavirus vaccine was introduced in Senegal. We determined the impact of rotavirus vaccine on hospitalizations for all-cause and rotavirus related AGE in children <60 months of age. METHODS: We examined two data sources from the national referral hospital. Using sentinel surveillance data from March 2011 to February 2017, we examined the proportion of AGE hospitalizations among children <60 months of age attributable to rotavirus, stratified by age groups (0-11, 12-23 and 24-59 months). Using pediatric logbook data from March 2010 to February 2017, we examined the proportion of all childhood hospitalizations attributable to AGE, among the same age groups. RESULTS: In sentinel surveillance, 673 patients <60 months were hospitalized for AGE, with 30% (203/673) due to rotavirus. In pre-vaccine years, the median proportion of rotavirus-positive hospitalizations was 42%; this proportion declined by 76% to 10% rotavirus positive in 2015-2016 (p < .001) and by 59% to 17% in 2016-2017 (p < .001). From the logbook data, among all children <60 months, a median of 11% of all hospitalizations in the pre-vaccine period were due to AGE, with 2015-2016 seeing a 16% decline (p < .001), to 9% of all hospitalizations, and 2016-2017 seeing a 39% decline (p < .001), to 7% of all hospitalizations. Declines in both rotavirus-associated and all-cause AGE hospitalizations were most marked among infants, with a suggestion of herd effect among older children seen in the surveillance data. CONCLUSION: Rotavirus vaccine demonstrated a significant impact on rotavirus-associated hospitalizations and all-cause AGE hospitalizations in the first two seasons after vaccine introduction in Senegal. Our data support the continued use of this vaccine in national immunization program.