Predicting high risk for human hantavirus infections, Sweden.
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ABSTRACT:
SUBMITTER: Olsson GE
PROVIDER: S-EPMC2660694 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hantavirus pulmonary syndrome (HPS) is a human disease caused by a newly identified hantavirus, which we will refer to as Four Corners virus (FCV). FCV is related most closely to Puumala virus (PUU) and to Prospect Hill virus (PHV). Twenty-five acute HPS serum samples were tested for immunoglobulin G (IgG) and IgM antibody reactivities to FCV-encoded recombinant proteins in Western blot (immunoblot) assays. All HPS serum samples contained both IgG and IgM antibodies to the FCV nucleocapsid (N) protein. FCV N antibodies cross-reacted with PUU N and PHV N proteins. A dominant FCV N epitope was mapped to the segment between amino acids 17 and 59 (QLVTARQKLKDAERAVELDPDDVNKSTLQSRRAAVSALETKLG). All HPS serum samples contained IgG antibodies to the FCV glycoprotein-1 (G1) protein, and 21 of 25 serum samples contained FCV G1 IgM antibodies. The FCV G1 antibodies did not cross-react with PUU G1 and PHV G1 proteins. The FCV G1 type-specific antibody reactivity mapped to a segment between amino acids 59 and 89 (LKIESSCNFDLHVPATTTQKYNQVDWTKKSS). One hundred twenty-eight control serum samples were tested for IgG reactivities to the FCV N and G1 proteins. Nine (7.0%) contained FCV N reactivities, 3 (2.3%) contained FCV G1 reactivities, and one (0.8%) contained both FCV N and FCV G1 reactivities. The epitopes recognized by antibodies present in control serum samples were different from the epitopes recognized by HPS antibodies, suggesting that the control antibody reactivities were unrelated to FCV infections. These reagents constitute a type-specific assay for FCV antibodies.
| S-EPMC236790 | biostudies-other
Project description:Hantaviruses are members of the Bunyaviridae family carried by small mammals and causing human hemorrhagic fevers worldwide. In Western Africa, where a variety of hemorrhagic fever viruses occurs, indigenous hantaviruses have been molecularly found in animal reservoirs such as rodents, shrews, and bats since 2006. To investigate the human contact to hantaviruses carried by these hosts and to assess the public health relevance of hantaviruses for humans living in the tropical rainforest regions of Western and Central Africa, we performed a cross-sectional seroprevalence study in the region of Taï National Park in Côte d'Ivoire and the Bandundu region near the Salonga National Park in the Democratic Republic (DR) of Congo. Serum samples were initially screened with enzyme-linked immunosorbent assays using nucleoproteins of several hantaviruses as diagnostic antigens. Positive results were confirmed by Western blotting and immunofluorescence testing. Seroprevalence rates of 3.9% (27/687) and 2.4% (7/295), respectively, were found in the investigated regions in Côte d'Ivoire and the DR Congo. In Côte d'Ivoire, this value was significantly higher than the seroprevalence rates previously reported from the neighboring country Guinea as well as from South Africa. Our study indicates an exposure of humans to hantaviruses in West and Central African tropical rainforest areas. In order to pinpoint the possible existence and frequency of clinical disease caused by hantaviruses in this region of the world, systematic investigations of patients with fever and renal or respiratory symptoms are required.
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Project description:BackgroundThe risk of incident high-risk human papillomavirus (HR-HPV) infection associated with recent sexual behaviors is undefined in mid-adult women (defined as women aged 25-65 years).MethodsTriannually, 420 female online daters aged 25-65 years submitted vaginal specimens for HPV testing and completed health and sexual behavior questionnaires. The cumulative incidence of and risk factors for incident HR-HPV detection were estimated by Kaplan-Meier and Cox proportional hazards methods.ResultsThe 12-month cumulative incidence of HR-HPV detection was 25.4% (95% confidence interval [CI], 21.3%-30.1%). Current hormonal contraceptive use was positively associated with incident HR-HPV detection. Lifetime number of male sex partners was also positively associated but only among women not recently sexually active with male partners. In analysis that adjusted for hormonal contraceptive use and marital status, women reporting multiple male partners or male partners who were new, casual, or had ≥1 concurrent partnership had a hazard of incident HR-HPV detection that was 2.81 times (95% CI, 1.38-5.69 times) that for women who reported no male sex partners in the past 6 months. Thus, among women with multiple male partners or male partners who were new, casual, or had ≥1 concurrent partnership, approximately 64% of incident HR-HPV infections were attributable to one of those partners.ConclusionsAmong high-risk mid-adult women with recent new male partners, multiple male partners, or male partners who were casual or had ≥1 concurrent partnership, about two thirds of incident HR-HPV detections are likely new acquisitions, whereas about one third of cases are likely redetections of prior infections.
