Abstract
Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.
Highlights
Worldwide, close to 4000 lives in a day are lost due to tuberculosis (TB)
We reported a relatively higher percentage of lineage 3 Spoligotype International Type (SIT) 21/CAS1-Kili strains among multidrug-resistant (MDR) M. tuberculosis strains in Zambia when compared to other southern African countries [18]
This study aims to investigate recent transmission of the MDR M. tuberculosis SIT21/CAS1-Kili strains in Lusaka, Zambia, by whole-genome sequencing (WGS)
Summary
Close to 4000 lives in a day are lost due to tuberculosis (TB). It is a major cause of death ascribed to antimicrobial resistance [1]. In Zambia, like many other developing countries, TB is the leading cause of death especially among people living with HIV/AIDS [2]. Mycobacterium tuberculosis, the cause of TB, has seven major human-adapted lineages. One of these is lineage 3 (L3) which is predominant in East Africa, the Middle East and. Central Asian Strain 1-Kili (CAS1-Kili) forms part of lineage 3 sub-clades and is more prevalent in the eastern part of Africa [3,5]
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