L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

14 septembre 19181918/09/14 (A19,N6445)

High <i>Plasmodium falciparum</i> longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali

<div><p>The effects of persistent <i>Plasmodium falciparum</i> (Pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. A longitudinal cohort study was conducted in a seasonal and high-transmission area of Mali, in which 500 subjects aged 1–65 years were followed for 1 year. Blood samples were collected every 2 weeks, and incident malaria cases were diagnosed and treated. Pf infection in each individual at each time point was assessed by species-specific nested-PCR, and Pf longitudinal prevalence per person (PfLP, proportion of Pf-positive samples over 1 year) was calculated. Multiclonality of Pf infection was measured using a 24-SNP DNA barcoding assay at 4 time-points (two in wet season, and two in dry season) over one year. PfLP was positively correlated with multiclonality at each time point (all r≥0.36; all <i>P</i>≤0.011). When host factors (e.g., age, gender), PfLP, and multiclonality (at the beginning of the transmission season) were analyzed together, only increasing age and high PfLP were associated with reduced clinical malaria occurrence or reduced number of malaria episodes (for both outcomes, <i>P</i><0.001 for age, and <i>P</i> = 0.005 for PfLP). When age, PfLP and baseline Pf positivity were analyzed together, the effect of high PfLP remained significant even after adjusting for the other two factors (<i>P</i> = 0.001 for malaria occurrence and <i>P</i><0.001 for number of episodes). In addition to host age and baseline Pf positivity, both of which have been reported as important modifiers of clinical malaria risk, our results demonstrate that persistent parasite carriage, but not baseline multiclonality, is associated with reduced risk of clinical disease in this population. Our study emphasizes the importance of considering repeated parasite exposure in future studies that evaluate clinical malaria risk.</p></div

Correlations between plasma levels of UA and those of sICAM-1 or sTM during an acute episode of <i>P. falciparum</i> malaria.

<p>The levels of UA, sICAM-1 and sTM were quantified in plasma samples from 487 Malian children at their first episode of uncomplicated <i>P. falciparum</i> malaria and their relationships analyzed. A. The graph shows a positive linear correlation between UA and sICAM-1 levels, but not at the lowest and highest UA levels measured. B. The graph shows a positive linear correlation between UA and sTM levels, but not at the lowest and highest UA levels measured. The blue line in each graph is the loess smooth using the default values <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054481#pone.0054481-WS1" target="_blank">[47]</a>, showing a moving average line with 95% pointwise confidence intervals.</p

Plasma levels of UA and biomarkers of endothelial activation/damage, stratified by disease severity.

a<p>The median (IQR) of each variable is shown.</p>b<p>p-values were calculated using the Mann-Whitney test.</p

Plasma UA levels increase during an acute episode of <i>P. falciparum</i> malaria and further increase with disease severity.

<p>A. UA levels were quantified in paired plasma samples from 69 Malian children before and after the 2009 malaria transmission season, and at their first episode of malaria in the interim. B. UA levels were quantified in plasma samples from Malian children with uncomplicated (UM, n = 487) or non-cerebral severe malaria (NCSM, n = 68). Boxplots show the median, interquartile range, with outliers shown as open circles beyond the range. Data points are displayed by density <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054481#pone.0054481-HintzeJ1" target="_blank">[45]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054481#pone.0054481-Atoh1" target="_blank">[46]</a>.</p

Demographic and clinical characteristics of patients.

a<p>The median (IQR) of each variable is shown, except for sex ratio.</p>b<p>p-values were calculated using the Mann-Whitney test, unless otherwise specified.</p>c<p>p-value was calculated using the Fisher’s exact test.</p

Cross-sectional prevalence of <i>P</i>. <i>falciparum</i> (Pf) infection and 2-week incidence of clinical malaria from June 2013 to May 2014.

<p>Left y-axis: Pf prevalence measured by nested-PCR; dark gray bars represent Pf prevalence. Right y-axis: number of clinical malaria cases recorded during each 2-week period preceding a blood sampling visit; light gray bars represent 2-week incidence. The time of visit is indicated on the x-axis, with V1 and V2 indicating the first and second blood sampling visits, respectively, for the months indicated.</p

Plasma levels of UA and biomarkers of endothelial activation/damage before, during and after an episode of <i>P. falciparum</i> malaria.

a<p>The median (IQR) of each variable is shown.</p>b<p>p-values were calculated using the Wilcoxon signed rank test.</p

Correlation between polymorphic proportion (PmP) and <i>P</i>. <i>falciparum</i> longitudinal prevalence (PfLP).

<p>PmP positively correlates with PfLP at all 4 time-points: (A) Jun-V1 (r = 0.47, 95% confidence interval = 0.30–0.61, <i>P</i><0.001, Spearman rank correlation test); (B) Nov-V1 (r = 0.36, 0.18–0.52, <i>P</i><0.001); (C) Feb-V1 (r = 0.42, 0.15–0.63, <i>P</i> = 0.003); and (D) Apr-V1 (r = 0.39, 0.09–0.63, <i>P</i> = 0.011)</p

Results of multivariate regression analysis of clinical malaria risk, including baseline Pf positivity^a.

<p>Results of multivariate regression analysis of clinical malaria risk, including baseline Pf positivity<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170948#t004fn001" target="_blank">^a</a>.</p