Inhibition of Plasmodium yoelii blood-stage malaria by interferon alpha through the inhibition of the production of its target cell, the reticulocyte.

The effect of a recombinant hybrid human interferon alpha (IFN-alpha) (which cross-reacts with murine cells) on C57BL/6 mice infected with Plasmodium yoelii sporozoites or parasitized erythrocytes was determined. IFN-alpha did not inhibit the development of the parasite in the liver, but it did reduce the blood parasite load and the hepatosplenomegaly induced by the infection in mice injected with blood-stage parasites. The extent of anemia in IFN-alpha-treated and control mice was similar, despite the lower parasite load in the IFN-alpha-treated mice. The reduced blood parasite load in IFN-alpha-treated mice was associated with reduced erythropoiesis and reticulocytosis. As reticulocytes are the preferred target cells for the strain of P yoelii used (P yoelii yoelii 265 BY), it was postulated that the inhibition of reticulocytosis in IFN-alpha-treated mice was causally related to the observed decreased blood parasite load. This was supported by the finding that IFN-alpha inhibited a different strain of P yoelii (17X clone A), which also displays a tropism for reticulocytes, but not a line of Plasmodium vinckei petteri, which infects only mature red blood cells. As human malaria species also display different tropism for reticulocytes, these findings could be relevant for people coinfected with multiple Plasmodium species or strains or coinfected with Plasmodium and virus. (Blood. 2001;97:3966-3971)

Involvement of IFN-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection.

IFN-gamma has been implicated in the pathogenesis of experimental cerebral malaria (ECM). We have used mice lacking the alpha chain of the IFN-gamma receptor (KO mice) to define its role in the pathogenesis of ECM. Infected KO mice did not develop ECM and showed no leukocyte or parasite sequestration in the brain, and no hemorrhages. The resistance of KO mice to ECM was associated with the absence of any increases of TNF-alpha and ICAM-1 proteins in the brain, which are both essential for ECM. Wild-type (WT) mice which do not develop ECM, despite increased local production of TNF-alpha protein, showed no leukocyte accumulation in the brain and this was correlated with the absence of ICAM-1 protein from brain microvessels. KO mice infected with 106 parasitized erythrocytes (PE) of Plasmodium berghei ANKA (PbA) did not develop ECM, but they had high parasitemia and died earlier than WT mice which did not develop ECM. However, KO mice did not develop higher parasitemia than WT mice when both groups were infected with a lower dose (5x10(5) PE) of PbA-infected red blood cells. This indicates that different doses of PE may trigger different IFN-gamma responses and that there may be a threshold concentration for protection against parasitemia.

Plasmodium berghei: selection of mefloquine-resistant parasites through drug pressure in mosquitoes.

Mefloquine is an antimalarial drug with schizonticidal activity on blood-stage parasites. Studies of the role of mefloquine on the development of Plasmodium berghei ANKA in anopheles stephensi have been carried out that showed a dose-dependent effect on the sporogonic cycle of these parasites, with changes in the numbers of oocysts and the extent of sporozoite invasion of salivary glands. In this study, we show that mefloquine-resistant P. berghei ANKA blood stage parasites could be selected through drug pressure during continuous cyclical transmission of Anopheles gambiae s.l.

Investigation of chloroquine intake in Biombo region, Guinea Bissau.

The use of chloroquine (CQ), during the dry season was determined for 236 patients from 5 villages in Biombo, Republic of Guinea Bissau, West Africa. The antimalarial drug was measured in whole blood (dried samples) using High Performance Liquid Chromatography (HPLC) and in urine samples by Enzyme Linked Immunosorbent Assay (ELISA). The results showed that CQ consumption is low.