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Am. J. Trop. Med. Hyg., 77(1), 2007, pp. 3-13
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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Clinico-Pathological Observations on the Pathogenesis of Severe Thrombocytopenia and Anemia Induced by Plasmodium vivax Infections During Antimalarial Drug Efficacy Trials in Aotus Monkeys

Nicanor Obaldía, III*
Malaria Drug and Vaccine Evaluation Center, Tropical Medicine Research, Panama City, Republic of Panama; Gorgas Memorial Institute of Health Studies (ICGES), Panama City, Republic of Panama

During routine antimalarial drug efficacy trials, we observed, for the first time, severe thrombocytopenia developing in Aotus monkeys infected with Plasmodium vivax. Data obtained from 26 Aotus infected with the AMRU-1 strain showed that 77% developed severe thrombocytopenia, whereas only 15% had severe anemia, with hemorrhagic diathesis ensuing in 31%. In general, thrombocytopenic monkeys either failed primary treatment with experimental antimalarial drugs or were found to have higher-density parasitemias, longer patency duration, and lower hematocrits. In these monkeys, severe thrombocytopenia inversely correlated to parasitemia (R = –1.0), and animals that received a blood transfusion had significantly higher platelet counts (P < 0.05) by day 38 after inoculation. In conclusion, the AMRU-1 strain of P. vivax, was considered to be highly pathogenic to Aotus monkeys, and thrombocytopenia rather than anemia should be regarded an early indicator of drug treatment failure with this strain.

Received December 22, 2005. Accepted for publication March 20, 2007.

Acknowledgments: The author thanks William Otero and Jorge Aparicio for microscopy and technical assistance, Camilo Marin and the animal care takers for assistance with animal handling and care, Maritza Brewer for secretarial assistance, Gladyz Calviño for administrative assistance, and the directors of Tropical Medicine Research (TMR), Malaria Drug and Vaccine Evaluation Center/Gorgas Memorial Institute (ICGES), in Panama City, Panama for their constant encouragement and support.

Financial support: This work was supported by USAMRDC Contract DAMD17-01-C0039.

Disclaimer: The opinions and assertions contained herein are the private ones of the author and are not to be construed as official or reflecting the views of the U.S. Army.

* Address correspondence to Nicanor Obaldía III, ICGES, Apdo 00816-02593, Panama, Republic of Panama. E-mail: nobaldia{at}gorgas.gob.pa

Author’s address: Nicanor Obaldía III, ICGES, Apdo 00816-02593, Panama, Republic of Panama. E-mail: nobaldia{at}gorgas.gob.pa.






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Copyright © 2007 by the American Society of Tropical Medicine and Hygiene.