| S-EPMC4978366 | biostudies-literature
Project description:Natural reservoirs of zoonotic pathogens generally seem to be capable of tolerating infections. Tolerance and its underlying mechanisms remain difficult to assess using experiments or wildlife surveys. High-throughput sequencing technologies give the opportunity to investigate the genetic bases of tolerance, and the variability of its mechanisms in natural populations. In particular, population genomics may provide preliminary insights into the genes shaping tolerance and potentially influencing epidemiological dynamics. Here, we addressed these questions in the bank vole Myodes glareolus, the specific asymptomatic reservoir host of Puumala hantavirus (PUUV), which causes nephropathia epidemica (NE) in humans. Despite the continuous spatial distribution of M. glareolus in Sweden, NE is endemic to the northern part of the country. Northern bank vole populations in Sweden might exhibit tolerance strategies as a result of coadaptation with PUUV. This may favor the circulation and maintenance of PUUV and lead to high spatial risk of NE in northern Sweden. We performed a genome-scan study to detect signatures of selection potentially correlated with spatial variations in tolerance to PUUV. We analyzed six bank vole populations from Sweden, sampled from northern NE-endemic to southern NE-free areas. We combined candidate gene analyses (Tlr4, Tlr7, and Mx2 genes) and high-throughput sequencing of restriction site-associated DNA (RAD) markers. Outlier loci showed high levels of genetic differentiation and significant associations with environmental data including variations in the regional number of NE human cases. Among the 108 outliers that matched to mouse protein-coding genes, 14 corresponded to immune-related genes. The main biological pathways found to be significantly enriched corresponded to immune processes and responses to hantavirus, including the regulation of cytokine productions, TLR cascades, and IL-7, VEGF, and JAK-STAT signaling. In the future, genome-scan replicates and functional experimentations should enable to assess the role of these biological pathways in M. glareolus tolerance to PUUV.
| S-EPMC6262921 | biostudies-literature
Project description:With the current climate change crisis and its influence on infectious disease transmission there is an increased desire to understand its impact on infectious diseases globally. Hantaviruses are found worldwide, causing infectious diseases such as haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS)/hantavirus pulmonary syndrome (HPS) in tropical regions such as Latin America and the Caribbean (LAC). These regions are inherently vulnerable to climate change impacts, infectious disease outbreaks and natural disasters. Hantaviruses are zoonotic viruses present in multiple rodent hosts resident in Neotropical ecosystems within LAC and are involved in hantavirus transmission. We conducted a systematic review to assess the association of climatic factors with human hantavirus infections in the LAC region. Literature searches were conducted on MEDLINE and Web of Science databases for published studies according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. The inclusion criteria included at least eight human hantavirus cases, at least one climatic factor and study from > 1 LAC geographical location. In total, 383 papers were identified within the search criteria, but 13 studies met the inclusion criteria ranging from Brazil, Chile, Argentina, Bolivia and Panama in Latin America and a single study from Barbados in the Caribbean. Multiple mathematical models were utilized in the selected studies with varying power to generate robust risk and case estimates of human hantavirus infections linked to climatic factors. Strong evidence of hantavirus disease association with precipitation and habitat type factors were observed, but mixed evidence was observed for temperature and humidity. The interaction of climate and hantavirus diseases in LAC is likely complex due to the unknown identity of all vertebrate host reservoirs, circulation of multiple hantavirus strains, agricultural practices, climatic changes and challenged public health systems. There is an increasing need for more detailed systematic research on the influence of climate and other co-related social, abiotic, and biotic factors on infectious diseases in LAC to understand the complexity of vector-borne disease transmission in the Neotropics.
| S-EPMC8778283 | biostudies-literature
Project description:BackgroundPuumala virus (PUUV) is the most important hantavirus species in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute renal injury (AKI) with thrombocytopenia and frequently gastrointestinal symptoms.Methods456 patients with serologically and clinically confirmed NE were investigated at time of follow-up in a single clinic. The course of the NE was investigated using medical reports. We identified patients who had endoscopy with intestinal biopsy during acute phase of NE. Histopathological, immunohistochemical and molecular analyses of the biopsies were performed.ResultsThirteen patients underwent colonoscopy or gastroscopy for abdominal pain, diarrhea, nausea and vomiting during acute phase of NE. Immunohistochemistry (IHC) revealed PUUV nucleocapsid antigen in 11 biopsies from 8 patients; 14 biopsies from 5 patients were negative for PUUV nucleocapsid antigen. IHC localized PUUV nucleocapsid antigen in endothelial cells of capillaries or larger vessels in the lamina propria. Rate of AKI was not higher and severity of AKI was not different in the PUUV-positive compared to the PUUV-negative group. All IHC positive biopsies were positive for PUUV RNA using RT-PCR. Phylogenetic reconstruction revealed clustering of all PUUV strains from this study with viruses previously detected from the South-West of Germany. Long-term outcome was favorable in both groups.ConclusionsIn patients with NE, PUUV nucleocapsid antigen and PUUV RNA was detected frequently in the intestine. This finding could explain frequent GI-symptoms in NE patients, thus demonstration of a more generalized PUUV infection. The RT-PCR was an effective and sensitive method to detect PUUV RNA in FFPE tissues. Therefore, it can be used as a diagnostic and phylogenetic approach also for archival materials. AKI was not more often present in patients with PUUV-positive IHC. This last finding should be investigated in larger numbers of patients with PUUV infection.
