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?

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.

Cortisol and proinflammatory cytokine profiles in type 1 (reversal) reactions of leprosy.

PURPOSE: Cortisol levels in the circulation and at the sites of peripheral inflammation regulate type 1 (Reversal) reactions in leprosy akin to delayed type hypersensitivity reactions (DTH). In this study we determine the extent to which the differential mRNA expression of genes encoding cortisone-cortisol shuttle enzymes (11 ß hydroxysteriod dehydrogenase I & II (11 ß HSD I & II)), circulatory levels of proinflammatory cytokines (IL-6, IL-7, IP-10, IL-17F, IL-23, TNF-α, IL-1ß, PDGF BB and CRP) and cortisol are associated with development of type 1 reactions in leprosy. METHODS: Urine, blood and incisional skin biopsy samples from site of lesions were collected from 49 newly diagnosed untreated leprosy cases in T1R and 51 cases not in reaction (NR). mRNA expression levels of genes encoding 11 ß HSD I & II in skin biopsy samples were determined by realtime PCR. Cortisol levels from the lesional skin biopsies, serum and urine samples and serum proinflammatory cytokine levels were measured using ELISA. RESULTS: The mean expression ratios of 11 ß HSD I & II are significantly lower in leprosy cases with T1R when compared to the NR leprosy cases. Cortisol levels in lesional skin biopsies and in urine are significantly lower (p=0.001) in leprosy cases with T1R. Serum cytokine levels of IP-10, IL-17F, IL-IL-6 and TNF-α are significantly higher (p<0.05) in leprosy cases with T1R when compared the NR leprosy cases. CONCLUSION: Our study indicated an association of urinary and lesional skin cortisol levels with the manifestation of T1R in leprosy. IP-10, IL-17F, IL-6 and TNF-α can be potential prognostic serological markers and gene expression markers for early detection of type 1 reactions in leprosy.

Resistance to intravenous inoculation of Mycobacterium tuberculosis H37Rv in mice of different inbred strains following immunization with a leprosy vaccine based on Mycobacterium w.

Four strains of mice, namely Balb/c, C57BL/6 NCrl (Bcgs), C3H/He NCrl and CBA/N (Bcgr) were experimentally infected with Mycobacterium tuberculosis H37Rv (Trudeau Institute, Saranac Lake, NY) to induce sub-lethal infection. The level of infection was assessed by screening tuberculin reaction, pulmonary lesions, and viable units of mycobacteria recovered from the lung, spleen and liver. On prior immunization with 10(7) heat-killed suspension of Mycobacterium w, an anti-leprosy vaccine currently under large scale human trials in India, protection was observed against tuberculosis in all the four strains of mice used in the study as assessed by significant reduction of both pulmonary lesions and viable units of mycobacteria recovered from different organs. In parallel experiments, live BCG was able to confer protection to mice of Bcgs strains but not to mice of the Bcgr strains. Results of these experiments suggest that a vaccine based on heat-killed Mycobacterium w has the potential also to confer protection against tuberculosis in mice of genetic strains whose immune system is less triggered by intravenous injection of viable BCG.

Experience with multidrug therapy in paucibacillary leprosy.

Eighty paucibacillary leprosy cases were randomly put on two different multidrug regimens for 6 months followed by dapsone monotherapy. Regimen I was according to WHO (1982) recommendations consisting of Dapsone and six once a month rifampicin. In regimen II in addition to above two constituents, clofazimine was added 100 mg on alternate days. Dapsone thereafter was continued in both the regimens upto one year. The efficacy, acceptability and side effects of multidrug regimens were observed for a period of one year. Histopathological assessment was done on completion of multidrug therapy in all cases. A comparative evaluation of effect of two multidrug regimens in paucibacillary leprosy patients is reported. Addition of clofazimine over WHO (1982) recommended regimen appears to have no added benefit. The duration of WHO (1982) recommended regimens was found to be inadequate in many cases.

Cardiovascular system in leprosy.

Involvement of cardiovascular system (CVS) in 50 multibacillary (MB) and 20 paucibacillary (PB) cases of leprosy was evaluated. 20 age and sex matched controls were also studied. In addition to detailed clinical examination and resting electro-cardiogram, Master's two step exercise test (DMT) was also carried out to find out the occult and asymptomatic cardiac involvement. We have not found any significant symptomatic or electrocardiographic evidence of CVS involvement in various groups of leprosy.