Review
Leprosy now: epidemiology, progress, challenges, and research gaps

https://doi.org/10.1016/S1473-3099(11)70006-8Get rights and content

Summary

Leprosy continues to be a challenge to health worldwide, with about 250 000 new cases being detected every year. Despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. A third of newly diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to several factors, including level of self-care. Women who develop leprosy continue to be especially disadvantaged, with rates of late diagnosis and disability remaining high in this subgroup. Leprosy was not a specified disease in the Millennium Development Goals, but improvements in the other areas they cover, such as education and levels of poverty, will help leprosy patients and services. We review data and make recommendations for research on diagnosis, treatment, and prevention, such as further use of molecular analysis of the Mycobacterium leprae genome, implementation of BCG vaccination, and administration of chemoprophylaxis to household contacts. We also suggest development of tools for early diagnosis and detection of infection and nerve damage, and formulation of strategies to manage the chronic complications of leprosy, such as immune-mediated reactions and neuropathy.

Introduction

Leprosy is the leading infectious cause of disability.1 Prevalence has fallen substantially in the past 50 years,2 but transmission continues and leprosy remains a public health problem.3 Various hindrances remain to reducing this prevalence further. The mode of transmission of leprosy is not well understood, although it is probably person to person via nasal droplets.4 How many infected people develop clinical disease and whether reactivation of past infections is important are unknown. Although making a clinical diagnosis is frequently straightforward, no good point-of-care test is available for confirming it. Delay in diagnosis can have important negative outcomes, such as increased risk of nerve damage. Various factors contribute to delay, but stigma is an important feature in many cultures.5 Additionally, the immune responses and the mechanisms involved in nerve damage are not clearly understood; there is no predictive test for the extent of nerve damage and no good evidence on the best treatment. Type 1 and type 2 immune-mediated reactions continue to be major complications, and affect around 30% of patients.

WHO has set a target for reducing the number of cases with grade 2 disability at diagnosis, but the feasibility of reporting disability accurately needs to be assessed. The integration of leprosy services into general health services has led to a loss of skills in the diagnosis and management of leprosy. WHO recommends multidrug therapy for 6 months in patients with paucibacillary disease (up to five skin lesions) and for 12 months in patients with multibacillary disease (more than five skin lesions).3 These regimens might, however, be insufficient for patients with lepromatous disease and high bacterial indices, and no alternative drug regimens are currently recommended.6 Drug resistance has not so far been an issue with multidrug therapy,7 but monitoring is essential.

Various areas of research are a priority in the worldwide management of leprosy. Contacts of leprosy patients are at increased risk of infection;8 chemoprophylaxis and BCG vaccination reduce this risk but the logistics, ethics, and the cost-effectiveness of offering chemoprophylaxis are not simple. Research is needed, therefore, to inform future policies. New avenues for basic science and clinical research have been opened by sequencing the genome of Mycobacterium leprae and genome-wide analysis of leprosy cases.9, 10, 11 Genomic data might be useful in the development of drugs and vaccines against leprosy. Health-care features that require research are how to ensure equality in access to facilities for early diagnosis and to rehabilitation services, and ways to reduce stigma.

In this Review we discuss the epidemiology of leprosy and the progress in and challenges to control, and make recommendations for research. The article is based on the review undertaken for the Disease-Specific Reference Group on tuberculosis, leprosy and buruli ulcer (one of the ten expert reference groups sponsored by the Special Programme for Research and Training in Tropical Diseases to assess the global research evidence on infectious diseases of poverty). We also take into account the WHO worldwide strategy for reducing the burden of disease related to leprosy,3 the decisions of its Technical Advisory Group on Leprosy Control,6 and the research findings in leprosy from 2002–09 drawn together by the International Federation of Anti-Leprosy Organisations Technical Commission.5

Section snippets

History of leprosy and leprosy control

DNA analysis of M leprae strains suggests that this bacterium originated in Africa and spread to Asia and South America.9 Dapsone monotherapy was effective and was started in the 1940s. Lifelong administration was required, however, and in the 1960s widespread resistance was reported.12 In 1981, WHO recommended that all patients should receive multidrug therapy comprising rifampicin and dapsone, or rifampicin, dapsone, and clofazimine for patients with multibacillary disease. In 1995, a

Epidemiology

The new case detection rate for leprosy remains high, with about 250 000 new cases being registered each year. Around 15 million people have been treated with multidrug therapy, and an estimated 2 million people have been prevented from developing disabilities.12 Although the leprosy prevalence values fell strikingly from 620 638 cases in 2002, to 213 036 in 2009,20, 21 this decrease is due partly to the prevalence vlaues being halved by the duration of treatment being reduced from 24 months to

Transmission

Leprosy is caused by M leprae. Most people infected with this organism are thought not to develop clinical disease, although there are no tools to diagnose subclinical infection. M leprae is slow growing and the incubation period of leprosy is long at 2–12 years. The mode of transmission is still not conclusively proven, although person-to-person spread via nasal droplets is believed to be the main route.4

Human beings are the principal reservoir of infection, except in the Americas, where

Clinical disease

Infection with M leprae leads to chronic granulomatous inflammation in skin and peripheral nerves. The type of leprosy that patients develop is determined by their cell-mediated immune response to infection. Types may be categorised according to the Ridley-Jopling classification,33 which is based on skin lesion type and bacterial load. Patients with tuberculoid disease have good cell-mediated immune response and few lesions with no detectable mycobacteria. Patients with lepromatous leprosy are

Treatment

WHO recommends multidrug therapy with rifampicin and dapsone for paucibacillary disease, or with rifampicin, dapsone, and clofazimine for patients with multibacillary disease. The recommended duration of therapy is 6 months for patients with paucibacillary disease and 12 months for those with multibacillary disease, and these regimens will effectively eradicate M leprae in most patients. The 2009 report of the WHO Technical Advisory Group on Leprosy Control stated clearly that “in public health

Diagnosis

Late diagnosis leads to continued transmission and to increased risk of disability.15 Factors associated with late diagnosis include delay by patients in presenting and delay by health services in making a diagnosis. Reasons behind patients delaying presentation vary from setting to setting,56 but stigma is likely to play a part in many cases.5 In some countries stigma is promoted by legislation against leprosy patients.5 Other inequalities also affect people with this disease. Reports from

Prevention

Chemoprophylaxis effectively lowers the incidence of leprosy in household contacts.61 Whether to use this approach more widely is under discussion. Single-dose rifampicin can prevent progression of disease in people infected with leprosy but only in non-close contacts with low bacterial loads.61 Fears of resistance with use of monotherapy, however, have led to the suggestion that one or two doses of 600 mg rifampicin, 400 mg ofloxacin, and 100 mg minocycline should be used.5 This regimen would,

Conclusions

Priorities for research in leprosy cover a wide range of areas, from basic science to health services. Further understanding is needed of the epidemiology, including transmission, the role of the armadillo, and relative contributions of transmission and reinfection to the overall disease burden, and of the pathogenesis of nerve damage. Effective tools must be developed for detection of early infection, for point-of-contact diagnosis, to predict nerve damage, and to grade disability. New

Search strategy and selection criteria

We reviewed the recommendations for research from the Leprosy International committees, and selected a list of relevant topics. We used the term “leprosy” with each of “drug resistance”, “nerve damage”, “detection and diagnosis of early infection”, “nerve damage”, “vaccines”, “chemoprophylaxis”, “diagnosis/grading disability”, “new treatment regimens for leprosy and for reactions”, “the role of armadillo, transmission”, “reactivation”, “patient and health services delays in diagnosis”,

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