Antimalarials

Publication Title: 
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

The treatment of choice for severe malaria is quinine. However, a gradual progression of resistance to quinine has become a concern in parts of the world. Artemisinin-related compounds are a relatively new class of drugs. This meta-analysis assesses the evidence regarding the clinical effectiveness of artemether for severe malaria. Computerized literature searches identified all randomized clinical trials of artemether in comparison with quinine. Standardized data extraction was independently performed by both authors.

Author(s): 
Pittler, M. H.
Ernst, E.
Publication Title: 
Bulletin of the World Health Organization

A randomized, controlled, malaria-clinic-based field trial was carried out to compare the cost-effectiveness of a 5-day 700-mg oral artesunate and a 7-day quinine + tetracycline regimen for the treatment of uncomplicated falciparum malaria in Thailand. Cost-effectiveness was determined from the providers' perspective and based on curative effectiveness. A total of 137 patients, aged 15-60 years, attending a malaria clinic were followed for 28 days, 60 of them received quinine + tetracycline and 77 received artesunate.

Author(s): 
Honrado, E. R.
Fungladda, W.
Kamoiratanaku, P.
Kitayaporn, D.
Karbwang, J.
Thimasarn, K.
Masngammueng, R.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Previous studies have shown that the proton pump inhibitor omeprazole has antimalarial activity in vitro. The interactions of omeprazole with commonly used antimalarial drugs were assessed in vitro. Omeprazole and quinine combinations were synergistic; however, chloroquine and omeprazole combinations were antagonistic. Artemisinin drugs had additive antimalarial activities with omeprazole.

Author(s): 
Skinner-Adams, T.
Davis, T. M.
Publication Title: 
Tropical medicine & international health: TM & IH

Glutathione-S-transferase (GST) activity has been detected in rodent (Plasmodium berghei, P. yoelii), simian (P. knowlesi) and human (P. falciparum) malarial parasites, and in different intraerythrocytic stages of P. knowlesi (schizont > ring > trophozoite). In chloroquine-resistant strains of rodent and human malarial parasites GST activity significantly increases compared to sensitive strains. Further, the increase in enzyme activity is directly related to drug pressure of resistant P. berghei. Complete inhibition of chloroquine-sensitive and resistant P.

Author(s): 
Srivastava, P.
Puri, S. K.
Kamboj, K. K.
Pandey, V. C.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826 patients, and mefloquine alone was used in 1,303 patients.

Author(s): 
Price, R.
van Vugt, M.
Phaipun, L.
Luxemburger, C.
Simpson, J.
McGready, R.
ter Kuile, F.
Kham, A.
Chongsuphajaisiddhi, T.
White, N. J.
Nosten, F.
Publication Title: 
Bulletin of the World Health Organization

Reported are the in vitro susceptibilities of Plasmodium falciparum to artesunate, mefloquine, quinine and chloroquine of 86 isolates and to dihydroartemisinin of 45 isolates collected from areas of high resistance to mefloquine within Thailand near the borders with Myanmar and Cambodia, and from southern Thailand where P. falciparum is generally still sensitive to mefloquine. All the isolates were highly sensitive to artesunate, but the geometric mean IC50S were higher in isolates from the Thai-Myanmar and Thai-Cambodian borders than in those from southern Thailand.

Author(s): 
Wongsrichanalai, C.
Wimonwattrawatee, T.
Sookto, P.
Laoboonchai, A.
Heppner, D. G.
Kyle, D. E.
Wernsdorfer, W. H.
Publication Title: 
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection.

Author(s): 
White, N.
Publication Title: 
The Journal of Biological Chemistry

Endoperoxide antimalarials based on the ancient Chinese drug Qinghaosu (artemisinin) are currently our major hope in the fight against drug-resistant malaria. Rational drug design based on artemisinin and its analogues is slow as the mechanism of action of these antimalarials is not clear. Here we report that these drugs, at least in part, exert their effect by interfering with the plasmodial hemoglobin catabolic pathway and inhibition of heme polymerization. In an in vitro experiment we observed inhibition of digestive vacuole proteolytic activity of malarial parasite by artemisinin.

Author(s): 
Pandey, A. V.
Tekwani, B. L.
Singh, R. L.
Chauhan, V. S.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The new oral fixed combination artemether-lumefantrine (CGP 56697) has proved to be an effective and well-tolerated treatment of multi-drug resistant Plasmodium falciparum malaria, although cure rates using the four-dose regimen have been lower than with the currently recommended alternative of artesunate-mefloquine.

Author(s): 
Vugt, M. V.
Wilairatana, P.
Gemperli, B.
Gathmann, I.
Phaipun, L.
Brockman, A.
Luxemburger, C.
White, N. J.
Nosten, F.
Looareesuwan, S.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The factors affecting the development of patent Plasmodium falciparum gametocytemia were assessed in 5,682 patients entered prospectively into a series of antimalarial drug trials conducted in an area of low and seasonal transmission on the western border of Thailand. Of the 4,565 patients with admission thick smear assessments, 110 (2.4%) had gametocytemia. During the follow-up period 170 (3%) of all patients developed patent gametocytemia, which in 89% had developed by day 14 following treatment.

Author(s): 
Price, R.
Nosten, F.
Simpson, J. A.
Luxemburger, C.
Phaipun, L.
ter Kuile, F.
van Vugt, M.
Chongsuphajaisiddhi, T.
White, N. J.

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