Abstract
Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.
Highlights
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a global public health concern ranked among the top 10 causes of mortality
Efforts to reduce the incidences of drug resistance, multidrug-resistant tuberculosis (MDR-TB), which is resistant to rifampicin (RIF) and isoniazid (INH), have led to a steady decline of global cases
Out of all the genotypes analyzed, CAS1_Kili (SIT 21) clade was more likely to have STR resistance compared to other spoligotype clades (OD: 3.9, p = 0.009)
Summary
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a global public health concern ranked among the top 10 causes of mortality. Zambia is among the 30 countries with the highest TB burden in the world. The emergence of drug resistance raises even more serious concern as it poses a threat to the strides made in controlling the disease. Efforts to reduce the incidences of drug resistance, multidrug-resistant tuberculosis (MDR-TB), which is resistant to rifampicin (RIF) and isoniazid (INH), have led to a steady decline of global cases. In Zambia, the incidences of MDR-TB show an upward trend. From 2014 to 2019, MDR-TB has risen from 0.3% to 2.4% in new cases and 8.1% to 18% in previously treated cases [2]
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