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At least 271 records · Page 15Linked to original sources
PubMed2003

Regulation of antigenic variation in Plasmodium falciparum: censoring freedom of expression?

Plasmodium falciparum employs a strategy of clonal antigenic variation to evade the host immune response during the intraerythrocytic stage of its life cycle. The major variant parasite molecule is the P. falciparum erythrocyte membrane protein (PfEMP)1, which is encoded by the var multigene family. The parasite switches between different PfEMP1 molecules through regulation of var transcription. Recent studies have shed considerable light on this process, but much remains unknown. However, striking parallels between transcriptional control of var and genes in other organisms provide direction for future studies.

Animals↗
PubMed2000

Blood group A antigen is a coreceptor in Plasmodium falciparum rosetting.

The malaria parasite Plasmodium falciparum utilizes molecules present on the surface of uninfected red blood cells (RBC) for rosette formation, and a dependency on ABO antigens has been previously shown. In this study, the antirosetting effect of immune sera was related to the blood group of the infected human host. Sera from malaria-immune blood group A (or B) individuals were less prone to disrupt rosettes from clinical isolates of blood group A (or B) patients than to disrupt rosettes from isolates of blood group O patients. All fresh clinical isolates and laboratory strains exhibited distinct ABO blood group preferences, indicating that utilization of blood group antigens is a general feature of P. falciparum rosetting. Soluble A antigen strongly inhibited rosette formation when the parasite was cultivated in A RBC, while inhibition by glycosaminoglycans decreased. Furthermore, a soluble A antigen conjugate bound to the cell surface of parasitized RBC. Selective enzymatic digestion of blood group A antigen from the uninfected RBC surfaces totally abolished the preference of the parasite to form rosettes with these RBC, but rosettes could still form. Altogether, present data suggest an important role for A and B antigens as coreceptors in P. falciparum rosetting.

ABO Blood-Group System↗
PubMed2006

Comparison of different diagnostic techniques in Plasmodium falciparum cerebral malaria.

BACKGROUND & OBJECTIVES: Plasmodium falciparum cerebral malaria remains a major health problem in India. The efficacy of treatment of cerebral malaria lies in its early diagnosis through rapid diagnostic methods. ParaSights-F test detects HRP-2 antigen secreted by parasitised red blood cells and quantitative buffy coat assay (QBC) is examination of buffy coat for the presence of malarial parasite stained with acridine orange. This study was performed to evaluate the effectiveness of ParaSight-F test and QBC assay as diagnostic methods in the patients of cerebral malaria. METHODS: Fifty clinically diagnosed patients of cerebral malaria were included in the study. ParaSight-F test, QBC and conventional blood smear examination was done. Patients who were in coma and there were no obvious features of bacterial or viral etiology were investigated for cerebral malaria by these diagnostic methods. RESULTS: ParaSight-F test, QBC and peripheral blood smears were examined. Patients were followed-up for signs of clinical recovery. ParaSight-F test was positive in 47 patients, QBC in 46 while blood smear examination was positive in 28 cases. INTERPRETATION & CONCLUSION: Sensitivity and specificity of ParaSight-F test were found to be 96.6 and 94% while QBC showed 97.8 and 100% respectively. ParaSight-F test and QBC were found to be novel methods for diagnosis of cerebral malaria especially in the cases where diagnosis can not be made by conventional blood smear examination due to low parasitaemia. These rapid diagnostic methods help in early therapeutic intervention.

Acridine Orange↗
PubMed2002

Transcriptional analysis of genes encoding enzymes of the folate pathway in the human malaria parasite Plasmodium falciparum.

Folate metabolism in Plasmodium falciparum is essential for cell growth and replication, and the target of important antimalarial agents. The pathway comprises a series of enzymes that convert GTP to derivatives of tetrahydrofolate, which are cofactors in one-carbon transfer reactions. We investigated the expression of five of the genes encoding these enzymes by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using a threshold detection technique. We followed changes in mRNA levels as parasites progress through the erythrocytic cell cycle and examined this process in two cloned lines of diverse origins, as well as under stress conditions, induced by either removal of important metabolites or challenge by folate enzyme inhibitors. Although conventionally regarded as performing housekeeping functions, these genes show disparate levels of and changes in expression through the cell cycle, but respond quite uniformly to folate pathway-specific stress factors, with no evidence of feedback at the transcriptional level. Overall, the two genes involved in the thymidylate cycle (encoding dihy-drofolate reductase-thymidylate synthase, dhfr-ts, and serine hydroxymethyltransferase, shmt) gave the most abundant transcripts. However, only the latter showed major variation across the cell cycle, with a peak around the time of onset of DNA replication, possibly indicative of a regulatory function.

