Abstract
Pathogen-based factors associated with tuberculosis (TB) in eastern Sudan are not well defined. We investigated genetic diversity, drug resistance, and possible transmission clusters of Mycobacterium tuberculosis complex (MTBC) strains by using a genomic epidemiology approach. We collected 383 sputum specimens at 3 hospitals in 2014 and 2016 from patients with symptoms suggestive of TB; of these, 171 grew MTBC strains. Whole-genome sequencing could be performed on 166 MTBC strains; phylogenetic classification revealed that most (73.4%; n = 122) belonged to lineage 3 (L3). Genome-based cluster analysis showed that 76 strains (45.9%) were grouped into 29 molecular clusters, comprising 2–8 strains/patients. Of the strains investigated, 9.0% (15/166) were multidrug resistant (MDR); 10 MDR MTBC strains were linked to 1 large MDR transmission network. Our findings indicate that L3 strains are the main causative agent of TB in eastern Sudan; MDR TB is caused mainly by transmission of MDR L3 strains.
Highlights
Pathogen-based factors associated with tuberculosis (TB) in eastern Sudan are not well defined
Before we shipped each sample to the National Reference Center (NRC) for Mycobacteria, Borstel, Germany, we transferred a volume of
Beyond the multidrug resistant (MDR) classification, we found that lineage 3 (L3) strains in eastern Sudan were more often found with drug resistances as compared with L4 strains (L3, 31/122, 25.4%; L4, 4/39, 10.3%; p = 0.048 by Fisher exact test)
Summary
45.9% (76/166) of the strains were grouped in 29 clusters comprising 2–8 isolates/patients (Appendix 1 Figure 2). Considering a stricter threshold (1 of the tested first-line antimicrobial drugs by pDST, including 15 (9.0%) MDR and 21 (12.7%) nonMDR strains (Appendix 2, https://wwwnc.cdc.gov/ EID/article/26/3/19-1145-App2.xlsx). We considered the gidB mutations (Phe12Ser, Arg39Pro, Trp45STP, Ser136STP, Iso114Ser, and deletions at positions 4408101, 4408017, and 4408116) to be mutations with an unclear effect These strains eventually tested phenotypically resistant to streptomycin, leading to a reduced sensitivity. These strains shared the same rpsL (Lys43Arg) and the katG (Ser315Thr) mutations but harbored different mutations in the rpoB gene; strains of cluster 4 had the Ser450Leu mutation,
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