LEPROSY

Leprosy is a chronic, communicable disease caused by Mycobacterium leprae

• The clinical spectrum of disease reflects the following:
  • bacterial proliferation and accumulation at the site of infection
  • the immunological response
  • peripheral neuritis
• Peripheral nerves, skin and mucous membranes are affected- M. leprae only grows on the colder surfaces of the body
• Leprosy is rarely an immediate cause of death

Incidence

• Leprosy occurs predominantly in South-East Asia, but also in Africa and the Americas
• There were about 1 million active cases world-wide in 1997, however, about 2 million people have irreversible deformities due leprosy
• Each year about 600 000 people are diagnosed as having leprosy
• The incidence is 2:1 males to females, although in Africa, it is 1:1

Incubation Period

• Leprosy can occur in a few weeks following exposure, however, cases developing 30 years after exposure have been described

Transmission

• M. leprae is not highly infectious
• Transmission is more common among household contacts
• Transmission is believed to occur through inhalation of infectious organisms
• Transmission through insect bites and inoculation through broken (or intact) skin have not been excluded
• Infectious people are thought to shed the organism from the nasal mucous membranes, especially if there is ulceration
• M. leprae can survive in nasal secretions for more than 36 hours
• Reinfection may account for cases of leprosy in older people
• At present there is conflicting information on the effect of HIV/AIDS on the incidence of leprosy
• Humans are considered to be the reservoir of infection
• M. leprae is found in wild, nine-banded, armadillos in the southern United States. This animal is the main source of M. leprae for research purposes.  Transfer from this organism to man has not been established firmly

Microbiology

• M. leprae resembles M. tuberculosis under the light microscope although pleomorphic forms may be present
• M. leprae has never been cultured in the laboratory
• M. leprae can be cultured transiently in the mouse footpad
• M. leprae is an intracellular pathogen- it escapes into the cytoplasm of the host cell
• M. leprae takes 20-30 days to divide (cf. E. coli which takes 20-40 minutes)
• The WHO recommends two indices for the quantification of infection: the bacteriological index (BI: a measure of bacterial load) and the morphological index (MI: a measure of bacterial viability)

Leprosy- Clinical Points

• Macules (flat), papules (raised) or nodular lesions  occur
• Areas of anesthesia
• Thickened nerves
• Superficial infection, on the cooler areas of the body
• Many of the clinical features are due to the loss of sensation and secondary injury to the areas of the body affected by this loss
• There is a continuum of disease from Lepromatous leprosy to Tuberculoid leprosy. Intermediate forms are borderline leprosy and indeterminate leprosy

lepromatous leprosy

• Diffuse or nodular lesions
• Contain many AFB's (multibacillary)
• Clumps of cells may occur as intra- and extracellular masses in capsular material known as globi
• Sensory loss due to nerve damage
• Predominant humoral response, little cell-mediated immunity

tuberculoid leprosy

• Few, well-defined lesions
• Few AFB's (puacibacillary)
• Predominant cell-mediated immunity
• Spontaneous regression of tuberculoid leprosy occurs in over 90% of cases in children

Leprosy WHO case definition

A person having one or more of the following features:

• Hypopigmented or reddish skin lesion(s) with definite loss of sensation
• Involvement of the peripheral nerves, as demonstrated by definite thickening with loss of sensation
• Skin smear positive for acid-fast bacilli

---

Diagnosis of Leprosy

A person living in an endemic area with the following cardinal signs is considered to have leprosy:

• Skin lesion (consistent with leprosy) with definite sensory loss, with or without thickened nerves
• Positive skin smear (found in a small proportion of cases)

In the eradication programmes, leprosy can be classified on the basis of clinical manifestations or on the results of skin smears.
Skin smears: if negative, patient has paucibacillary leprosy; if positive, patient has multibacillary leprosy
Clinical classification: if there is a single lesion the patient has paucibacillary leprosy; if there are multiple lesions the patient has multibacillary leprosy

The clinical criteria are often used in regions where smear diagnosis is unreliable

The Lepromin skin test- PPD based on proteins isolated from M. leprae can be used in epidemiological surveys to detect the occurrence of sub-clinical infection
(See also: Tuberculin Skin Tests)

Leprosy Treatment

• Multidrug Therapy (MDT) is highly effective
• Leprosy is never treated with a single drug to avoid the emergence of resistant strains
• Wound treatment and anti-inflammatory agents and supportive therapy may be required

Multibacillary leprosy

• Rifampicin: 600 mg once a month
• Dapsone: 100 mg daily
• Clofazimine: 300 mg once a month and 50 mg daily
• Duration 12 months 

Paucibacillary leprosy

• Rifampicin: 600 mg once a month
• Dapsone: 100 mg daily
• Duration 6 months

Single skin lesion paucibacillary leprosy (ROM Therapy)

• Rifampicin: 600 mg once a month
• Ofloxacin: 400 mg
• Minocycline: 100mg
• Single dose

  Treatment Notes

• Rifampicin kills >99.9% of the infecting microorganisms following a  single dose, this effect is not enhanced by more frequent doses. In addition,  rifampicin appears to have a  prolonged effect on inhibiting the division of the organism. Thus it is only administered once a month
• Clofazimine is a depot drug that is stored in the body and released slowly from the tissues, thus there is a need for a monthly 'loading dose.'

Elimination of Leprosy

Leprosy is an ancient disease that evokes strong emotion through fear and ignorance. The causative organism, M. leprae, was the first pathogen to be recognised and demonstrated in human tissue (Hansen, 1872). The slow growth of the pathogen, the apparent lack of environmental or animal reservoirs, low infectivity, and availability of effective therapy, make it an ideal target for elimination.

The World Health Organisation has introduced a multi-national programme based on the syndromic management of leprosy with the objective of eliminating the disease. The programme involves active case finding and multidrug therapy (MDT), as outlined above. Over the past 10 years there has been a 5-fold reduction in the prevalence of leprosy due to the success of this programme.

Thus leprosy may again gain historical prominence, but this time as the first bacterial disease to be eliminated from Earth.