See Artemether.
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
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