Susceptibility of Panamanian Aotus lemurinus lemurinus to sporozoite-induced Plasmodium falciparum (Santa Lucia) infection.

Aotus monkeys are good models for erythrocyte-induced Plasmodium falciparum and P. vivax infections and have been extensively used in malarial drug and vaccine development. Recently, it has been shown that certain species of Aotus can be infected with sporozoites, and that the degree of susceptibility varies among species. We demonstrate here that Panamanian Aotus lemurinus lemurinus are susceptible to a sporozoite-induced infection, opening the possibility that this species of Aotus could be used as models for testing the efficacy of pre-erythrocytic P. falciparum vaccines and drug candidates directed at the pre-erythrocytic stages of P. falciparum and P. vivax malaria. In this species, we compared sporozoite infection rates. Two of four animals splenectomized prior to infection with sporozoites developed patent parasitemias. Seven of eight animals splenectomized either 7 or 35 days after infection became parasitemic. Additionally, we used a P. falciparum-specific polymerase chain reaction (PCR) method to detect the early appearance of parasitized erythrocytes in the blood prior to detection by conventional microscopy, and found that the parasitemia was detected first in five animals by the PCR method, first in three animals by blood film, with one parasitemia detected simultaneously. We also demonstrated the feasibility of infecting monkeys located in Panama with sporozoites isolated at an insectary in Atlanta, thus documenting the feasibility of similar studies where the insectary and monkey colony are not in the same location. A subsequent attempt to infect these monkeys using sporozoites was not successful, suggesting that this model of human malaria is not yet ready for routine use in vaccine or drug efficacy screening. This model merits further study because of the importance of testing pre-erythrocytic P. falciparum malaria vaccines and drugs in animals.

WR 238605, chloroquine, and their combinations as blood schizonticides against a chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys.

The compound WR 238605 is a primaquine analog being developed by the U.S. Army as an antimalarial drug. Currently, there is no established treatment for Plasmodium vivax parasitemias that are not cured by chloroquine. This study tested WR 238605, chloroquine, and their combinations against a chloroquine-resistant strain of P. vivax (AMRU 1) in Aotus monkeys. A total dose of 3 mg/kg of WR 238605 given at a dosage of 1 mg/kg/day for three days cleared patent parasites in all eight monkeys but recrudescence of parasitemia occurred 15-25 days after initiation of treatment. A total dose of 9 mg/kg of WR 238605 over a three-day period cured all three monkeys of their infections. A total dose of 30 mg/kg of chloroquine did not clear patent infections in three monkeys, whereas a total dose of 60 mg/kg generally (two of three) cleared patent parasitemia but did not cure. Whereas total doses of 30 mg/kg of chloroquine or 3 mg/kg of WR 238605 given alone failed to cure, both drugs given in combination at these dosages cured two of three infections. These results indicate that WR 238605 may be an alternative treatment for chloroquine-resistant vivax malaria.

Adaptation of the Panama II strain of Plasmodium falciparum to Panamanian owl monkeys.

The Panama II strain of Plasmodium falciparum, acquired at the second passage level in splenectomized Colombian owl monkeys, was adapted to owl monkeys of Panamanian origin. Patent infections were induced in 22 of 27 unaltered and 20 of 21 splenectomized recipients during 19 serial passages. The infections were significantly more virulent in splenectomized than normal Panamanian owl monkeys, however recrudescences in seven normal monkeys achieved peak parasitemias 48 times greater than in the primary attack. These results describe the first reproducible infections of indigenous falciparum malaria in Panamanian owl monkeys.

Comparison of Plasmodium falciparum infections in Panamanian and Colombian owl monkeys.

