Protection against Plasmodium falciparum malaria in chimpanzees by immunization with the conserved pre-erythrocytic liver-stage antigen 3.

In humans, sterile immunity against malaria can be consistently induced through exposure to the bites of thousands of irradiated infected mosquitoes. The same level of protection has yet to be achieved using subunit vaccines. Recent studies have indicated an essential function for intrahepatic parasites, the stage after the mosquito bite, and thus for antigens expressed during this stage. We report here the identification of liver-stage antigen 3, which is expressed both in the mosquito and liver-stage parasites. This Plasmodium falciparum 200-kilodalton protein is highly conserved, and showed promising antigenic and immunogenic properties. In chimpanzees (Pan troglodytes), the primates most closely related to humans and that share a similar susceptibility to P. falciparum liver-stage infection, immunization with LSA-3 induced protection against successive heterologous challenges with large numbers of P. falciparum sporozoites.

Malaria transmission in a region of savanna-forest mosaic, Haut-Ogooué, Gabon.

During the 2 years 1993 to 1995, an entomological survey was carried out in the savanna-forest area of Franceville, Gabon, investigating malaria transmission in one suburban district of Franceville (Akou) and in one rural village (Benguia). The biting rates of the Anopheles vectors were 10 times higher in the rural zone compared to the suburban zone. Anopheles funestus Giles was the predominant species in both zones followed by Anopheles gambiae s.l. Giles. The densities of Anopheles nili Theobald and Anopheles moucheti Evans were very low. In the suburban zone, transmission was maintained throughout the year by An. funestus and An. gambiae s.l., whereas in rural zones the secondary vectors An. nili and An. moucheti were also involved in transmission. Humans in a suburban setting received one infective bite per person every 4 days, whereas in the rural area the infective biting rate was 4 times higher. Considering each vector, the observed entomological inoculation rates (EIRs) were one infective bite per person every 6 and 17 days for An. funestus and An. gambiae s.l., respectively, at Akou. At Benguia, the EIRs were one infective bite per person every 2, 3, 6, and 19 days for the 4 An. funestus, An. gambiae s.l., An. nili, and An. moucheti, respectively. The predominance of An. funestus over An. gambiae s.l. and its high EIR make it the most important malaria vector in this region of Haut-Ogooué.

Plasmodium coatneyi: differential clinical and immune responses of two populations of Macaca fascicularis from different origins.

Two species of macaques, including two Macaca fascicularis from the Philippines, two M. fascicularis from Mauritius, and one Macaca mulatta, were experimentally infected with blood stages of Plasmodium coatneyi and followed during their clinical, parasitological, biological, and immunological evolution. Plasma cytokine (TNF-alpha, IL-1beta, IL-6, IFN-gamma) production peaked for all monkeys 11 days after inoculation, concomitantly with peaks of parasitemia. Only the M. fascicularis from the Philippines survived the infection. The main features, which discriminated nonfatal from fatal cases, were the observation in M. fascicularis from the Philippines of a mean CD4+/CD8+ ratio below I and of their ability, as revealed by mitogenic stimulation of whole blood, to produce increasing amounts of IFN-gamma as infection evolved. The contribution of environmental and genetic factors, which may differentiate the three groups of monkeys and therefore explain fatal or nonfatal evolution of the infection among them, is discussed.

Lack of malaria parasite transmission between apes and humans in Gabon.

The International Center for Medical Research (CIRMF) is located in an area highly endemic for malaria in southeastern Gabon, where humans and apes (gorillas and chimpanzees) are living in the same geographic area. The presence of the CIRMF primate center housing apes (59 chimpanzees and nine gorillas in 1994) within the city of Franceville provided an opportunity to investigate the capability of cross-transmission of malaria species from humans to apes. The main vector of human malaria, Anopheles gambiae, was found in the primate center and in a nearby populated area of Franceville. Despite high malaria transmission in humans of both Plasmodium falciparum and P. malariae (mean of 43% cumulative prevalence in schoolchildren), none of the apes were found infected with plasmodia during a six-month investigation. However, low antibody levels against sporozoite and blood stages of both P. falciparum and P. malariae were detected in a few chimpanzees and gorillas. These results demonstrate that only rarely would apes be bitten in the field by mosquitoes infected with human malaria parasites. In the case of infection proven by serology, we did not find any evidence that blood-stage malaria parasites were able to the gametocyte stage. The absence of any established malaria transmission cycle within the primate colony of CIRMF indicates that apes cannot be considered as animal reservoirs for human malaria parasites in this environment.