Leprosy

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, primarily affecting the peripheral nerves and skin.

The clinical picture depends on the individual's immune response to M. leprae, ranging from tuberculoid leprosy with few skin lesions to lepromatous leprosy (MB) with uncontrolled bacterial spread and skin and mucosal infiltration. Peripheral nerve damage occurs across the spectrum. Nerve damage may occur before, during, or after treatment, in some cases putting people at risk of developing deformity and contractures. Visible deformities cause stigmatization. Classification is based on clinical appearance and bacterial index of lesions. The WHO field leprosy classification is based on the number of skin lesions: paucibacillary leprosy (PB: 1–5 skin lesions) and multibacillary leprosy (MB: more than 5 skin lesions).

Disease Burden: 

Worldwide, about 220,000 new cases of leprosy are reported each year, and about 2 million people have leprosy-related disabilities. Three major endemic countries (India, Brazil, and Indonesia) account for nearly 80% of all new cases in the world.

Complications of leprosy include nerve damage, immunological reactions, and bacillary infiltration. Without treatment, tuberculoid infection eventually resolves spontaneously. Most people with borderline tuberculoid and borderline lepromatous leprosy gradually develop lepromatous infection. Many people have peripheral nerve damage at the time of diagnosis, ranging from 15% to 55% in Ethiopia. Immunological reactions can occur with or without antibiotic treatment. Further nerve damage occurs through immune-mediated reactions (type 1 reactions) and neuritis. Erythema nodosum leprosum (type 2 reactions) is an immune complex-mediated reaction causing fever, malaise, and neuritis, which occurs in 20% of people with lepromatous leprosy, and in 5% with borderline lepromatous leprosy. Secondary impairments (wounds, contractures, and digit resorption) occur in 33% to 56% of people with established nerve damage.

Transmission Dynamics: 

M. leprae is discharged from the nasal mucosa of people with untreated lepromatous leprosy, and spreads, via the recipient's nasal mucosa, to infect their skin and nerves. It is a hardy organism and has been shown to survive outside human hosts in India for many months. Risk factors for infection, when known, include household contact with a person with leprosy.

Interventions: 

The current leprosy control strategy is formulated by the WHO as the ‘Enhanced global strategy for further reducing the disease burden due to leprosy 2011–2015’. The strategy aims to reduce the global rate of new cases with grade-2 (i.e. visible) disabilities per 100,000 population by at least 35% by the end of 2015, compared with the baseline at the end of 2010. The approach underlines the importance of early detection and treatment with multidrug therapy and quality of care in an integrated service setting. WHO expects this strategy to reduce the transmission in the community and thus lower the occurrence of new cases.

The main partners in leprosy control are the WHO (through the Global Programme for Leprosy based in New Delhi), the national leprosy control units in endemic countries, and the leprosy NGOs, jointly represented by ILEP (The International Federation of Anti-Leprosy Associations).

Modelling Questions: 

The policy questions concern the adequacy of the current intervention of case detection and treatment and their effectiveness in different settings and locations. The global new case detection figures are determined primarily by India, and to a lesser extent Brazil and Indonesia. Global analysis is therefore not very meaningful and model analyses should be done at country or regional level. 

  1. What is the rate of decline of new case detection in the most highly endemic countries/regions of the world? These estimates determine whether specific targets are likely to be met.
  2. How do the reproduction numbers vary between countries/regions? In particular, are there countries/regions in which chains of transmission continue, suggesting that leprosy will remain endemic in the face of the current intervention strategy? If there are such situations, then additional efforts are required.
  3. What is the likely impact of introducing interventions targeting contacts of leprosy patients, in addition to population-based interventions? Interventions targeting contacts are: 1) contact tracing; 2) post-exposure prophylaxis (single dose rifampicin); 3) immune-prophylaxis (BCG, specific leprosy vaccine); and 4) early diagnosis of (pre-clinical) leprosy (specific T-cell or serological tests). Population-based interventions include BCG vaccination and mass treatment of leprosy foci with post-exposure prophylaxis.
  4. Is there evidence of a significant impact of reservoir hosts on transmission? In the USA transmission of leprosy from wild armadillos has been demonstrated; however, it is not clear if such transmission from animal reservoirs will pose a barrier to meeting goals. Eradication of disease will require eradication from reservoirs.

Modelling publications