12 research outputs found
L'Écho : grand quotidien d'information du Centre Ouest
11 avril 19371937/04/11 (A52)-1937/04/12.Appartient à l’ensemble documentaire : PoitouCh
Bead-based immunoassay allows sub-picogram detection of histidine-rich protein 2 from <i>Plasmodium falciparum</i> and estimates reliability of malaria rapid diagnostic tests
<div><p>Detection of histidine-rich protein 2 (HRP2) from the malaria parasite <i>Plasmodium falciparum</i> provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs. Here we present a new HRP2 immunoassay based on antigen capture through a bead-based system capable of detecting HRP2 at sub-picogram levels. The assay is highly specific and cost-effective, allowing fast processing and screening of large numbers of samples. We utilized the assay to assess results of HRP2-based rapid diagnostic tests (RDTs) in different <i>P</i>. <i>falciparum</i> transmission settings, generating estimates for true performance in the field. Through this method of external validation, HRP2 RDTs were found to perform well in the high-endemic areas of Mozambique and Angola with 86.4% and 73.9% of persons with HRP2 in their blood testing positive by RDTs, respectively, and false-positive rates of 4.3% and 0.5%. However, in the low-endemic setting of Haiti, only 14.5% of persons found to be HRP2 positive by the bead assay were RDT positive. Additionally, 62.5% of Haitians showing a positive RDT test had no detectable HRP2 by the bead assay, likely indicating that these were false positive tests. In addition to RDT validation, HRP2 biomass was assessed for the populations in these different settings, and may provide an additional metric by which to estimate <i>P</i>. <i>falciparum</i> transmission intensity and measure the impact of interventions.</p></div
HRP2 bead assay only detects HRP2-producing <i>P</i>. <i>falciparum</i>.
<p>Plasma from non-infected persons, or persons with symptomatic <i>Plasmodium</i> spp. infection was assayed at a 1:10x dilution for presence of HRP2. <b>P. mal</b>: <i>P</i>. <i>malariae</i>; <b>P. ova</b>: <i>P</i>. <i>ovale</i>.</p
MOESM1 of Malaria surveys using rapid diagnostic tests and validation of results using post hoc quantification of Plasmodium falciparum histidine-rich protein 2
Additional file 1: Table S1. Point estimates and 95% confidence intervals for logistic dose-response model fit to data on rapid diagnostic test positivity as a function of HRP2 concentration in six field survey
Test comparison between bead assay and HRP2 RDTs.
<p>(<b>A</b>) Persons from Mozambique tested for presence of HRP2 by RDT (SD Bioline Pf) and bead assay, and comparison statistics for the two tests. For this purpose, the RDT was treated as the standard classification predictor and the bead assay as the novel test. The same analysis in (<b>B</b>) for persons from Angola where the SD Bioline Malaria Ag P.f/P.v RDT was used and in (<b>C</b>) Haiti where the First Response HRP2 RDT was used.</p
Comparison of bead-based HRP2 assay with HRP2 ELISA.
<p>(<b>A</b>) Completed scaffolding of bead complex when HRP2 is present in a sample. (<b>B</b>) Serial dilutions of Type A, B, and C rHRP2 assayed by bead assay (solid lines) and ELISA (hashed lines), and (<b>C</b>) comparison of signal intensities of same dilutions between bead assay and ELISA. (<b>D</b>) Serial dilutions of cultured <i>P</i>. <i>falciparum</i> strains assayed by bead assay (solid lines) and ELISA (hashed lines), and (<b>E</b>) scatterplot for signal intensities of same dilutions between immunoassays. Vertical and horizontal dashed lines in (<b>C</b>) and (<b>E</b>) represent lower limits of reliable detection for the ELISA and bead assay, respectively.</p
Distribution of HRP2 bead assay signal intensity by RDT result in different populations.
<p>(<b>A</b>) MFI-bg signal at log scale for entire Haiti, Angola, and Mozambique study populations. In order to show entire range of signal distribution, any sample which gave MFI-bg signal below zero had log taken of absolute value and then multiplied by -1, making negative values possible. Signal distributions by RDT test positivity given at the time of DBS sample collection for Haiti (<b>B</b>), Angola (<b>C</b>), Mozambique (<b>D</b>) surveys, with Angola and Mozambique populations providing enough RDT positives to allow for age categorization. For each age category, the bead assay was assessed at the novel classification predictor by ROC analysis and calculation of area under the curve.</p
Seropositivity by age for antibodies to three <i>P</i>. <i>falciparum</i> antigens in community members sampled during household surveys in Nacala-a-Velha and Mecubúri Districts, Northern Mozambique, 2013–2014.
<p>Points represent estimates and 95% confidence intervals for seropositivity for each age category, curves represent the fit of a catalytic conversion model, and shaded areas represent the 95% confidence intervals of model fit: blue for 2013, red for 2014, and purple for the overlap.</p
Coverage with LLINs immediately following a mass LLIN distribution campaign in 2013 in Nacala-a-Velha and Mecubúri Districts, Mozambique.
<p>Coverage with LLINs immediately following a mass LLIN distribution campaign in 2013 in Nacala-a-Velha and Mecubúri Districts, Mozambique.</p
Demographic data on study population of household surveys in Nacala-a-Velha and Mecubúri Districts, Mozambique, 2013–2014.
<p>Demographic data on study population of household surveys in Nacala-a-Velha and Mecubúri Districts, Mozambique, 2013–2014.</p