The tissue stages and sporogony of Plasmodium knowlesi

Abstract

1. (1) Two strains of P. knowlesi were passed through mosquitoes. Oocysts from the “Nuri” strain developed fairly readily in Anopheles stephensi but degenerated before maturity and sporozoites were rarely seen. Oocysts from a recently isolated strain of P. knowlesi, however, developed well in A. stephensi and numerous sporozoites reached the salivary glands where they quickly died; in A. aztecus, oocysts developed much more abundantly, fewer degenerated, and sporozoites remained viable in the glands. 2. (2) In monkeys inoculated by intraperitoneal or intravenous routes, gametocytes appeared in the peripheral blood 4 days later. The optimum time for feeding the mosquitoes was on the 5th and 6th days, while after this time few mosquitoes became infected. 3. (3) Infection resulted 9 days after the intraveneous inoculation of rupturing oocysts from A. stephensi into two rhesus monkeys. 4. (4) The “new strain” of P. knowlesi was transmitted to three rhesus monkeys and one kra monkey by the inoculation of sporozoites from glands and/or rupturing oocysts: the pre-patent period was 5 1 2 days. 5. (5) The oocyst and sporozoite of P. knowlesi are described. The former becomes mature between the 8th and 9th day after the blood meal, at 26° C. and in a relative humidity of 80 per cent. 6. (6) The pre-erythrocytic schizogony of P. knowlesi is described from forms seen in liver biopsies made 3 3 4 , 4 3 4 and 5 1 4 days after the intravenous inoculation of sporozoites. Phagocytosis of a ruptured schizont was seen at 5 3 4 days, but no exo-erythrocytic or merocystic forms of the parasite were found in liver taken on the 11th and 13th days of infection. 7. (7) The pre-erythrocytic schizont is about 25 μ in diameter at 3 3 4 days and 40 μ at 5 1 4 days: it is usually smooth, unlobulated, and oval or subspherical in contour. The cytoplasm and nuclei show a remarkable degree of dissociation, and only late in development do the flocculi of cytoplasm become “seeded” with chromatin. The nuclei themselves are often in the form of a cluster of four minute dots (chromosomes?) which give the effect of a red “peppering” to the schizont. From 3 3 4 days onward these nuclei are Feulgen-positive. 8. (8) A tentative scheme of the nature of the changes in the growing schizont is given. 9. (9) Small forms in the early and late biopsies of liver were thought to be retarded rather than representing pre-destined, special exo-erythrocytic schizonts. 10. (10) It is suggested that P. knowlesi is very probably the fifth species that can cause human malaria, and that the infection may be a zoonosis, involving man and monkeys in Malaya and the East Indies.