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?

Abstract

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.

High Prevalence of Resistance to Anti-Leprosy Drugs in Leprosy Cases with Chronic Erythema Nodosum Leprosum

“…Resistance to rifampicin and dapsone was reported in 8.3% and 12.5% of patients with recurrent/chronic ENL respectively, in a recent study from a tertiary care institute in North India. [ 3 ] Five of the six cases with chronic ENL in the present study had resistance to one or more drugs, with two having rifampicin resistance. Modification of treatment regimens in both resulted in excellent control of their type 2 reaction.…”

“…[ 2 ] However, a recent study has suggested modifying these criteria to include those presenting with chronic/recurrent erythema nodosum leprosum (ENL) as well. [ 3 ]…”

“…Indian studies from diverse regions report variable rates of drug resistance ranging from 0 to 16.4%. [ 3 5 6 7 ] The first prospective open survey for determining AMR in leprosy was conducted by a WHO surveillance network for 2009-2015. [ 8 ] MB cases from 19 countries were studied for resistance to rifampicin, dapsone, and ofloxacin.…”

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

“…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 ].…”

“…( a ) The forest plot of the Ser mutation in RpoB. ( b ) The forest plot of the Pro mutation in Folp1 [ 14 , 20 , 21 , 24 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 37 , 38 ].…”