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In the current phase of the COVID-19 pandemic, waves of SARS-CoV-2 infection are driven by novel variants and their sublineages, which continue to cause illness and death with potential to [...]

BACKGROUND. The biology of Plasmodium vivax is markedly different from that of P. falciparum; how this shapes the immune response to infection remains unclear. To address this shortfall, we inoculated human volunteers with a clonal field isolate of P. vivax and tracked their response through infection and convalescence. METHODS. Participants were injected intravenously with blood-stage parasites and infection dynamics were tracked in real time by quantitative PCR. Whole blood samples were used for high dimensional protein analysis, RNA sequencing, and cytometry by time of flight, and temporal changes in the host response to P. vivax were quantified by linear regression. Comparative analyses with P. falciparum were then undertaken using analogous data sets derived from prior controlled human malaria infection studies. RESULTS. P. vivax rapidly induced a type I inflammatory response that coincided with hallmark features of clinical malaria. This acute-phase response shared remarkable overlap with that induced by P. falciparum but was significantly elevated (at RNA and protein levels), leading to an increased incidence of pyrexia. In contrast, T cell activation and terminal differentiation were significantly increased in volunteers infected with P. falciparum. Heterogeneous [CD4.sup.+] T cells were found to dominate this adaptive response and phenotypic analysis revealed unexpected features normally associated with cytotoxicity and autoinflammatory disease. CONCLUSION. P. vivax triggers increased systemic interferon signaling (cf P. falciparum), which likely explains its reduced pyrogenic threshold. In contrast, P. falciparum drives T cell activation far in excess of P. vivax, which may partially explain why falciparum malaria more frequently causes severe disease. TRIAL REGISTRATION. ClinicalTrials.gov NCT03797989. FUNDING. The European Union's Horizon 2020 Research and Innovation programme, the Wellcome Trust, and the Royal Society., Introduction Plasmodium vivax causes more than half of all malaria cases in the Americas and Southeast Asia (1) and its distinct biology (cf P falciparum) presents unique challenges for control [...]

Chronic hepatitis C virus (HCV) infection is characterized by persistent high-level viremia and defective cellular immunity, including a lack of functional HCV-specific [CD4.sup.+] T cells. We previously described an exceptional period of viral control that occurs in some chronically infected women after childbirth. Here, we investigated whether reduced HCV replication after pregnancy is associated with recovery of [CD4.sup.+] T cell immunity. Class II tetramer analysis revealed significantly greater frequencies of circulating HCV-specific [CD4.sup.+] T cells at 3 months postpartum in women with concurrent declines in viremia compared with those with stable viremia. These HCV-specific [CD4.sup.+] T cells had an effector-memory phenotype. Inhibitory coreceptor expression on these cells corresponded to the degree of viral control. Circulating [CD4.sup.+] T cells produced IL-2 and IFN-[[gamma]] after HCV antigen stimulation, demonstrating Th1 functionality. These data provide direct evidence that the profound loss of HCV-specific [CD4.sup.+] T cell help that results in chronic infection is reversible following pregnancy, and this recovery of [CD4.sup.+] T cells is associated with at least transient control of persistent viral replication., Introduction Hepatitis C virus (HCV) infections persist indefinitely in approximately three-quarters of infected individuals, predisposing to late complications, including hepatic cirrhosis and hepatocellular carcinoma (1). One of the strongest predictors [...]

Yaws, a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue, predominantly affects children living in low-income, rural communities of warm and humid regions (1). Clinical manifestations include [...]

