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Treatment of malaria: the present status and update on new antimalarials

Abstract number: 1133_18

Looareesuwan S., Wilairatana P., Tangpukdee N., Krudsood S.

New antimalarial drugs that have been investigated at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, in recent years are as follows. atovaquone, a hydroxynaphthoquinone, was evaluated and it was found that atovaquone alone proved safe and effective. All patients treated had clinical cure, however, one third of patients had late recrudescence (RI). When it was combined with proguanil, the cure rate increased to 100%. This combination has now been developed into a fixed drug named Malarone. Artemisinine derivatives such as artesunate, artemether, arteether and dihydroartemisinin are also tested at the Bangkok Hospital for Tropical Diseases. Artesunate and artemether alone at a total dose of 600 to 750 mg. given over 5–7 days produced cure rates of 80 to 95%. Artesunate or dihydroartemisinin suppositories at a dose of 10 mg/kg/day have been proved successful for the treatment of severe malaria. The artemisinin derivatives, (4 mg/kg/day) when used in combination with mefloquine (8 mg/kg/day) given once a day for 3 days gave improved cure rates, up to 95–100%. Dihydroartemisinin alone with a total dose of 480 mg given over 5 days gave a cure rate of 90%. Arteether, a WHO/TDR supported drug, has been evaluated in the Hospital and now has been registered for use (the same dose of artemether) in severe malaria under the name Artemotil.® Other combinations (artemisinin derivatives combined with tetracycline or doxycycline and mefloquine combined with tetracycline or doxycycline) have also been evaluated with improvement in cure rates. Recently, a fixed drug (artemether plus lumefantrine) named Coartem® (six doses given over 72 hours) proved to be a safe and effective drug (cure rate over 95%) for the treatment of falciparum malaria and it has been registered for use in many western countries. At present, studies with combinations of artemisinin derivatives plus mefloquine (in various doses and durations of treatment) are being investigated. Recently we have finished the double-blind, randomized, comparative study of 200 patients (adults and children) with falciparum malaria treated by a pre-packed blister approach (4 mg/kg/day artesunate and 8 mg/kg/day given once a day for 3 days) and found that this approach proved safe and effective and this approach could translate clinically into a better patient compliance. Other fix-combinations (Artecom®, Artekin®) proved safe and efficious (cure rate over 98%) and could be an alternative antimalarial drugs. In general, artemisinin derivatives (12 mg/kg total dose given in 3 days) combined with mefloquine (25 mg/kg total dose given in 3 days) have been a standard regimen for the treatment of multidrug resistant falciparum malaria in Thailand. Until proven otherwise, drug combinations are still recommended for all adult patients suffering from acute uncomplicated falciparum malaria contracted in multidrug resistant areas. The treatment for uncomplicated malaria is aimed at producing a radical cure using the combination of either (1) artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg/day) for 3 days; (2) a fixed dose of artemether and lumefantrine (20/120 mg tablet) named Coartem (4 tablets twice a day for three days for adults weighing more than 35 kg); (3) quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg once a day for 7 days as an alternative to tetracycline) in patients aged 8 years and over; and (4) a combination of atovaquone and proguanil called Malarone (in adult, 4 tablets given daily 3 days). In treating severe malaria, early diagnosis and early treatment with a potent antimalarial drug is recommended to save the patient's life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 days; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then daily for 5 days; artemether i.m. (Artemotil ) with the same dose of artemether; artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days). Oral artemisinin derivatives (artesunate, artemether, dihydroartemisinin with the dose 4 mg/kg/day should replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.

The treatment of vivax malaria in Thailand is still using chloroquine and primaquine. However with the ineffective to primaquine (15 mg/kg/day for 14 days with relapse rate of 15%) the higher dose (30 mg/kg/day for 14 days) is recommended. The efficacy studies of primaquine in various regimen given together with Sulfadoxin/Pyrimethamine or artemisinin derivatives are in progress. Tefenoquine® phase III study in the planning stage for clinical trial in our setting in Thailand is in progress.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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