Red cell surface changes and erythrophagocytosis in children with severe plasmodium falciparum anemia.

Severe anemia is one of the most lethal complications in children infected with Plasmodium falciparum. The pathogenesis of this anemia is not completely understood. Experimental data from malaria-infected humans and animal models suggest that uninfected red cells have a shortened life span. This study looked for changes in the red cell surfaces of children with severe malarial anemia that could explain this accelerated destruction. A prospective case-control study was conducted of children with severe P falciparum anemia (hemoglobin of 5 g/dL or lower) admitted to a large general hospital in western Kenya. Children with severe anemia were compared with children who had symptoms of uncomplicated malaria and with asymptomatic children. Cytofluorometry was used to quantify in vitro erythrophagocytosis and to measure red cell surface immunoglobulin G (IgG) and the complement regulatory proteins CR1, CD55, and CD59. Red cells from patients with severe anemia were more susceptible to phagocytosis and also showed increased surface IgG and deficiencies in CR1 and CD55 compared with controls. Red cell surface CD59 was elevated in cases of severe anemia compared with asymptomatic controls but not as compared with symptomatic controls. The surface of red cells of children with severe P falciparum anemia is modified by the deposition of IgG and alterations in the levels of complement regulatory proteins. These changes could contribute to the accelerated destruction of red cells in these patients by mechanisms such as phagocytosis or complement-mediated lysis. (Blood. 2000;95:1481-1486)

Interleukin-10 responses to liver-stage antigen 1 predict human resistance to Plasmodium falciparum.

The design of an effective vaccine against Plasmodium falciparum, the most deadly malaria parasite of humans, requires a careful definition of the epitopes and the immune responses involved in protection. Liver-stage antigen 1 (LSA-1) is specifically expressed during the hepatic stage of P. falciparum and elicits cellular and humoral immune responses in naturally exposed individuals. We report here that interleukin-10 (IL-10) production in response to LSA-1 predicts resistance to P. falciparum after eradication therapy. Resistance was not related to gamma interferon or tumor necrosis factor alpha production. This is the first report that human IL-10 responses are associated with resistance after eradication therapy, and our findings support the inclusion of LSA-1 in a vaccine against malaria.

Trypanosoma congolense: comparative effects of a primary infection on bone marrow progenitor cells from N'Dama and Boran cattle.

Using in vitro clonogenic assays, the changes in haemopoietic progenitor cell levels were compared in the bone marrow of three adult trypanotolerant N'Dama cattle and three age-matched trypanosusceptible Boran cattle over 17 weeks (119 days) of a primary Trypanosoma congolense (clone IL 1180) infection. As the infection progressed, a clear tendency of the parasitaemia to decrease was seen in the N'Damas, while it remained high throughout the infection in the Borans. The decline in the colony-forming units-granulocyte macrophage (CFU-GM) between 7 and 42 days postinfection (dpi) corresponded with the decreased numbers of neutrophils and monocytes in the blood observed in both breeds. Thereafter, a further significant drop in the CFU-GM levels was observed in the Borans which may partially explain the continued decrease in the numbers of neutrophils and monocytes in blood. In contrast, a significant peak of CFU-GM above preinfection levels was observed in the N'Damas on 49 dpi, which could partially explain the subsequent recovery of the numbers of neutrophils and monocytes in blood. When compared to the N'Damas, the Borans had a more dramatic drop in the packed cell volume (PCV) from 25 dpi onwards, resulting in significantly lower PCV. From 46-49 dpi onwards, the mean PCV stabilised at significantly lower levels in the Borans than in the N'Damas. The mean corpuscular volume (MCV) levels increased in both breeds, but at a much faster rate in the Borans. The clonogenic assays demonstrated an erythropoietic response, characterised by peaks above pre-infection levels of both the early and late erythroid progenitor cells (respectively, burst-forming units-erythroid, BFU-E, and colony-forming units-erythroid, CFU-E), occurring between 35 and 70 dpi in both breeds of cattle. However, despite a more severe anaemia in the Borans, the magnitude of their erythroid response was similar to that of the N'Damas, suggesting that the response of the Borans was insufficient to compensate for the greater degree of anaemia. Moreover, the mean PCV did not improve in the Borans, indicating the ineffectiveness of their erythropoietic response. An increased rate of erythrocyte destruction and/or a defective differentiation and maturation of erythroid precursors have also been shown to be partially responsible for this persistent anaemia. From 98 dpi onwards, despite the persistent low PCV, the MCV decreased to preinfection levels and low CFU-E numbers were observed in the Borans. Over the same period, in the N'Damas the mean PCV progressively increased to reach 25%, which fell within the low normal range for cattle.(ABSTRACT TRUNCATED AT 400 WORDS)