Background/Objectives The iron-binding affinity of vaginal lactoferrin (Lf) reduces iron available to genital pathogens. We describe host reproductive, nutritional, infection and iron biomarker profiles affecting vaginal Lf concentration in young nulliparous and primigravid women in Burkina Faso. Subjects/Methods Vaginal eluates from women who had participated in a randomized, controlled periconceptional iron supplementation trial were used to measure Lf using a competitive double-sandwich ELISA. For this analysis samples from both trial arms were combined and pregnant and non-pregnant cohorts compared. Following randomization Lf was measured after 18 months (end assessment) for women remaining non-pregnant, and at two antenatal visits for those becoming pregnant. Associations between log Lf levels and demographic, anthropometric, infection and iron biomarker variables were assessed using linear mixed models. Results Lf samples were available for 712 non-pregnant women at end assessment and for 303 women seen at an antenatal visit. Lf concentrations of pregnant women were comparable to those of non-pregnant, sexually active women. Lf concentration increased with mid-upper-arm circumference, (P = 0.047), body mass index (P = 0.018), Trichomonas vaginalis (P < 0.001) infection, bacterial vaginosis (P < 0.001), serum C-reactive protein (P = 0.048) and microbiota community state types III/IV. Adjusted Lf concentration was positively associated with serum hepcidin (P = 0.047), serum ferritin (P = 0.018) and total body iron stores (P = 0.042). There was evidence that some women maintained persistently high or low Lf concentrations from before, and through, pregnancy. Conclusion Lf concentrations increased with genital infection, higher BMI, MUAC, body iron stores and hepcidin, suggesting nutritional and iron status influence homeostatic mechanisms controlling vaginal Lf responses., Author(s): S. A. Roberts [sup.1], L. Brabin [sup.2], S. Diallo [sup.3], S. Gies [sup.4], A. Nelson [sup.5], C. Stewart [sup.6], D. W. Swinkels [sup.7] [sup.8], A. J. Geurts-Moespot [sup.7], A. [...]

Introduction: This paper examines the extent to which an intervention succeeded in locating people who had recently become infected with HIV in the context of the large-scale Ukrainian epidemic. Locating and intervening with people who recently became infected with HIV (people with recent infection, or PwRI) can reduce forward HIV transmission and help PwRI remain healthy. Methods: The Transmission Reduction Intervention Project (TRIP) recruited recently-infected and longer-term infected seeds in Odessa, Ukraine, in 2013 to 2016, and asked them to help recruit their extended risk network members. The proportions of network members who were PwRI were compared between TRIP arms (i.e. networks of recently-infected seeds vs. networks of longer-term infected seeds) and to the proportion of participants who were PwRI in an RDS-based Integrated Biobehavioral Surveillance of people who inject drugs in 2013. Results: The networks of PwRI seeds and those of longer-term infected seeds had similar (2%) proportions who were themselves PwRI. This was higher than the 0.25% proportion in IBBS (OR = 7.80; p = 0.016). The odds ratio among the subset of participants who injected drugs was 11.17 (p = 0.003). Cost comparison analyses using simplified ingredients-based methods found that TRIP spent no more than US $4513 per PwRI located whereas IBBS spent $11,924. Conclusions: Further research is needed to confirm these results and improve TRIP further, but our findings suggest that interventions that trace the networks of people who test HIV-positive are a cost-effective way to locate PwRI and reduce HIV transmission and should therefore be implemented. Keywords: HIV; treatment as prevention; social network; intervention; recent HIV infection; PWID; Ukraine, 1 INTRODUCTION A major part of the global HIV/AIDS prevention strategy focuses on treatment as prevention [1]. Finding and intervening with people soon after they get infected is an important [...]

Purpose Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score [greater than or equal to] 2 at 24 h and/or 72 h following ED presentation). Methods In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3). Results Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity. Conclusions From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection. Clinical trial registration NCT02188992., Author(s): Manu Shankar-Hari [sup.1] [sup.2], Deepankar Datta [sup.3], Julie Wilson [sup.1] [sup.2], Valentina Assi [sup.4] [sup.5], Jacqueline Stephen [sup.5], Christopher J. Weir [sup.4] [sup.5], Jillian Rennie [sup.3], Jean Antonelli [sup.4], [...]

