A Brik1, A Terrade2, E Hong2, A Deghmane2, M K Taha2, A Bouafsoun3, M Khmiri4, K Boussetta5, S Boukhir6, N Ben Jaballah7, A Kechrid3, H Smaoui8. 1. University of Tunis El Manar, Children's Hospital of Tunis, Laboratory of Microbiology, LR18ES39, Beb Saadoun, 1007 Tunis, Tunisia; Institut Pasteur, Invasive Bacterial Infections Unit, 25-28 Rue du Docteur Roux, 75015 Paris, France. 2. Institut Pasteur, Invasive Bacterial Infections Unit, 25-28 Rue du Docteur Roux, 75015 Paris, France. 3. University of Tunis El Manar, Children's Hospital of Tunis, Laboratory of Microbiology, LR18ES39, Beb Saadoun, 1007 Tunis, Tunisia. 4. Department of Paediatrics A, Children's Hospital of Tunis, Beb Saadoun, 1007 Tunis, Tunisia. 5. Department of Paediatrics B, Children's Hospital of Tunis, Beb Saadoun, 1007 Tunis, Tunisia. 6. Department of Paediatrics C, Children's Hospital of Tunis, Beb Saadoun, 1007 Tunis, Tunisia. 7. Intensive Care Unit, Béchir Hamza Children's Hospital of Tunis, Beb Saadoun, 1007 Tunis, Tunisia. 8. University of Tunis El Manar, Children's Hospital of Tunis, Laboratory of Microbiology, LR18ES39, Beb Saadoun, 1007 Tunis, Tunisia. Electronic address: hanen.smaoui@gmail.com.
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.
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 IMDpatients. 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.