Leprosy is a chronic mycobacterial infection that affects some 10 to 12 million people, mainly in Africa, Asia and South America.

The causative organism, Mycobacterium leprae, is a slow-growing intracellular bacillus that infiltrates the skin, the peripheral nerves, the nasal and other mucosae and the eyes. The disease is transmitted directly from person to person when bacilli are shed from the nose and open skin lesions of patients harbouring large numbers of organisms. M. leprae can enter the body through skin abrasions but the respiratory tract is probably the main portal of entry. The leprosy bacilli presumably cross the pulmonary alveoli without causing a primary lesion and reach their sites of nidation by haemogenous spread. The household contacts of leprosy patients are at greatest risk of acquiring the disease. However, most individuals have considerable natural immunity and many infections are suppressed. Indeed, clinical leprosy can be regarded as a consequence of deficient cell-mediated immunity in susceptible individuals.

Paucibacillary leprosy¹ results when cellular immunity is only partially deficient. Relatively few bacilli are demonstrable in skin smears. Granulomatous lesions in the dermis, which occasionally heal spontaneously, present as hypopigmented and hypo-aesthetic or anaesthetic patches. Peripheral nerve involvement may result in no more than minor, localized impairment of sensation but, in severe cases, extensive sensory and motor loss induces trophic changes, muscle wasting and contractures.

¹ Includes: smear-negative indeterminate and tuberculoid leprosy (Madrid classification); smear-negative indeterminate, polar tuberculoid, and borderline tuberculoid leprosy (Ridley and Jopling classification).

Multibacillary leprosy² occurs when cellular immunity is largely deficient. Rugose, nodular skin lesions result from infiltration of the dermis by incompetent macrophages loaded with M. leprae. Nerve damage also commonly occurs which, if left untreated, may lead to crippling deformities. This damage is mostly sustained during immunologically mediated inflammatory exacerbations, which are of two types:

• Type I (reversal reactions) resulting from a cell-mediated immune process and characterized by acute exacerbation of skin lesions and by focal or more generalized attacks of neuritis, sometimes resulting in permanent nerve damage.

• Type II (erythema nodosum leprosum) resulting from an immune-complex reaction and characterized by an antibody- dependent response. Discrete acute inflammatory lesions develop in the skin. Systemic symptoms, when they occur, include fever, lymphadenopathy, acute iridocyclitis and, less frequently, neuritis, polyarthritis and glomerulonephritis.

² Includes: lepromatous and borderline leprosy (Madrid classification); polar lepromatous, borderline lepromatous and mid -borderline leprosy (Ridley and Jopling classification); and smear-positive cases of other types of leprosy.

Visual impairment or blindness is frequent in both paucibacillary and multibacillary leprosy. It results either from mycobacterial infiltration and inflammation of structures in the anterior segment of the eye, or from trophic changes following damage to the trigeminal and facial nerves, resulting in lagophthalmos, deformed eyelids or corneal anaesthesia.

Control

Effective control of leprosy depends upon:

• efficient case detection, case-holding and treatment, and
• surveillance of contacts.

Those at risk, and particularly close family contacts, should remain under periodic surveillance whenever possible.

Vaccines containing a suspension of killed M. leprae are currently being field-tested but none is yet available for routine use.

Chemotherapy

Dapsone has served as the mainstay of treatment for many years. Its action is essentially bacteriostatic and long-term continuous daily dosage was necessary when it was used alone. Because resistant strains of M. leprae are now widespread, this simple approach to treatment can no longer be recommended. Combination therapy has become essential to inhibit the emergence of resistance. Rifampicin and clofazimine, which are relatively expensive, are most frequently used with dapsone in this way. A thioamide (ethionamide or protionamide) is sometimes used instead of clofazimine, but close medical supervision and monitoring of liver function are then required since these drugs are markedly hepatotoxic. Minocycline and some fluoroquinolones have shown promising bactericidal effects against M. leprae in mice but data from formal trials in humans are still awaited.

Recommended treatment regimens for leprosy^a

^a Doses are for adults of 50-70 kg.
^b Minimum duration of treatment: 6 months.
^c Minimum duration of treatment: 2 years and, when monitoring is feasible, until skin smears are negative.

Relatively short courses of oral multidrug therapy are currently recommended by WHO¹ on the assumption that the combined drugs will kill any single-drug-resistant strains initially present and will prevent their subsequent emergence during the period of treatment (see table above). It has been shown that compliance with the shorter-term treatment is better than with the older, longer-term regimens and it is expected that, with the current widespread adoption of the combined regimens by national control programmes, the intensity of transmission of M. leprae will be reduced.

¹A guide to leprosy control, 2nd ed. Geneva, World Health Organization, 1988, and WHO Technical Report Series, No. 768, 1988 (WHO Expert Committee on Leprosy, sixth report).

After treatment, patients with paucibacillary disease should remain under supervision for at least a further 2 years and those with multibacillary leprosy for a further 5 years.

Management of exacerbations

Chemotherapy should never be suspended during an exacerbation. Acute neuritis must be treated as a medical emergency. Type I reactions frequently respond to corticosteroids administered immediately in high dosage (for adults, 40-60 mg of prednisolone daily) for several days and subsequently in gradually reduced dosage over a period of several weeks or months in accordance with the clinical response. Surgery may be needed to relieve focal compression of peripheral nerves. The pain and inflammation associated with type II reactions (erythema nodosum leprosum) may be largely suppressed by analgesics and anti-inflammatory agents. Thalidomide, which is a potent anti-inflammatory agent, can offer valuable relief, but should not be used in women of childbearing age. The initial adult dosage of 100-400 mg each evening, which may cause drowsiness, should be reduced gradually. Corticosteroids and clofazimine are alternatives.

Care of ocular lesions

The eyes should be examined regularly even in patients with no ocular symptoms. Closure of the eyelids can often be improved in mild degrees of lagophthalmos simply by application of a good quality dermal tape, but in severe cases tarsorrhaphy is necessary. In the absence of corneal ulcers, iridocyclitis should be treated with topical corticosteroids applied six times daily and with daily instillations of atropine or another long-acting mydriatic until the attack subsides. Corticosteroid application should then be gradually reduced in frequency over a week, and continued twice daily for at least one further week before final withdrawal. Mydriatics should similarly be administered two or three times weekly for 2-4 weeks after the initial attack has subsided.

Corneal abrasions need to be treated as early as possible with an antibiotic eye ointment (tetracycline 1%). This is particularly important in patients with lagophthalmos and when corneal sensitivity is impaired. Several applications daily may be needed for a prolonged period. The patient should be referred urgently to an ophthalmologist if a corneal ulcer develops.

Care of trophic lesions

For details of the initial care of trophic lesions, see A guide to leprosy control, 2nd ed. (Geneva, World Health Organization, 1988). Secondary bacterial infection of trophic ulcers may lead to osteomyelitis, necessitating antibiotic therapy and surgical care.