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

Badell, Edgar; Alharazi, Abdulilah; Criscuolo, Alexis; Almoayed, Khaled Abdullah; Lefrancq, Noémie; Bouchez, Valérie; Guglielmini, Julien; Hennart, Mélanie; Carmi–Leroy, Annick; Zidane, Nora; Pascal-Perrigault, Marine; Lebreton, Manon; Martini, Helena; Salje, Henrik; Toubiana, Julie; Dureab, Fekri; Dhabaan, Ghulam; Brisse, Sylvain; Rawah, Abdulaziz A; Aldawla, Mohammed A; Al-Awdi, Ekram M; Al-Moalmy, Nabila M; Al-Shami, Huda Zaid; Al-Somainy, Ali Abdullah

doi:10.1016/s2666-5247(21)00094-x

Cited by 33 publications

(40 citation statements)

References 21 publications

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“…While this work was in progress, additional C. diphtheriae genomes were published from Austria [27], the USA [23], Yemen [9], France [11], Spain [28] and India [29]. We included these 162 genomes in a joint phylogenetic analysis with the 440 above genomes (Figure…”

Section: Isolates and Outbreak Sets Included In The Studymentioning

confidence: 99%

“…The allele call rate of the cgMLST scheme loci was determined using posteriorly published genomes from Austria [27], the USA [23], Yemen [9], France [11], Spain [28] and India [29] and was found to be 98.6%  1.5%. We also calculated the call rate using 337 additional, prospectively collected genome sequences from the French NRC for diphtheria (unpublished).…”

Section: Definition and Evaluation Of A Cgmlst Scheme For Genotyping Isolates Of C Diphtheriae C Belfantii And C Rouxiimentioning

confidence: 99%

“…In these settings, transmission is rare and only small clusters of patients or carriers are observed [5,6]. Differently, in settings where public health action is disrupted and vaccination coverage has decreased, several large outbreaks of diphtheria in its typical clinical form have occurred in recent years [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Cryptic cluster 3 involved two strains from Brazil, which were isolated in 1981 and 1993. Finally, we also revisited the clades defined in a recent study of the isolates from the large diphtheria outbreak in Yemen and found 13 groups, one of which (genetic cluster 217) corresponded to the predominant Yemen sublineage A.1.1, which was estimated to have originated in March 2015[9].…”

mentioning

confidence: 98%

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Genomic epidemiology and strain taxonomy ofCorynebacterium diphtheriae

Guglielmini

Hennart

Badell

et al. 2021

Preprint

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Background: Corynebacterium diphtheriae is highly transmissible and can cause large diphtheria outbreaks where vaccination coverage is insufficient. Sporadic cases or small clusters are observed in high-vaccination settings. The phylogeography and short timescale evolution of C. diphtheriae are not well understood, in part due to a lack of harmonized analytical approaches of genomic surveillance and strain tracking. Methods: >We combined 1,305 genes with highly reproducible allele calls into a core genome multilocus sequence typing (cgMLST) scheme. We analyzed cgMLST genes diversity among 602 isolates from sporadic clinical cases, small clusters or large outbreaks. We defined sublineages based on the phylogenetic structure within C. diphtheriae and strains based on the highest number of cgMLST mismatches within documented outbreaks. We performed time-scaled phylogenetic analyses of major sublineages. Results: The cgMLST scheme showed high allele call rate in C. diphtheriae and the closely related species C. belfantii and C. rouxii. We demonstrate its utility to delineate epidemiological case clusters and outbreaks using a 25 mismatches threshold, and reveal a number of cryptic transmission chains, most of which are geographically restricted to one or a few adjacent countries. Subcultures of the vaccine strain PW8 differed by up to 20 cgMLST mismatches. Phylogenetic analyses revealed short timescale evolutionary gain or loss of the diphtheria toxin and biovar-associated genes. We devised a genomic taxonomy of strains and deeper sublineages (defined using a 500 cgMLST mismatches threshold), currently comprising 151 sublineages, only a few of which are geographically widespread based on current sampling. The cgMLST genotyping tool and nomenclature was made publicly accessible at https://bigsdb.pasteur.fr/diphtheria. Conclusions: Standardized genome-scale strain genotyping will help tracing transmission and geographic spread of C. diphtheriae. The unified genomic taxonomy of C. diphtheriae strains provides a common language for studies into the ecology, evolution and virulence heterogeneity among C. diphtheriae sublineages.

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Section: Isolates and Outbreak Sets Included In The Studymentioning

confidence: 99%

Section: Definition and Evaluation Of A Cgmlst Scheme For Genotyping Isolates Of C Diphtheriae C Belfantii And C Rouxiimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 98%

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Genomic epidemiology and strain taxonomy ofCorynebacterium diphtheriae

Guglielmini

Hennart

Badell

et al. 2021

Preprint

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“…However, recent reports highlight that diphtheria remains endemic in several low-income settings. Outbreaks have been reported in India, Laos, Bangladesh and the Yemen and also in high-income settings regions with low immunisation coverage as seen in Norway [4][5][6][7][8][9]; in 2017 the estimated number of cases globally remained >16 000 [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Endemic erythromycin resistant Corynebacterium diphtheriae in Vietnam in the 1990s

et al. 2022

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Diphtheria is a potentially fatal respiratory disease caused by toxigenic forms of the Gram-positive bacterium Corynebacterium diphtheriae . Despite the availability of treatments (antitoxin and antimicrobials) and effective vaccines, the disease still occurs sporadically in low-income countries and in higher income where use of diphtheria vaccine is inconsistent. Diphtheria was highly endemic in Vietnam in the 1990s; here, we aimed to provide some historical context to the circulation of erythromycin resistant organisms in Vietnam during this period. After recovering 54 C . diphtheriae isolated from clinical cases of diphtheria in Ho Chi Minh City between 1992 and 1998 we conducted whole genome sequencing and analysis. Our data outlined substantial genetic diversity among the isolates, illustrated by seven distinct Sequence Types (STs), but punctuated by the sustained circulation of ST67 and ST209. With the exception of one isolate, all sequences contained the tox gene, which was classically located on a corynebacteriophage. All erythromycin resistant isolates, accounting for 13 % of organisms in this study, harboured a novel 18 kb erm(X)-carrying plasmid, which exhibited limited sequence homology to previously described resistance plasmids in C. diphtheriae . Our study provides historic context for the circulation of antimicrobial resistant C. diphtheriae in Vietnam; these data provide a framework for the current trajectory in global antimicrobial resistance trends.

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Child Health During War and Disasters: Building Resilience

Scales,

Guha-Sapir

2024

Indian Pediatr

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

Cited by 33 publications

References 21 publications

Genomic epidemiology and strain taxonomy ofCorynebacterium diphtheriae

Genomic epidemiology and strain taxonomy ofCorynebacterium diphtheriae

Endemic erythromycin resistant Corynebacterium diphtheriae in Vietnam in the 1990s

Child Health During War and Disasters: Building Resilience

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