Sporozoite-induced Infections Research Articles

Early activity in sporozoite-induced Plasmodium falciparum infections.

Early activity in sporozoite-induced Plasmodium falciparum infections.

Merozoite size in exoerythrocytic infections of Plasmodium gallinaceum, P. fallax, P. lophurae, and P. cathemerium

The diameter of merozoites was chosen as the quantitative measure for comparison of exoerythrocytic stages of avian malaria, since it was possible to obtain this measurement with the greatest accuracy. Statistical studies, using this measure, on the exoerythrocytic stages of P. gallinaceum, P. lophurae, P. fallax, and P. cathemerium revealed the following information: 1. 1. The mean diameter of P. gallinaceum was significantly smaller than the diameters of P. fallax and P. lophurae; the diameters of the latter two species were not significantly different. The morphology of the merozoites of P. cathemerium is such as to prevent the use of the diameter as a measure of comparison of merozoite size with the other three species. 2. 2. Significant differences were found between the merozoites in certain individual hosts of the same species and between the merozoites of P. gallinaceum in the duck and the quail. These differences between the parasites in different individuals of the same species and in different species of host were of the same order of magnitude. 3. 3. Significant differences among merozoites from different organs of the host were found only between those of P. gallinaceum in the brain of the chick as compared with those in spleen, lung, and kidney. A corresponding difference was not found between the merozoites of P. fallax in the brain and lung of the turkey. 4. 4. The merozoites of P. gallinaceum in blood-induced infections were significantly smaller in early (4-day) as compared with late (10, 16, 17 days) infections. This smaller size of the merozoites in early, blood-induced infections is interpreted as a persistence of a characteristic of the parasites following a conversion of its host cell preferences from erythrocytes to cells other than erythrocytes. The differences between 5-day and 10-day merozoites from sporozoite-induced infections were not significant. 5. 5. Although statistically significant differences were found between exoerythrocytic merozoites (of P. gallinaceum and P. fallax) in blood-induced as compared with those from sporozoite-induced infections, it is believed that the bias in the sampling of the merozoites either invalidates these differences completely or reduces them in degree. If differences do exist between the size of exoerythrocytic merozoites in blood-induced and sporozoite-induced infections these differences must be very small. 6. 6. The absence of any evidence of bimodality in the distributions of all sets of the data collected indicates that the absence of two categories of exoerythrocytic merozoites is probably a general phenomenon in avian malaria.

The effect of milk diets on the course of sporozoite-induced Plasmodium gallinaceum infections in chicks.

The effect of milk diets on the course of sporozoite-induced Plasmodium gallinaceum infections in chicks.

Relationship between time of administration, dose, and prophylactic activity of pyrimethamine on sporozoite-induced Plasmodium gallinaceum infections.

Relationship between time of administration, dose, and prophylactic activity of pyrimethamine on sporozoite-induced Plasmodium gallinaceum infections.

The effect of pyrimethamine on the BI strain of Plasmodium gallinaceum.

Summary Pyrimethamine, in large single doses administered on the seventh day of a sporozoite-induced BI strain Plasmodium gallinaceum infection, did not cure the infection though it did prevent death from exoerythrocytic parasites. After a period in which there were no microscopically detectable parasites and which varied slightly with the dose of drug, normal pigmented parasites were found. Erythrocytic parasites could be demonstrated by subinoculation of blood into susceptible recipients as early as 11 to 13 days after inoculation. Variable and reduced numbers of exoerythrocytic parasites were found rarely on direct examination as late as 36 days after inoculation, and more frequently by subinoculation of blood at least as late as the nineteenth day. Mosquitoes could be infected when parasitemia was on the increase. The resulting sporozoites produced only exoerythrocytic infections in untreated recipients, indicating no essential change in the characteristics of the strain. The response of the parasite to the drug remained unchanged during four such serial transfers, using treated chicks as donors.

The effect of pyrimethamine (daraprim) against Plasmodium gallinaceum infections in chicks.

