Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15.

OBJECTIVES: Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. METHODS: From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. RESULTS: Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. CONCLUSIONS: This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.

Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial.

UNLABELLED: We conducted randomized double-blind trial for single-dose of Rifampicin, Ofloxacin and Minocycline (ROM) compared to WHO-PB-MDT among paucibacillary (PB) leprosy patients with 2-5 skin lesions. We enrolled 1526 patients from five centres (ROM=762; WHO-PB-MDT=764) and followed them for 36 months posttreatment during 1998-2003. We generated information on clearance of skin lesions and relapse rates per 100 person-years (PY) for all the five centres. At base-line, the patients in the two arms were comparable. Complete clearance of skin lesions was similar (72% vs. 72.1%; p=0.95) in both the arms. Clinical scores declined steadily and equally. Difference in relapse rates was statistically highly significant (ROM=1.13 and WHO-PB-MDT=0.35 per 100 PY; mid-p exact=0.001016). Twenty eight of 38 of these relapses occurred within 18 months. In all, 10 suspected adverse drug reactions were.observed (ROM=2; WHO-PB-MDT=8). We extended the follow-up to 48 months for 1082 of 1526 patients from two programme-based centres. No further relapses occurred. Decline in clinical score was not dependent on age, gender, number of lesions or affected body parts. Single dose ROM, though less effective than the standard WHO-PB-MDT regimen conceptually offers an alternative treatment regimen for PB leprosy patients with 2-5 lesions only when careful follow-up for relapse is possible. Registered at the Clinical Trials Registry of India; REGISTRATION NUMBER: CTRI/2012/05/002645

International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results.

OBJECTIVE: To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up. METHODS: We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. RESULTS: A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). CONCLUSION: U-MDT appears to be promising with respect to clinical status of skin lesions.

Defining a case of leprosy.

The biological and technical hurdles confronting the development of new diagnostic tools are manifestly great in leprosy. Leprosy diagnosis in the field, for control as well as for research purposes, will have to remain, for the time being, predominantly clinical. It is important that the significance and relevance of diagnosing so-called 'early' lesions must be viewed in the context of the objectives of leprosy control. All evidence suggests that the majority of these 'cases' are not likely to progress in the individual, nor is there any evidence that these 'cases' are of any importance for the transmission of the disease. At its best, such 'cases' may be a sign of temporary infection which will disappear spontaneously within a few months without leaving any residual signs. It is more likely that the majority of these are not cases of leprosy. In making such a diagnosis its ethical implications on the individual, his family and the local society must be considered, given the intense social stigma this diagnosis will generate; besides the cost of treatment and the potential risk of serious side-effects due to treatment. It may be justifiable to have a broad definition if the incidence of leprosy is still high and all reported cases are to be accepted as valid. But once the backlog of cases has been detected and, as a result of control efforts, the number of new cases begins to decrease, there is a need to narrow the case definition for national statistics.(ABSTRACT TRUNCATED AT 250 WORDS)

Foot soaks for callosities and fissures.

A study to assess the effect of soap soaks and plain water soaks on the dry anaesthetic sole of 15 leprosy patients bearing multiple fissures and callouses is reported. A callous scraper devised by us was found effective. It is recommended that a hypotonic keratolytic solution such as toilet soap or plain water be used for soaking which has the effect of softening the keratin. It may be better to use soap solution for this purpose.

Infectivity of secondary dapsone-resistant cases.

The incidence rate of leprosy among 517 household contacts of 113 cases of secondary dapsone resistance with 5074 person years at risk were studied. The incidence rate of leprosy was 4.3 per 1000 person years at risk, which is very similar to the incidence rate (4.8) among household contacts of lepromatous cases. Two, possibly three, cases of primary dapsone resistance were detected among the 27 contacts who developed multibacillary leprosy. There was no evidence of dapsone resistance among 48 paucibacillary leprosy cases assessed when treated with dapsone monotherapy. The possibility that secondary dapsone-resistant cases will infect and will result in an increase in the number of primary dapsone-resistant cases needs to be investigated further.

Effect of epicondylectomy in early ulnar neuritis treated with steroids.

Sixty-two ulnar nerves belonging to 44 patients with early neuritis were studied to assess the benefits offered by medial epicondylectomy and external decompression in addition to steroid therapy. The patients were randomly allocated to the surgical or the medical group. In those cases where there was bilateral involvement, surgery was carried out only on one side. All cases were assessed prior to treatment, and at predetermined intervals following treatment. This study presents the results after a 12-month follow-up. There was statistically significant improvement in both groups following treatment as assessed by improvement in motor and sensory functions and in the reduction of pain and tenderness. The study, however, failed to demonstrate any added benefit with surgical intervention as compared to steroid therapy alone in the treatment of early ulnar neuritis.

A clinico-pathological study of primary neuritic leprosy.

Normally neural involvement in leprosy is an ascending neuritis from the nerve involvement in the dermal lesions. However, in some cases neural involvement is seen in the absence of any dermal lesions. In some of these pure neuritic cases, dermal lesions appear sometime later. It is, therefore, more appropriate to designate such cases as 'primary neuritic' cases. This study is aimed at diagnosing primary neuritic leprosy among patients presenting with only neuritic symptoms. An attempt is also made to classify primary neuritic leprosy on a clinical and histopathological basis. During the period 1979-80, 30 patients reported to the out patient department of Schieffelin Leprosy Research and Training Centre, Karigiri with complaints of neuritic origin. In addition to clinical examination and routine skin smears, investigations such as skin, nerve and nasal biopsies, nerve conduction velocity and lepromin testing were carried out where feasible. 17 of these patients were diagnosed as primary neuritic leprosy and in 7 patients other neurological conditions were diagnosed. The remaining 6 patients were kept under observation and have not shown evidence of leprosy during a two year period of following-up. It is interesting that 4 of the 17 primary neuritic cases developed patches during follow-up period of two years. In the final analysis 7 patients (41.2%) were classified into the lepromatous group and 10 patients (58.8%) in the non-lepromatous group (Table-6). This classification will have a bearing on duration of treatment and for their subsequent release from control.