A Model in Vitro System to Test the Susceptibility of Human Malarial Parasites to Antimalarial Drugs

Siddiqui, Wasim A.; Schnell, Jerome V.; Geiman, Quentin M.

doi:10.4269/ajtmh.1972.21.392

Cited by 30 publications

(10 citation statements)

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“…Ideally, the evaluation should be pursued in owl monkeys infected with a chloroquine-resistant strain of P. falciparum well established in the laboratory (e.g., the Smith strain), but this may not be possible because of limited availability of these subjects. Even if they were in unlimited supply, it would probably be wise to initiate studies of new derivatives in vitro, starting with culture procedures such as have been developed by Rieckmann et al (34) and Siddiqui et al (38). In these systems, groups of test compounds could be compared for activities against parasites of chloroquine-susceptible and chloroquine-resistant strains of P. falciparum derived from infected owl monkeys.…”

Section: Discussionmentioning

confidence: 99%

“…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. Results indicated no change in purity.…”

Section: Methodsmentioning

confidence: 99%

“…Geiman related results of studies, published in detail 3 years later (38), that indicated that there were distinct differences in the capacities of chloroquine and amodiaquin to inhibit development of the chloroquine-resistant Vietnam Monterey strain. Briefly stated, he had found that chloroquine, added to culture medium at concentrations of 0.3 ,ug or less per ml, was without effect on maturation of parasites of this strain.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…Immunity to parasite challenge was established using the Vietnam Oak Knoll (FVO) strain of P. falciparum 1 . The heterologous strain challenge was performed using the CAMP strain of P. falciparum which was originally isolated in Malaysia.…”

Section: Monkeysmentioning

confidence: 99%

“…We therefore studied the response to repeated infections with the highly virulent Vietnam Oak Knoll (FVO) strain of P. falciparum, 1 and the response of monkeys immune to repeated challenge with FVO to challenge with a different strain of P. falciparum, CAMP. Our goals were to determine 1) how many exposures were required before the monkeys were able to control the parasitemia, 2) if the monkeys developed sterile protective immunity, and 3) if monkeys immune to challenge with FVO were susceptible to challenge with CAMP.…”

Section: Introductionmentioning

confidence: 99%

Repeated infection of Aotus monkeys with Plasmodium falciparum induces protection against subsequent challenge with homologous and heterologous strains of parasite.

Jones

Obaldía²,

Gramzinski³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. We evaluated repeated blood-stage infections with Plasmodium falciparum in eight Aotus lemurinus lemurinus monkeys. Over the course of seven infections with 10 4 P. falciparum (the Vietnam Oak Knoll [FVO] strain), the pre-patent period lengthened from 8.2 to 30.8 days; the peak parasitemia decreased from 4.5 ϫ 10 5 to 0 parasites/l (Challenges 6 and 7), and the requirement for treatment decreased from 100% to 0% (Challenges 3 to 7). Five weeks after the seventh FVO challenge, the eight immune and three naïve monkeys received 10 4 parasitized erythrocytes infected with P. falciparum (CAMP strain). The three control animals experienced uncontrolled parasitemias reaching between 4.8 and 7.7 ϫ 10 5 parasites/l (pre-patency ϭ 6.3 days) and all required drug treatment; six of the eight immune monkeys became parasitemic (pre-patency ϭ 8.8 days), but self-cured. Two of three of the monkeys having the greatest reductions in hematocrit (50-60%) also had the highest parasitemias (ϳ10 4 parasites/ l) before self-curing. Repeated homologous infections induced sterile immunity to homologous challenge; during heterologous challenge the monkeys developed clinically relevant, but not life-threatening, parasitemias and anemia.

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In Vitro Techniques for Antimalarial Development and Evaluation

Desjardins¹

1984

Handbook of Experimental Pharmacology

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A Model in Vitro System to Test the Susceptibility of Human Malarial Parasites to Antimalarial Drugs

Cited by 30 publications

References 0 publications

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

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

Repeated infection of Aotus monkeys with Plasmodium falciparum induces protection against subsequent challenge with homologous and heterologous strains of parasite.

In Vitro Techniques for Antimalarial Development and Evaluation

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