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

Abstract

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.

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review

“…More recently, a commercial TaqMan Array card has been developed that can detect multiple meningitis-associated pathogens [47] . This assay was tested in CSF samples originating from West Africa and results indicated that diverse infectious aetiological agents were present.…”

Toward Establishing Integrated, Comprehensive, and Sustainable Meningitis Surveillance in Africa to Better Inform Vaccination Strategies

“…Although data collected through all these surveillance programs were used to support the implementation of vaccines and monitor vaccine impact, there remain large gaps in the understanding of meningitis across most African countries, particularly beyond early childhood and the 3 main bacterial pathogens (pneumococcus, meningococcus and H. influenzae ) [ 30 ].…”

Impact of a Rapid Diagnostic Meningitis/Encephalitis Panel on Antimicrobial Use and Clinical Outcomes in Children

“…More recent data show that the global incidence of meningitis increased from 2.5 million cases in 1990 to 2.82 million cases in 2016, with the highest rates found in sub-Saharan African countries, also known as the meningitis belt [ 4 ]. Kwambana-Adams et al published the prevalence of bacterial, viral and parasitic infection in children younger than 5 years of age in West Africa following the rollout of conjugate vaccines against pneumococcus (PVC), meningococcus (MenAfriVac) and Haemophilus influenzae [ 5 ]. Escherichia coli (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%), were the most prevalent etiologies of meningitis in this age group.…”