Both Glycolipid and Protein Components are Required for Plasmodium falciparum induced TNF-α and IL-1β Production in Human Monocytic Cells

Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are the endogenous pyrogens which mediate fever in malaria. The excessive production of TNF-α is associated with pathology of human malaria. The nature and properties of malaria antigens, which stimulate monocyte to secrete these cytokines were studied in vitro using human monocytic cell line THP-1. THP-1 cells produced the cytokines in response to Plasmodium falciparum malaria antigens similar to the response of peripheral blood monocytes. Malaria parasite components of infected erythrocytes and their culture supernatant were separately analyzed. Soluble and insoluble components of the infected erythrocytes and their culture supernatant stimulated cytokine production by THP-1 cells. Acid, base and pronase treatments of malaria culture supernatant greatly reduced the cytokine inducing activity, suggesting that both glycolipid and protein components are essential for cell stimulation. Considering the ultrafiltration results together, we assume that a complex of glycolipid and protein stimulates host cells to induce cytokine secretion. Application of Triton X-114 solubilization and phase separation procedures to the infected erythrocytes revealed that the membrane-free hemozoin pellet did not have any stimulation activity, whereas the hydrophobic components seemed to contribute to TNF-α and IL-1β production

Coexistence of GP195 Alleles of Plasmodium Falciparum in a Small Endemic Area

Dimorphic variations in the genotype of the precursor to Plasmodium falciparum major merozoite surface antigens or gp195, among wild isolates in a small malaria parasite population were examined using Southern blot hybridization techniques. Hybridization, with DNA fragment probes and oligonucleotide probes derived from variable blocks of known gp195 alleles against 18 wild isolates from Mae Sod district in Thailand, revealed the existence of seven gp195 alleles, two of which were newly identified in this study. In four out of 17 patients, two different alleles coexisted in the circulation. It was furthermore noted that the seven alleles did not occur at the same frequency, but rather several alleles predominated in the population of P. falciparum in this small malaria field

Naturally acquired Plasmodium knowlesi malaria in human, Thailand

We describe a case of naturally acquired infection with Plasmodium knowlesi in Thailand. Diagnosis was confirmed by the small subunit ribosomal RNA and the mitochondrial cytochrome b sequences. The occurrence of simian malaria in human has signified the roles of wild primate populations in disease transmission in some malaria-endemic areas

Allelic Variation in the Circumsporozoite Protein of Plasmodium falciparum from Thai Field Isolates

Allelic variation in the Plasmodium falciparum circumsporozoite (CS) protein gene has been examined by sequencing the entire gene in 15 isolates from an endemic area of Thailand. The isolates contain a total of six new allelic forms of the tetrapeptide repeats and eight variants of the T cell epitope (TCE) region of the CS gene. All nucleotide substitutions in the TCE are nonsynonymous. There is no apparent association between the sequence patterns in the repeats and in the TCE. Comparison of the TCE with published sequences has shown that most variants of our isolates are not identical to those found in different geographic areas, suggesting geographic variation in genetic diversity of the CS protein. In a phylogenetic tree, the new Thai alleles did not cluster together, suggesting a considerable heterogeneity within some geographic areas. Furthermore, analyses of tetrapeptide repeats from a number of isolates and strains showed evidence of three genetic mechanisms for the generation of variation in the repeats of the CS gene: point mutation, duplication of one or more repeat units, and intragenic recombination

Loss of Tumor Necrosis Factor Production by Human Monocytes in Falciparum Malaria after Their Maturation in Vitro

In Plasmodium-infected mammals, phagocytosis and production of tumor necrosis factor (TNF) by monocytes and macrophages are prominent features. The present work aimed at clarifying the relationship between the maturation of human monocytes to macrophages and their TNF productivity and phagocytic ability in the presence of Plasmodium falciparum-infected erythrocytes. Fresh monocytes produced a significantly higher quantity of TNF in the presence of schizont-infected erythrocytes than macrophages obtained by in vitro monocyte maturation on autologous serum, whereas phagocytic activity of macrophages was much higher than that of fresh monocytes. This indicated that the TNF-inducing factors from P. falciparum-infected erythrocytes could stimulate fresh monocytes, but not macrophages, to release TNF, regardless of their development of phagocytosis. Activation of macrophages by interferon-{gamma} could not recover their TNF productivity in the presence of P. falciparum-infected erythrocytes, but it enhanced their TNF productivity in the presence of lipopolysaccharide(s). The TNF-inducing factors were contained mainly in erythrocytes infected with mature schizonts but not in erythrocytes infected with the younger stages of the parasites. Fractionation of infected erythrocytes revealed that both soluble and insoluble components almost equally contained those factors

Naturally Acquired Plasmodium knowlesi Malaria in Human, Thailand

We describe a case of naturally acquired infection with Plasmodium knowlesi in Thailand. Diagnosis was confirmed by the small subunit ribosomal RNA and the mitochondrial cytochrome b sequences. The occurrence of simian malaria in human has signified the roles of wild primate populations in disease transmission in some malaria-endemic areas