Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia

Chizimu, Joseph Yamweka; Solo, Eddie Samuneti; Bwalya, Precious; Kapalamula, Thoko Flav; Akapelwa, Mwangala Lonah; Lungu, Patrick; Shrestha, Dibas; Fukushima, Yukari; Mukonka, Victor; Thapa, Jeewan; Nakajima, Chie; Suzuki, Yasuhiko

doi:10.1016/j.ijid.2021.10.044

Cited by 9 publications

(13 citation statements)

References 47 publications

(56 reference statements)

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“…The SIT21/CAS1-Kili M. tuberculosis strains were previously shown to be associated with the clonal spread of MDR-TB in the Lusaka District [ 18 , 19 ]. In this study, we applied WGS to investigate recent transmission events among SIT21/CAS1-Kili strains that was suggested by the combination of 24-MIRU-VNTR loci and spoligotyping.…”

Section: Discussionmentioning

confidence: 99%

“…We used strains from the previous study conducted in Lusaka from 2013 to 2017 [ 18 ]. In the previous study, 87 MDR-TB strains were typed by spoligotyping and 24-loci MIRU-VNTR, of which 25 CAS1-Kili strains formed the largest clonal cluster and were suspected to represent a recent transmission event [ 18 ]. All CAS1-Kili strains were considered for WGS though only 13 were successfully sequenced.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, 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 ]. Despite its low proportions in the region compared to predominant lineage 4, lineage 3 strains (SIT21/CAS1-Kili) were associated with MDR-TB and implicated for its spread in Lusaka, Zambia [ 18 , 19 ]. Among the studied MDR M. tuberculosis strains, 24-loci MIRU-VNTR and spoligotyping showed clonal expansion of the SIT21/CAS1-Kili strains [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite its low proportions in the region compared to predominant lineage 4, lineage 3 strains (SIT21/CAS1-Kili) were associated with MDR-TB and implicated for its spread in Lusaka, Zambia [ 18 , 19 ]. Among the studied MDR M. tuberculosis strains, 24-loci MIRU-VNTR and spoligotyping showed clonal expansion of the SIT21/CAS1-Kili strains [ 18 ]. The findings in those studies supported the possibility of recent transmission, though this could not be concluded due to the limitations of the genotyping methods used in discriminating between closely related strains.…”

Section: Introductionmentioning

confidence: 99%

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Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

et al. 2021

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“…MIRU-VNTR typing was performed according to the international standard 24 loci method. [ 9 ] The primers were synthesized by Sangon Biotech (Shanghai) Co., Ltd. Each locus amplification reaction was performed in a total volume of 20 μL consisting of 10 μL 2 × Taq PCR MasterMix (CWBIO), 2 μL 2 μmol/L each primer, 1 μL DNA lysate and 5 μL ddH 2 O. The PCR products were analyzed in a 1.5%∼2.0% agarose gel using a 100 bp DNA ladder as the molecular weight standard.…”

Section: Methodsmentioning

confidence: 99%

Transmission of multidrug-resistant Mycobacterium tuberculosis in Wuhan, China

et al. 2022

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How multidrug-resistant tuberculosis (MDR-TB) spreads and expands in Wuhan population is not clear. The study aimed to determine the transmission patterns of MDR-TB in Wuhan city, China, including 149 patients with MDR-TB. Tuberculosis isolates were genotyped by deletion-targeted multiplex polymerase chain reaction, mycobacterial interspersed repetitive unit-variable number tandem repeat typing, and sequencing of drug resistance-associated genes. The risk factors of genomic-clustering were analyzed with logistic regression. The genomic-clustering patients were deeply investigated. The analysis identified 111 unique and 11 clustered genotypes (38 isolates). The clustering rate was 25.50% and the minimum estimate proportion of recent transmission was 18.12%. Two clusters (5 isolates) shared the same mutation, the remain 9 clusters (33 isolates) had different mutation. Logistic regression showed that older than 60 years (adjusted OR 2.360, 95% CI:1.052-5.292) was an independent factor associated with the genomic-clustering of MDR-TB. Among the 38 genomic-clustering cases, 14 cases had epidemiological transmission links. The most common type of transmission link was social contact. The local transmission of MDR-TB in Wuhan was really an issue. The elderly population might be the high-risk groups for transmission of MDR-TB, and the community or public transportation might be the main transmission places.

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Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management

Nyasulu,

Doumbia,

Ngah

et al. 2024

Current Opinion in Pulmonary Medicine

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Purpose of review This review addresses the escalating global challenge of multidrug-resistant tuberculosis (MDR-TB) in Sub-Saharan Africa, with a focus on its complex comorbidity with HIV/AIDS. Emphasizing the urgency of the issue, the review aims to shed light on the unique healthcare landscape shaped by the convergence of high prevalence rates and intersecting complexities with HIV/AIDS in the region. Recent findings A notable increase in MDR-TB cases across Sub-Saharan Africa is attributed to challenges in timely diagnoses, treatment initiation, and patient treatment defaulting. The literature underscores the critical need for proactive measures to address diagnostic and treatment gaps associated with MDR-TB, particularly concerning its comorbidity with HIV/AIDS. Summary To effectively manage MDR-TB and its co-morbidity with HIV/AIDS, proactive screening programs are imperative. The review highlights the necessity of active follow-up strategies to ensure treatment adherence and reduce default rates, offering evidence-based insights for improved disease management in the region.

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Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia

Cited by 9 publications

References 47 publications

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

Transmission of multidrug-resistant Mycobacterium tuberculosis in Wuhan, China

Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management

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