Plasmodium Falciparum and Plasmodium Vivax Infections in the Owl Monkey (Aotus Trivirgatus)

Abstract

The studies described in this report were designed to determine the responses of established infections with eight strains of Plasmodium falciparum and two strains of P. vivax in owl monkeys to treatment with chloroquine, quinine, and pyrimethamine. Responses with these different strains ranged from cure via application of well-tolerated doses of two of the above drugs and refractoriness to treatment with maximally tolerated doses of the third, to complete resistance to maximally tolerated doses of all three compounds. The results of treatment exhibited in infected owl monkeys correlated well in two respects with those reported in humans infected with the same plasmodial species. First, calculated on a milligram per M2 basis, the doses of chloroquine, quinine, or pyrimethamine required for a CD90 response in owl monkeys infected with strains susceptible to these drugs were remarkably similar to the doses required and/or employed for cure of infections with so-called drug-susceptible strains in human patients. Secondly, with few exceptions, the responses to the above drugs in owl monkeys infected with the ten specially selected strains were essentially identical with those exhibited by human volunteers or patients infected with the same strains. Together, these findings and correlations provide strong support for use of owl monkeys infected with appropriate strains of P. falciparum and P. vivax in the search for more broadly effective antimalarial drugs.

Human Malaria in Immunocompromised Mice: New In Vivo Model for Chemotherapy Studies

“…Thus, it is important to note that now P. falciparum infections can be obtained not only in South American monkeys (32,33) but also in small experimental animals. Whereas mice are easy to reproduce under laboratory conditions, mon- a Human response data were collected from previously published reports of chemotherapy field studies (2, 5, 6, 8, 9, 11-14, 16, 20-22, 28, 29, 33-37, 39).…”

Testing the efficacy of a recombinant merozoite surface protein (MSP-1(19) of Plasmodium vivax in Saimiri boliviensis monkeys.

“…Although Aotus monkeys are usually less susceptible to infection via sporozoite inoculation, many strains of this parasite have been adapted to develop in Aotus monkeys. [20][21][22][23][24][25][26][27][28][29][30] Further studies to assess the efficacy of yP 2 P 30 Pv200 19 and other blood-stage candidate vaccines may better be conducted in Aotus monkeys using a strain of P. vivax shown to induce predictably high-density parasitemia in intact animals. Attempts will be made to establish such a model using strains of the parasite already adapted to monkeys.…”

Resistance to Therapies for Infection by Plasmodium vivax

“…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.…”