Dapsone Health Dictionary

Also known as Hansen’s disease, this is a chronic bacterial infection caused by Mycobacterium leprae affecting the skin, mucous membranes, and nerves. Infection is now almost con?ned to tropical and subtropical countries – mostly in Africa and India. There are two distinct (polarised) clinical forms: tuberculoid and lepromatous. The former usually takes a benign course and frequently burns out, whereas the latter is relentlessly progressive; between these two polar forms lies an intermediate/dimorphous group. Susceptibility may be increased by malnutrition. Nasal secretions (especially in lepromatous disease) are teeming with M. leprae and constitute the main source of infection; however, living in close proximity to an infected individual seems necessary for someone to contract the disease. M. leprae can also be transmitted in breast milk from an infected mother.

Only a small minority of those exposed to M. leprae develop the disease. The incubation period is 3–5 years or longer. The major clinical manifestations involve skin and nerves: the former range from depigmented, often anaesthetic areas, to massive nodules; nerve involvement ranges from localised nerve swelling(s) to extensive areas of anaesthesia. Advanced nerve destruction gives rise to severe deformities: foot-drop, wrist-drop, claw-foot, extensive ulceration of the extremities with loss of ?ngers and toes, and bone changes. Eye involvement can produce blindness. Laryngeal lesions produce hoarseness and more serious sequelae. The diagnosis is essentially a clinical one; however, skin-smears, histological features and the lepromin skin-test help to con?rm the diagnosis and enable the form of disease to be graded.

Although the World Health Organisation had originally hoped to eliminate leprosy worldwide by 2000, that has proved an unrealistic target. The reason is an absence of basic information. Doctors are unable to diagnose the disorder before a patient starts to show symptoms; meanwhile he or she may have already passed on the infection. Doctors do not know exactly how transmission occurs or how it infects humans – nor do they know at what point a carrier of the bacterium may infect others. The incidence of new infections is still more than 650,000 cases a year or about 4.5 cases per 10,000 people in those countries worst affected by the disease.

Treatment Introduction of the sulphone compound, dapsone, revolutionised management of the disease. More recently, rifampicin and clofazimine have been added as ?rst-line drugs for treatment. Second-line drugs include minocycline, o?oxacin and clarithromycin; a number of regimens incorporating several of these compounds (multi-drug regimens – introduced in 1982) are now widely used. A three-drug regime is recommended for multi-bacillary leprosy and a two-drug one for parcibacillary leprosy. Dapsone resistance is a major problem worldwide, but occurs less commonly when multi-drug regimens are used. Older compounds – ethionamide and prothionamide

– are no longer used because they are severely toxic to the liver. Corticosteroids are sometimes required in patients with ‘reversal reaction’. Supportive therapy includes physiotherapy; both plastic and orthopaedic surgery may be necessary in advanced stages of the disease. Improvement in socio-economic conditions, and widespread use of BCG vaccination are of value as preventive strategies. Early diagnosis and prompt institution of chemotherapy should prevent long-term complications.... leprosy

A combination of PYRIMETHAMINE and DAPSONE which is used for the prevention of MALARIA in limited circumstances. It has the advantage of only needing to be taken once weekly. It should not be taken by anyone hypersensitive to sulphonamides, and should not be used for the treatment of an acute attack.... maloprim

An antimalarial drug used with either sulfadoxine or DAPSONE to treat Plasmodium falciparum malariae (see MALARIA). It should not be used for PROPHYLAXIS because of potentially severe side-effects when used in the long term.... pyrimethamine

A chronic bacterial infection, also called leprosy, that damages nerves, mainly in the limbs and facial area, and may cause skin damage. The disease is caused by a bacterium,MYCOBACTERIUM LEPRAE, which is spread in droplets of nasal mucus. Hansen’s disease is not highly contagious, and a person is infectious only in the early stages. Prolonged close contact puts people at risk. The disease is most prevalent in Asia, Central America, South America, and Africa.

Hansen’s disease has a long incubation period – about 3–5 years. There are 2 main types: the lepromatous type, in which damage is widespread, progressive, and severe; and the tuberculoid type, which is milder. In both types, damage is initially confined to peripheral nerves supplying the skin and muscles. Skin areas supplied by affected nerves become lighter or darker and sensation and sweating are reduced. As the disease progresses, the peripheral nerves swell and become tender. Hands, feet, and facial skin eventually become numb and muscles become paralysed, leading to deformity. Other possible features include blindness, destruction of bone, and sterility.

The presence of the causative bacteria is confirmed by a skin biopsy. Drug treatment may be with a combination of dapsone, rifampicin, and clofazimine, which kills most of the bacteria in a few days. Any damage that has occurred before treatment, however, is irreversible. Plastic surgery may be necessary to correct deformities; and nerve and tendon transplants may improve the function of damaged limbs.... hansen’s disease

n. one of a group of drugs closely related to the *sulphonamides in structure and therapeutic actions. Sulphones possess powerful activity against the bacteria that cause leprosy and tuberculosis. The best known sulphone is *dapsone.... sulphone

A parasitic disease caused by four species of PLASMODIUM: P. falciparum, P. vivax, P. ovale, and P. malariae. Clinically, malaria is characterised by recurrent episodes of high fever, sometimes associated with RIGOR; enlargement of the SPLEEN is common. P. falciparum infection can also be associated with several serious – often fatal – complications (see below): although other species cause chronic disease, death is unusual.

During a bite by the female mosquito, one or more sporozoites – a stage in the life-cycle of the parasite – are injected into the human circulation; these are taken up by the hepatocytes (liver cells). Following division, merozoites (minute particles resulting from the division) are liberated into the bloodstream where they invade red blood cells. These in turn divide, releasing further merozoites. As merozoites are periodically liberated into the bloodstream, they cause the characteristic fevers, rigors, etc.

Malaria occurs in many tropical and subtropical countries; P. falciparum is, however, con?ned very largely to Africa, Asia and South America. Malaria is present in increasingly large areas; in addition, the parasites are developing resistance to various preventative and treatment drugs. The disease constitutes a signi?cant problem for travellers, who must obtain sound advice on chemoprophylaxis before embarking on tropical trips – especially to a rural area where intense transmission can occur. Transmission has also been recorded at airports, and following blood transfusion.

The World Health Organisation (WHO) has listed malaria as one of Europe’s top ten infectious diseases. In 1992, 20,000 cases were reported: this had risen to more than 200,000 by the late 1990s. The resurgence of malaria has been worldwide, in part the result of the development of resistant strains of the disease, and in part because many countries have failed (or been unable) to implement environmental measures to eliminate mosquitoes. Nearly 40 years ago the WHO forecast that by 1980 only four million people would be affected worldwide; now, at the beginning of the 21st century, around 500 million people a year are contracting malaria with about 3,000 people a day dying from the infection – as many as 70 per cent of them children under the age of ?ve, according to WHO ?gures. The apparently steady advance of global warming means that countries with temperate climates may well warm up su?ciently to enable malaria to become established as an ENDEMIC disease. In any case, the great increase in international air travel has exposed many more people to the risk of malaria, and infected individuals may not exhibit symptoms until they are back home. Doctors seeing a recent traveller with unexplained pyrexia and illness should consider the possibility of malarial infection.

Diagnosis is by demonstration of trophozoites – a stage in the parasite’s life-cycle that takes place in red blood cells – in thick/thin blood-?lms of peripheral blood. Serological tests are of value in deciding whether an individual has had a past infection, but are of no value in acute disease.

P. vivax and P. ovale infections cause less severe disease than P. falciparum (see below), although overall there are many clinical similarities; acute complications are unusual, but chronic ANAEMIA is often present. Primaquine is necessary to eliminate the exoerythrocytic cycle in the hepatocyte (liver cell).

P. falciparum Complications of P. falciparum infection include cerebral involvement (see BRAIN – Cerebrum), due to adhesion of immature trophozoites on to the cerebral vascular endothelium; these lead to a high death rate when inadequately treated. Renal involvement (frequently resulting from HAEMOGLOBINURIA), PULMONARY OEDEMA, HYPOTENSION, HYPOGLYCAEMIA, and complications in pregnancy are also important. In complicated disease, HAEMODIALYSIS and exchange TRANSFUSION have been used. No adequate controlled trial using the latter regimen has been carried out, however, and possible bene?ts must be weighed against numerous potential side-effects – for instance, the introduction of a wide range of infections, overload of the circulatory system with infused ?uids, and other complications.

