Elsevier

The Lancet

Volume 363, Issue 9416, 10 April 2004, Pages 1209-1219
The Lancet

Seminar
Leprosy

https://doi.org/10.1016/S0140-6736(04)15952-7Get rights and content

Summary

Leprosy remains an important health problem worldwide. The disease is caused by a chronic granulomatous infection of the skin and peripheral nerves with Mycobacterium leprae. The clinical range from tuberculoid to lepromatous leprosy is a result of variation in the cellular immune response to the mycobacterium. The resulting impairment of nerve function causes the disabilities associated with leprosy. This review summarises recent advances in understanding of the biology of leprosy, clinical features of the disease, the current diagnostic criteria, and the new approaches to treatment of the infection and the immune-mediated complications. Supervised multi-drug therapy (MDT) for fixed durations is highly effective for all forms of the disease. The widespread implementation of MDT has been associated with a fall in the prevalence of the leprosy but as yet no reduction in the case-detection rate globally. Thus, leprosy control activities must be maintained for decades to interrupt transmission of infection.

Section snippets

Epidemiology of leprosy

During the 1990s a bold, ambitious leprosy elimination campaign was launched, after the adoption by the World Health Assembly of the goal of the “elimination of leprosy as a public health problem by the year 2000”.3 Elimination was defined as a reduction in the prevalence of leprosy patients receiving antimicrobial therapy to less than 1 per 10000 population. The rationale for this definition lay in the recognition that combination antibiotic therapy was highly effective and the assumption that

Biology of M leprae

The completion of the genomic sequence of M leprae is a major advance,28 which will assist in elucidation of the unique biology of the organism. Previously, detailed studies on M leprae were prevented by the inability to grow the mycobacteria in culture. M leprae is an acid-fast gram-positive bacillus and an obligate intracellular parasite with tropism for macrophages and Schwann cells. The bacilli show preference for growth in cooler regions of the body. The organism can replicate in the mouse

Host response

Host genetic factors have a partial effect on both the development of leprosy and the pattern of disease. Whole-genome screening has identified susceptibility loci on chromosome 10p13, close to the gene for the mannose receptor C type 1, a phagocytic receptor on macrophages, and on chromosome 6 within the MHC.57 Within this region linkage has been shown to HLA class II genes in Indian patients with leprosy and to the gene for tumour necrosis factor (TNF) in Brazilian patients.58 Polymorphisms

Clinical features of disease

Leprosy affects skin, nerves, and eyes, and causes systemic features in lepromatous disease. Patients commonly present with skin lesions, weakness or numbness caused by a peripheral-nerve lesion, or a burn or ulcer in an anaesthetic hand or foot. Borderline patients may present in leprosy reactions with nerve pain, sudden palsy, many new skin lesions, eye pain, or a systemic febrile illness.

Diagnostic criteria for leprosy

Diagnosis of leprosy is clinical and is based on patients having one or more of three cardinal signs (panel).1 The reliability of these signs has been extensively reviewed.4 In Ethiopia, use of these three criteria resulted in sensitivity of 97% with a positive predictive value of 98% for the diagnosis of leprosy.4 In Bangladeshi and Ethiopian cohorts of patients, 96% and 91% of patients with multibacillary disease and 86% and 76% of those with paucibacillary disease had enlargement of one or

Classification of disease

Classification of patients according to the Ridley-Jopling scale14 is clinically useful. Borderline-tuberculoid leprosy can be associated with rapid and severe nerve damage, whereas lepromatous disease is associated with chronicity and long-term complications. Borderline disease is unstable and can be complicated by reactions. There is also a simpler field classification determined by the number of skin patches: s(more than five patches). Patients with multibacillary leprosy are more likely

Serology and PCR for diagnosis

A simple diagnostic test to support the diagnosis of paucibacillary leprosy would be useful. Neither serology nor PCR has a role for this at present.4 Antibodies to the M leprae specific PGL-I are present in 90% of patients with untreated lepromatous disease, but only 40–50% of patients with paucibacillary disease, and 1–5% of healthy controls.37, 99 PCR for detection of M leprae DNA encoding specific genes or repeat sequences is potentially highly sensitive and specific, since it detects M

Chemotherapy

The first-line drugs against leprosy are rifampicin, clofazimine, and dapsone. All patients should receive a multidrug combination with monthly supervision (table 2). Current controversies focus on the length of treatment, the mode of treatment, and relapse rates. Dapsone was the first effective antimicrobial agent against M leprae.65 The multidrug combinations were introduced without formal clinical trials in the 1982 when rates of primary and secondary dapsone resistance of 30% were reported.

Prophylaxis against leprosy

BCG gives variable protective efficacy against leprosy in different countries, ranging from 34% to 80%. In a trial in Malawi, BCG induced 50% protective efficacy against clinical leprosy, both tuberculoid and lepromatous forms,137 and reimmunisation with BCG increased the protective effect by a further 50%. This protective effect of BCG has been confirmed in many case-control studies. Therefore, BCG immunisation of children for tuberculosis can also contribute to leprosy control. The addition

Women and leprosy

Women with leprosy are in double jeopardy, because not only might they develop postpartum nerve damage, but also they are at particular risk of social ostracism with rejection by spouses and family.141 There is little evidence that pregnancy itself causes new disease or relapse. There is, however, a clear temporal association between the development of type 1 reactions and neuritis and parturition, when cell-mediated immunity returns to prepregnancy intensity.142 In an Ethiopian study, 42% of

What is necessary to eradicate leprosy?

The major commitment of national governments, WHO, non-governmental organisations, and international donor bodies has resulted in improved leprosy control and the large fall in leprosy prevalence observed over the past decade. However, the perception that leprosy has reached an arbitrary point at which it is no longer a public-health problem could lead to a reduction in control measures at the very time when further efforts are required. The continuing detection of new leprosy cases at an

Search strategy and selection criteria

Papers for this review were identified by searches of MEDLINE and PubMed with the search terms “Mycobacterium leprae”, “leprosy”, “immunology”, “leprosy reactions”, and “treatment” from 1993 to December, 2002. Only papers published in English were considered. Furthermore, we both identified any new work of relevance reported at the International Leprosy Congress in Salvador, Brazil, in August, 2002. DL was a member of the International Leprosy Association Technical Forum that undertook a

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