Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo

Adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of Plasmodium falciparum malaria. The prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. Irbc of the rodent parasite Plasmodium berghei ANKA sequester in a fashion analogous to P. falciparum by adhering to the host receptor CD36. To experimentally determine the significance of sequestration for parasite growth, we generated a mutant P. berghei ANKA parasite with a reduced CD36-mediated adherence. Although the cognate parasite ligand binding to CD36 is unknown, we show that nonsequestering parasites have reduced growth and we provide evidence that in addition to avoiding spleen removal, other factors related to CD36-mediated sequestration are beneficial for parasite growth. These results reveal for the first time the importance of sequestration to a malaria infection, with implications for the development of strategies aimed at reducing pathology by inhibiting tissue sequestration.Host-parasite interactio

Equity-specific effects of 26 Dutch obesity-related lifestyle interventions

Context Reducing health inequalities is a policy priority in many developed countries. Little is known about effective strategies to reduce inequalities in obesity and its underlying behaviors. The goal of the study was to investigate differential effectiveness of interventions aimed at obesity prevention, the promotion of physical activity or a healthy diet by SES. Evidence acquisition Subgroup analyses in 2010 and 2011 of 26 Dutch studies funded by The Netherlands Organization for Health Research and Development after 1990 (n=17) or identified by expert contact (n=9). Methodologic quality and differential effects were synthesized in harvest plots, subdivided by setting, age group, intensity, and time to follow-up. Evidence synthesis Seven lifestyle interventions were rated more effective and four less effective in groups with high SES; for 15 studies no differential effects could be demonstrated. One study in the healthcare setting showed comparable effects in both socioeconomic groups. The only mass media campaign provided modest evidence for higher effectiveness among those with high SES. Individually tailored and workplace interventions were either more effective in higher-SES groups (n=4) or no differential effects were demonstrated (n=9). School-based studies (n=7) showed mixed results. Two of six community studies provided evidence for better effectiveness in lower-SES groups; none were more effective in higher-SES groups. One high-intensity community-based study provided best evidence for higher effectiveness in low-SES groups. Conclusions Although for the majority of interventions aimed at obesity prevention, the promotion of physical activity, or a healthy diet, no differential effectiveness could be demonstrated, interventions may widen as well as reduce socioeconomic inequalities in these outcomes. Equity-specific subgroup analyses contribute to needed knowledge about what may work to reduce socioeconomic inequalities in obesity and underlying health behaviors