Injection Of Sporozoites Research Articles

The Schizonticidal Activity of Hydroxynaphthoquinones against Plasmodium berghei Infections in Mice

Two decades ago 2-hydroxy-1,4-naphthoquinones were reported to have considerable suppressive and prophylactic activity against avian malaria. A few compounds were selected for clinical testing but were ineffective in human malarias presumably because of oxidation in the human body into inactive products. Recently homologs with longer n-alkyl side-chains than those of earlier compounds in the series have been synthesized and tested against rodent malarias. In four of the five series of 2-hydroxy-1,4-naphthoquinones reported in this study, peak activity occurred when the methylene groups adjacent to the alicyclic or terminal methyl group numbered 8 or 9. The higher members of the series have been demonstrated to possess not only schizonticidal activity at a dose level lower than that required for the older hydroxynaphthoquinones but also curative activity at high doses. The discovery of strains of Plasmodium falciparum refractory to either suppressive or therapeutic doses of 4-aminoquinolines (chloroquine, hydroxychloroquine, amodiaquine) and a-aminoacridines (quinacrine, propoquine) made reappraisal of malaria chemotherapy mandatory largely because of the known limitations of alternate drugs (chlorguanide, pyrimethamine, quinine, cycloguanil, primaquine, etc.). In an effort to discover new antimalarial drugs our attention was drawn to a group of 2-hydroxy-l,4-naphthoquinone compounds synthesized by Fieser and his associates at Harvard University's Chemical Laboratory as a part of the antimalarial survey conducted on a national scale during World War II. Two of these naphthoquinones (M-1916 and M-285) were shown to possess suppressive and curative effects against avian plasmodia (P. lophurae and P. gallinaceum), but they did not prove to have significant effects against P. vivax and P. falciparum infections of humans (Fieser et al., 1948a). These and other related naphthoquinone antimalarials received scant attention at that time because of the marked suppressive and therapeutic efficacy of 4aminoquinoline antimalarials at well tolerated dose levels. After the discovery of rodent plasmodial infections (P. berghei, P. vinckei, P. chabaudi), it became possible to screen drugs on a wide scale against mammalian rather than avian plasmodia. Several of the old and a few of the more recently synthesized hydroxynaphthoquinone antimalarials (Fieser et al., 1967a, Received for publication 12 March 1968. b) were screened and evaluated against bloodinduced rodent infections and were found to be effective following oral administration. The discovery by Yoeli and Most in 1960 of means for facilitating the transfer of P. berghei through the bites of infected anophelines under laboratory conditions made it possible for us to test the efficacy of the new hydroxynaphthoquinone derivatives against sporozoiteinduced as well as blood-induced P. berghei infections in mice. This paper describes the antimalarial screening procedures used and presents the activity of several compounds belonging to each of the various series of 3-substituted alkyl-2-hydroxy-1,4-naphthoquinones against blood-induced P. berghei infections in mice. A few selected derivatives from the various series of hydroxynaphthoquinones were administered to mice infected by injection of sporozoites of P. berghei. The details of these tests are the basis for a separate paper. MATERIALS AND METHODS Rodent plasmodia Four strains of Plasmodium berghei (NYU-2, NK-65, KSP-11, and subspecies yoelii), two other rodent plasmodia (P. vinckei and P. chabaudi), and a strain of P. berghei maintained under chloroquine pressure were used in our studies. In this paper the results of screening against two strains of P. berghei (NYU-2 and NK-65) will be presented. The NYU-2 strain was isolated on 6 January 1959 by Dr. Van Braeckel from infected salivary glands of Anopheles dureni caught in the vicinity of Kasapa (near Elizabethville, Congo). Dr. Yoeli of New York University obtained the strain from Professor Jadin of Belgium on 20 February 1959. Although originally a vigorous gametocyte producer, it gradually lost this ability through numer-

East Coast Fever: Experiments with the Tissues of Infected Ticks

SUMMARY The tissues of Rhipicephalus appendiculatus infected with Theileria parva and fed for 3 1 2 − 4 1 2 days were used to induce experimental East Coast fever. Freshly prepared tissues infected 76 per cent of thirty-four cattle and killed 81 per cent of these reactors. Infective tissues stored for 24 hours at 4°c before injection produced a lower number of reactors and a smaller number of infected cattle died; of fourteen inoculated six (45 per cent) reacted and two ( 33 1 3 per cent) of those infected, died. Neither X-irradiation nor storage at − 79°c for 24 hours appeared to affect the infectivity or the virulence of the sporozoites. Attempts to obtain sporozoites in free suspension by irrigation and incubation failed. No immunogenesis resulted from injection of inactivated sporozoites in the presence of adjuvants. Those cattle which reacted and recovered were invariably immune (9/9) to a subsequent ten-tick challenge. Those which did not react to the primary infection including those receiving tissues plus adjuvants, proved on challenge to be susceptible (31/32).

Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei.

