The consequences of malaria infection in pregnant women and their infants

Preliminary results are presented from this study which indicate that 84.8 of pregnant women present at first antenatal visit with anemia (Hb 11g/dl) an 8.7 of their infants (n = 230) have a hemoglobin at birth below 14g/dl. There is an association between pregnancy anemia and malaria. A case control study in pregnant women and an infant cohort study to 18 months of age, are employed to study the cause and effects of anemia and malaria on women and their infants health.

Immune mechanisms underlying the premunition against Plasmodium falciparum malaria

The most unique characteristic of a parasite when it is in its normal host is the ability to make itself tolerated, which clearly indicates that it has sophisticated means to ensure the neutrality of its host. This is true also in the case of Plasmodium falciparum, since after numerous malaria attacks an equilibrium is reached with a chronic stage of infection, characterized by a relatively low parasitemia, and low or no disease (Sergent & Parrot 1935). We shall briefly review the main characteristics of this state of "premunition", and present data suggesting that the underlying mechanisms of defense rely on the cooperation between cell and antibodies, leading to an antibody dependent cellular inhibition of the intra-erythrocytic growth of the parasite.

Immunogenicity of multiple antigen peptides containing Plasmodium vivax CS epitopes in BALB/c mice

Multiple antigen peptide systems (MAPs) allow the incorporation of various epitopes in to a single synthetic peptide immunogen. We have characterized the immune response of BALB/c mice to a series of MAPs assembled with different B and T cell epitopes derived from the Plasmodium vivax circumsporozoite (CS) protein. A B-cell epitope from the central repeat domain and two T-cell epitopes from the amino and carboxyl flanking regions were used to assembled eight different MAPs. An additional universal T cell epitope (ptt-30) from tetanus toxin protein was included. Immunogenicity in terms of antibody responses and in vitro T lymphocyte proliferation was evaluated. MAPs containing B and T cell epitopes induced high titers of anti-peptides antibodies, which recognized the native protein on sporozoites as determined by IFAT. The antibody specificity was also determined by a competitive inhibition assay with different MAPs. A MAP containing the B cell epitope (p11) and the universal epitope ptt-30 together with another composed of p11 and the promiscuous T cell epitope (p25) proved to be the most immunogenic. The strong antibody response and specificity for the cognate protein indicates that further studies designed to assess the potential of these proteins as human malaria vaccine candidates are warranted.

Transport pathways in the malaria-infected erythrocyte: characterization and their use as potential targets for chemotherapy

The intraerythrocytic malarial parasite is involved in an extremely intensive anabolic activity while it resides in its metabolically quiescent host cell. The necessary fast uptake of nutrients and the discharge of waste product, are guaranteed by parasite-induced alterations of the constitutive transporters of the host cell and the production of new parallel pathways. The membrane of the host cell thus becomes permeable to phospholipids, purine bases and nucleosides, small non-electrolytes, anions and cations. When the new pathways are quantitatively unimportant, classical inhibitors of native transporters can be used to inhibit parasite growth. Several compounds were found to effectively inhibit the new pathways and consequently, parasite growth. The pathways have also been used to introduce cytotoxic agents. The parasitophorous membrane consists of channels which are highly permeable to small solutes and display no ion selectivity. Transport of some cations and anions across the parasite membrane is rapid and insensitive to classical inhibitors, and in some cases it is mediated by specific antiporters which respond to their respective inhibitors. Macromolecules have been shown to reach the parasitophorous space through a duct contiguous with the host cell membrane, and subsequently to be endocytosed at the parasite membrane. The simultaneous presence of the parasitophorous membrane channels and the duct, however, is incompatible with experimental evidences. No specific inhibitors were found as yet that would efficiently inhibit transport through the channels or the duct.

