Malaria Eradication in the European World: Historical Perspective and Imminent Threats

Malaria was introduced to Europe from the southeast during the Neolithic period and subsequently became established throughout the continent, due to the combination of favorable geomorphological and climatic conditions with the presence of adequately sized human and competent vector populations. Plasmodium vivax, P. malariae and P. falciparum all occurred in various areas of the continent, transmitted by numerous Anopheles species, mainly An. atroparvus in the northwest, An. labranchiae and An. sacharovi in the south. The height of malaria endemicity in the Early Modern Age was followed by decline in the twentieth century, particularly in the northwest, owing mainly to man-made contraction of vector breeding sites and improvement of living standards. Eradication was accomplished in 1974 through widespread drug treatment and residual insecticide spraying. Since then, despite the sustained presence of competent vectors and numerous malaria cases imported by travelers and immigrants, autochthonous transmission has been sporadic in Europe, probably due to prompt diagnosis and treatment afforded by robust healthcare services. Current and projected climatic conditions are conducive to malaria transmission, particularly vivax malaria, in several areas of Southern Europe. Moreover, the continuing immigration crisis may facilitate the buildup of an infectious parasite reservoir in the area. Although malaria resurgence is currently unlikely particularly in northwest Europe, it is of crucial importance to maintain disease awareness, diagnostic and clinical competence and robust public health infrastructure for surveillance and vector control to diminish the possibility of malaria transmission in Europe’s most vulnerable areas

An efficient and novel technology for the extraction of parasite genomic DNA from whole blood or culture

The aim of this study was to assess pathogen DNA extraction with a new spin column-based method (DNA-XT). DNA from either whole-blood samples spiked with Plasmodium falciparum or Leishmania donovani amastigote culture was extracted with DNA-XT and compared with that produced by a commercial extraction kit (DNeasy®). Eluates from large and small sample volumes were assessed by PCR and spectroscopy. Using a small volume (5 μl) of blood, the DNA-XT and DNeasy methods produced eluates with similar DNA concentrations (0.63 vs 1.06 ng/μl, respectively). The DNA-XT method produced DNA with lower PCR inhibition than DNeasy. The new technique was also twice as fast and required fewer plastics and manipulations but had reduced total recovered DNA compared with DNeasy

An efficient and novel technology for the extraction of parasite genomic DNA from whole blood or culture

The aim of this study was to assess pathogen DNA extraction with a new spin column-based method (DNA-XT). DNA from either whole-blood samples spiked with Plasmodium falciparum or Leishmania donovani amastigote culture was extracted with DNA-XT and compared with that produced by a commercial extraction kit (DNeasy®). Eluates from large and small sample volumes were assessed by PCR and spectroscopy. Using a small volume (5 μl) of blood, the DNA-XT and DNeasy methods produced eluates with similar DNA concentrations (0.63 vs 1.06 ng/μl, respectively). The DNA-XT method produced DNA with lower PCR inhibition than DNeasy. The new technique was also twice as fast and required fewer plastics and manipulations but had reduced total recovered DNA compared with DNeasy

