MAINTENANCE OF THE HUMAN MALARIAL PARASITE, PLASMODIUM-FALCIPARUM, INSCID MICE AND TRANSMISSION OF GAMETOCYTES TO MOSQUITOS

The study of human malaria has been hampered by the lack of small anim al models for the human-infecting malarial parasites. To approach this problem, the erythrocytic stages of the human malarial parasite Plasm odium falciparum were adapted to in vitro growth in the presence of as cites fluid from mice homozygous for the severe-combined immunodeficie ncy (scid) mutation. Human red blood cells (hRBCs) infected with these adapted parasites were then injected i.p. into nonobese diabetic scid /scid (NOD/LtSz-scid) mice. With daily supplemental intraperitoneal bo osts of uninfected hRBCs, parasites were detected in the peripheral ci rculation of these mice for an average of 7 d after injection. Splenec tomy of NOD/LtSz-scid mice increased both the level and duration of pa rasitemia in the periphery, and it also promoted the circulation of ma ture sexual stage parasites (gametocytes). When Anopheline mosquitoes were allowed to feed on the splenectomized mice, the gametocytes were ingested by the mosquitoes and developed into oocysts in the mosquito midguts. To our knowledge, these results are the first demonstration o f human malarial parasite propagation in mice and transmission of thes e parasites to the invertebrate vector.