Molecular and epidemiologic characterization of the diphtheria outbreak in Venezuela

Abstract

In 2016, Venezuela faced a large diphtheria outbreak that extended until 2019. Nasopharyngeal or oropharyngeal samples were prospectively collected from 51 suspected cases and retrospective data from 348 clinical records was retrieved from 14 hospitals between November 2017 and November 2018. Confirmed pathogenic Corynebactrium isolates were biotyped. Multilocus Sequence Typing (MLST) was performed followed by next-generation-based core genome-MLST and minimum spanning trees were generated. Subjects between 10 and 19 years of age were mostly affected (n = 95; 27.3%). Case fatality rates (CFR) were higher in males (19.4%), as compared to females (15.8%). The highest CFR (31.1%) was observed among those under 5, followed by the 40 to 49 age-group (25.0%). Nine samples corresponded to C. diphtheriae and 1 to C. ulcerans. Two Sequencing Types (ST), ST174 and ST697 (the latter not previously described) were identified among the eight C. diphtheriae isolates from Carabobo state. Cg-MLST revealed only one cluster also from Carabobo. The Whole Genome Sequencing analysis revealed that the outbreak seemed to be caused by different strains with C. diphtheriae and C. ulcerans coexisting. The reemergence and length of this outbreak suggest vaccination coverage problems and an inadequate control strategy.

Figure 1

Distribution of suspected and confirmed diphtheria cases by month, Venezuela, June 2016 and July 2019 (N = 349).

Figure 2

Distribution of deceased and survived diphtheria cases by month, Venezuela, June 2016 and July 2019 (N = 349 of whom 262 had information on survival status available).

Figure 3

(a) Distribution of origin of diphtheria cases by epidemiological month of onset of symptoms, Venezuela, June 2016 and July 2019 (N = 349 of whom 346 had information on state available). (b) Map of Venezuela and affected regions.

Figure 4

Minimum-spanning tree of core genome multilocus sequence typing with 1423 targets of the toxigenic Corynebacterium diphtheriae isolates from Venezuela. Allele distances between isolates are indicated, cluster with allele difference ≤ 5 is shaded in pink, and the reference genomes are shown in grey (only the reference genome used as seed and the closest reference genome to Venezuelan isolates are shown).