Diagnostic value of laboratory markers of infection in patients with fever

Objective: The aim of this study was to assess the diagnostic value of CRP, IL-6 and PCT in the diagnosis of infection and bacteremia in patients with fever. Methods: 113 patients were included in the study divided in two groups. Those with clinically and/or microbiologically documented infection and those with fever without documented infection CRP was measured using a turbidimetric assay, IL-6 with an enzyme-linked immunosorbent assay (ELISA) and PCT with chemoluminescence. The correlation of CRP, IL-6, PCT with the diagnosis of infection and bacteremia was investigated. ROC curves were plotted for the estimation of cutoff values. Results: CRP, IL-6 and PCT were significantly associated with the diagnosis of infection IL-6 and PCT but not CRP, were also significantly associated with the diagnosis of bacteremia. Conclusions: CRP, IL-6 and PCT were found to be useful diagnostic markers of infection in the population studied. Furthermore the novel IL-6 and PCT were found to be useful for the detection of bacteremia.Στόχος: Να εκτιμηθεί η διαγνωστική αξία των δεικτών CRP, IL-6 και PCT στη διερεύνηση εμπύρετων νοσημάτων. Διερευνήθηκε η συμβολή τους στη διάγνωση λοίμωξης και τον εντοπισμό των λοιμώξεων που συνοδεύονται από βακτηριαιμία. Μέθοδοι: Περιελήφθησαν 113 ασθενείς με εμπύρετο, με και χωρίς τεκμηριωμένη κλινικά ή/και εργαστηριακά διάγνωση λοίμωξης. Στο ορό προσδιορίστηκαν η CRP με νεφελομετρία, η ιντερλευκίνη-6 με ELISA και η προκαλβιτονίνη με χημειοφωταύγεια. Διερευνήθηκε η σχέση των τιμών CRP, IL-6 και PCT με την διάγνωση λοίμωξης και βακτηριαιμίας. Σχεδιάστηκαν καμπύλες ROC για καθορισμό οριακών τιμών. Αποτελέσματα: Οι δείκτες CRP, IL-6 και PCT συσχετίζονται σε στατιστικά σημαντικό βαθμό με τη διάγνωση λοίμωξης και βακτηριαιμίας. Οι IL-6 και PCT αλλά όχι η CRP συσχετίζονται με τη διάγνωση βακτηριαιμίας. Συμπεράσματα: Οι εργαστηριακοί δείκτες CRP, IL-6 και PCT μπορούν να χρησιμοποιηθούν ως διαγνωστικοί δείκτες λοίμωξης στο συγκεκριμένο πληθυσμό ασθενών που εξετάστηκε. Επιπλέον οι IL-6 και PCT μπορούν να υποδείξουν τους ασθενείς με λοίμωξη και βακτηριαιμία

Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective

The leishmaniases constitute a group of parasitic diseases caused by species of the protozoan genus Leishmania. In humans it can present different clinical manifestations and are usually classified as cutaneous, mucocutaneous, and visceral (VL). Although the full range of parasite—host interactions remains unclear, recent advances are improving our comprehension of VL pathophysiology. In this review we explore the differences in VL immunobiology between the liver and the spleen, leading to contrasting infection outcomes in the two organs, specifically clearance of the parasite in the liver and failure of the spleen to contain the infection. Based on parasite biology and the mammalian immune response, we describe how hypoxia-inducible factor 1 (HIF1) and the PI3K/Akt pathway function as major determinants of the observed immune failure. We also summarize existing knowledge on pancytopenia in VL, as a direct effect of the parasite on bone marrow health and regenerative capacity. Finally, we speculate on the possible effect that manipulation by the parasite of the PI3K/Akt/HIF1 axis may have on the myelodysplastic (MDS) features observed in VL

Molecular screening of cat and dog ectoparasites for the presence of Bartonella spp. in Attica, Greece.

The purpose of this study was the molecular detection of Bartonella spp. in fleas and ticks parasitizing cats and dogs from 39 locations in Attica, Greece. One hundred and forty five ectoparasites (104 fleas and 41 ticks) from 92 cats and 53 dogs were investigated individually using PCRs targeting the 16S-23S ribosomal RNA intergenic spacer (ITS) and the citrate synthase (gltA) genetic loci. Bartonella spp. were detected in 14 out of 104 fleas (13.5%) and in none of the ticks examined. Consequent sequence analysis of the amplicons from the two loci identified 3 strains as Bartonella henselae, and 11 as Bartonella clarridgeiae. Οur study demonstrates the presence of B. henselae and B. clarridgeiae in Ctenocephalides felis fleas from cat and dog in Greece. We also report a novel ITS sequence for B. clarridgeiae. Considering that fleas could pose a risk for human bartonellosis from their infected hosts, further studies on the public health risk of Bartonella presence in animal ectoparasites are warranted