Purpose Sepsis contributes considerably to global morbidity and mortality, while reasons for its increasing incidence remain unclear. We assessed risk adjusted secular trends in sepsis and infection epidemiology in Germany. Methods Retrospective cohort study using nationwide German hospital discharge data. We assessed incidence, outcomes and trends of hospital-treated sepsis and infections between 2010 and 2015. Sepsis was identified by explicit ICD-10 sepsis codes. As sensitivity analysis, results were compared with sepsis cases identified by implicit sepsis coding (combined infection and organ dysfunction codes). Results Among 18 664 877 hospital admissions in 2015, 4 213 116 (22.6%) patients had at least one infection code. There were 320 198 patients that had explicit sepsis codes including 136 542 patients with severe sepsis and septic shock; 183 656 patients were coded as sepsis without organ dysfunction. For patients with explicitly coded sepsis (including severe sepsis), or with severe sepsis alone, mortality rates over the period 2010-2015 decreased from 26.6 to 23.5%, and from 47.8 to 41.7%, respectively. Conclusions Sepsis and infection remain significant causes of hospital admission and death in Germany. Sepsis-related mortality is higher and has declined to a lesser degree than in other high-income countries. Although infection rates steadily increased, the observed annual increase of sepsis cases seems to result, to a considerable degree, from improved coding of sepsis., Author(s): C. Fleischmann-Struzek [sup.1], A. Mikolajetz [sup.2], D. Schwarzkopf [sup.1], J. Cohen [sup.3], C. S. Hartog [sup.4] [sup.5], M. Pletz [sup.6], P. Gastmeier [sup.7] [sup.8], K. Reinhart [sup.1] [sup.2] [sup.9] [...]

Purpose The optimal target blood glucose concentration for acute glycemic control remains unclear because few studies have directly compared 144-180 with 110-144 or >180 mg/dL. Accordingly, we performed a network meta-analysis to compare four different target blood glucose levels (180 mg/dL) in terms of the benefit and risk of insulin therapy. Methods We included all of the studies from three systematic reviews and searched the PubMed and Cochrane databases for other studies investigating glucose targets among critically ill patients. The primary outcome was hospital mortality, and the secondary outcomes were sepsis or bloodstream infection and the risk of hypoglycemia. Network meta-analysis to identify an optimal target glucose concentration. Results The network meta-analysis included 18,098 patients from 35 studies. There were no significant differences in the risk of mortality and infection among the four blood glucose ranges overall or in subgroup analysis. Conversely, target concentrations of 180 mg/dL. However, there were no significant differences between the target concentrations of 144-180 and >180 mg/dL. Conclusions This network meta-analysis found no significant difference in the risk of mortality and infection among four target blood glucose ranges in critically ill patients, but indicated that target blood glucose levels of 180 mg/dL. Further studies are required to refute or confirm our findings., Author(s): Tomoaki Yatabe [sup.1], Shigeaki Inoue [sup.2], Masahiko Sakaguchi [sup.3], Moritoki Egi [sup.4] Author Affiliations: (1) grid.278276.e, 0000000106599825, Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, , Kohasu, [...]

