Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia

Abstract

The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes.

Assessment of antimicrobial resistance laboratory-based surveillance capacity of hospitals in Zambia: findings and implications for system strengthening

“…Of the global death rates reported in 2019, approximately 24/100,000 were from sub-Saharan Africa [ 7 ]. The region has high incidences of infectious diseases such as human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), malaria and tuberculosis [ [11] , [12] , [13] , [14] , [15] , [16] , [17] ]. Therefore, high trends of AMR to the agents causing infections in resource-constrained regions further weaken the already stressed health systems [ 18 ].…”

Community antibiotic consumption and associated factors in Lusaka district of Zambia: findings and implications for antimicrobial resistance and stewardship

“… 94 , 104–108 Consequently, there is evidence of antimicrobial-resistant pathogens across the human and animal sectors. 37 , 38 , 41 , 99 , 109–115 A study by Masich et al 116 revealed that about 67% of antimicrobials were inappropriately prescribed to non-critically ill adult patients admitted to the University Teaching Hospital in Lusaka, Zambia. Intriguingly, the Zambian government has put in measures to promote the appropriate use of antibiotics by developing and implementing the National Action Plan (NAP) on AMR.…”