The dynamics of drug resistance in Plasmodium falciparum

Wernsdorfer, W. H.; Payne, D. J.

doi:10.1016/0163-7258(91)90074-v

Cited by 174 publications

(122 citation statements)

References 58 publications

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“…[14][15][16][17] The significant positive correlation between the in vitro responses to chloroquine and monodesethylamodiaquine or quinine and between the response to mefloquine and halofantrine is in agreement with in vivo resistance to amodiaquine, quinine, and halofantrine observed in Southeast Asia where a high level of resistance to chloroquine and mefloquine has emerged. 41,42 Cross-resistance between pyrimethamine and cycloguanil has also been observed in vitro and in vivo. 41,43 Cross-resistance patterns between these drugs may be, at least in part, explained on the basis of similar chemical structures.…”

Section: Discussionmentioning

confidence: 97%

“…41,42 Cross-resistance between pyrimethamine and cycloguanil has also been observed in vitro and in vivo. 41,43 Cross-resistance patterns between these drugs may be, at least in part, explained on the basis of similar chemical structures. Our study suggests in vitro cross-resistance between dihydroartemisinin and aminoalcohols (mefloquine and halofantrine), which do not share any similar chemical features.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon.

Ringwald¹,

Bickii²,

Basco³

1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. The in vitro activities of dihydroartemisinin (the biologically active metabolite of artemisinin derivatives), chloroquine, monodesethylamodiaquine (the biologically active metabolite of amodiaquine), quinine, mefloquine, halofantrine, and pyrimethamine were assessed in 65 African isolates of Plasmodium falciparum from Yaoundé, Cameroon using an isotopic microtest. The 50% inhibitory concentration (IC 50 ) values for dihydroartemisinin were within a narrow range from 0.25 to 4.56 nM, with a geometric mean of 1.11 nM (95% confidence interval ϭ 0.96-1.28 nM). Dihydroartemisinin was equally active (P Ͼ 0.05) against the chloroquine-sensitive isolates (geometric mean IC 50 ϭ 1.25 nM, 95% confidence interval ϭ 0.99-1.57 nM) and the chloroquine-resistant isolates (geometric mean IC 50 ϭ 0.979 nM, 95% confidence interval ϭ 0.816-1.18 nM). A significant positive correlation was observed between the responses to dihydroartemisinin and mefloquine (r ϭ 0.662) or halofantrine (r ϭ 0.284), suggesting in vitro crossresistance. There was no correlation between the responses to dihydroartemisinin and other antimalarial drugs.Artemisinin (qinghaosu) has been used for centuries in traditional Chinese medicine for antimalarial treatment. 1 In 1972, Chinese scientists isolated the active principle from the plant Artemisia annua. 2 Artemisinin is a sesquiterpene lactone characterized by the presence of an endoperoxide that is associated with a potent antimalarial activity. Because artemisinin is chemically unstable and poorly soluble in water or oil, the carbonyl group at C-10 of the parent compound was reduced to obtain dihydroartemisinin. Several derivatives have been developed by adding an ether, ester, or other substituents to the hydroxyl group of dihydroartemisinin. These semi-synthetic derivatives include the water-soluble derivatives, sodium artesunate and artelinic acid, and the oilsoluble derivatives, artemether and arteether. With the exception of arteether and artelinic acid, these compounds are used to treat malarial infections in endemic countries, mainly in Southeast Asia and, to a lesser extent, in Africa and South America.Artemisinin derivatives are available in different formulations for oral, parenteral, and rectal administration. Clinical studies have shown that artemisinin derivatives are highly potent, rapidly acting, and well-tolerated blood schizontocides, resulting in shorter parasite clearance times than other antimalarial drugs. 3,4 Artemisinin derivatives are highly effective against Plasmodium falciparum isolates that are resistant to other drugs. These derivatives are indicated for the emergency treatment of severe and complicated falciparum malaria by parenteral administration and for the oral treatment of uncomplicated multidrug-resistant malaria. 5 So far, resistance to artemisinin derivatives has not been reported in clinical studies. However, because of the high recrudescence rate when used as monotherapy, many current therapeutic regimens used in Southeast Asia include a combination of o...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon.

Ringwald¹,

Bickii²,

Basco³

1999

The American Journal of Tropical Medicine and Hygiene

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“…Chloroquine resistance has been reported from wherever falciparum is endemic in Southeast Asia (Wernsdorfer 1991;WHO 2001a, b). Resistance of P. falciparum to chloroquine was apparent in the late 1950s almost concurrently in Southeast Asia (on the Thai-Cambodian border) and South America (Brazil).…”

Section: Chloroquine Resistancementioning

confidence: 99%

Current Malaria Status and Distribution of Drug Resistance in East and Southeast Asia with Special Focus to Thailand

Na‐Bangchang

Congpuong²

2007

Tohoku J. Exp. Med.

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“…Resis tance concerns the two main series of blood schizonticicles, lysosomotropic agents and the antifol combi nation group with a rapid worldwide spread (Werndorfer & Payne, 1991 ). Indeed, malaria patho gens are highly adaptable to chemical changes in their environment.…”

Section: Current Antimalarial Drugsmentioning

confidence: 99%

Recent developments and rationale towards new strategies for malarial chemotherapy

Vial¹

1996

Parasite

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Summary :The major problem facing world research for new antimalarials lies in encountered difficulties in the search for new promising paths. The past 20 years have witnessed a very impressive increase in our understanding of the biochemistry and molecular biology of malaria parasites, with attention focused on specific parasite molecules that are keys to the parasite life cycle or the induction of its pathogenesis. Directed pharmacology research has involved the identification and characterization of targets that can be specifically pharmacologically affected, including the replicating machinery of the parasites, various metabolisms such as the purine salvage pathway, and biosynthesis of pyrimidines or phospholipids. Protease inhibitors (e.g. those degrading haemoglobin], the use of iron chelators or inhibition of heme polymerization, induction of oxidative stress or inhibition of antioxidant enzymes are also investigated. Some pathways have already been validated with current antimalarials but, due to the development of resistance, complete characterization of the molecular structure of the target should allow attack of these exceptional molecules at novel and distinct sites with new drug concepts. The problem in the quest to develop new antimalarials is the fact that the results are not being materialized, but there is no lack of pharmacological targets.

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The dynamics of drug resistance in Plasmodium falciparum

Cited by 174 publications

References 58 publications

In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon.

In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon.

Current Malaria Status and Distribution of Drug Resistance in East and Southeast Asia with Special Focus to Thailand

Recent developments and rationale towards new strategies for malarial chemotherapy

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