Parameters of blood-induced infections of the Vietnam Oak Knoll, Vietnam Smith, and Uganda Palo Alto strains of Plasmodium falciparum studied in 395 Panamanian owl monkeys in this laboratory between 1976-1984 were compared with those reported from another laboratory for 665 Colombian owl monkeys, studied between 1968-1975, and, at the time, designated Aotus trivirgatus griseimembra. The virulence of these strains was less in Panamanian than in Colombian owl monkeys, as indicated by lower mortality rates of the Panamanian monkeys during the first 30 days of patency. Maximum parasitemias of the Vietnam Smith and Uganda Palo Alto strain, in Panamanian owl monkeys dying during the first 15 days of patent infection, were significantly higher than in Colombian owl monkeys. Panamanian owl monkeys that survived the primary attack had significantly higher maximum parasitemias than the surviving Colombian owl monkeys. Peak parasitemias were attained significantly earlier after patency in Panamanian than in Colombian owl monkeys, irrespective of the strain of P. falciparum. More Panamanian than Colombian owl monkeys evidenced self-limited infection after the primary attack of either the Vietnam Smith or Uganda Palo Alto strain. The duration of the primary attacks and recrudescences were significantly shorter in Panamanian than in Colombian owl monkeys. Mean peak parasitemias during recrudescence were usually higher in Panamanian owl monkeys than in Colombian monkeys. Differences of infection parameters were probably attributable, in part, to geographical origin of the two monkey hosts and parasite strains.

Adaptation of a Nigerian strain of Plasmodium falciparum to Panamanian Aotus trivirgatus.

A patent infection (more than 190 days duration) with Plasmodium falciparum, obtained directly from a patient who had been exposed to malaria in Nigeria, was established in a splenectomized Panamanian owl monkey, Aotus trivirgatus griseimembra. Subinoculations from the original monkey recipient into one splenectomized and two normal A. t. griseimembra produced primary patient parasitemias of 18-54 days duration. These results represent the first successful adaptation of P. falciparum from man to a monkey of Panamanian origin.

Banding patterns of the chromosomes of two new karyotypes of the owl monkey, Aotus, captured in Panama.

Two new chromosome complements of Aotus trivirgatus griseimembra are described making a total of five different karyotypes observed in this subspecies inhabiting Panama and the northwestern part of Colombia, South America. Detailed comparisons of the G-banded chromosomes of these five karyotypes suggest that the polymorphism of chromosome numbers 56 and 55 in Panamanian Aotus and 54, 53, and 52 in Colombian Aotus stems primarily from a Robertsonian translocation mechanism involving pairs B13 and B14 (or A1). A second Robertsonian translocation mechanism involving pairs B28 and B29 (or A2) constitutes the karyotypic differences between the two chromosomal races.

The prevalence of trypanosomes and microfilariae in Panamanian monkeys.

A total of 3,523 wild caught monkeys from Panama was examined for blood parasites from August 1968 through June 1972. Trypanosomes or microfilariae were observed in the blood of 31.1% of the monkeys. Mixed infections, with microfilariae and trypanosomes, were detected in 6.6% of the animals. Trypanosoma cruzi was found in marmosets. Saguinus geoffroyi (12.2%), in white-faced capuchins, Cebus capucinus (5.0%), in squirrel monkeys, Saimiri sciureus (1.7%) and in black spider monkeys, Ateles fusciceps (1.2%). Trypanosoma rangeli was found in S. geoffroyi (55.8%) and C. capucinus (12.5%). Other trypanosomes found in Panamanian monkeys included T. minasense, and T. mycetae. Saguinus geoffroyi showed the highest infection rate (88.9%) with trypanosomes and/or microfilariae; trypanosomes were seen in 68.1%, and microfilariae in 73.0%, of the animals examined. The marmosets, white-faced capuchins, and squirrel monkeys should be considered as significant hosts of T. cruzi in sylvatic habitats and may serve as reservoir hosts of Chagas' disease in Panama. The microfilariae seen in monkeys from Panama were tentatively identified as larval forms of Dipetalonema gracile in Aotus trivirgatus; D. obtusa in C. capucinus and S. geoffroyi; and D. marmosetae in Alowatta villosa, C. capucinus, A. trivirgatus, S. sciureus, A. fusciceps, and S. geoffroyi.