Background Campylobacter jejuni is a zoonotic pathogen that infects the human gut through the food chain mainly by consumption of undercooked chicken meat, raw chicken cross-contaminated ready-to-eat food or by raw milk. In the last decades, C. jejuni has increasingly become the most common bacterial cause for food-born infections in high income countries, costing public health systems billions of euros each year. Currently, different whole genome sequencing techniques such as short-read bridge amplification and long-read single molecule real-time sequencing techniques are applied for in-depth analysis of bacterial species, in particular, Illumina MiSeq, PacBio and MinION. Results In this study, we analyzed a recently isolated C. jejuni strain from chicken meat by short- and long-read data from Illumina, PacBio and MinION sequencing technologies. For comparability, this strain is used in the German PAC-CAMPY research consortium in several studies, including phenotypic analysis of biofilm formation, natural transformation and in vivo colonization models. The complete assembled genome sequence most likely consists of a chromosome of 1,645,980 bp covering 1665 coding sequences as well as a plasmid sequence with 41,772 bp that encodes for 46 genes. Multilocus sequence typing revealed that the strain belongs to the clonal complex CC-21 (ST-44) which is known to be involved in C. jejuni human infections, including outbreaks. Furthermore, we discovered resistance determinants and a point mutation in the DNA gyrase (gyrA) that render the bacterium resistant against ampicillin, tetracycline and (fluoro-)quinolones. Conclusion The comparison of Illumina MiSeq, PacBio and MinION sequencing and analyses with different assembly tools enabled us to reconstruct a complete chromosome as well as a circular plasmid sequence of the C. jejuni strain BfR-CA-14430. Illumina short-read sequencing in combination with either PacBio or MinION can substantially improve the quality of the complete chromosome and epichromosomal elements on the level of mismatches and insertions/deletions, depending on the assembly program used. Keywords: Campylobacter jejuni, Long read sequencing, Hybrid assemblies, Assembler comparison, Antibiotic resistance, Author(s): Lennard Epping[sup.1], Julia C. Golz[sup.2], Marie-Theres Knüver[sup.2], Charlotte Huber[sup.3], Andrea Thürmer[sup.4], Lothar H. Wieler[sup.4], Kerstin Stingl[sup.2] and Torsten Semmler[sup.1] Background Campylobacter jejuni is a Gram-negative bacterium that colonizes a [...]

Objective To assess the impact of a decade of biennial mass administration of praziquantel on schistosomiasis in school-age children in Burkina Faso. Methods In 2013, In a national assessment based on 22 sentinel sites, 3514 school children aged 7-11 years were checked for Schistosoma haematobium and Schistosoma mansoni infection by the examination of urine and stool samples, respectively. We analysed the observed prevalence and intensity of infections and compared these with the relevant results of earlier surveys In Burkina Faso. Findings 5. haematobium was detected In 287/3514 school children (adjusted prevalence: 8.76%, range across sentinel sites: 0.0-56.3%; median: 2.5%). The prevalence of 5. haematobium Infection was higher in the children from the Centre-Est, Est and Sahel regions than in those from Burkina Faso's other eight regions with sentinel sites (P< 0.001). The adjusted arithmetic mean Intensity of S. haematobium infection, among all children, was 6.0 eggs per 10 ml urine. Less than 1 % of the children in six regions had heavy S. haematobium infections --i.e. at least 50 eggs per 10 ml urine-but such infections were detected in 8.75% (28/320) and 11.56% (37/320) of the children from the Centre-Est and Sahel regions, respectively. Schistosoma mansoni was only detected in two regions and 43 children--i.e. 1 (0.31%) of the 320 from Centre-Sud and 42 (8.75%) of the 480 from Hauts Bassins. Conclusion By mass use of preventive chemotherapy, Burkina Faso may have eliminated schistosomiasis as a public health problem in eight regions and controlled schistosome-related morbidity in another three regions. Objectif Evaluer l'impact d'une decennie de distribution biennale massive de praziquantel sur la schistosomiase chez les enfants d'age scolaire au Burkina Faso. Methodes En 2013, dans le cadre d'une evaluation nationale basee sur 22 postes-sentinelles, un examen des urines et des echantillons des selles ont respectivement ete utilises pour deceler des infections a la Schistosoma haematobium et a la Schistosoma mansoni chez 3514 ecoliers ages de 7 a 11 ans. Nous avons analyse Ia prevalence et llntensite des infections, puis nous les avons comparees avec les resultats pertinents de precedentes etudes realisees au Burkina Faso. Resultats La Schistosoma haematobium a ete detectee chez 287 des 3514 ecoliers (prevalence ajustee: 8,76%; etendue entre les postessentinelles: 0,0-56,3%; moyenne: 2,5%). La prevalence de l'infection a la Schistosoma haematobium etait plus elevee chez les enfants des regions Centre-Est, Est et du Sahel que chez les enfants des huit autres regions du Burkina Faso comprenant des postes-sentinelles (P Conclusion Grace a un recours massif a la chimiotherapie preventive, le Burkina Faso a peut-etre eradique la schistosomiase en tant que probleme de sante publique dans huit regions et endigue la morbidite liee a la schistosomiase dans trois autres regions. Objetivo Evaluar el efecto de una decada de administracion bienal de praziquantel en masa para la esquistosomiasis en los ninos en edad escolar de Burkina Faso. Metodos En 2013, en una evaluacion nacional basada en 22 sitios centinela, se examino a 3 514 alumnos de entre 7 y 11 anos para saber si estaban infectados por Schistosoma haematobium y Schistosoma mansoni mediante un examen de muestras de orina y heces, respectivamente. Se analizo la prevalencia e intensidad observadas de las infecciones y se compararon con los resultados relevantes de examenes anteriores en Burkina Faso. Resultados Se encontro S. haematobium en 287/3 514 alumnos (prevalencia ajustada: 8,76%, rango entre sitios centinela: 0,0-56,3%; mediana: 2,5%). La prevalencia de la infeccion por S. haematobium era mayor en los ninos de las regiones Centro-Este, Este y del Sahel que en los ninos de las otras ocho regiones con sitios centinela de Burkina Faso (P< 0,001). La intensidad aritmetica ajustada media de la infeccion por S. haematobium, entre todos los ninos, era de 6,0 huevos por cada 10 mi de orina. Menos del 1 % de los ninos en seis regiones sufria de infecciones fuertes por 5. haematobium (es decir, al menos 50 huevos por 10 mi de orina), pero se detectaron tales infecciones en un 8,75% (28/320) y un 11,56% (37/320) de los ninos del Centro-Este y de las regiones del Sahel, respectivamente. Solo se detecto Schistosoma mansonien dos regiones y 43 ninos, es decir, 1 (0,31%) de los 320 del Centro-Sur y 42 (8,75%) de los 480 de las altas cuencas. Conclusion Gracias al uso masivo de quimioterapia preventiva, Burkina Faso puede haber eliminado la esquistosomiasis como un problema de salud publica en ocho regiones y controlado la morbilidad relacionada con la esquistosomiasis en otras tres regiones., Introduction Human schistosomiasis is endemic in 78 countries or territories. (1,2) It has been estimated that, in 2013, there were nearly 261 million people--including about 240 million in Africa--who required [...]