P. malariae usually produces a chronic infection, and chronic renal disease (nephrotic syndrome) is an occasional sequel, especially in tropical Africa.

Gross SPLENOMEGALY (hyper-reactive malarious splenomegaly, or tropical splenomegaly syndrome) can complicate all four human Plasmodium spp. infections. The syndrome responds to long-term malarial chemoprophylaxis. BURKITT’S LYMPHOMA is found in geographical areas where malaria infection is endemic; the EPSTEIN BARR VIRUS is aetiologically involved.

Prophylaxis Malaria specialists in the United Kingdom have produced guidance for residents travelling to endemic areas for short stays. Drug choice takes account of:

risk of exposure to malaria;

extent of drug resistance;

e?cacy of recommended drugs and their side-effects;

criteria relevant to the individual (e.g. age, pregnancy, kidney or liver impairment). Personal protection against being bitten by

mosquitoes is essential. Permethrinimpregnated nets are an e?ective barrier, while skin barrier protection and vaporised insecticides are helpful. Lotions, sprays or roll-on applicators all containing diethyltoluamide (DEET) are safe and work when put on the skin. Their e?ect, however, lasts only for a few hours. Long sleeves and trousers should be worn after dark.

Drug prophylaxis should be started at least a week before travelling into countries where malaria is endemic (two or three weeks in the case of me?oquine). Drug treatment should be continued for at least four weeks after leaving endemic areas. Even if all recommended antimalarial programmes are followed, it is possible that malaria may occur any time up to three months afterwards. Medical advice should be sought if any illness develops. Chloroquine can be used as a prophylactic drug where the risk of resistant falciparum malaria is low; otherwise, me?oquine or proguanil hydrochloride should be used. Travellers to malaria-infested areas should seek expert advice on appropriate prophylactic treatment well before departing.

Treatment Various chemoprophylactic regimes are widely used. Those commmonly prescribed include: chloroquine + paludrine, me?oquine, and Maloprim (trimethoprim + dapsone); Fansidar (trimethoprim + sulphamethoxazole) has been shown to have signi?cant side-effects, especially when used in conjunction with chloroquine, and is now rarely used. No chemotherapeutic regimen is totally e?ective, so other preventive measures are again being used. These include people avoiding mosquito bites, covering exposed areas of the body between dusk and dawn, and using mosquito repellents.

Chemotherapy was for many years dominated by the synthetic agent chloroquine. However, with the widespread emergence of chloroquine-resistance, quinine is again being widely used. It is given intravenously in severe infections; the oral route is used subsequently and in minor cases. Other agents currently in use include me?oquine, halofantrine, doxycycline, and the artemesinin alkaloids (‘qinghaosu’).

Researchers are working on vaccines against malaria.... malaria

n. an inflammatory condition of the skin caused by outside agents (compare eczema, an endogenous disease in which such agents do not play a primary role, although some use the two terms interchangeably). Irritant contact dermatitis may occur in anyone who has sufficient contact with such irritants as acids, alkalis, solvents, and (especially) detergents. It is the commonest cause of occupational dermatitis in hairdressers, nurses, cooks, etc. (See also napkin rash.) In allergic contact dermatitis skin changes resembling those of eczema develop as a delayed (type IV) reaction to a particular allergen, which may be present at low concentrations. Common examples include nickel dermatitis (from costume jewellery, clothing fasteners, zips, etc.) and fragrance allergy (from toiletries, deodorants, perfumes, etc.). Treatment of dermatitis depends on identifying the allergen by *patch testing and removing the cause, which is not always possible.

Dermatitis herpetiformis is an uncommon very itchy rash with symmetrical blistering, especially on the knees, elbows, buttocks, and shoulders. It is associated with *gluten sensitivity and responds well to treatment with dapsone or a gluten-free diet.... dermatitis