Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. Here we show that the two main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR-BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil redundant functions during infection by the rodent parasite P. berghei. Genetic analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a major parasite determinant of host cell receptor usage. Our data provide molecular insights into the invasion pathways used by different malaria parasites to infect hepatocytes, and establish a functional link between a sporozoite putative ligand and host cell receptors.DOI: http://dx.doi.org/10.7554/eLife.25903.001
Background: People living with HIV (PLWHIV) have a 2-fold higher risk of having a cardiovascular event than HIV-negative individuals. Objectives: The objective of this article is to estimate the pooled proportion of moderate-high cardiovascular risk in PLWHIV obtained through different scores. In addition, this study also aims to establish the prevalence of dyslipidemia, smoking habits, diabetes and high blood pressure in the included studies. Methods: A bibliographic search was conducted in MEDLINE for studies on cardiovascular risk assessment in PLWHVI that took place during the period of inception to July 2018. The eligibility criteria for inclusion were: cross-sectional or longitudinal studies on HIV-positive adults in which the prevalence of moderate-high cardiovascular risk (or data to calculate it) was reported, and included at least one of the following cardiovascular risk scores: Framingham, ASCVD, D:A:D, Progetto Cuore, PROCAM, SCORE, Regicor, and World Health Organization scores. Results: Bibliographic search identified 278 studies. Finally, thirty-nine peer-reviewed publications were identified for a collective total of 13698 subjects. The pooled prevalence of moderate-high cardiovascular risk in PLWHIV obtained with nine different scores through random-effect modeling was 20.41% (95% CI: 16.77-24.31). The most prevalent concomitant cardiovascular risk factor was dyslipidemia (39.5%), smoking (33.0 %), high blood pressure (19.8%) and diabetes (7.24%). Conclusions: Data obtained in this systematic review indicate that more than 1 in every five subjects with HIV have a moderate-high cardiovascular risk. In consequence, the burden of cardiovascular disease in PLWHIV represents a public health problem. There is an urgent need to develop strategies to prevent and detect cardiovascular risk effectively in PLWHIV.
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