Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

Abstract

The burden of multidrug-resistant tuberculosis (MDR-TB) has been reported to be increasing in Zambia. The reasons for the increase are still unclear. This study determined the diversity of Mycobacterium tuberculosis genotypes among isolates in Lusaka, the capital city, and investigated their association with MDR-TB. Methods: Spoligotyping, large sequence polymorphism (LSP) analysis, and sequencing of MDR associated genes were performed on a total of 274 M. tuberculosis clinical isolates stored at the University Teaching Hospital from 2013 to 2017. Of these, 134 were MDR-TB while 126 were pan-susceptible. Results: Spoligotyping showed the LAM family as the most predominant genotype (149/274, 54.4%) followed by the CAS family (44/274, 16.1%), T family (39/274, 14.2%), and minor proportions of X, S, Harleem, EAI and Beijing spoligofamilies were identified. Three M. bovis isolates were also observed. Among those, CAS1-Kili (SIT 21) and LAM1 (SIT 20) subfamilies showed a propensity for MDR-TB with p = 0.0001 and p = 0.001, respectively. Conclusions: This phenomenon might explain the future increase in the MDR-TB burden caused by specific lineages in Zambia. Therefore, it is recommended that the National TB control program in the country complements conventional control strategies with molecular analysis for monitoring and surveillance of MDR-TB epidemiology.

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

“…Spoligotyping was conducted as previously described [5,43]. Briefly, the direct repeat region was amplified by PCR using primers DRa GGTTTTGGGTCTGACGAC and DRb CCGAGAGGGGACGGAAAC, and the resulting products were hybridized to 43 spacerspecific oligonucleotide probes on a membrane.…”

“…This practice could have led to the undetected emergence and silent spread of drug-resistant TB. In a previous study, it was demonstrated that the increase in MDR-TB in Zambia is not the result of transborder transmission but local emergence and possible spread within Zambia [4,5]. The mismanagement of MDR-TB could further the evolution of resistance to other anti-TB drugs.…”

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

“…A few studies in Zambia have described M. tuberculosis diversity using 15 loci MIRU-VNTR in Ndola and Namwala districts (Mulenga et al 2010;Malama et al 2014). Further, we previously described an association of drug resistance with specific genotypes in Lusaka based on spoligotyping (Solo et al 2020b). Nevertheless, information on the transmission of MDR M. tuberculosis strains in Lusaka, Zambia is still inadequate.…”

Diversity of Mycobacterium tuberculosis Complex Lineages Associated with Pulmonary Tuberculosis in Southwestern, Uganda

“…L4 is phylogenetically complex, with at least ten distinct sublineages that differ in geographical distribution, with local genotypes accounting for a larger proportion of circulating strains in certain regions [ 15 ]. For instance, the L4-Cameroon family is almost exclusively found in West Africa [ 14 ] while the Latin American-Mediterranean (LAM) family is most predominant in Zambia [ 38 , 39 ]. Similarly, the L4-U family is more predominant in Uganda as opposed to anywhere else [ 4 , 28 , 31 , 40 ].…”