Ongoing diphtheria outbreak in Yemen: a cross-sectional and genomic epidemiology study
Edgar Badell, Abdulilah Alharazi, Alexis Criscuolo, Khaled Abdullah Almoayed, Noémie Lefrancq, Valérie Bouchez, Julien Guglielmini, Mélanie Hennart, Annick Carmi–Leroy, Nora Zidane, Marine Pascal-Perrigault, Manon Lebreton, Helena Martini, Henrik Salje, Julie Toubiana, Fekri Dureab, Ghulam Dhabaan, Sylvain Brisse, Abdulaziz A Rawah, Mohammed A Aldawla, Ekram M Al-Awdi, Nabila M Al-Moalmy, Huda Zaid Al-Shami, Ali Abdullah Al-Somainy
Abstract
BACKGROUND: An outbreak of diphtheria, declared in Yemen in October, 2017, is ongoing. We did a cross-sectional study to investigate the epidemiological, clinical, and microbiological features of the outbreak. METHODS: Probable cases of diphtheria that were defined clinically and recorded through a weekly electronic diseases early warning system (from 2017, week 22, to 2020, week 17) were used to identify trends of the outbreak (we divided the epidemic into three time periods: May 29, 2017, to June 10, 2018; June 11, 2018, to June 3, 2019; and June 4, 2019, to April 26, 2020). We used the line list of diphtheria reports for governorate-level descriptions. Vaccination coverage was estimated using the 2017 and 2018 annual reports by the national Expanded Programme on Immunization. To confirm cases biologically, Corynebacterium diphtheriae was isolated and identified from throat swabs using standard microbiological culture and identification procedures. We assessed differences in the temporal and geographical distributions of cases, including between different age groups. For in-depth microbiological analysis, tox gene and species-specific rpoB real-time PCR, Illumina genomic sequencing, antimicrobial susceptibility analysis (disk diffusion, E-test), and the Elek diphtheria toxin production test were done on confirmed cases. We used genomic data for phylogenetic analyses and to estimate the nucleotide substitution rate. FINDINGS: substitutions per site per year, placing its most recent common ancestor in 2015, and indicating silent circulation of C diphtheriae in Yemen before the outbreak was declared. INTERPRETATION: In the Yemen outbreak, C diphtheriae shows high phylogenetic, genomic, and phenotypic variation. Laboratory capacity and real-time microbiological monitoring of diphtheria outbreaks need to be scaled up to inform case management and transmission control of diphtheria. Catch-up vaccination might have provided some protection to the targeted population (children aged 0-4 years). FUNDING: National Centre of the Public Health Laboratories (Yemen), Institut Pasteur, and the French Government Investissement d'Avenir Programme. TRANSLATION: For the Arabic translation of the abstract see Supplementary Materials section.