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For a better definition of the polymorphic features of Plasmodium falciparum parasite populations, the polymerase chain reaction (PCR) typing technique was used to investigate the genetic diversity and complexity of parasites harbored by acute P. falciparum carriers from three yet unexplored malaria-mesoendemic areas with different transmission levels: two localities in northwestern Brazil (Ariquemes and Porto Velho) and a village in Madagascar (Ankazobe). A total of 89 DNA samples were analyzed by amplification of polymorphic domains from genes encoding merozoite surface antigens 1 and 2 (MSP-1, MSP-2) and thrombospondin-related anonymous protein (TRAP) and by hybridization with allelic-family-specific probes or random-fragment-length polymorphism (RFLP). In all three localities, extensive polymorphism was observed for each marker, but the MSP-2 central repeat was the most diverse one. Similar levels of genetic diversity, allelic frequency, and infection complexity were observed in the two Brazilian localities, although the isolates had been sampled at 2-year intervals, suggesting the stability of the infecting parasite populations presenting in these regions of the Brazilian Amazon. Unexpectedly, although the entomologic inoculation rate was at least 3 times lower in Ankazobe than in the Brazilian areas. Malagasi samples appeared more complex than the Brazilian ones. The implications of these data with regard to parasite population-dynamics studies are discussed.

Several questions regarding the production and functioning of autoantibodies (AAb) during malaria infection remain open. Here we provide an overview of studies conducted in our laboratory that shed some light on the questions of whether antiphospholipid antibodies (aPL) and other AAb associated with autoimmune diseases (AID) can recognize Plasmodia antigens and exert anti-parasite activity; and whether anti-parasite phospholipid antibodies, produced in response to malaria, can inhibit phospholipid-induced inflammatory responses and protect against the pathogenesis of severe malaria. Our work showed that sera from patients with AID containing AAb against dsDNA, ssDNA, nuclear antigens (ANA), actin, cardiolipin (aCL) and erythrocyte membrane antigens recognize plasmodial antigens and can, similarly to monoclonal AAb of several specificities including phospholipid, inhibit the growth of P. falciparum in vitro. However, we did not detect a relationship between the presence of anti-glycosylphosphatidylinositol (GPI) antibodies in the serum and asymptomatic malaria infection, although we did register a relationship between these antibodies and parasitemia levels in infected individuals. Taken together, these results indicate that autoimmune responses mediated by AAb of different specificities, including phospholipid, may have anti-plasmodial activity and protect against malaria, although it is not clear whether anti-parasite phospholipid antibodies can mediate the same effect. The potential effect of anti-parasite phospholipid antibodies in malarious patients that are prone to the development of systemic lupus erythematosus or antiphospholipid syndrome, as well as the (possibly protective?) role of the (pathogenic) aPL on the malaria symptomatology and severity in these individuals, remain open questions.

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S u m m a r y :This study evaluates the differences in host immune responses to defined plasmodial antigens in four geographically different regions in which malaria is endemic. Sera from 5 2 7 individuals were tested for the presence of antibodies specific for three types of plasmodial antigen : liver-stage antigen (LSA-1), blood-stage antigen (SPF 70) and circumsporozoite (CS) antigen (NANP)4.The individuals taking part in the study comprised : patients with transfusional malaria due to Plasmodium falciparum or P. vivax; non-immune migrants residing in an endemic area in Rondônia;Amazonian Indians from the states of Para (Xingu PA) and Mato Grosso (Xingu MT); people living in a hyperendemic area in Africa (Burkina-Faso); and controls that had never been to a mala ria endemic area. None of the transfusional sera displayed antibo dies against sporozoite or to liver stage antigen, although 80% of the P. falciparum transfusional malaria sera contained IgG antibo dies against the blood-stage peptide. A low percentage of Indians from Xingu PA and of non-immune migrants displayed antibodies against liver-stage (27% and 17%) and sporozoite (11% and 12%) peptides, although a greater frequency of antibodies against blood-stage peptide (50% and 49%) was observed in both cases.Indians from Xingu MT exhibited a greater frequency of antibodies against liver, sporozoite and blood-stage peptides (45%, 50% and 58%). Only hyperimmune African individuals exhibited higher percentages of antibodies against liver-(64%) and blood-stage antigens (87%), contrasting with a low frequency of antibodies against the CS repeat (33%). Taken together, the present data confirm that Rondonian migrants and Indians from Xingu PA consti tute populations with limited exposure and immunity to P. falcipa rum malaria infection and conversely, Xingu MT Indians and Africans have been more exposed to malaria infection. In conclu sion this study indicates that the immune response to these malaria parasite peptides can be used to assess malaria transmission in epidemiological surveys. (0 2 1 )5 9 0 -3 5 4 5 ; P h o n e : (0 2 1 )2 8 0 -1 4 8 6 . Financial support : th e w o rk w as sup ported by th e C om m ission o f th e E u ro p e a n C o m m u n ities and th e B ra z ilia n N ation al R esearch C ouncil. R ésum é : RÉPONSE ANTICORPS À DES PEPTIDES SYNTHÉTIQUES DES STADES SANGUINS HÉPATIQUE ET SPOROZOITE DE P . FALCIPARUM DANS DIFFÉRENTES RÉGIONS ENDÉMIQUES