Chemotherapy of Plasmodium vivax in Saimiri and Aotus Models *

Rossan, Richard N.; Young, Martin D.; Baerg, David C.

doi:10.4269/ajtmh.1975.24.168

Cited by 20 publications

(9 citation statements)

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“…The owl and squirrel monkeys have emerged as the favored model by virtue of availability and ease of care and infection (54). Infections by chloroquine-sensitive strains of P. vivax have been treated using these models, including the Chesson, Palo Alto, and Achiote strains (58,186,194). This record of sensitivity of strains isolated well before the onset of prevalent resistance serves as a therapeutic benchmark against which other strains may be classified as being susceptible or resistant to chloroquine.…”

Section: Diagnosismentioning

confidence: 99%

Resistance to Therapies for Infection by Plasmodium vivax

2009

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SUMMARY The gravity of the threat posed by vivax malaria to public health has been poorly appreciated. The widely held misperception of Plasmodium vivax as being relatively infrequent, benign, and easily treated explains its nearly complete neglect across the range of biological and clinical research. Recent evidence suggests a far higher and more-severe disease burden imposed by increasingly drug-resistant parasites. The two frontline therapies against vivax malaria, chloroquine and primaquine, may be failing. Despite 60 years of nearly continuous use of these drugs, their respective mechanisms of activity, resistance, and toxicity remain unknown. Although standardized means of assessing therapeutic efficacy against blood and liver stages have not been developed, this review examines the provisional in vivo, ex vivo, and animal model systems for doing so. The rationale, design, and interpretation of clinical trials of therapies for vivax malaria are discussed in the context of the nuance and ambiguity imposed by the hypnozoite. Fielding new drug therapies against real-world vivax malaria may require a reworking of the strategic framework of drug development, namely, the conception, testing, and evaluation of sets of drugs designed for the cure of both blood and liver asexual stages as well as the sexual blood stages within a single therapeutic regimen.

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Section: Diagnosismentioning

confidence: 99%

Resistance to Therapies for Infection by Plasmodium vivax

2009

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“…6 For more than 40 years, the Panamanian Aotus ( Aotus lemurinus. lemurinus ) has been used to adapt new strains of malaria [7][8][9] study its biology, [10][11][12] pathogenesis of its infection, [13][14][15] and to test the efficacy and pharmacokinetics of antimalarial compounds [16][17][18][19][20][21][22][23][24][25][26][27] against these new strains. More recently, this model has also been used to test the efficacy and immunogenicity of antimalarial vaccines through the use of repeated challenge, 28 plasmid DNA vaccines, [29][30][31][32] temperature-sensitive mutants, 33 synthetic peptides, 34 recombinant proteins, [35][36][37] and even to test the immunogenicity of hepatitis B DNA vaccines.…”

Section: Introductionmentioning

confidence: 99%

Adaptation of a Thai Multidrug-Resistant C2A Clone of Plasmodium falciparum to Aotus Monkeys and Its Preliminary in vivo Antimalarial Drug Efficacy-Resistance Profile

Obaldía¹,

Milhous²,

Kyle³

2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. A multidrug-resistant (MDR) clone of Plasmodium falciparum (C2A) from Thailand was adapted through serial passage to Aotus monkeys. During adaptation, the parasite showed resistance to a single 20 or 40 mg/kg oral dose of mefloquine (MQ). Infection was only cured when MQ was administered orally at 40 mg/kg once in combination with intravenous artesunic acid at 20 mg/kg for 3 days. Similarly, the parasite clone was found to be resistant to quinine, failing at 20 mg/kg orally for 5 days in combination with an experimental dihydrofolate reductase (DHFR) inhibitor (WR297608) at 10, 20, or 40 mg/kg orally for 3 days, and with atovaquone/proguanil at 25 mg/kg for 3 days. This new model will allow in vivo testing of new antimalarial compounds or their combinations against a currently circulating MDR P. falciparum strain.

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“…Testing of novel antimalarial compounds also relies heavily on the use of P. vivax - and P. falciparum - infected monkeys (Powers and Jacobs, 1972; Rossan et al 1975; Bitonti et al 1988; Nayar et al 1997; Wengelnik et al 2002; Ye et al 2013). Indeed, many efforts have been undertaken to adapt strains of human malaria to growth in monkeys for the purpose of drug testing (Herrera et al 2002; Obaldía et al 2009).…”

Section: Use Of Non-human Primates Infected With Human Malariamentioning

confidence: 99%

Non-human primate malaria parasites: out of the forest and into the laboratory

Martinelli

Culleton

2016

Parasitology

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The study of malaria in the laboratory relies on either the in vitro culture of human parasites, or the use of non-human malaria parasites in laboratory animals. In this review, we address the use of non-human primate malaria parasite species (NHPMPs) in laboratory research. We describe the features of the most commonly used NHPMPs, review their contribution to our understanding of malaria to date, and discuss their potential contribution to future studies.

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Chemotherapy of Plasmodium vivax in Saimiri and Aotus Models *

Cited by 20 publications

References 0 publications

Resistance to Therapies for Infection by Plasmodium vivax

Resistance to Therapies for Infection by Plasmodium vivax

Adaptation of a Thai Multidrug-Resistant C2A Clone of Plasmodium falciparum to Aotus Monkeys and Its Preliminary in vivo Antimalarial Drug Efficacy-Resistance Profile

Non-human primate malaria parasites: out of the forest and into the laboratory

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