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.

Dynamics of impairment during and after treatment: the AMFES cohort.

This study investigates the dynamics of impairment during and after multidrug therapy treatment for the patient cohort of the prospective ALERT MDT Field Evaluation Study (AMFES). The impairment status was compared at intake, at release from treatment (rft), and at the time of the latest survey between 24 and 48 months after release from treatment (follow-up). The eye-hand-foot impairment score (EHF score), which is the sum of the WHO impairment grades of the eyes, hands, and feet, was used as tool for comparison. In all, 433 out of the 592 patients (224 PB and 209 MB) completed treatment in time and were assessed at release from treatment. The risk of getting impaired was 4% for the 113 PB and 21% for the 91 MB patients who were initially free from impairment. Out of the 111 initially impaired PB patients, 41% recovered or improved and 13% worsened in EHF score. For the 118 initially impaired MB patients, these figures were: recovery or improvement 43% and worsening 13%. Three hundred and twenty-three out of the 433 patients (158 PB and 165 MB) had a follow-up examination in between the next 24-48 months after rft. The risks of impairment at follow-up were 6% for the 79 PB and 18% for the 77 MB patients without impairment at rft. Out of the 79 PB patients with impairment at rft, 35% recovered or improved and 28% worsened. For the 88 impaired MB patients, these figures were: recovery or improvement 26% and worsening 27%. Patients showed a tendency to compensate EHF score improvement before rft by worsening after rft and vice versa. The first main conclusion is that the impairment status at intake was by far the most important determinant for future impairment. The second one is that the dynamics of impairment were less favourable after rft than before. Little is known about the long-term fate of leprosy patients with irreversible nerve damage and the associated risk of developing severe secondary impairment. Especially in this era of the leprosy elimination goal, we should give this accumulating patient group due attention in research and health policy agendas.

The ALERT MDT Field Evaluation Study (AMFES): a descriptive study of leprosy in Ethiopia. Patients, methods and baseline characteristics.

The ALERT MDT Field Evaluation Study (AMFES) is a long-term prospective study of 650 patients (594 new cases and 56 relapses after dapsone monotherapy), treated with fixed-duration multiple-drug therapy (MDT), as recommended by WHO. Follow-up has continued for up to 11 years from the start of treatment. This paper presents the methodology of the study and the baseline characteristics of the cohort, while accompanying papers examine the incidence of, and possible risk factors for, the various complications of leprosy, including relapse, reactions and nerve function impairment. The methods of diagnosis, classification and treatment with MDT are described; nerve function was assessed at every visit to the clinic using a standardized methodology, so that reactions and new impairment could be detected early and treated. Eighty-four per cent of new case had at least one thickened nerve, with the ulnar nerve most commonly involved. Seventy-seven per cent of cases completed treatment and only one adverse reaction to the MDT drugs was noted. Twenty-eight per cent of all patients were given steroids at one time or another, almost always for new nerve function impairment, and 3% of these developed significant complications of steroid treatment. Twenty-nine patients (5%) received hospital care, including 14 patients who underwent major surgery. Sixty-one per cent of the women over 19 years of age had at least one pregnancy, but pregnancies were much less common after leprosy was diagnosed.

Which physical signs help most in the diagnosis of leprosy? A proposal based on experience in the AMFES project, ALERT, Ethiopia.

As integration of leprosy control programmes proceeds, general health staff will have responsibility for the diagnosis of most new cases of leprosy. The training required by these workers has not yet been set out in detail. In this paper the criteria for making the diagnosis of leprosy in the AMFES cohort of 594 new cases are examined. Since this study does not include details of suspects in whom leprosy was excluded on clinical grounds, true sensitivity and specificity values cannot be calculated, but the positive predictive value of the diagnostic criteria can be measured. Sensory loss in a typical skin patch is the most important sign of early leprosy, but was not present in 132 (49%) of the 268 cases with a positive skin smear. Thickening of the ulnar nerve is a valuable sign of leprosy in Ethiopia. It can be taught to health workers, who can practise by examining their own ulnar nerves. It is more likely to be present than nerve function impairment and is particularly important when skin smears are difficult to do or are unreliable. We recommend that five basic signs are used, the presence of any two being diagnostic of leprosy: Skin lesion(s) consistent with leprosy. Loss of sensation in such a lesion. Thickening of either ulnar nerve. Loss of sensation in the palm of the hand or the sole of the foot. The presence of acid-fast bacilli in skin smears. Exact policies for the diagnosis of leprosy should be worked out and validated for each national programme.