Treatment of Acute Falciparum Malaria from Vietnam with Trimethoprim and Sulfalene *

Canfield, Craig J.; Whiting, Edward G.; Hall, William H.; MacDonald, Bruce S.

doi:10.4269/ajtmh.1971.20.524

Cited by 14 publications

(4 citation statements)

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“…It has been widely used in phase II clinical studies in human volunteers and has retained its susceptibility to chloroquine, quinine, and pyrimethamine. The Vietnam Smith strain, obtained in 1969 from an American soldier at the Walter Reed Army Medical Center, was first reported by Craig J. Canfield in 1971 (2). That patient, showing an R-I level of resistance to the combination of sulfalene and trimethoprim after treatment failures with other antimalarial drugs, provided the parasite isolate designated Smith strain (2).…”

Section: Methodsmentioning

confidence: 99%

“…The Vietnam Smith strain, obtained in 1969 from an American soldier at the Walter Reed Army Medical Center, was first reported by Craig J. Canfield in 1971 (2). That patient, showing an R-I level of resistance to the combination of sulfalene and trimethoprim after treatment failures with other antimalarial drugs, provided the parasite isolate designated Smith strain (2). This strain was later adapted to owl monkeys (24) and has also been used extensively in human volunteer studies, where its resistance to chloroquine, quinine, and pyrimethamine has been amply documented (10).…”

Section: Methodsmentioning

confidence: 99%

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Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique

Desjardins¹,

Canfield²,

Haynes³

et al. 1979

Antimicrob Agents Chemother

2,377

1,645

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique

Desjardins¹,

Canfield²,

Haynes³

et al. 1979

Antimicrob Agents Chemother

2,377

1,645

View full text Add to dashboard Cite

“…Hyg., in press). During 1967During -1969, some of these patients with recrudescent infections were treated in the United States with a combination of trimethoprim and sulfalene (2). Although this combination terminated most recrudescent attacks, it produced a radical cure in only about 72% of the cases.…”

mentioning

confidence: 99%

Treatment of Falciparum Malaria from Vietnam with a Phenanthrene Methanol (WR 33063) and a Quinoline Methanol (WR 30090)

Canfield

Hall

MacDonald

et al. 1973

Antimicrob Agents Chemother

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Two new investigational antimalarial drugs developed by the U.S. Army Malaria Research Program were tested in patients with multi-drug-resistant falciparum malaria from Vietnam. WR 33063, a phenanthrene methanol, cured 13 patients treated in the United States. All of these patients had suffered multiple recrudescences after treatment with standard antimalarial drugs. In addition, 23 of 25 patients with acute attacks of falciparum malaria treated in Vietnam were cured. The rate of clinical response was prompt. WR 30090, a quinoline methanol, similarly cured eight patients with multiple recrudescences in the United States and 23 of 26 patients in Vietnam. Adverse effects associated with the drugs were not seen. These drugs signify a major advance in the chemotherapy of drug-resistant falciparum malaria.

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“…Using novel chromatographic techniques to study purine metabolism in malaria infected RBC in vitro, we have identified the major metabolic pathways used by IE P. falciparum to synthesize both guanosine and adenosine nucleotides from the precursor purine base, hypoxanthine (10) (12,13) and used in human volunteer studies (14).…”

Section: Introductionmentioning

confidence: 99%

Antimalarial properties of bredinin. Prediction based on identification of differences in human host-parasite purine metabolism.

Webster¹,

Whaun²

1982

J. Clin. Invest.

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A B S T R A C T Human malaria parasites (Plasmodium falciparum) grown in continuous erythrocyte culture utilize hypoxanthine for synthesis of both guanosine and adenosine nucleotides. Unlike the mature human erythrocyte, the malaria parasite depends on a constant supply of guanylates, primarily for synthesis of nucleic acids. This parasite specific requirement for guanylates led us to predict that a block in the hypoxanthine to quanosine monophosphate pathway would be selectively lethal to the parasite. Bredinin (4 -carbamoyl-1 -,B-D -ribofuranyosyl -imidazolium -5-olate) inhibited the synthesis of guanosine monophosphate from inosine monophosphate by parasitized erythrocytes. This block in guanylate synthesis was fatal to both a drug-sensitive (FCR-3) and a drug-resistant (VNS) strain of the malaria parasite at a bredinin concentration of 50 MM, arresting growth of the parasite at the trophozoite stage of development. These studies emphasize the essential role of guanylates and their synthesis from hypoxanthine in the metabolism of malaria parasite. They further suggest that bredinin or similar agents that selectively interfere with parasite guanylate metabolism may have potential for antimalarial chemotherapy.

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Treatment of Acute Falciparum Malaria from Vietnam with Trimethoprim and Sulfalene *

Cited by 14 publications

References 0 publications

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique

Treatment of Falciparum Malaria from Vietnam with a Phenanthrene Methanol (WR 33063) and a Quinoline Methanol (WR 30090)

Antimalarial properties of bredinin. Prediction based on identification of differences in human host-parasite purine metabolism.

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