Phenotypic and genotypic characterization of meningococcal isolates in Tunis, Tunisia: High diversity and impact on vaccination strategies

Abstract

Objectives: The aim of this study was to characterize Neisseria meningitidis (Men) isolates in Tunisian paediatric patients with invasive meningococcal disease (IMD) in order to target therapeutic and preventive strategies. Methods: Fifty-nine isolates of Men and four cerebrospinal fluid samples that were culture-negative but Men-positive by PCR (NC-MenPPCR) (2009–2016) were collected from IMD patients. Isolates were analysed for their antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to characterize isolates and multilocus sequence typing for NC-MenPPCR. Coverage of Men serogroup B (MenB) was determined by Genetic Meningococcal Antigen Typing System (gMATS) and fHbp expression by ELISA. Results: MenB was the predominant type (88.9%). The majority of isolates (81%) had reduced susceptibility to penicillin G with altered penA alleles. The clonal complex CC461 (27.1%) was the most frequent. Among the MenB vaccine targets neisserial heparin binding antigen (NHBA) and fHbp, the predominant variants were NHBA118 (30.8%) and fHbp peptide 47 (25%), respectively. The nadA gene was present in 17.3% of isolates. Using gMATS, 36.5% of MenB were predicted to be covered by the 4CMenB vaccine. ELISA showed that 92.4% of the MenB were expected to be killed by anti-fHbp antibodies. Conclusions: MenB was the leading serogroup in IMD, and more than 90% had a sufficient level of fHbp expression for vaccine coverage. The study results will be useful for the Tunisian vaccination programme. Keywords: Invasive meningococcal disease, Neisseria meningitidis serogroup B, Whole-genome sequencing, Meningococcal vaccine, fHbp expression, Tunisia