Antimalarial drugs prophylaxis

Antimalarial drugs are designed to prevent or treat malaria. Antimalarial drugs currently used for treatment for prophylaxis are mefloquine, primaquine, chloroquine, pyrimethamine, amodiaquin, quinine/quinidine, chloroguanide. 

Clinical Use. Mefloquine (Lariam) has emerged as one of the most important antimalarial agents.61 This drug is especially important in the prevention and treatment of malaria that is resistant to traditional antimalarial drugs such as chloroquine and quinine.50 Mefloquine is often the drug of choice for antimalarial prophylaxis, especially in areas of the world where chloroquine-resistant strains of malaria are common.23 Mefloquine can be used alone, but combining this... 

A postal survey of the incidence of psychiatric disturbances in 2500 returning Israeli travellers (505) showed that travellers with this class of adverse effects were more likely to have taken mefloquine than other antimalarial drugs. Of 117 travellers with psychiatric adverse effects, 115 had taken mefloquine compared with 948/1340 for the entire cohort. This was a retrospective postal study with a response rate of 54% (1340 out of 2500), and of those who responded 71% had taken mefloquine, 5% had taken chloroquine, and 24% had taken no prophylaxis. In this study 11% (117) of the respondents reported psychiatric disturbances, mainly sleep disturbance, fatigue, vivid dreams, or lack of mood. Only 16 of the respondents had symptoms lasting 2 months or more. Those who had had a psychiatric disturbance were also more likely to have been female and to have taken recreational drug use. 

The adverse effects of mefloquine have been extensively reviewed both for prophylaxis (when rare neuropsychiatric adverse effects make its use controversial) and in treatment doses, when it has been linked to an increased incidence of the postmalaria neurological syndrome. A retrospective review of 5120 Itahan soldiers showed an overall chemoprophylaxis curtailment rate of less than 1%, which was not significantly different from the combination of chloroquine and proguanil (11). A semi-systematic review also suggested no significant difference in tolerabihty compared with other antimalarial drugs (12). 

Proguanil is one of the antimalarial drugs most widely used for prophylactic purposes, usually in combination with chloroquine or atovaquone in malaria prophylaxis, and with atovaquone in malaria treatment (SEDA-21, 297). A biguanide, it is rapidly absorbed in standard doses and mainly excreted by the kidneys. Its antimalarial effect is due to its metabolite cycloguanU. However, its metabolism varies individually, and this is reflected in a variable degree of efficacy (SEDA-17, 328). 

Pyrimethamine is a folic acid antagonist that for many years has been used as an antimalarial drug [193-195], specially for chloroquine-resistant P. falciparum. Due to its synergistic activity, pyrimethamine also has been used, in combination with sulfadiazine or dapsone for the treatment or prophylaxis of cerebral toxoplasmosis or PCP in patients with AIDS [196]. 

Several drugs (for example amiodarone, androgens, glucocorticoids, phenytoin, and salicylates) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. These have been reviewed (90). In patients taking levothyroxine serum TSH rises after treatment with sertraline (91) and antimalarial prophylaxis with chloroquine and proguanil... 

A number of histidine analogues, including 2-azido-L-histidine (201), have been evaluated by the NIH as part of a programme directed towards the development of new antimalarials for the prophylaxis and treatment of drug-resistant Plasmodium falciparum malaria [261]. Asexual P. falciparum parasites have a much higher histidine content than mammalian cells, and several histidine-rich proteins are thought to be functionally important in... 

Unfortunately, many persons experience extreme side effects from antimalarial medications. Further, chloroquine-resistant strains of falciparum malaria are on the increase worldwide. For this resistant parasite, the drug mefloquine is the preferred method of prophylaxis and treatment, although resistance to this drug may emerge rapidly, and resistant strains have been found in areas where the drug has never been used. 

Schwartz E, Regev-Yochay G. Primaquine as prophylaxis for malaria for nonimmune travelers A comparison with mefloquine and doxycycline. Clin Infect Dis I999 29(6) 1502-6. Lobel HO, Coyne PE, Rosenthal PJ. Drug overdoses with antimalarial agents prescribing and dispensing errors. JAMA 1998 280(17) 1483. 

The chemotherapy and prophylaxis of malaria have been undermined by the development of worldwide resistance of P. falciparum to the 4-aminoquinoline chloroquine, first observed in the 1960s, as well as resistance to the antifolates pyrimethamine and cycloguanil. Resistance to quinine and other more recently developed drugs, for example mefloquine, have also been reported [4, 5]. The search for alternative antimalarials is one of the main themes of this chapter. 

Quinine (Fig. 9) is probably the oldest effective therapeutic agent for the prophylaxis and therapy of Plasmodium infections and, although now largely superseded for routine use, it is of considerable value in the treatment of chloroquine-resistant P. falciparum, for which it is used in combination with other antimalarials. The main side effects of quinine therapy comprise a syndrome of classical cinchonism, i.e., tinnitus, vision defects, nausea, headache and gastrointestinal effects, but im-munologically the much rarer complication, drug-induced thrombocytopenia is of more interest. 

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