Chimpanzees and supporting models in the study of malaria pre-erythrocytic stages

Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

Simian malaria at two sites in the Brazilian Amazon: I-The infection rates of Plasmodium brasilianum in non-human primates

The parasite that causes simian malaria in the Brazilian Amazon, Plasmodium brasilianum, is infective to man. In this region, where humans live within and in close proximity to the forest, it was suspected that this parasite could be the cause of a zoonosis. A study was performed in the areas surrounding two hydroelectric plants in the Amazon, Balbina and Samuel, aiming at determining the zoonotic potential of this parasite. P. brasilianum was detected in, respectively, 15.8% and 9.9% of 126 and 252 primates belonging to seven and eight species examined from Balbina and Samuel. The highest malaria infection rates were found among the red-howler monkey Alouatta seniculus straminea (32.3%), the bearded-saki Chiropotes satanas chiropotes (50%) and the spider-monkey Ateles paniscus paniscus (2[1+]) from Balbina and in the squirrel-monkey Saimiri ustus (21%) and the black-faced-spider-monkey Ateles paniscus chamek (28.6%) from Samuel.

Life history correlates of adult size in the malaria vector Anopheles darlingi

Adult dry weights of laboratory-reared Anopheles darlingi were highly correlated with wing lengths, which were used to estimate size variation in natural populations of this species. Significant differences in mean wing lengths of females trapped at baits were detected among collections in the same week at one site, but not between three sites in Brazil and Boliva. Relatively higher variability of wing lengths, compared to collections of other Anopheles (Nyssorhynchus), and platykurtic size distributions in large, single-night collections suggested that An. darlingi females caught at baits emerged from heterogenous larval habitats. No relationship was detected between parous state and the body size of wild-caught females. Adult males and females of laboratory-reared An. darlingi did not differ in body size. This absence of sexual size dimorphism is rare among mosquitoes and has not been noted previously in the genus Anopheles.

The epidemiology of malaria in Prábis, Guinea-Bissau

This article reports upon a community survey of malaria in Prábis, Guinea-Bissau. A house to house census of the population was initially carried out from August to December 1991(rainy season). After completing the census of each village, the population was invited to come, a week later, to a central point, where they were medically examined and finger-prick blood samples were collected for epidemiological characterization of the malaria situation in the area. The blood films of the one single village were used to compare the sensitivity and specificity of Polymerase Chain Reaction (PCR) with optical microscopy detection of parasites. In another village, the occurrence of parasitaemia was compared in children with and without fever. During the dry season, from March to June 1992, the population in each village was again invited to come to a central point. Some of the field procedures were repeated. The study revealed Prábis as an administrative Sector of Guinea-Bissau with endemic malaria, mostly due to Plasmodium falciparum, but with a significant rate of mixed infections. Active transmission occurred throughout the year, but it was more intensive during the rainy season and in the northwestern quadrant of the Sector. The level of endemicity of the villages varied from hypo to holoendemic. The factors associated with the differences among villages included village size and predominant economic activity (closeness to rice fields). The transmission paradigm was, most likely, a mixture of malaria of the African wet Savannah and malaria associated with irrigated paddy fields. PCR proved to be a sensitive method with low specificity during the dry season. Pyraexia of 37.4ºC or higher in children aged 2-9 years is not a sensitive indicator of parasitaemia but, it is highly specific and it has a clinically useful predictive value.

Diagnosis of malaria by acridine orange fluorescent microscopy in an endemic area of Venezuela

Fluorescent (acridine orange) microscopical examination of capillary centrifuged blood (quantitative buffy coat [QBC®] analysis) and Giemsa stained thick blood smears (GTS) were compared for diagnosis of malaria in blood specimens from adults living in malaria transmission areas of the States of Bolivar and Amazonas in southeastern and south Venezuela, respectively. Of a total of 198 GTS examined, 95 subjects (48%) showed parasitaemia. Among the 95 blood films with a positive GTS, 94 were judged positive by the QBC. However, positive QBC tubes were found in 29 out of 103 blood specimens with a negative GTS. Thus, relative to a GTS standard, the sensitivity and specificity of the QBC-test was 99.2% and 72%, respectively. Young trophozoites of Plasmodium vivax and P. falciparum could not be distinguished with certainty. It is confirmed that the QBC offers many advantages compared with the standard diagnosis of malaria parasites, specifically in the speed of staining and ease of interpretation. However, in places where P. falciparum and P. vivax occur, species and stage differentiation should be confirmed with the GTS.