Report of rpoB mutation in clinically suspected cases of drug resistant leprosy: A study from Eastern India

Reja, Abu Hena Hasanoor; Biswas, Nibir; Biswas, Supratik; Lavania, Mallika; Vedithi, Sundeep Chaitanya; Banerjee, Sushmita; Patra, Prasanta; Gupta, Umesh; Patra, P.K.; Sengupta, Utpal; Bhattacharya, Basudev

doi:10.4103/0378-6323.152185

Cited by 13 publications

(5 citation statements)

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“…However, as we observed them in combination with mutations at codon positions 441 and 438, we reported mutations at positions 432 and 437 as resistant. In a study from eastern India, 2 of 50 cases of relapse were found to have resistance to rifampicin and both cases had the mutation Glu442His in the rpoB gene 7 . Nevertheless, it was later found, using the mouse footpad method, that this codon position does not confer resistance to rifampicin 16 .…”

Section: Discussionmentioning

confidence: 99%

“…In a study from eastern India, 2 of 50 cases of relapse were found to have resistance to rifampicin and both cases had the mutation Glu442His in the rpoB gene. 7 Nevertheless, it was later found, using the mouse footpad method, that this codon position does not confer resistance to rifampicin. 16 In another study from India, rifampicin resistance was seen in 4 of 111 (3.6%) cases of relapse, with two new mutations (Phe439Leu and Gln442His in rpoB).…”

Section: Discussionmentioning

confidence: 99%

“…4 In studies from India, the rate of drug resistance in leprosy (relapse and new cases) has ranged from 3.9% to 8.1%. [4][5][6][7] More recently, there have been reports of drug resistance as a cause for recalcitrant leprosy lesions and chronic type 2 reactions. 8,9 Erythema nodosum leprosum (ENL) is the cutaneous manifestation of a Type 2 reaction and this can be classified as acute, chronic or recurrent.…”

Section: Introductionmentioning

confidence: 99%

“…Primary drug resistance even before starting MDT has also been increasingly reported 4 . In studies from India, the rate of drug resistance in leprosy (relapse and new cases) has ranged from 3.9% to 8.1% 4–7 . More recently, there have been reports of drug resistance as a cause for recalcitrant leprosy lesions and chronic type 2 reactions 8,9 .…”

Section: Introductionmentioning

confidence: 99%

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Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug‐resistance testing in leprosy?

Narang

Kamat

Thakur

et al. 2021

Clin Experimental Derm

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Background. Leprosy relapse/recurrence is a serious concern particularly in a leprosy-endemic nation such as India. It is believed that bacilli persisting even after multidrug therapy can cause relapse; recently, however, drug resistance as a cause for recurrences and chronic erythema nodosum leprosum (ENL) has been speculated. Aim. To study drug-resistance patterns in cases of leprosy relapse and chronic/ recurrent (c/r)ENL. Methods. This cross-sectional study conducted over a period of 1 year included patients diagnosed as having leprosy relapse and those with c/rENL. Skin biopsy specimens were examined by conventional PCR for resistance testing for rifampicin, dapsone and ofloxacin, respectively targeting the rpoB, folP and gyrA genes of Mycobacterium leprae. Results. In total, 61 patients (25 smear-negative) were included in the study. Of these, 37 were diagnosed as having leprosy relapse and 24 as having c/rENL. Drug resistance to at least one drug was identified in 10 cases (16.4%). Rates of drug resistance were 5.4% (2 of 37) for dapsone, 10.8% (4 of 37) for rifampicin and 2.7% (1 of 37) for ofloxacin among cases of relapse, whereas it was 12.5% (3 of 24) and 8.3% (2 of 24) for dapsone and rifampicin respectively among those with c/ rENL. Multidrug resistance was seen in 3.3% patients (2 of 61). Conclusion. Drug-resistance rate among those with c/rENL was almost equalled that of relapse. Smear-negative leprosy relapse cases also had resistance to bactericidal drugs. These findings call for modifications in criteria for testing under leprosy drug-resistance surveillance and all cases of relapse and those with recalcitrant c/ rENL should be tested.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug‐resistance testing in leprosy?

Narang

Kamat

Thakur

et al. 2021

Clin Experimental Derm

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“…The incidence and 95% CI of the drug−resistance rate for each study are represented. Forest plot of drug−resistance rates of Mycobacterium leprae isolates in studies meeting inclusion criteria (n = 25) [ 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Section: Figurementioning

confidence: 99%

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

Li,

Yang

et al. 2022

IJMS

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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.

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Neglected Tropical Bacterial Diseases

Saxena

Azad

2016

Topics in Medicinal Chemistry

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Report of rpoB mutation in clinically suspected cases of drug resistant leprosy: A study from Eastern India

Abstract: The study indicates the existence of rifampicin drug resistance in Eastern India.

Cited by 13 publications

References 11 publications

Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug‐resistance testing in leprosy?

Equal rates of drug resistance in leprosy cases with relapse and recurrent/chronic Type 2 reaction: time to revise the guidelines for drug‐resistance testing in leprosy?

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

Neglected Tropical Bacterial Diseases

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