Comparison of Plasmodium Falciparum Infections in Panamanian and Colombian Owl Monkeys

Rossan, Richard N.; Harper, James S.; Davidson, David E.; A, Escajadillo; Christensen, Howard A.

doi:10.4269/ajtmh.1985.34.1037

Cited by 18 publications

(13 citation statements)

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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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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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“…In vivo trials of 2-F-HIS and 2-I-HIS were performed with adult male and female Panamanian owl monkeys (A. lemurinus subsp. lemurinus), each weighing between 730 and 943 g, and maintained as previously described (12). Each animal was inoculated with 5 x 106 asexual blood stage parasites of the Uganda Palo Alto strain of P. falciparum (12).…”

Section: Methodsmentioning

confidence: 99%

“…lemurinus), each weighing between 730 and 943 g, and maintained as previously described (12). Each animal was inoculated with 5 x 106 asexual blood stage parasites of the Uganda Palo Alto strain of P. falciparum (12). Six monkeys were infected for each trial.…”

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo studies of the effects of halogenated histidine analogs on Plasmodium falciparum

Panton

Rossan

et al. 1988

Antimicrob Agents Chemother

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The effects of four halogenated analogs of histidine on in vitro growth of Plasmodium falciparum malaria parasites were monitored by measurement of the incorporation of 3H-labeled amino acids into parasite proteins and by light and electron microscopy. The uptake of [3H]isoleucine was reduced to 50% of the control value by addition of 70 microM 2-fluoro-L-histidine (2-F-HIS) or 420 microM 2-iodo-L-histidine (2-I-HIS). [3H]histidine uptake into acid-insoluble material was affected equally by these two compounds, 50% inhibition resulting at 200 microM concentration. Morphological analysis of parasite development proved a sensitive assay, since development of mature trophozoites was inhibited 50% by 25 microM 2-F-HIS or 100 2-I-HIS. Electron microscopy studies suggested different mechanisms of action of 2-F-HIS and 2-I-HIS on P. falciparum. 2-F-HIS produced a decrease in knob number at the erythrocyte surface and accumulation of electron-dense material under the parasite membrane. 2-I-HIS had no obvious effect on knobs or electron-dense material but affected parasite morphology. Surprisingly, 2-chloro-L-histidine and 2-bromo-L-histidine did not inhibit P. falciparum in vitro, even though their halogen atom substituents are intermediate in size between F and I atoms. 2-F-HIS and 2-I-HIS were tested in vivo against P. falciparum in owl monkeys (Aotus sp.) but were ineffective at doses that were nontoxic.

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“…(3) The course of untreated infections, essential for comparison with treated infections, has been documented in Panamanian Aotus (3).…”

Section: Body I Experimental Methodsmentioning

confidence: 99%

“…The course of untreated infections in Panamanian Aotus has been characterized and compared with that in Aotus of Colombia (3). Overall, the virulence of these strains was less in Panamanian than in Colombian owl monkeys, as indicated by lower mortality rates of Panamanian monkeys during the first 30 days of patency.…”

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confidence: 99%

Drug Evaluation in the Plasmodium falciparum - Aotus Model

Rossan¹

1984

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Comparison of Plasmodium Falciparum Infections in Panamanian and Colombian Owl Monkeys

Cited by 18 publications

References 0 publications

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

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

In vitro and in vivo studies of the effects of halogenated histidine analogs on Plasmodium falciparum

Drug Evaluation in the Plasmodium falciparum - Aotus Model

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