SummaryThe effect of single and multiple doses of pyrimethamine (Daraprim) against blood- and sporozoite-induced Plasmodium gallinaceum infections in chicks was examined. When administered twice daily for 4 days, the maximum tolerated dose for the chick was 0.016 mg./gm.; the minimum effective dose, 0.00002 mg./gm.; the drug was completely prophylactic at 0.00025 mg./gm. and partially prophylactic at 0.00003 mg./gm. When administered as a single dose, the minimum effective dose was 0.00025 mg./gm.; the completely prophylactic dose, 0.004 mg./gm.; and the partially prophylactic dose, 0.0005 mg./gm. When chicks were pretreated with single doses of pyrimethamine, about 50 per cent of the antimalarial activity disappeared per day. Single doses of 0.005 mg./gm. given to chicks with well established sporozoite-induced infections prevented deaths from tissue forms, but doses as high as 0.016 mg./gm. did not cure the infection.

The response of blood-inoculated and sporozoite-induced infections of Plasmodium relictum to drugs

1. When sporozoite-induced infections of Plasmodium relictum are treated with atebrin (mepacrine) in doses suppressive to blood-inoculated infections, for periods exceeding that of normal incubation, parasites devoid of pigment appear in the erythrocytes of the peripheral blood. A small proportion of these may develop into schizonts, but the number of merozoites produced is fewer than normal.2. A similar phenomenon occurs when quinine is substituted for atebrin, but the drug appears to be excreted more rapidly so that the inhibitive effect upon growth is less marked.3. When plasmoquine is given in the maximum tolerated dose to birds infected with sporozoites, parasites are not seen in the peripheral blood during treatment, though the infection is not sterilized. With smaller doses parasites, including a few small schizonts, are found in the erythrocytes during treatment.4. Merozoites produced in the erythrocytes during drug treatment are not capable of further multiplication when inoculated into uninfected birds having a similar blood-concentration of drug, so long as treatment continues, though they develop normally when transferred to untreated birds.5. No indication of drug resistance has been observed.6. The possible mechanisms by which blood-inoculated infections are eradicated, or resist eradication, are discussed.We wish to thank Miss Vincent (Mrs Thorpe) and Dr Parr Tate for access to their preliminary unpublished experiments, and the latter for helpful criticism.

The Prevention of Sporozoite-Induced Infections of Plasmodium cathemerium in the Canary by Metachloridine

The Prevention of Sporozoite-Induced Infections of Plasmodium cathemerium in the Canary by Metachloridine

ACTIVITY OF A NEW ANTIMALARIAL AGENT, CHLOROQUINE (SN 7618)

An intensive exploration of the effects of SN 7618 on animals and man has been in progress during the past two years. This has included an evaluation of the activity of this compound in avian infections, a study of the pharmacology and toxicology in animals and man and finally of its potentialities as an antimalarial against vivax and falciparum infections in man. Included in the latter category are: Extensive studies on its prophylactic activity against domestic and Southwest Pacific strains of vivax malaria, on its curative activity against sporozoite-induced infections when administered alone and in combination with other compounds, and its suppressive activity. Extensive investigations in service installations of the potentialities of this drug for use in the termination of the acute attack and in the suppression of the disease. The pharmacology of SN 7618 has been examined in fairly extensive experiments with mice, rats, dogs, monkeys and

A Method for Collecting Sporozoites of Plasmodium gallinaceum by Feeding Infected Aedes aegypti through Animal Membranes

THE well-known difference between the resistance of blood-inoculated and mosquito-induced malaria indicates that sporozoites, or the stages arising immediately from them, are very resistant to the action of the known anti-malarial drugs. Since a true prophylactic drug, that is, one which will prevent sporozoite-induced infections, is the most urgent requirement in the chemotherapy of malaria, a method for testing drugs directly on sporozoites is of great importance. Hitherto the only method of doing this was to obtain sporozoites by the dissection of salivary glands from infected mosquitoes, which is both laborious and unsatisfactory, as the sporozoites are always mixed with and may be protected by fragments of the salivary gland cells. Thus it is difficult to obtain them in uniform suspension and to be sure that they are all exposed equally to the action of the admixed drugs being tested.

The Tissue Distribution of Exoerythrocytic Schizonts in Sporozoite-Induced Infections with Plasmodium Cathemerium

The Tissue Distribution of Exoerythrocytic Schizonts in Sporozoite-Induced Infections with Plasmodium Cathemerium