STUDIES with avian malaria have shown that killed sporozoites as well as sporozoites inactivated with ultraviolet light can produce a partial immunity after injection into birds1,2. On the other hand, attempts to use the erythrocytic stages of the parasite as the source of antigen have met with only limited success with avian3, rodent4 and monkey malaria5,6. Previous attempts to use killed sporozoites of the rodent malarial parasite, Plasmodium berghei, to immunize rodents have been unsuccessful. We therefore sought to determine whether protective immunity to this parasite could be achieved by partial inactivation of the injected sporozoites as opposed to injection of dead parasites. X-irradiation was chosen as the inactivating agent, because of the partial immunity obtained by vaccination with irradiated blood forms of malaria parasites7–9. This communication reports preliminary results on the production of protective immunity in mice by vaccination with X-irradiated sporozoites of P. berghei.

The host-restriction of Haemoproteus sp. indet. of the wood-pigeon Columba p. palumbus.

SYNOPSIS. Earlier experiments suggested that the species of Haemoproteus which infects English wood‐pigeons (Columba p. palumbus) and is transmitted by the hippoboscid dipteran fly Ornithomya avicularia, was unable to infect Columba livia domestica, a host of H. columbae. This has now been confirmed by the injection of sporozoites into two pairs of pigeons, one of each species; in both experiments the C. palubus developed parasitemia while the C. livia did not. It has also been shown that this species of Haemoproteus can complete sporogony in a small proportion (2/73) of Pseudolynchla canariensis, the vector of H. columbae.

Active and passive immunization of chickens against intravenously induced infections of Eimeria tenella

The intravenous inoculation of Eimeria tenella sporozoites gave larger infections and more reliable results than oocysts or sporozoites inoculated by any other parenteral route. Fowls given E. tenella oocysts orally and those which had received injections of disintegrated parasite material were both resistant to attempts at infection with sporozoites given intravenously. The injection of serum globulin from resistant (orally dosed) fowls protected susceptible birds from parenteral infection. When this serum fraction was injected shortly before parenteral challenge, protection was almost complete; globulin given 19 hours after injection of sporozoites was less effective. The injection of a serum globulin fraction from normal birds gave no protection.

TRANSMISSION OF LEUCOCYTOZOON BONASAE CLARKE TO RUFFED GROUSE (BONASA UMBELLUS L.) BY THE BLACK FLIES SIMULIUM LATIPES MG. AND SIMULIUM AUREUM FRIES

Specimens of Simulium aureum, S. latipes, S. venustum, and S. rugglesi feed on ruffed grouse although relatively few engorged specimens of the two latter species were obtained. S. aureum and S. latipes are suitable hosts for Leucocytozoon bonasae as shown by infections produced in grouse following injections of sporozoites removed from the salivary glands of these flies. The parasitaemia in grouse infected naturally and experimentally was relatively low and no gross signs of disease were noted in any of the infected birds.

Changes in infectivity of Plasmodium relictum for avian hosts

1. 1. Establishment of infections of strain 1P1-1 of Plasmodium relictum in pigeons is reported, with frank parasitemias as high as 5000 parasitized cells per 10 4 red cells. The strain was maintained in pigeons by intravenous blood transfer for a period of 255 days, through 15 successive transfers. 2. 2. Blood transfer was readily obtained from canary to pigeon, pigeon to pigeon, and pigeon to canary. 3. 3. Mosquito transfer was obtained from canary to canary by the bite of infected Culex tarsalis, and from canary to pigeon by intramuscular injection of sporozoites into the latter host.

Indian Research Fund Association

THE report of the Scientific Advisory Board of the Indian Research Fund Association (New Delhi) for the year ended December 31, 1946, gives some account of the researches carried out during the year on cholera, malaria, nutrition, leprosy, plague, pharmacology, maternity and child welfare, filariasis and other"subjects, and includes the reports of the advisory committees as Well as a list of papers published under the auspices of the Association, and the programme of researches and miscellaneous grants recommended for the financial year 1947–48. A cholera inquiry commenced at the Central Research Institute, Kasauli, is concerned with the substance and variability of the vibrios which may affect the efficiency of the vaccine used in cholera prophylaxis. The insecticide and mosquito repellent inquiry under the director of the Malaria Institute of India, Delhi, has covered the preparation of D.D.T. emulsion concentrates and aqueous suspensions, and field trials of D.D.T. solution, emulsions and suspensions and of ‘Gammexane' solutions as residual sprays, as well as of turpentine, turpentine-toluene, and turpentine-rosin soap emulsions. A mammalian malaria inquiry covered studies of the experimental mosquito transmission of Plasmodium cynomolgi to Macaca muletta monkeys and the course of the infection and of the transmission of P. cynomolgi by blood and tissue sub-inoculation during the incubation period following sporozoite injection. An investigation of adult Anopheles stephensi was initiated at the School of Tropical Medicine, Calcutta, and another on the control of sand-flies, Phlebotomus argentipes, by spraying with D.D.T.

Bird Malaria Transmitted by the Intravenous Injection of Sporozoites

Bird Malaria Transmitted by the Intravenous Injection of Sporozoites

Preliminary Studies on the Production of Bird Malaria Infections by the Injection of Sporozoites

Preliminary Studies on the Production of Bird Malaria Infections by the Injection of Sporozoites