The effect of pyrimethamine (daraprim) on the gametocytes and oocysts of Plasmodium falciparum and Plasmodium vivax.
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T lymphocytes that express T-cell receptors encoded by the gamma and delta T-cell receptor genes (gamma delta T cells), and preferentially those expressing the V gamma 9 and V delta 2 gene segments, are activated by microbial and parasitic organisms in vitro and have been implicated in the pathogenesis of the fever and rigors during acute malaria. We have found, in a cohort of nine nonimmune patients who contracted malaria during travel to endemic areas (five with Plasmodium falciparum and four with P. vivax infections) that gamma delta T lymphocytes expanded to comprise 17.92% +/- 11% of the peripheral blood mononuclear cells (vs 3.08% +/- 2.4% gamma delta cells in normal control subjects). Although V delta 2+ cells predominated among the gamma delta subset, gamma delta lymphocytes expressing the V delta 1 gene segment also expanded significantly in some patients. Importantly, the gamma delta cells continued to expand for 2 months after the infection, and the mean level of gamma delta cells peaked during the second month after the acute clinical syndrome, when patients were free of symptoms. Thus although gamma delta T cells may contribute to the pathogenesis of the acute clinical syndrome, our findings suggest that gamma delta lymphocytes could also play a role in generating an immune response to plasmodia.
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User-friendly, reliable, and inexpensive methods for diagnosing malaria are needed at the primary health care level. During a randomized treatment trial, the Parasight-F test was assessed on days 0, 3, 7, and 28 against standard light microscopy of Giemsa-stained thick blood smears for diagnosing Plasmodium falciparum parasitemia in patients with P. falciparum (n = 84) or P. vivax (n = 59) malaria. The median P. falciparum parasite count on day 0 was 2,373/microL (range = 20-74,432/microL). At the start of treatment, the Parasight-F test had a sensitivity of 95.2% (80 of 84; 95% confidence interval [CI] = 88.2-98.7), and a specificity of 94.9% (56 of 59; 95% CI = 85.8-98.9). On day 7, this test showed false-positive results in 17 (16.3%) of 104 patients (95% CI = 9.8-24.9). The Parasight-F test performed well when compared with light microscopy in detecting P. falciparum parasitemia in patients presenting with clinical malaria. However, the high false-positive rate on day 7 limits its use for patient follow-up.
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Medical and entomological surveys were conducted to determine the risk factors of Plasmodium falciparum and P. vivax infections on Lombok Island, Indonesia, to find the risk factors and the main mosquito vectors for each malaria. Multivariate longitudinal analysis demonstrated two significant risk factors for infection with P. falciparum: disappearance of P. vivax parasitemia (p<0.001) and a specific study site (p<0.001). In contrast, younger age (p=0.024) and the interpolated virtual density of An. subpictus (p=0.041) were significantly associated with increased risk of infection with P. vivax. Thus, it seems that the distribution of P. vivax was determined largely by the presence of An. subpictus, whilst that of P. falciparum was influenced by antagonism with P. vivax. This result shows the importance of following-up treated P. vivax patients to identify recrudescence of P. falciparum in this area.
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Variations in the intensity of Plasmodium infections were observed in the surveyed regions of Saudi Arabia. The highest incidence had been recorded from the Southern region and the lowest form the Northern and Eastern regions. The Western region, however, showed a regular and uniform occurrence of infection throughout the year. Five anopheline vectors were identified in the country.
An IgM monoclonal antibody (Mab 36) which reacts with the circumsporozoite (CS) proteins of both P. falciparum and P. berghei was isolated from Plasmodium falciparum sporozoite-immunized mice. In assays of biological activity, Mab 36 induces the CS precipitation reaction with live sporozoites and blocks the invasion of hepatoma cells by sporozoites in vitro at concentrations much lower than those observed for previously reported CS protein-specific monoclonal antibodies. Mab 36 also provided complete protection against P. berghei sporozoite challenge in mice at low doses. Linear epitope mapping revealed that the epitope specificities recognized by Mab 36 are completely encompassed by other monoclonals previously shown to be associated in vivo with protection against P. falciparum or P. berghei sporozoite infection. These results suggest that the ability to make high-affinity IgM antibody to specific CS protein repeat epitopes may be important for eliciting protection against malarial infection.
A simple and rapid method for detecting Plasmodium falciparum in human blood was used in this study. The assay is based on DNA-DNA spot hybridization. For this purpose, the total genomic DNA of P. falciparum was isolated and purified from the parasite cultured in vitro. Then the total genomic DNA was used as a probe and labelled with [alpha-32P]-dATP by nick-translation. Twenty-five test samples, ten-microliter lysed infected blood each, were spotted onto dry nitrocellulose paper and hybridized with labelled genomic DNA. After hybridization, the paper was exposed to X-ray film for autoradiography, resulting in an image in places where hybridization occurred. The result shows that the assay appears to be sensitive enough to detect parasitaemia up to 0.0009%. No visible hybridization was detected in normal human blood or human leukocytes. Many samples can be processed simultaneously. This may be applicable to mass survey for detecting P. falciparum in epidemiological study (Fig. 2).