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At least 415 records · Page 23Linked to original sources
PubMed2000

Evaluation of immunogenicity and protective efficacy of carrier-free Plasmodium falciparum R23 antigen in pre-exposed saimiri sciureus monkeys.

We have reported previously that the recombinant Glutathione S-transferase GTR23, induced protection after immunisation of naive or previously exposed Saimiri monkeys. We investigated the immunogenicity of carrier-free R23 repeats in pre-exposed animals in two adjuvant formulations. Three of five monkeys immunised with alum-formulated repeats and one of two animals immunised with the Polyalphaolefine formulation produced high titres of cytophilic antibodies with a primary type kinetics, indicating that the anti-P. falciparum antibodies present on the day of challenge were R23-specific. The four responders in R23-specific antibodies were protected against a challenge infection with the virulent FUP/SP strain. The other three animals failed to respond to immunisation and experienced an infection that required drug treatment. Unlike the other three animals that experienced an infection requiring drug treatment. These experiments support further development of the R23 repeats as a vaccine candidate.

Adjuvants, Immunologic↗
PubMed1999

[Comparison of two techniques for detection of anti-Plasmodium falciparum antibodies: Falciparum-spot IF (Biomérieux) and Malaria IgG Celisa (BMD). Preliminary results].

We compared a new Elisa assay to detect malaria antibodies: Malaria IgG Celisa (BMD) with the IFAT technique Falciparum-spot IF (Biomérieux): sensitivity, specificity, predictive positive and negative values were 81%, 99%, 95%, 95%, respectively. Eight patients had positive thick blood smear out of 23 performed. For these eight confirmed acute malaria cases, the Elisa assay was negative in five instances. For two recent malaria attacks both Elisa and IFI were negative. With blood donors, two sera were IFAT positive and Elisa negative; 16 were IFAT doubtful and Elisa negative. Doubtful results rose up to 13.5% by IFAT against 1.5% by Elisa assay. We preferred kappa coefficient instead of chi 2 test for data analysis, which measures the concordance degree between the two techniques. Here concordance is moderate. Choosing an Elisa assay to detect the transmission of malaria for at-risk blood donors collides with the method sensitivity compared with IFAT as reference.

Animals↗
PubMed1999

Antigenic variation in Plasmodium falciparum: mechanisms and consequences.

In the past year, the major advances in malaria antigenic variation have been concerned with the transcription and switching of variant antigen genes, and the functional expression of regions of the major variant antigen. Also, new variant gene families have been discovered as a result of the Malaria Genome Project.

Animals↗
PubMed2002

The pH of the Plasmodium falciparum digestive vacuole: holy grail or dead-end trail?

The maintenance of acidic pH in the digestive vacuole of the malaria parasite is thought to be crucial to the digestion of host cell haemoglobin and the subsequent process of heme detoxification. It may also be important in the mode of action of chloroquine and in the mechanism of resistance to the drug. Obtaining a definitive measurement of digestive vacuole pH has been surprisingly difficult. Some of the techniques for the measurement of pH in acid vesicles are outlined here along with some key aspects that are specific to malaria parasites. The use of acridine orange and dextran-tagged dyes as probes for the measurement of digestive vacuole pH has proved problematic, yet some surprising findings have emerged from work with these compounds.

Acridine Orange↗
PubMed1997

Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine.

The 4-aminoquinolines chloroquine (CQ) and amodiaquine (AM) were used to treat Gambian children with uncomplicated falciparum malaria in a randomized drug trial. Blood samples were taken immediately before treatment (day 0), and at day 7 and day 28 after treatment. Samples from those parasitologically positive at day 7 following treatment ('early positives') and those positive at day 28 but negative at day 7 ('late positives') have been studied by PCR followed by restriction enzyme digestion to determine the allelic status of the pfmdr 1 locus at the codon-86 position (asparagine or tyrosine), previously associated with resistance to CQ. A significantly higher prevalence of the tyr-86 allele was observed in samples taken immediately before treatment (day 0) in the early positives group when compared with the late positives group. This suggests the tyr-86 allele contributes to drug resistance in the early positives group. This association remained significant for both CQ and AM groups, implying a common genetic basis of resistance. Predominance of the allele at day 7 is consistent with a strong selection in the first week following treatment. In the late positives group, a significantly higher prevalence of the tyr-86 allele was observed in the samples at day 28 when compared with those at day 0, suggestive of selection during the period day 7 to day 28. Differences were observed in the extent of this selection in the CQ and AM groups. The samples were genotyped at 3 unlinked polymorphic loci. These analyses suggested that most parasites observed at day 7 were probably recrudescences whereas most of those at day 28 were reinfections.

ATP-Binding Cassette Transporters↗
PubMed2001

Haemoglobin C protects against clinical Plasmodium falciparum malaria.

Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.

Adolescent↗
PubMed1993

Neutralizing monoclonal antibodies to glycosylphosphatidylinositol, the dominant TNF-alpha-inducing toxin of Plasmodium falciparum: prospects for the immunotherapy of severe malaria.

Tumour necrosis factor-alpha (TNF-alpha) is an endogenous mediator of shock and inflammation. Many of the life-threatening and severe pathologies associated with complicated and cerebral malaria are thought to result from the overproduction of this cytokine in response to agents of parasite origin. The identification and characterization of these agents may therefore provide the molecular basis for a detailed understanding of the disease process. Recently it has been shown that glycosylphosphatidylinositols are a novel class of glycolipid toxin produced by the parasite, which substitute for the endogenous inositolglycan-based signal transduction pathways of the host. Glycosylphosphatidylinositol stimulates high levels of TNF-alpha and interleukin-1 production by macrophages and induces hypoglycaemia through an insulin-mimetic activity, and may therefore contribute to the cerebral syndrome and other malarial pathophysiology. That monoclonal antibodies to parasite-derived glycosylphosphatidylinositol can neutralize the toxic activities of whole parasite extracts is also demonstrated here. These findings suggest a central role for glycosylphosphatidylinositol of parasite origin in the aetiology of severe malaria and suggest novel approaches for the immunotherapy or immunoprophylaxis of disease.

Animals↗