Animals↗
PubMed2001

Expression of the erythrocyte-binding antigen 175 in sporozoites and in liver stages of Plasmodium falciparum.

Screening of a Plasmodium falciparum genomic expression library for antigens expressed at the pre-erythrocytic stages resulted in the isolation of a recombinant phage (DG249) whose insert corresponded to regions II and III of a 175-kDa erythrocyte-binding antigen (EBA-175). EBA-175 is a parasite ligand implicated in red blood cell invasion. Reverse-transcriptase polymerase chain reaction, indirect immunofluorescent antibody test, and Western blot analysis confirmed that EBA-175 is expressed not only in blood-stage parasites but also in infected hepatocytes and on the sporozoite surface. The presence of EBA-175 on pre-erythrocytic parasites enhances the vaccine potential of this antigen by adding another target to the immune responses elicited by immunization.

Animals↗
PubMed2006

Cord blood dendritic cell subsets in African newborns exposed to Plasmodium falciparum in utero.

Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring of Gabonese mothers with different infection histories. Cord blood from newborns of mothers with malarial infection at delivery had significantly more mDC than that from nonexposed newborns (P = 0.028) but mDC and pDC HLA-DR expression was unrelated to maternal infection history. Independently of these findings, cord blood mDC and pDC numbers declined significantly as a function of increasing maternal age (P = 0.029 and P = 0.033, respectively). The inducible antigen-specific interleukin-10-producing regulatory-type T-cell population that we have previously detected in cord blood of newborns with prolonged in utero exposure to P. falciparum may directly reflect the altered DC numbers in such neonates, while the maintenance of cord blood DC HLA-DR expression contrasts with that of DC from P. falciparum malaria patients.

Animals↗
PubMed1996

Clinical trials of a new immunochromatographic test for diagnosis of Plasmodium falciparum malaria in Goa.

Plasmodium falciparum histidine rich protein-2 (PfHRP-2) based immunochromatographic test kit (ICT Malaria Pf) for the rapid diagnosis of P. falciparum malaria was evaluated at the clinic of Malaria Research Centre (Field Station), Goa. Of the 98 febrile patients screened, 22 were ICT positive for P. falciparum. Simultaneous microscopic examination of the blood smears of these ICT positive patients showed that 20 were positive for P. falciparum alone, whereas one had mix infection of both P. vivax and P. falciparum suggesting 100% sensitivity. Only one slide negative patient who had taken 600 mg chloroquine the previous day was positive in the ICT. Out of the remaining 76 blood smears, 41 showed P. vivax infection and none cross-reacted with P. falciparum HRP-2 antigen and were ICT negative except one mix infection case in which P. vivax and P. falciparum infections occurred concomitantly suggesting species specificity of 98.7%. The positive predictive value, negative predictive value and efficacy of the ICT were 95.4, 100 and 98.9% respectively. The band intensity of the ICT positive cases significantly correlated with P. falciparum parasitaemia (p < 0.01). The usefulness and the disadvantages of this diagnostic kit have been discussed in context of prevailing malaria situation in the country.

Animals↗
PubMed2005

[Preparation of monoclonal antibodies specific to lactate dehydrogenase of Plasmodium falciparum].

