Drug-resistant parasites constitute a persistent
TABLE 14.3 Antimalarial drugs and their locus of action
Drug Biological activity
Blood Tissue schizontocide schizontocide
problem. Plasmodium falciparum is now resistant to chloroquine in many parts of the world and the picture is changing monthly. Areas of high risk for resistant parasites include Sub-Saharan Africa, Latin America, Oceania (Papua New Guinea, Solomon Islands, Vanuatu) and some parts of South-East Asia. Chloroquine-resistant Plasmodium vivax is also reported. Any physician who is not familiar with the resistance pattern in the locality from which patients have come or to which they are going, is well advised to check the current position. Because prevalence and resistance rates are so variable, advice on therapy and prophylaxis in this section is given for general guidance only and readers are referred to specialist sources for up-to-date information.
CHEMOTHERAPY OF AN ACUTE ATTACK OF MALARIA2
Successful management demands attention to the following points of principle:
2 Treatment regimens vary in detail; those quoted here accord with the recommendations in the British National Formulary 2002, and the BNF is a good source of contact numbers, addresses and websites to obtain expert advice on therapy and prophylaxis of malaria.
chloroquine Arylarmnoalcohols quinine mefloquine Pitenanthrcnc methanol halofantrine Antimeiciboijies proguanil pyrimethamine sulfadoxine dapsone Antibiotics tetracycline doxycycline minocycline ÉMmjrioquinofone primaquine Sesquiterpenes artesunate artemether
• Whenever possible, the diagnosis should be confirmed before treatment by examination of blood smears.
• When the infecting organism is not known or infection is mixed, treatment should begin as for Plasmodium falciparum (below).
• Drugs used to treat Plasmodium falciparum malaria must always be selected with regard to the prevalence of local patterns of drug resistance.
• Patients not at risk of reinfection should be reexamined several weeks after treatment for signs of recrudescence which may result from inadequate chemotherapy or survival of persistent hepatic forms.
Falciparum ('malignant') malaria
The regimen depends on the condition of the patient; the doses quoted are for adults. Chloroquine resistance is now usual.
If the patient can swallow and there are no serious complications such as impairment of consciousness, treatment options are as follows:
• A quinine salt3 600 mg 8-hourly by mouth for 7 days followed by pyrimethamine plus sulfadoxine (Fansidar) 3 tablets as a single dose. Where there is resistance to Fansidar, doxycycline 200 mg, should be given after the course of quinine daily for at least 7 days. This additional therapy is necessary as quinine alone tends to be associated with a higher rate of relapse.
• Mefloquine 20-25 mg/kg (base) to a maximum of 1.5 g by mouth may be given as 2-3 divided doses 6-8 h apart.
• Malarone (atovaquone and proguanil hydrochloride) 4 tablets once daily for 3 days.
It is not necessary to add Fansidar or tetracycline after mefloquine or Malarone, but resistance to these agents has been reported from some countries. Seriously ill patients should be treated with:
• a quinine salt3 20 mg/kg as a loading dose4 (maximum 1.4 g) infused i.v. over 4 h
3 Acceptable as quinine hydrochloride, dihydrochloride or sulphate, but not quinine bisulphate which contains less quinine.
• followed 8 h later by a maintenance infusion of 10 mg/kg (maximum 700 mg) infused over 4 h
• repeated every 8 h,5 until the patient can swallow tablets to complete the 7-day course.
• Fansidar or doxycycline should be given subsequently, as above (mefloquine is an alternative, but this must begin at least 12 hours after parenteral quinine has ceased).
Treatment in pregnancy should always be discussed with an expert.
Non-falciparum ('benign') malarias
These are usually due to Plasmodium vivax or less commonly to Plasmodium ovale or Plasmodium malar-iae; the drug of choice is chloroquine, which should be given by mouth as follows:
• initial dose: 600 mg (base),6 then 300 mg as a single dose 6-8 h later
The total dose of chloroquine base over 3 days should be approximately 25 mg/kg base. This is sufficient for Plasmodium malariae infection but, for Plasmodium vivax and Plasmodium ovale eradication of the hepatic parasites is necessary to prevent relapse, by giving:
• primaquine, 15 mg/d for 14—21 days started after the chloroquine course has been completed (30 mg once weekly for 8 weeks will suffice without undue risk of haemolysis). Longer courses may be needed for some Plasmodium vivax strains from south-east Asia and the Western Pacific.
4 The loading dose should not be given if the patient has received quinine, quinidine or mefloquine in the previous 24 h; see also warnings about halofantrine (below).
5 Reduced to 5-7 mg/kg if the infusion lasts for > 72 h.
6 The active component of many drugs, whether acid or base, is relatively insoluble and may present a problem in formulation. This is overcome by adding an acid to a base or vice versa; the weight of the salt differs according to the acid or base component, i.e. chloroquine base 150 mg = chloroquine sulphate 200 mg = chloroquine phosphate 250 mg (approximately). Where there may be variation, therefore, the amount of drug prescribed is expressed as the weight of the active component, in the case of chloroquine, the base.
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