Drug Resistance (Dapsone, Rifampicin, Ofloxacin) and Resistance-Related Gene Mutation Features in Leprosy Patients: A Systematic Review and Meta-Analysis

Abstract

Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85–12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46–15.33) vs. 6.59% (3.66–9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65–9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82–18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02–5.77), 3.66% (95% CI: 2.41–4.90) and 1.28% (95% CI: 0.87–1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83–2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.

Epidemiological characteristics of leprosy during the period 2005–2020: A retrospective study based on the Chinese surveillance system

“…However, there was an increasing trend in the detection rate of leprosy during 2005–2009 in Jiangsu Province. The trend was mainly due to the relaxation of leprosy control and the appearance of drug resistance (dapsone, rifampin, and ofloxacin), which has led to an increase in new cases ( 31 , 52 ). As a result, the government took adequate measures to control the disease, and the epidemic was brought under control.…”

“…As the result indicated, 55 (15.15%) newly detected cases came from other provinces but lived in Jiangsu. Most came from highly endemic areas (Sichuan and Guizhou) ( 25 , 52 ). These people came to Jiangsu mainly for work, and there was a potential risk of inter-provincial transmission.…”

Current understanding of genetic associations with delayed hypersensitivity reactions induced by antibiotics and anti-osteoporotic drugs

“…Dapsone, a sulfone drug with anti-microbial and anti-inflammatory effects, has been used for leprosy and dermatitis herpetiformis ( Reunala et al, 2021 ; Li et al, 2022 ). The prevalence of dapsone-induced SCARs was 0.5%–3.6% after 4–6 weeks treatment ( Rao and Lakshmi, 2001 ).…”

The perennial pursuit for an ideal anti-leprosy treatment

“…Ofloxacin resistance rates of up to 25.9% have been reported among leprosy patients in various studies. [20][21][22][23] A recent meta-analysis reported mutation rates of 3.66% and 1.28% for RpoB and GyrA, respectively. 21 Recommendation of a regimen in which two of the three drugs have rising rates of resistance does not seem very prudent.…”

“…[20][21][22][23] A recent meta-analysis reported mutation rates of 3.66% and 1.28% for RpoB and GyrA, respectively. 21 Recommendation of a regimen in which two of the three drugs have rising rates of resistance does not seem very prudent. Adoption of ROM as first line management of leprosy would warrant formulation of an alternative second-line regimen, creating more challenges than it would solve.…”