OBJECTIVE: To prepare monoclonal antibodies specific to lactate dehydrogenase of Plasmodium falciparum. METHODS: The Plasmodium falciparum lactate dehydrogenase (pLDH) gene was amplified from whole blood of malaria patients by PCR and cloned into expression vector pGEX-3X. Recombinant pLDH protein was expressed and purified, and used for immunizing mice to prepare monoclonal antibodies (McAbs). The McAbs were characterized by Western blotting analysis. RESULTS: The Plasmodium falciparum lactate dehydrogenase gene was amplified and cloned into ex pression vector pGEX-3X. The recombinant pLDH plasmid was expressed in E. coli) BL-21 cells. 15 cell lines of McAbs with high titer against pLDH were obtained using the recombinant pLDH as immunogen. Western blotting analysis showed that these McAbs recognized a Mr 33,000 of native Plasmodium falci parvum protein without cross reaction with constituents of red blood cell of febrile patients from endemic area of malaria. CONCLUSION: Fifteen hybridoma cell lines secreting high titer of McAb specific to Plasmodium falciparum LDH were established based on the recombinant pLDH.

Animals↗
PubMedDate not supplied

Malaria and pregnancy in Cameroonian women. Naturally acquired antibody responses to asexual blood-stage antigens and the circumsporozoite protein of Plasmodium falciparum.

Antibody responses to Plasmodium falciparum antigens in women during pregnancy were investigated in Mfou, a rural community in Cameroon. The study consisted of cross-sectional analyses involving 225 pregnant women and 75 non-pregnant controls. Blood samples were collected from each woman to determine serological reactivity to intraerythrocytic malarial antigens, ring-infected erythrocyte surface antigen (RESA) and circumsporozoite (CS) repeat peptide (NANP)5 by the indirect fluorescent antibody assay, modified immunofluorescent antibody assay, and enzyme-linked immunosorbent assay, respectively. Reactivity to intraerythrocytic asexual blood-stage antigens and to the CS repeat region was similar in both pregnant and non-pregnant women, and no correlation with parasitaemia was found. In contrast, anti-RESA antibody levels were significantly lower in pregnant than in non-pregnant women (P = 0.02) and in primigravidae than in multigravidae (P = 0.002), and were inversely correlated with parasitaemia (r = -0.36; P < 0.01). These data suggest that the increased susceptibility to malarial infection in pregnant women may be explained in part by their lower reactivity to RESA.

Adult↗
PubMed2005

Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum.

The malaria parasite Plasmodium falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family. We demonstrate that both a subtelomeric transgene and var genes are subject to reversible gene silencing. Var gene silencing involves the SIR complex as gene disruption of PfSIR2 results in activation of this gene family. We also demonstrate that perinuclear gene activation involves chromatin alterations and repositioning into a location that may be permissive for transcription. Together, this implies that locus repositioning and heterochromatic silencing play important roles in the epigenetic regulation of virulence genes in P. falciparum.

Animals↗
PubMed1999

Phagocytosis does not play a major role in naturally acquired transmission-blocking immunity to Plasmodium falciparum malaria.

Phagocytosis of Plasmodium falciparum sexual stages in vitro and within the mosquito midgut was assayed in order to assess its role in transmission-blocking immunity to malaria. Both monocytes/macrophages (MM) and polymorphonuclear neutrophils (PMN) phagocytosed malarial gametes in vitro, but levels of phagocytosis were low. Intraerythrocytic gametocytes were not susceptible to phagocytosis. In vitro phagocytosis was positively correlated with levels of antibodies against the gamete surface proteins Pfs230 and Pfs48/45. Immunoglobulin G (IgG) subclass analysis revealed that phagocytosis was correlated with levels of antigamete IgG1. In vivo membrane-feeding experiments were performed in the presence of both pooled and individual malaria immune sera. The phagocytic process proceeded less efficiently in vivo than in vitro, which may be related to the lower ambient temperature (26 degrees C, compared with 37 degrees C). Finally, although we found a correlation between the ability of a serum to promote phagocytosis in vitro and the presence of antibodies against transmission-blocking target antigens, we were unable to demonstrate a role for MM- or PMN-mediated phagocytosis in reduction of infectivity of the malarial parasite to mosquitoes.

Animals↗
PubMed2003

Thioredoxin reductase and glutathione synthesis in Plasmodium falciparum.

