In the past, leprosy sufferers were strictly avoided or isolated in a leprosarium. This completely disrupted the social lives of the people affected. Patients hid themselves and withdrew from care. Until the Second World War chaulmoogra oil, applied orally, topically or by injection, was the only treatment available. This oil was obtained from the seeds of the Hydnocarpus tree (H. kurzii or H. anthelmintica, family Flacourtiaceae). Similar oil was obtained from the related trees Gynocardia odorata (family Flacourtiaceae) or Taraktagenos (family Bixaceae). The round brown fruits of the Hydnocarpus tree are the size of an orange and contain many seeds measuring 2 cm long which are very rich in oil. The use of the oil was described in 1854 by Dr Mouat of the Bengal Medical Service. No one in the West then knew, however, the precise source of this oil. The oil was used widely and it was important to know from where it came. It was known that the fruit could be found from time to time at markets in China, Burma and India, and that the plant belonged to the Flacourtiaceae family. After an expedition organised by the USDA the tree was finally found in 1920 in central Burma by John Rock, a man with the reputation of being able to do the impossible. Plantations were set up with the seeds collected, in Hawaii and elsewhere. In 1975 it was shown via the mouse-footpad model that chaulmoogric acid, a component of the oil, did indeed possess activity against M. leprae. The use of this oil has been abandoned at present.

Dapsone was first synthesised by Fromm and Whitmann in 1908, but it was used exclusively in veterinary medicine for streptococcal mastitis. In 1941 it was discovered that Promin® (sodium glucosulphone) PO and IV could produce an improvement in leprosy. Diasone, another sulphone, was better tolerated, but was later replaced by dapsone. The first cases of dapsone resistance were reported in 1964. In the '60s the efficacy of clofazimine was discovered. In 1965 the activity of thalidomide in ENL was ascertained. In the late ‘60s and early ‘70s rifampicine was developed, and this exhibited exceptional efficacy. Because of the increasing resistance to dapsone, in 1982 the WHO proposed to use only combination regimens. With modern therapy the infectivity falls very swiftly (a few weeks). People are being cared for more and more in their normal environment. This requires huge efforts in follow-up. Rehabilitation, orthopaedic aids, good shoes and eye care are very important. Surgical reconstruction, tendon transplantations etc. have their place, but require specialised physicians. The instruction of patients, chiefly concerning checking wounds and foot hygiene, is very important. Prompt treatment of wounds can prevent much suffering.

The antileprosy activity of this sulphone was ascertained in the ‘40s and until 1980 it was often used in monotherapy (initially IM, later PO). It is safe during pregnancy. Dapsone (=DDS; Diamino Diphenyl Sulphone) is a slow-acting bacteriostatic product. It is swiftly absorbed from the intestine and undergoes enterohepatic circulation. A steady-state serum concentration is reached approximately eight days after beginning the treatment. It has a half-life of 28 hours and should therefore be taken just once daily. Dapsone resistance is presently spread world-wide. Dapsone is generally well tolerated. In particular at higher dosages skin rash, haemolysis (even if there is no G6PD deficiency) and methaemoglobinaemia occur (cyanosis and signs of hypoxia due to oxidation of haem Fe²⁺ ® Fe³⁺: the latter does not bind to oxygen. Methaemoglobinaemia is treated with IV methylene blue, 1-2 mg per kg). A "dapsone syndrome" may occur rarely. This is a hypersensitivity reaction, characterised by skin rash, fever, icterus and eosinophilia within 6 weeks after beginning dapsone. Desensitisation may need to be carried out. Dapsone is also used in the treatment and prevention of Pneumocystis carinii, in the treatment of toxoplasmosis, in dermatitis herpetiformis, in Loxosceles bites (see the chapter "spiders") and in a number of other more rare disorders. Dapsone is contained in Lapdap® and Maloprim®, agents for malaria prophylaxis now seldom used.

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Note: Some applications of dapsone:

• Treatment of leprosy
• Prevention of Pneumocystis carinii
• Prevention of Toxoplasma gondii
• Prevention of malaria
• Loxosceles bites (spiders)
• Treatment of dermatitis herpetiformis

Rifampicin (Rifadin®, Rimactan®) (id. Rifampin) is a highly active but expensive bactericidal agent. It sometimes causes liver damage. See also tuberculosis. It may be used during pregnancy, although there are isolated reports of congenital deformities. Spina bifida and hare lip were observed in the progeny of rodents when the product was administered at high doses during pregnancy.

Clofazimine is a weak bactericidal agent. It has anti-lepromatous and anti-inflammatory properties. This lipophilic drug is best taken after a meal for better absorption. It accumulates slowly in the skin, where it may cause dryness and red discoloration. The latter may sometimes cause difficulties in white patients. The urine, tears and sweat are also stained red. Sometimes there is nausea. In rare cases there is severe enteritis with paralytic ileus. The tissue half-life is very long (70 days). If clofazimine is used in type 2 leprosy reactions, the effect is usually only noticeable after 4 to 6 weeks. Clofazimine passes the placental barrier and is present in breast milk. Neonates may then also exhibit hyperpigmentation. It is probably safe during pregnancy.

Some combination therapies may still be used. Other regimens are being tested at present (including ofloxacin and minocycline).

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For 6 months

• Rifampicin 600 mg/once per month under supervision
• Dapsone 100 mg/day without supervision

Then keep under supervision for a further 2 years, for late leprosy reactions and any relapse.

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For 2 years

• Rifampicin 600 mg/once per month under supervision
• Clofazimine 300 mg/once per month under supervision
• Clofazimine 50 mg/day without supervision
• Dapsone 100 mg/day without supervision

Then keep under supervision for a further 5 years (or life-long in LL).

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These regimens are usually quickly accepted and have little toxicity. Relapses seldom occur. Sometimes a few variations are used. For example, in India multibacillary patients initially receive oral rifampicin daily for 14 days and paucibacillary patients are treated for one year.

Brief therapies with Rifampicin-Ofloxacin-Minocycline ± Clofazimine ("ROM" and "ROMC") have been tested for both paucibacillary and multibacillary leprosy. The final results of these trials are expected around 2004. According to the interim analysis there is a 2 per 100 patient years relapse after 6 years (daily ROM and weekly minocycline for 6 weeks). More recent data point to higher failure rates and this short-course treatment is not likely to become the standard treatment.

There are very few data on leprosy and pregnancy. During pregnancy there is progressive reduction of the cellular resistance, but the humoral immunity is probably stimulated. In theory fewer type 1 reactions would be expected during pregnancy. On the other hand, type 2 reactions may be more frequent. Possibly there is an increase in the bacillary load in untreated patients. Since the disease may become worse during pregnancy, the medication is continued unchanged. The use of thalidomide during pregnancy is of course forbidden.