Comparison of apoptosis in human primary pulmonary endothelial cells and a brain microvascular endothelial cell line co-cultured with Plasmodium falciparum field isolates

Abstract Background Plasmodium falciparum infection can progress unpredictably to severe forms including respiratory distress and cerebral malaria. The mechanisms underlying the variable natural course of malaria remain elusive. Methods The cerebral microvascular endothelial cells-D3 and lung endothelial cells both from human were cultured separately and challenged with P. falciparum field isolates taken directly from malaria patients or 3D7 strain (in vitro maintained culture). The capacity of these P. falciparum isolates to induce endothelial cell apoptosis via cytoadherence or not was then assessed. Results Overall, 27 P. falciparum isolates were collected from patients with uncomplicated malaria (n = 25) or severe malaria (n = 2). About half the isolates (n = 17) were able to bind brain endothelial cells (12 isolates, 44%) or lung endothelial cells (17 isolates, 63%) or both (12 isolates, 44%). Sixteen (59%) of the 27 isolates were apoptogenic for brain and/or lung endothelial cells. The apoptosis stimulus could be cytoadherence, direct cell-cell contact without cytoadherence, or diffusible soluble factors. While some of the apoptogenic isolates used two stimuli (direct contact with or without cytoadherence, plus soluble factors) to induce apoptosis, others used only one. Among the 16 apoptogenic isolates, eight specifically targeted brain endothelial cells, one lung endothelial cells, and seven both. Conclusion These results indicate that the brain microvascular cell line was more susceptible to apoptosis triggered by P. falciparum than the primary pulmonary endothelial cells and may have relevance to host-parasite interaction

Marked Rise in the Prevalence of Asymptomatic <i>Plasmodium falciparum</i> Infection in Rural Gabon

<div><p>Control strategies implemented a decade ago led to a marked reduction in the prevalence of malaria in many countries. In Dienga, southeastern Gabon, the prevalence of microscopic <i>P</i>. <i>falciparum</i> infection was 7% in 2003, close to the pre-elimination threshold of 5%. The aim of this work was to determine the prevalence of <i>P</i>. <i>falciparum</i> infection in the same community a decade later. A cohort of 370 individuals aged from 3 to 85 years living in Dienga was investigated for <i>P</i>. <i>falciparum</i> infection; during six passages (P) in 15-month period. Demographic data were collected, along with behaviors and attitudes towards malaria. <i>Plasmodium</i> infection was diagnosed by microscopy (ME), followed by PCR to detect submicroscopic infection. The prevalence of <i>P</i>. <i>falciparum</i> infection in P1, P2, P3, P4, P5 and P6 was respectively 43.5% (25.1% ME+, 18.4% PCR+); 40.9% (27.0% ME+, 13.9% PCR+), 52.7% (26.1% ME+, 26.6% PCR+); 34.1% (14.1% ME+, 20% PCR+), 57.7% (25.4.% ME+, 32.3% PCR+); and 46.2% (21.4% ME+, 24.8% PCR+) with an overall average of 45.9% (95%CI [37.0–54.7], 23.2% ME+ and 22.7% PCR+). P4 and P5 prevalences were statically different throughout the six passages. Microscopic prevalence was significantly higher than that observed ten years ago (23% [n = 370] vs 7% [n = 323], p < 0.001). Asymptomatic infections were the most frequent (96%). Gametocytes were detected in levels ranging from 5.9% to 13.9%. Insecticide-treated nets, indoor residual insecticides, and self-medication were used by respectively 33.2% (95%CI [29.0–37.4]), 17.7% (95%CI [15.5–19.9]) and 12.1% (95%CI [10.6–13.6]) of the study population. A near-threefold increase in <i>P</i>. <i>falciparum</i> infection has been observed in a rural area of southeastern Gabon during a 10-year period. Most infections were asymptomatic, but these subjects likely represent a parasite reservoir. These findings call for urgent reinforcement of preventive measures.</p></div

Attitudes and behaviors concerning malaria.

<p>Attitudes and behaviors concerning malaria.</p

Baseline Characteristics of the study subjects.

<p>Baseline Characteristics of the study subjects.</p

Mean prevalence according to the age groups.

<p><b>*</b> Significant difference between the prevalence of males obtained by PCR and that observed among females.</p

Mean prevalence according to the age groups.

<p><b>*</b> Significant difference between the prevalence of individuals higher than 18years and other groups.</p

Global <i>P</i>. <i>falciparum</i> prevalences in Dienga.

<p>Global <i>P</i>. <i>falciparum</i> prevalences in Dienga.</p

Stepwise multivariate logistic regression analysis of significant variables.

<p>Stepwise multivariate logistic regression analysis of significant variables.</p

Nucleotide primers used in STEVOR gene amplification.

<p>Nucleotide primers used in STEVOR gene amplification.</p