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Larvae of Anopheles quadrimaculatus were exposed to Bacillus sphaericus. The surviving adults took blood meals on hamsters infected with Plasmodium berghei. Fewer mosquitoes were infected than were the paired controls. The inhibitory action appeared to occur during the early stages of the infection in the mosquito gut.

Three standard antimalarial compounds were tested against trophozoite or sporozoite induced infections of the Panamanian Achiote strain of Plasmodium vivax in two species of monkeys. In Saimiri sciureus (24 subjects) and Aotus trivirgatus (11 subjects), parasite clearance from the peripheral blood averaged 3 days after initiating chloroquine therapy (total dose of 25 mg base/kg body weight over 3 days or single dose of 10 mg base/kg. Trophozoite induced infections were cured in all of 10 Saimiri and all of 6 Aotus, as indicated by the absence of relapses. Relapses did occur in 3 of 11 tests with Saimiri and 3 of 5 tests with Aotus against sporozoite induced infections. Subpatent periods ranged from 38 to 111 days among intact and splenectomized hosts. This is the first chemotherapeutic evidence for the persistence of exoerythrocytic stages of P. vivax in New World monkeys. Pyrimethaminr (single dose of 1 mg/kg) cured trophozoite induced infections in all of five Saimiri hosts. Radical cure of sporozoite induced infections was accomplished in each of six trials with chloroquine (25 mg base/kg) plus primaquine (1 mg base/kg for 14 days). The primary attack or relapse was treated. These models warrant further investigation in chemotherapy.

Aotus monkeys have been shown to be susceptible to the three most important species of human malaria as well as to simian, ape, and rodent malaria. The parasites natural to man were maintained by serial passages using trophozoite infected blood. It was then possible to transfer the infections to, and among, other New World monkeys which previously were refractory. The parasites retained their viability in the monkey, were infective to mosquitos, and were transmitted between monkeys and back to man. Exoerythrocytic stages, similar to those demonstrated in man, occurred in the Aotus liver. Drugs exerted similar action against the parasites in the monkey as against parasites in man. The human malaria-Aotus model has made possible other extensive studies in various disciplines important to the understanding of the parasites in man. These included parasite biology, host-parasite-vector relationships, immunology, pathology, and physiology.

Plasmodium hermani was experimentally transmitted from domestic turkey poults (Meleagris gallopavo) to pen-reared bobwhites (Colinus virginianus) and then from these bobwhites back to domestic turkey poults. Transmission was achieved by Culex nigripalpus both by bites of the mosquito and by intraperitoneal injection of sporozoites. All of the 23 bobwhites and the 13 turkeys exposed to sporozoites became infected. These results indicate that the bobwhite might be a reservoir host for this malaria of wild turkeys in nature.

The authors present the results of a study carried out to determine the efficacy of chloroquine- and pyrimethamine-salt mixtures as a suppressive against sporozoite-induced vivax malaria (Chesson strain). The test subjects used in this study were volunteers of military age in the US Penitentiary at Atlanta, Ga. The subjects chosen were all in good physical condition and had no previous history of malaria.Both drug-salt mixtures were entirely acceptable to the volunteers, were indistinguishable in taste and appearance from ordinary salt, and remained stable under the conditions of food preparation. The weekly dosage of the drugs (300 mg of chloroquine base or 25 mg of pyrimethamine per 50 g of salt) had in each case been adjusted to the average salt consumption. Suppression of malaria was found to be complete throughout the salt-drug regimen and for 28-43 days thereafter, even though the subjects were exposed to repeated heavy doses of sporozoites. In contrast, the control subjects, exposed to the same infective doses, all exhibited parasitaemia 13-15 days after exposure.The procedures for preparing the drug-salt mixtures are described in detail and a simple method for determining the salt consumption by measurement of the urinary chloride excretion is outlined.

Sixteen patent P. falciparum infections (McLendon and Panama strains) in non-immunes were treated with single doses of pyrimethamine. The schizontocidal and sporontocidal response to the initial dose was rapid.Seven blood-induced infections, of which three were treated with 100 mg and four with 50 mg, did not relapse. Of seven cases observed after 25-mg treatment, five relapsed.Delayed treatment of the relapsing infections (Panama strain) with single doses of 25 mg or 50 mg, and subsequently 100 mg, had virtually no schizontocidal or sporontocidal effect. In one case the resistant infection was transmitted by mosquitos to another patient; the subsequent infection was also highly resistant to the drug.It is concluded that under the experimental conditions of this study resistance to pyrimethamine by P. falciparum may occur rapidly after a single dose of 25 mg, being manifested during relapses on the second challenge with the drug. Increasing the drug dosage does not overcome the resistance. The resistant character is readily transmitted by mosquitos.

P. vivax infection (Korean, St Elizabeth or Chesson strain) was induced in 17 neurosyphilitic patients. Pyrimethamine in single doses of either 25, 50, 100 or 200 mg was given to test the schizontocidal and sporontocidal effects.The first single-dose treatment of 25 mg or 100 mg was given between the 8th and 61st days of parasite patency and gave moderately rapid schizontocidal and very rapid sporontocidal effects. All observed cases relapsed.The second treatment, usually three weeks or longer after the first and with the same or higher doses, had either a diminished effect or none on the schizogonous and sporogonous cycles. Subsequent treatment, even at weekly intervals, had no effect.The resistant quality was undiminished in subsequent infections transmitted by mosquito bites, by the injection of preserved sporozoites, or by transfusion of infected blood. Preserving sporozoites or erythrocytic parasites at very low temperatures did not materially affect the resistant quality.In view of the evidence presented, it appears that resistance could also occur in the field when large single doses of pyrimethamine alone are given at less than monthly intervals to febrile persons having active P. vivax infections.