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    • The public health implications of our study are

    2018-11-14

    The public health implications of our study are significant, shedding light on the overarching question of whether iron supplements cause harm. We acknowledge that in vitro parasite growth might not translate directly to malaria susceptibility. Yet there are no other viable alternatives for addressing this safety aspect regarding iron supplementation in malarious regions. While our system only examined the RBC impact of anemia on malaria growth, eliminating the impact of serum iron or immune cells, the fact that we still observe such profound growth effects highlights the protection afforded by anemia and the need for caution regarding iron supplementation. Furthermore, our results provide insight into why other clinical studies on this topic produce such variable results – given we find increased malaria susceptibility is transient, other studies may miss the window of enhanced susceptibility. We detect significant changes in parasite growth rates despite relatively small changes in hemoglobin levels, emphasizing the impact of iron and RBC population dynamics on P. falciparum pathogenesis. Our data clearly show that the safety of iron supplementation must be addressed, even if additional unknown mechanisms contribute to increased malaria susceptibility. We thus advocate temporary malaria prophylaxis should always accompany iron supplementation for anemic children in malaria endemic areas, though the period of enhanced susceptibility has not been accurately identified by this study. Finally, quantifying the sizeable contribution of anemia to population level protection against malaria, our research raises the question of whether consistently reduced hemoglobin and MCV values in people of African descent are genetic signatures of cisapride manufacturer under significant malaria pressure, much like the hemoglobinopathies. The following are the supplementary data related to this article.
    Role of the Funding Source
    Author Contributions MMG, RW, AB, AMP, and CC designed the study and were involved in data analysis and interpretation, as well as writing. MMG, BD, ED, and DG participated in data collection. MA provided clinical P. falciparum isolates. JCP provided statistical support for data analysis. All authors reviewed and approved the final version.
    Declaration of Interests
    Acknowledgments
    Introduction Magnetic resonance diffusion weighted imaging (DWI) remains the best neuroimaging technique to detect acute ischemia, above all since the new tissular definition of transient ischemic attack (TIA) has become essential in the evaluation of TIA patients (Easton et al., 2009). According to a recent meta-analysis, despite transient clinical symptoms, one out of three patients with definite TIA has an acute DWI lesion (Brazzelli et al., 2014). Moreover, DWI has been shown to be an important predictor of early stroke recurrence (Purroy et al., 2004) and it has been proposed to add to clinical prognostic scales like ABCD2I (Giles et al., 2011) and ABCD3I (Merwick et al., 2010). Furthermore, not only the presence but also the patterns of DWI are important both for the etiological classification and for patient prognosis (Purroy et al., 2011). However, despite the increased availability of magnetic resonance imaging (MRI) not all TIA patients undergo DWI. Therefore, the discovery of a plasmatic biomarker related to neuroimaging findings is of enormous interest. The use of metabolomics on TIA patients has started a new era in biomarker discovering for clinical purpose (Jove et al., 2015a). Metabolomics allows the study of the complete set of low-molecular-weight intermediates (metabolites), which vary according to the pathologic state of the cell, tissue, organ, or organism and are context-dependent (Jove et al., 2014; Mauri-Capdevila et al., 2013). The aim of the present study was to perform a metabolomic analysis to find new biomarkers associated with the presence of acute DWI lesion and the volume and patterns of these lesions. As previously (Jove et al., 2015a), results were validated in an independent cohort.