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PROFESSIONALS
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MALARIA PROPHYLAXIS FOR PATIENTS WITH PORPHYRIA TRAVELLING IN SOUTHERN AFRICA
INTRODUCTION Malaria is the disease which results from infection by the malaria parasite called Plasmodium, which is spread by a particular type of mosquito, with infection resulting from a mosquito bite. There are four species of Plasmodium. In southern Africa, by far the most common species is Plasmodium falciparum. This is somewhat unfortunate since it not only causes the most severe disease, but has a strong tendency to become resistant to the drugs used for prevention and treatment. In particular, chloroquine, a drug which was widely used until fairly recently in southern Africa, is now useless because of widespread chloroquine resistance in Plasmodium falciparum. The other three species of parasite, P. vivax, P. malariae and P. ovale are uncommonly encountered in southern Africa. Though they are mostly chloroquine-sensitive, the treatment is more complicated in that they require treatment with a second drug, primaquine, since these parasites have the ability to shelter in the liver as well as the bloodstream, unlike Plasmodium falciparum which confines itself to the bloodstream. PREVENTION OF MALARIA In order to reduce the risk of developing malaria, sensible precautions must be taken. Simple steps to lessen the risk of being bitten by mosquitoes in the first place will substantially reduce the risk of malaria. Wear adequate clothing, use insect-repellent sprays and employ impregnated sleeping nets. Avoid being out of doors at dusk when mosquitoes are most active. The frequency of malaria in southern Africa is also highly seasonal, and cases of malaria are very much less likely during the dry season than in the rainy season. All travelers must understand the necessity of recognising possible malaria, and should seek urgent medical assistance in the event that any suspicious symptoms occur. Should you travel in a country with unreliable medical services, it is wise to carry a course of quinine tablets so that you can begin treatment yourself in the event that you develop symptoms of malaria. You should, however, return urgently to a country such as South Africa with appropriate medical services, since self treatment is not a substitute for prompt consultation with a doctor with the knowledge and resources to undertake diagnosis and treatment. In addition to the sensible precautions, appropriate prophylactic use of antimalarial drugs is important. DRUGS USED FOR THE PREVENTION OF MALARIA The following recommendations are intended for patients with acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP). Patients with porphyria cutanea tarda (PCT) and erythropoietic protoporphyria (EPP) are not drug-sensitive, and may use antimalarial drugs freely. DISCLAIMER Note that the safety of the drugs recommended here cannot be guaranteed. These are newer drugs and there is still little actual clinical experience of their use in porphyria. However, on current information, they would not be expected to result in an exacerbation of porphyria.
Drugs recommended for use The following are the drugs recommended for use in porphyria. Atovaquone plus proguanil These drugs are combined in a single tablet as Malanil in South Africa and Malarone elsewhere. The combination is effective in preventing malaria in southern Africa. Proguanil is known to be safe in porphyria. Atovaquone appears on consideration to be safe since it is not significantly metabolised. Common side effects reported with this combination include abdominal pain, nausea, vomiting, skin rashes and headache. The drug is contraindicated in children weighing less than 11 kg, in pregnant or breast-feeding women and in patients with severe renal impairment. Mefloquine (Lariam ) There is some clinical experience with mefloquine in patients with porphyria and the drug appears to be well tolerated in these patients. Common side effects include headache, nausea, dizziness, poor sleeping, anxiety and dreaming. More serious side effects include depression, psychosis and seizures. The drug is contraindicated in people with a history of depression, psychosis or other major psychiatric problems, seizures and disturbances of heart rhythm.
Drugs which should not be used Dapsone-pyrimethamine (Maloprim ) Dapsone is known to be dangerous in porphyria, and as a combination is any event no longer useful for prevention of malaria because of widespread resistance. Chloroquine Chloroquine is safe in porphyria, however, all falciparum malaria is chloroquine-resistant in southern Africa and chloroquine therefore has no place in the prevention of porphyria. Proguanil, (Paludrine ) and proguanil/chloroquine combination (Daramol ) Both agents are safe for use in porphyria but are considerably less effective in preventing malaria than mefloquine and atovaquone/proguanil and are therefore not recommended for use in southern Africa.
Drugs which should be used with extreme caution only Doxycycline Though previously reported as unsafe in porphyria, more recent work has suggested that doxycycline may be safer than was previously thought since it undergoes little hepatic metabolism. However, since its safety is contentious we do not recommend it unless there are strong contraindications to the use of the drugs recommended above, mefloquine or atovaquone/proguanil. Where doxycycline is used, you must remain extremely cautious. Any symptoms suggestive of an incipient acute attack, particularly abdominal pain, indicating urgent need to stop the drug and to seek the assistance of a doctor experienced in the management of porphyria consulted; this will almost certainly mean an urgent interruption of your travels. Halofantrine There is no information on the safety of halofantrine in porphyria. However the use of halofantrine is generally discouraged because of the risk of cardiovascular side effects. Artemisinin-lumefantrine (Coartem ) This is a potentially useful drug combination in the management of malaria. Unfortunately the safety of either component in porphyria is not yet established. Both are metabolized by the cytochrome P450 system which implies that porphyria induction is a possibility. It should therefore be used with extreme caution only, and any experience with its use in porphyria should be reported to us.
TREATMENT OF MALARIA Drugs recommended for use Quinine sulphate Quinine sulphate as a single agent is highly effective in the treatment of porphyria and should be given for a fall 10-day course. This is the recommended treatment in porphyria. Mefloquine This is used in higher doses for treatment than for prophylaxis and therefore has a higher incidence of side-effects. Though not entirely proven to be safe in porphyria, it would appear to be an acceptable alternative to quinine. Drugs to be avoided Chloroquine All falciparum malaria is chloroquine-resistant in southern Africa, and chloroquine therefore has no place in the treatment of malaria. Doxycycline, tetracycline and clindamycin Most guidelines for the management of malaria suggest that doxycycline, tetracycline or clindamycin be given in addition to quinine in order to shorten the length of the course of treatment. This is however unnecessary provided that a full 10 day course of quinine is given. Since these three agents may potentially be hazardous in porphyria, their use is not recommended Fansidar (Sulfadoxine and pyrimethamine combination) Sulfadoxine is absolutely contraindicated in porphyria as it may induce acute attacks.
NON-FALCIPARUM MALARIA The Plasmodium parasites responsible for the vivax, malariae and ovale forms of malaria are typically still sensitive to chloroquine. Therefore chloroquine therapy remains appropriate treatment for these infections provided that the possibility of coexistent falciparum malaria has been excluded. Since these forms of malaria also have a hepatic phase as well as a blood phase (as described in introduction), chloroquine must be followed by additional primaquine therapy to eradicate parasites within the liver. Primaquine is safe in porphyria.
FURTHER INFORMATION For comprehensive information on malaria in southern Africa, consult the malaria pages of the US Centers for Disease Control.
TRAVELLING TO AREAS OTHER THAN SOUTHERN AFRICA These notes are intended for people traveling in southern Africa. Recommendations for other areas of the world in which malaria may be encountered will differ since different types of malaria, with varying degrees of drug-resistance are encountered. If you are traveling to another area, we suggest that you consult the appropriate authorities or else the Centers for Disease Control web site to determine which prophylactic regimens are recommended. With this information, you should check their safety of the recommended drugs against the information contained in this document or approach us for advice on prophylaxis in your with your specific circumstances. You can also contact the Medicines Safety Centre (Dept of Pharmacology, University of Cape Town, Tel. +27 (0) 21-4066427) for updated information on risk profiles for particular destinations.
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