The malaria parasite Plasmodium falciparum is still a major threat to human health in the non-industrialised world mainly due to the increasing incidence of drug resistance. Therefore, there is an urgent need to identify and validate new potential drug targets in the parasite's metabolism that are suitable for the design of new anti-malarial drugs. It is known that infection with P. falciparum leads to increased oxidative stress in red blood cells, implying that the parasite requires efficient antioxidant and redox systems to prevent damage caused by reactive oxygen species. In recent years, it has been shown that P. falciparum possess functional thioredoxin and glutathione systems. Using genetic and chemical tools, it was demonstrated that thioredoxin reductase, the first step of the thioredoxin redox cycle, and gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting step of glutathione synthesis, are essential for parasite survival. Indeed, the mRNA levels of gamma-GCS are elevated in parasites that are oxidatively stressed, indicating that glutathione plays an important antioxidant role in P. falciparum. In addition to this antioxidant function, glutathione is important for detoxification processes and is possibly involved in the development of resistance against drugs such as chloroquine.

Animals↗
PubMed2005

Drug resistance and genetic diversity of Plasmodium falciparum parasites from suriname.

Plasmodium falciparum in Suriname was studied for the presence of drug resistance and genetic variation in blood samples of 86 patients with symptomatic malaria. Drug resistance was predicted by determining point mutations in the chloroquine resistance marker of the P. falciparum chloroquine resistance transporter (pfcrt) gene (codon 76) and the pyrimethamine-sulfadoxine resistance markers in the dihydrofolate reductase (dhfr) gene (codons 16, 51, 59, 108, and 164) and dihydropteroate synthase (dhps) gene (codons 436, 437, 540, 581, and 613). Genetic variability was determined by sequence analysis of the polymorphic segments of the merozoite surface protein 2 (msp-2) and glutamate-rich protein (glurp) genes. Mutations in the pfcrt, dhps, and dhfr genes were found in all samples tested, suggesting that resistance to chloroquine and antifolate drugs is present at a high frequency. A low number of alleles was found for the msp-2 and glurp genes. This indicates limited genetic diversity and, based on geographic data, a genetically homogeneous P. falciparum population in Suriname.

Amino Acid Sequence↗
PubMed1986

[Bacterial infections and early Plasmodium falciparum malaria].

Two cases of Plasmodium falciparum malaria associated with bacterial infections--streptococcus A septicemia and Legionnaires' disease--are described. The association of these two infections is probably not incidental, and the hypothesis of Plasmodium falciparum induced immuno-deficiency is discussed.

Adult↗
PubMed2005

In vitro activity of artemisinin alone and in combination with retinol against Plasmodium falciparum.

Increasing resistance of Plasmodium falciparum to antimalarial drugs is an important public health problem, demanding novel therapeutic approaches. This study had the objective of assessing the in vitro activity of artemisinin and its combination with retinol in fresh isolates of P. falciparum in an area with a high proportion of multidrug-resistant strains. The tests were based on the inhibition of schizont maturation. In 45 successfully tested isolates, the mean effective concentrations (ECs) of artemisinin were 10.29 nM for the EC-50 and 34.86 nM for the EC-90. The EC50 and EC90 for artemisinin in the artemisinin-retinol mixture were 2.71 nM and 13.37 nM, respectively. The combination showed synergistic activity. Retinol appears to be a promising partner for the antimalarial therapy with artemisinins.

Adolescent↗
PubMedDate not supplied

Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand.

Plasmodium falciparum isolates were obtained from Thai patients attending a malaria clinic on the Thai-Kampuchean border over 4 cross-sectional surveys carried out at 3-monthly intervals. The genetic structure of the parasite populations was determined by nested polymerase chain reaction (PCR) amplification of polymorphic regions of 3 P. falciparum antigen genes: msp1, msp2 and glurp. Although a high degree of diversity characterized these isolates, the overall population structure of the parasites associated with patent malaria infections was observed to remain relatively stable over time. The highest degree of polymorphism was observed with msp2, and the mean number of lines per infection (multiplicity of infection) calculated with this marker was higher than that obtained using msp1 or glurp alone, or combined. Infections with > or = 2 parasite lines were seen in 76% of the samples, and were proportionally more numerous at the start and end of the rainy season. Two interesting exceptions to the random distribution were observed and involved 2 allelic variants which in one case were found dissociated (msp1 MAD20-family) and in the other were associated (msp2 FC27-family). The epidemiological significance of these types of data is discussed.

Animals↗