Drug Resistance

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: 
Antimicrobial Agents and Chemotherapy

The influence of different metalloporphyrin derivatives on the antimalarial activity of artemisinin was studied with two chloroquine-resistant strains of Plasmodium falciparum (FcB1-Colombia and FcM29-Cameroon) cultured in human erythrocytes. This potentiation study indicates that the manganese complex of meso-tetrakis(4-sulfonatophenyl)porphyrin has a significant synergistic effect on the activity of artemisinin against both Plasmodium strains.

Author(s): 
Benoit-Vical, F.
Robert, A.
Meunier, B.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisinin and its derivatives are important new antimalarials which are now used widely in Southeast Asia. Clinically relevant artemisinin resistance has not yet been reported but is likely to occur. In order to understand how the malaria parasite might become resistant to this drug, we studied artemisinin resistance in the murine malaria parasite Plasmodium yoelii. The artemisinin-resistant strain (ART), which is approximately fourfold less sensitive to artemisinin than the sensitive NS strain, accumulated 43% less radiolabeled drug in vitro (P < 0.01).

Author(s): 
Walker, D. J.
Pitsch, J. L.
Peng, M. M.
Robinson, B. L.
Peters, W.
Bhisutthibhan, J.
Meshnick, S. R.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

To define the current efficacy of Fansidar (F. Hoffmann-La Roche Ltd., Basel Switzerland) (pyrimethamine and sulfadoxine), primaquine in a high dose, and artesunate for treating acute Plasmodium vivax malaria, we conducted a comparative clinical trial of these 3 drugs in an open-label study. Patients (15-65 years old) were assigned to 1 of 4 treatments regimens in a serial order. Ninety percent of the patients were infected at Thailand-Myanmar border.

Author(s): 
Wilairatana, P.
Silachamroon, U.
Krudsood, S.
Singhasivanon, P.
Treeprasertsuk, S.
Bussaratid, V.
Phumratanaprapin, W.
Srivilirit, S.
Looareesuwan, S.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.0 microM and the geometric mean IC50 for the 71 isolates was 11.3 microM (95% confidence interval = 9.5-13.4 microM).

Author(s): 
Pradines, B.
Spiegel, A.
Rogier, C.
Tall, A.
Mosnier, J.
Fusai, T.
Trape, J. F.
Parzy, D.
Publication Title: 
Antimicrobial Agents and Chemotherapy

The in vitro potentiation of artemisinin by synthetic manganese porphyrin complexes has been recently reported (F. Benoit-Vical, A. Robert, and B. Meunier, Antimicrob. Agents Chemother. 43:2555-2558, 1999). Since the activity of artemisinin and synthetic antimalarial endoperoxides is related to their interaction with heme (S. R. Meshnick, A. Thomas, A. Ranz, C. M. Xu, and H. Z. Pan, Mol. Biochem. Parasitol. 49:181-190, 1991), an improvement of their efficiency may be expected in the presence of a synthetic metalloporphyrin having the same activating role as endogenous heme.

Author(s): 
Benoit-Vical, F.
Robert, A.
Meunier, B.
Publication Title: 
Tropical medicine & international health: TM & IH

BACKGROUND: Chloroquine (CQ) and Sulfadoxine-Pyrimethamine (SP) are the predominantly used antimalarials in Zambia and other parts of East Africa, but increasing resistance of P. falciparum is a major concern. METHODS: Seventy consecutive patients with uncomplicated falciparum malaria were enrolled. In 43 patients, no prior CQ use could be demonstrated by history and urianalysis (qualitative test, Dill & Glazko) and these patients were given CQ; the other 27 had taken CQ before and received SP.

Author(s): 
Bijl, H. M.
Kager, J.
Koetsier, D. W.
van der Werf, T. S.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The antimalarial peroxide, dispiro-1,2,4,5-tetraoxane WR 148999, was synergistic with chloroquine, quinine, mefloquine, and artemisinin against both D6 and W2 clones of Plasmodium falciparum. In consideration of the contrasting antagonism between artemisinin and chloroquine, these drug combination data imply that WR 148999 and artemisinin may not share a common mechanism of action.

Author(s): 
Vennerstrom, J. L.
Ager, A. L.
Andersen, S. L.
Grace, J. M.
Wongpanich, V.
Angerhofer, C. K.
Hu, J. K.
Wesche, D. L.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Desbutyl-benflumetol (DBB) is a novel antimalarial compound closely related to benflumetol (lumefantrine), of which it is a putative metabolite. The in vitro response of Plasmodium falciparum to DBB was studied in Mae Hong Son and Mae Sot, in northwest Thailand, in 1997 and 1998. In total, 155 fresh isolates were successfully tested using the World Health Organization standard in vitro microtest system (Mark II). The mean 50% effective concentration (EC(50)) and 90% effective concentration of DBB were 6.36 and 31.09 nmol/liter, respectively.

Author(s): 
Noedl, H.
Allmendinger, T.
Prajakwong, S.
Wernsdorfer, G.
Wernsdorfer, W. H.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms.

Author(s): 
Lefèvre, G.
Looareesuwan, S.
Treeprasertsuk, S.
Krudsood, S.
Silachamroon, U.
Gathmann, I.
Mull, R.
Bakshi, R.

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