Ongoing diphtheria outbreak in Yemen: a cross-sectional and genomic epidemiology study

Autor: Badell Edgar, Alharazi Abdulilah, Criscuolo Alexis, Almoayed Khaled Abdullah Ali, Lefrancq Noémie, Bouchez Valerie, Guglielmini Julien, Hennart Melanie, Carmi-Leroy Annick, Zidane Nora, Pascal-Perrigault Marine, Lebreton Manon, Martini Helena, Salje Henrik, Toubiana Julie, Dureab Fekri, Dhabaan Ghulam, Brisse Sylvain, NCPHL diphtheria outbreak working group
Přispěvatelé: Lefrancq, Noemie [0000-0001-5991-6169], Salje, Henrik [0000-0003-3626-4254], Apollo - University of Cambridge Repository, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Centre national de Référence des Corynebactéries du Complexe Diphtheriae - National Reference Center Corynebacteria of the diphtheriae complex (CNR), National Centre of the Public Health Laboratories [Sana'a, Yemen], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Ministry of Public Health and Population [Sana'a, Yemen], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Collège Doctoral, Sorbonne Université (SU), Vrije Universiteit Brussel (VUB), University of Cambridge [UK] (CAM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Akkon University of Human Sciences - Akkon Hochschule für Humanwissenschaften [Berlin, Allemagne], Universität Heidelberg [Heidelberg] = Heidelberg University, University of Toronto, This work was supported financially by institutional funding from the NCPHL (Sana'a, Yemen) and Institut Pasteur. The French National Reference Center for Corynebacteria of the diphtheriae complex received support from Institut Pasteur and Public Health France (Santé publique France, Saint Maurice, France). This work was also supported financially by the French Government Investissement d'Avenir Programme Laboratoire d'Excellence, Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID)., NCPHL diphtheria outbreak working group (Abdulaziz A Rawah, Mohammed A Aldawla, Ekram M Al­Awdi, Nabila M Al­Moalmy, Huda Z Al­Shami, Ali A Al­Somainy), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Department of Clinical Microbiology, Brussels Heritage Lab, Supporting clinical sciences, Microbiology and Infection Control, Clinical Biology, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Universität Heidelberg [Heidelberg]
Rok vydání: 2021
Předmět:
Zdroj: The Lancet Microbe
The Lancet Microbe, 2021, ⟨10.1016/s2666-5247(21)00094-x⟩
The Lancet Microbe, Elsevier, 2021, ⟨10.1016/s2666-5247(21)00094-x⟩
ISSN: 2666-5247
DOI: 10.1016/s2666-5247(21)00094-x⟩
Popis: 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 diphtheriaewas 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,toxgene and species-specificrpoBreal-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 The Yemen diphtheria outbreak affected almost all governorates (provinces), with 5701 probable cases and 330 deaths recorded up to April 26, 2020. We collected clinical data for 888 probable cases with throat swab samples referred for biological confirmation, and genomic data for 42 positive cases, corresponding to 43 isolates (two isolates from one culture were included due to distinct colony morphologies). The median age of patients was 12 years (range 0·2–80). The proportion of cases in children aged 0–4 years was reduced during the second time period, after a vaccination campaign, compared with the first period (19% [95% CI 18–21] in the first periodvs14% [12–15] in the second period, pC diphtheriaephylogenetic sublineages, four of which are genetically related to isolates from Saudi Arabia, Eritrea, and Somalia. Inter-sublineage genomic variations in genes associated with antimicrobial resistance, iron acquisition, and adhesion were observed. The predominant sublineage (30 [70%] of 43 isolates) was resistant to trimethoprim and was associated with unique genomic features, more frequent neck swelling (p=0·0029) and a younger age of patients (p=0·060) compared with the other sublineages. Its evolutionary rate was estimated at 1·67 × 10−6substitutions per site per year, placing its most recent common ancestor in 2015, and indicating silent circulation ofC diphtheriaein Yemen before the outbreak was declared. Interpretation In the Yemen outbreak,C diphtheriaeshows 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.
Databáze: OpenAIRE
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