Medicine (Northwest Academic Centre) - Research Publications

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Type: Journal Article × Start date: 2004 × End date: 2009 × Author: Beeson, James ×

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    Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection
    Mount, AM ; Mwapasa, V ; Elliott, SR ; Beeson, JG ; Tadesse, E ; Lema, VM ; Molyneux, ME ; Meshnick, SR ; Rogerson, SJ (ELSEVIER SCIENCE INC, 2004-06-05)
    BACKGROUND: HIV infection increases the risk of malaria infection in pregnant women. Antibodies to variant surface antigens (VSA) on infected erythrocytes might protect against malaria in pregnancy. We postulated that HIV-induced impairment of humoral immunity to VSA mediates the increased susceptibility to malaria. METHODS: We compared serum concentrations of antibodies to VSA by flow cytometry or agglutination, and to merozoite proteins AMA-1 and MSP119 by ELISA, in 298 pregnant Malawian women, and related the findings to malaria and HIV infection, CD4-positive T-cell count, and HIV-1 viral load. FINDINGS: Concentrations of IgG to placental type VSA were lower in HIV-infected women than in HIV-uninfected women (median 8 units [IQR 4-23] vs 20 [12-30]; p<0.0001), among women with malaria (p=0.009) and those without malaria (p=0.0062). The impairment was greatest in first pregnancy. Agglutinating antibodies to placental VSA were present in a lower proportion of HIV-infected than HIV-uninfected women (58 [35.1%] of 165 vs 50 [53.8%] of 93, p<0.001). The degree of antibody binding by flow cytometry was correlated with CD4-positive T-cell count (r=0.16, p=0.019) and inversely with HIV-1 viral load (r=-0.16, p=0.030). Concentrations of antibodies to AMA-1 were lower in HIV infection (p<0.0001) but were not correlated with CD4-positive T-cell count or viral load. Responses to MSP119 were little affected by HIV infection. In multivariate analyses, HIV was negatively associated with amount of antibody to both VSA and AMA-1 (p<0.001 for each) but not MSP119. INTERPRETATION: HIV infection impairs antimalarial immunity, especially responses to placental type VSA. The impairment is greatest in the most immunosuppressed women and could explain the increased susceptibility to malaria seen in pregnant women with HIV infection.
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    A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria.
    Voss, Till ; HEALER, JULIE ; Marty, Allison ; DUFFY, MICHAEL ; Thompson, Jennifer ; BEESON, JAMES ; REEDER, JOHN ; COWMAN, ALAN ( 2006)
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    Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype
    Duffy, MF ; Byrne, TJ ; Elliott, SR ; Wilson, DW ; Rogerson, SJ ; Beeson, JG ; Noviyanti, R ; Brown, GV (WILEY, 2005-05)
    Transcription of the majority of the members of the Plasmodium falciparum var multigene family were analysed in two isolates by a quantitative approach. Both of these isolates had been repeatedly selected for adhesion to chondroitin sulphate A (CSA) and one had also been selected for adhesion to hyaluronic acid (HA). These adhesion phenotypes are expressed by many parasites isolated from placentae and are associated with malaria disease in pregnancy. Increased transcription of the var gene var2csa, or its homologue IT4 var4, was associated with the CSA and HA adhesion phenotypes in all parasites suggesting that it was the dominant, if not the only, var gene that encoded adhesion to CSA in these allogeneic isolates. Some var genes were consistently transcribed at higher levels than others regardless of expressed adhesion phenotypes suggesting a transcriptional hierarchy. Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription.