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[Malaria chemoprophylaxis in traveling children].

In France, 4,000 imported malaria cases are reported each year (7,000 to 8,000 estimated). Chemoprophylaxis is essential for prevention in travelers. When malaria is susceptible to chloroquine, this drug (Nivaquine) has to be used. It is given daily in France (1.5 mg/kg per day), from departure to four weeks after return. When low levels of chloroquino-resistance are reported, French authorities recommend the use of chloroquine + proguanil (Savarine) if the body weight is >50 kg or Nivaquine) + Paludrine), if <50 kg), or atovaquone + proguanil (Malarone). Nivaquine) (1.5 mg/kg per day) and Paludrine) (3 mg/kg per day) have to be pursued for one month after return, although Malarone) (1 pediatric tablet/10 kg per day, in children >10 kg weight) may be disrupted after one single week. Adverse events are rarer with atovaquone + proguanil, than with chloroquine + proguanil. When chloroquino-resistance is high, Malarone) or mefloquine (Lariam) are used. Weekly drug regimen is recommended with mefloquine (5 mg/kg per weight) for the travel duration and four weeks after return and the drug tolerance is good in pediatric prophylaxis. Doxycycline is used under conditions in children >8 years of age. New drugs as for tafenoquine, an amino-8 quinoleine, might enhance patients compliance if given monthly.

Antimalarials↗

Effect of oral proguanil on human lymphocyte proliferation.

In vitro studies have indicated that the antifolates pyrimethamine [4, 6] and cycloguanil (the active metabolite of proguanil) suppress the proliferation of stimulated human lymphocytes; proguanil has no effect [2]. During the early growth phase of the cells, 14C-thymidine (14C-TdR) incorporation is increased by pyrimethamine and cycloguanil, reflecting blockage of endogenous TdR synthesis [3]. Proguanil (Paludrine) is increasingly being used for malaria prophylaxis. It is considered the most innocuous of the antimalarials currently employed. Since nothing is known about the effect of oral proguanil on human lymphocytes, the present study was undertaken. Little information is available about the serum levels of proguanil and cycloguanil following ingestion of prophylactic doses [8]. Therefore, the serum concentrations of proguanil and cycloguanil were estimated, to allow comparison with previous in vitro studies [2].

Adult↗

Malaria prophylaxis in travellers: the current position.

Malaria prevention is a main challenge for physicians, nurses, health officers and tour operators. The attack rate of malaria in travellers is 1-10/10,000 departures, and the case fatality rate of imported malaria is around 0.5/100. Travellers should be informed about the risk they are going to take, how to protect against mosquito bites, about the antimalarials they will have to take and what to do when a malaria breakthrough should occur. The 4-aminoquinolines (chloroquine, amodiaquine) remain the drug of choice for the prevention of Plasmodium vivax and of sensitive P. falciparum infections. The problem is to find an effective and safe drug combination for travellers to areas where P. falciparum is either resistant to chloroquine, to Fansidar (the combination of pyrimethamine plus sulfadoxine) or to both. These travellers will probably best be protected by an individually tailored drug combination, which includes amodiaquine or mefloquine as baseline drugs, and a supplementation with Fansidar, Maloprim (the combination of pyrimethamine with dapsone), paludrine or an antibiotic.

Africa↗

Tropical splenomegaly syndrome (T.S.S.) in a European.

A case of tropical splenomegaly syndrome in a 66-year-old white man who had lived in Tanzania for 34 years is described. He had taken anti-malarial prophylaxis continuously and regularly. He had had malaria in 1955 but there was no history of alcoholism or jaundice. He was treated with proguanil hydrochloride and, after return to Tanzania, took paludrine as prophylactic. One year later he had no further complaints, the spleen was no longer palpable and the liver only just palpable.

Aged↗

Prophylaxis for malaria. Helping world travelers come home healthy.

Malaria is largely preventable, so travelers should be taught general protective measures and given appropriate chemoprophylaxis before they leave on their trip. Chloroquine phosphate (Aralen) is still the drug of choice in locations where malaria remains chloroquine-sensitive. However, chloroquine-resistant areas infested with Plasmodium falciparum are becoming more numerous. In such areas, mefloquine hydrochloride (Lariam), doxycycline, or proguanil (Paludrine) (obtainable outside the United States) may be used. A single dose of pyrimethamine-sulfadoxine (Fansidar) may be used to treat presumptive malarial infection if medical care is not immediately available. For prevention of relapse of Plasmodium vivax and Plasmodium ovale infection, primaquine phosphate is recommended for the final 2 weeks of chemoprophylaxis on return from a malarious area.

Antimalarials↗

Conflicts of interest: the genesis of synthetic antimalarial agents in peace and war.

Malaria has had an enormous impact on human history, not least in times of war. The disease has been treatable by a natural remedy, quinine, since the 17th century, but the production of synthetic antimalarial agents was first achieved in Germany in the wake of the Great War of 1914-1918, in which malaria had caused immense problems. In the 1920s research workers in the Bayer laboratories of the IG Farbenindustrie consortium developed the 8-aminoquinoline plasmoquine (the forerunner of primaquine). They went on to develop the acridine dye, atebrin (mepacrine) and the 4-aminoquinolines, Resochin (developed at the end of the Second World War in America as chloroquine) and Sontochin. British attempts to match the advances achieved by the Germans were at first unproductive, partly because collaboration between academic and industrial organizations in the UK was beset by concerns over patent rights. However, with the outbreak of World War II, when supplies of antimalarials were scarce, ICI succeeded in the large-scale production of mepacrine (essential to prosecution of the war, particularly in the Far East) and also initiated a programme of collaborative research that eventually led to the discovery of proguanil (Paludrine); this, in its turn led to the diaminopyrimidine, pyrimethamine. A massive cooperative screening programme in the USA during World War II eventually bore fruit in the realization of the therapeutic potential of chloroquine, and in the later development of amodiaquine and primaquine. Some of this work also influenced the subsequent discovery of mefloquine and halofantrine at the Walter Reed Army Institute of Research.

Animals↗