Purpose There is an urgent need to develop diagnostic tests to improve the detection of pathogens causing life-threatening infection (sepsis). SeptiFast is a CE-marked multi-pathogen real-time PCR system capable of detecting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here a systematic review and meta-analysis of diagnostic accuracy studies of SeptiFast in the setting of suspected sepsis. Methods A comprehensive search strategy was developed to identify studies that compared SeptiFast with blood culture in suspected sepsis. Methodological quality was assessed using QUADAS. Heterogeneity of studies was investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in receiver operator characteristic space. Bivariate model method was used to estimate summary sensitivity and specificity. Results From 41 phase III diagnostic accuracy studies, summary sensitivity and specificity for SeptiFast compared with blood culture were 0.68 (95 % CI 0.63-0.73) and 0.86 (95 % CI 0.84-0.89) respectively. Study quality was judged to be variable with important deficiencies overall in design and reporting that could impact on derived diagnostic accuracy metrics. Conclusions SeptiFast appears to have higher specificity than sensitivity, but deficiencies in study quality are likely to render this body of work unreliable. Based on the evidence presented here, it remains difficult to make firm recommendations about the likely clinical utility of SeptiFast in the setting of suspected sepsis., Author(s): Paul Dark [sup.1] [sup.2] [sup.3], Bronagh Blackwood [sup.4], Simon Gates [sup.5], Danny McAuley [sup.4], Gavin D. Perkins [sup.5] [sup.6], Ronan McMullan [sup.7], Claire Wilson [sup.1] [sup.3], Daniel Graham [sup.1] [...]