Visceral leishmaniasis and COVID-19 coinfection - A case report

As the COVID-19 pandemic spreads across the globe, it will undoubtedly cross paths with long endemic infectious diseases in different areas. Interactions between SARS-CoV2 and well-known pathogens will likely give rise to unfamiliar clinical presentations, depending on complex and as yet unknown immunological interactions. We present a case of coinfection with COVI19 and visceral leishmaniasis and discuss recent reports regarding coexistence of SARS-CoV2 and Leishmania spp. to date. (C) 2021 Published by Elsevier Ltd

Bioenergetic profiling of the differentiating human MDS myeloid lineage with low and high bone marrow blast counts

Myelodysplastic syndromes (MDS) encompass a very heterogeneous group of clonal hematopoietic stem cell differentiation disorders with malignant potential and an elusive pathobiology. Given the central role of metabolism in effective differentiation, we performed an untargeted metabolomic analysis of differentiating myeloid lineage cells from MDS bone marrow aspirates that exhibited <5% (G1) or ≥5% (G2) blasts, in order to delineate its role in MDS severity and malignant potential. Bone marrow aspirates were collected from 14 previously untreated MDS patients (G1, n = 10 and G2, n = 4) and age matched controls (n = 5). Following myeloid lineage cell isolation, untargeted mass spectrometry-based metabolomics analysis was performed. Data were processed and analyzed using Metabokit. Enrichment analysis was performed using Metaboanalyst v4 employing pathway-associated metabolite sets. We established a bioenergetic profile coordinated by the Warburg phenomenon in both groups, but with a massively different outcome that mainly depended upon its group mitochondrial function and redox state. G1 cells are overwhelmed by glycolytic intermediate accumulation due to failing mitochondria, while the functional electron transport chain and improved redox in G2 compensate for Warburg disruption. Both metabolomes reveal the production and abundance of epigenetic modifiers. G1 and G2 metabolomes differ and eventually determine the MDS clinical phenotype, as well as the potential for malignant transformation.This study was supported in part by research funding from the Special Account for Research Grants of National and Kapodistrian University of Athens, and the Hellenic Society of Hematology to M.V. This study was also partially supported by a European Commission grant (H2020-668353) awarded to G.P.P

Dissemination of Clinical Isolates of Klebsiella oxytoca Harboring CMY-31, VIM-1, and a New OXY-2-Type Variant in the Community

The aim of the present study was to investigate the epidemiological link of multidrug-resistant Klebsiella oxytoca isolates causing community-onset infections among patients attending our outpatient department and to investigate the underlying resistance mechanisms. The isolates were tested by agar dilution MICs, phenotypic carbapenemase testing, enterobacterial repetitive intergenic consensus-PCR, and pulsed-field gel electrophoresis (PFGE). PCR assays and nucleotide sequencing were employed for the identification of bla gene types and the mapping of the integron-containing metallo-beta-lactamase (MBL) gene. During the study period (January 2005 to April 2007), nine broad-spectrum cephalosporin-resistant K. oxytoca clinical isolates were prospectively collected from separate outpatients with urinary tract infections. In all cases, the patients had been hospitalized or exposed to health care facilities during the preceding year. Molecular typing revealed that all isolates belonged to the same K. oxytoca clonal type, which contained five PFGE subtypes. A novel chromosomal OXY-2 beta-lactamase type variant (OXY-2-9) was detected in all isolates, but no mutations in the promoter region justifying bla OXY gene overproduction were detected. In addition, all isolates harbored the plasmidic CMY-31 (LAT-4) AmpC cephalosporinase, while three of them harbored VIM-1 MBL in a class 1 integron structure. This is the first study to present the dissemination in the community of multidrug-resistant K. oxytoca isolates causing extrahospital infections