The Evaluation of Sulfonamides, Alone or in Combination with Pyrimethamine, in the Treatment of Multi-Resistant Falciparum Malaria

Chin, William; Pg, Contacos; Gr, Coatney; Hk, King

doi:10.4269/ajtmh.1966.15.823

Cited by 71 publications

(20 citation statements)

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“…Short-acting sulfonamides soon gave way to longeracting sulfonamides such as sulfadoxine and sulfalene. As had been shown earlier with the shorter-acting sulfonamides (8,19), the addition of pyrimethamine to sulfadoxine was appreciably more effective in curing chloroquine-and pyrimethamine-resistant P. falciparum infections than sulfadoxine alone (3,14).…”

mentioning

confidence: 52%

Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Korsinczky

Fischer

Chen³

et al. 2004

Antimicrob Agents Chemother

106

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Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as well as P. falciparum were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivax is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing dhps genes from a limited set of geographically different P. vivax isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino acid mutations were observed in some P. vivax isolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivax to sulfadoxine.

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mentioning

confidence: 52%

Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Korsinczky

Fischer

Chen³

et al. 2004

Antimicrob Agents Chemother

106

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“…The patient origins of these. strains have been described by others (2,6,21,38,41 (1971). The procedures involved in establishing these strains in the owl monkey have been described by these investigators (7,38,41 Prior to use in the current investigations, these old compounds were checked for purity via countercurrent distribution to determine whether they had deteriorated during protracted storage.…”

Section: Methodsmentioning

confidence: 99%

Activities of Various 4-Aminoquinolines Against Infections with Chloroquine-Resistant Strains of Plasmodium falciparum

Schmidt

Vaughan

Mueller

et al. 1977

Antimicrob Agents Chemother

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The studies reported here stemmed from a personal report by Geiman on the capacity of the 4-aminoquinoline amodiaquin to inhibit in vitro maturation of ring stages of the chloroquine-resistant Monterey strain ofPlasmodium falciparum. This observation, confirmed in owl monkeys infected with this strain, led to a comparison of the activities of chloroquine, amodiaquin, amopyroquin, and dichlorquinazine (12,278 RP) against infections with various chloroquine-susceptible and chloroquine-resistant strains. The results showed that: (i) these 4-aminoquinolines were essentially equally active against infections with chloroquine-susceptible strains and (ii) the activities of amodiaquin, amopyroquin, and dichlorquinazine were reduced significantly in the face of chloroquine resistance, but (iii) well-tolerated doses of these compounds would cure infections with strains that fully resisted treatment with maximally tolerated doses of chloroquine. Two other 4-aminoquinolines, SN-8137 and SN-9584, which also exhibited activity against chloroquine-resistant parasites in vitro, displayed curative activity in monkeys infected with a chloroquine-resistant strain. These observations show that there is cross-resistance among the 4-aminoquinolines, confirming earlier findings, but indicate that the dimensions of this phenomenon are sufficiently limited so that some derivatives are therapeutically effective against infections refractory to maximally tolerated doses of chloroquine.

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“…A 1959 study found that sulfadoxine potentiated pyrimethamine in human falciparum infections, demonstrating that combined pyrimethamine and sulfadoxine was more effective than either drug alone (Greenberg and Richeson, 1950;Hurly, 1959). In other field studies of pyrimethamine combined with a sulfonamide, in pyrimethamine-resistant or multidrug-resistant infections, the combination was superior to either drug or chloroquine alone (McGregor et al, 1963;DeGowin and Powell, 1964;Chin et al, 1966;Harinasuta et al, 1967;Laing, 1968bLaing, , 1970bMartin and Arnold, 1968b). Sulfadoxine schizontocidal activity remained slower than that of chloroquine (DeGowin and Powell, 1964;Chin et al, 1966) or of quinine, even in the presence of low-level quinine resistance (Peters, 1970).…”

Section: Mechanisms Of Resistance Of Malaria Parasites To Antifolatesmentioning

confidence: 99%

“…In other field studies of pyrimethamine combined with a sulfonamide, in pyrimethamine-resistant or multidrug-resistant infections, the combination was superior to either drug or chloroquine alone (McGregor et al, 1963;DeGowin and Powell, 1964;Chin et al, 1966;Harinasuta et al, 1967;Laing, 1968bLaing, , 1970bMartin and Arnold, 1968b). Sulfadoxine schizontocidal activity remained slower than that of chloroquine (DeGowin and Powell, 1964;Chin et al, 1966) or of quinine, even in the presence of low-level quinine resistance (Peters, 1970). However, faster schizontocidal activity and improved clinical response was seen when sulfadoxine was combined with pyrimethamine (Richards, 1966;Harinasuta et al, 1967;Laing, 1968aLaing, , 1970a or cycloguanil (in mice Thompson et al, 1965).…”

Section: Mechanisms Of Resistance Of Malaria Parasites To Antifolatesmentioning

confidence: 99%

Mechanisms of Resistance of Malaria Parasites to Antifolates

2005

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The Evaluation of Sulfonamides, Alone or in Combination with Pyrimethamine, in the Treatment of Multi-Resistant Falciparum Malaria

Cited by 71 publications

References 0 publications

Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Activities of Various 4-Aminoquinolines Against Infections with Chloroquine-Resistant Strains of Plasmodium falciparum

Mechanisms of Resistance of Malaria Parasites to Antifolates

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