Introduction: Eosinophilia and anemia are very common hematological alterations in the tropics but population-based studies scrutinizing their value for diagnosing parasitic infections are rare. Methodology: A cross-sectional study was conducted in a rural district in northeast Brazil where parasitic infections are common. Stool and blood samples were collected and individuals were clinically examined for the presence of ectoparasites. Results: In total, 874 individuals were examined. Infection with intestinal helminths occurred in 70% (95% CI 67 -75), infestation with ectoparasites in 45% (95% CI 42 -49) and co-infection with both helminths and ectoparasites was found in 33% (95% CI 29% -36%) of all inhabitants. Eosinophil counts ranged from 40/µl to 13.800/µl (median: 900/µl). Haemoglobin levels ranged from 4.8 g/dl to 16.8 g/dl (median: 12.5 g/dl), and anemia was present in 24% of the participants. Leukocytosis was found in 13%, eosinophilia in 74%, and hypereosinophilia in 44% of the participants. Eosinophilia was more pronounced in individuals co-infected with intestinal helminths and ectoparasites (p < 0.001) and correctly predicted parasitic infection in 87% (95% CI 84%-90.7%) of all cases. Conclusions: Eosinophilia is strongly associated with the presence of intestinal helminthiases and accentuated by co-infestation with ectoparasites. Our study confirms in a population with high prevalence of intestinal helminthiases and ectoparasites that eosinophilia can be used to accurately diagnose current parasitic infection and initiate treatment.
Background: Acute myocardial infarction (AMI) results from obstruction of a coronary artery and affects around 126 million individuals globally. We have shown in a small pilot study that intracardiac delivery of autologous CD34+ cells after myocardial infarction is safe and leads to long term improvement. The improvement was such that three patients initially recommended for early heart transplantation in this study, no longer required it years after the cell injection. After the successful results of this pilot study, we started a multicenter, randomized, controlled Phase I/IIb study in post-AMI to investigate the safety and efficacy of intramyocardial injection of expanded autologous CD34+ cells (ProtheraCytes®) (NCT02669810). While patient recruitment is ongoing, we have developed a potency assay for the batch release of ProtheraCytes®. Methods: The proposed mechanisms of action by which ProtheraCytes® promote cardiac regeneration and revascularisation of damaged myocardial tissue is via the secretion of angiogenic factors and endothelial differentiation. We conducted a series of in vitro studies characterizing the growth factor secretion, exosome secretion, gene expression, cell surface markers, differentiation potential, and angiogenic potential of ProtheraCytes® clinical batches to develop a potency assay. Results: Here we show that ProtheraCytes® secrete vascular endothelial growth factor (VEGF) and its concentration is significantly correlated with the number of CD34+ cells obtained after expansion (Pearson r = 0.7484; p-value = 0.0009). ProtheraCytes® also secrete exosomes containing proangiogenic miRNAs (126, 130a, 378, 26a), antiapoptotic miRNAs (21 and 146a), antifibrotic miRNAs (133a, 24, 29b, 132), and miRNAs promoting myocardial regeneration (199a and 590). We also show that ProtheraCytes® have in vitro angiogenic activity, express surface markers of endothelial and cardiomyocyte progenitor cells, and can differentiate in vitro into endothelial cells. Conclusions: The potency assay should represent the product's mechanism of action, quantitatively measure the relevant biological product attribute, and have lot to lot consistency. Developing a potency assay is a required step before commencing the pivotal Phase 3 clinical studies. After the in vitro characterization of multiple ProtheraCytes® clinical batches, we established that measuring the concentration of VEGF provided the most practical, reliable, and consistent potency assay.
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