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Project description:We investigated whether chloroquine can prevent hantavirus infection and disease in vitro and in vivo, using the Hantaan virus newborn C57BL/6 mice model and the Syrian hamster model for Andes virus. In vitro antiviral experiments were performed using Vero E6 cells, and Old World and New World hantavirus species. Hantavirus RNA was detected using quantitative RT-PCR. For all hantavirus species tested, results indicate that the IC50 of chloroquine (mean 10.2 ± 1.43 μM) is significantly lower than the CC50 (mean 260 ± 2.52 μM) yielding an overall selectivity index of 25.5. We also investigated the potential of chloroquine to prevent death in newborn mice after Hantaan virus infection and its antiviral effect in the hantavirus Syrian hamster model. For this purpose, C57Bl/6 mother mice were treated subcutaneously with daily doses of chloroquine. Subsequently, 1-day-old suckling mice were inoculated intracerebrally with 5 x 102 Hantaan virus particles. In litters of untreated mothers, none of the pups survived challenge. The highest survival rate (72.7% of pups) was found when mother mice were administered a concentration of 10 mg/kg chloroquine. Survival rates declined in a dose-dependent manner, with 47.6% survival when treated with 5 mg/kg chloroquine, and 4.2% when treated with 1 mg/kg chloroquine. Assessing the antiviral therapeutic and prophylactic effect of chloroquine in the Syrian hamster model was done using two different administration routes (intraperitoneally and subcutaneously using an osmotic pump system). Evaluating the prophylactic effect, a delay in onset of disease was noted and for the osmotic pump, 60% survival was observed. Our results show that chloroquine can be highly effective against Hantaan virus infection in newborn mice and against Andes virus in Syrian hamsters.
| S-EPMC8006394 | biostudies-literature
Project description:West Nile virus (WNV) has become established across the Americas with recent heightened activity causing significant human illness. Surveillance methods to predict the risk of human infection are urgently needed to initiate timely preventative measures and justify the expense of implementing costly or unpopular control measures, such as aerial spraying or curfews. We quantified the links between mosquito surveillance data and the spatiotemporal patterns of 3,827 human WNV cases reported over 5 years in Colorado from 2003 to 2007. Mosquito data were strongly predictive of variation in the number of human WNV infections several weeks in advance in both a spatiotemporal statewide analysis and temporal variation within counties with substantial numbers of human cases. We outline several ways to further improve the predictive power of these data and we quantify the loss of information if no funds are available for testing mosquitoes for WNV. These results demonstrate that mosquito surveillance provides a valuable public health tool for assessing the risk of human arboviral infections, allocating limited public health resources, and justifying emergency control actions.
| S-EPMC3755645 | biostudies-literature
Project description:BackgroundTick-borne diseases have become increasingly common in recent decades and present a health problem in many parts of Europe. Control and prevention of these diseases require a better understanding of vector distribution.AimOur aim was to create a model able to predict the distribution of Ixodes ricinus nymphs in southern Scandinavia and to assess how this relates to risk of human exposure.MethodsWe measured the presence of I. ricinus tick nymphs at 159 stratified random lowland forest and meadow sites in Denmark, Norway and Sweden by dragging 400?m transects from August to September 2016, representing a total distance of 63.6 km. Using climate and remote sensing environmental data and boosted regression tree modelling, we predicted the overall spatial distribution of I. ricinus nymphs in Scandinavia. To assess the potential public health impact, we combined the predicted tick distribution with human density maps to determine the proportion of people at risk.ResultsOur model predicted the spatial distribution of I. ricinus nymphs with a sensitivity of 91% and a specificity of 60%. Temperature was one of the main drivers in the model followed by vegetation cover. Nymphs were restricted to only 17.5% of the modelled area but, respectively, 73.5%, 67.1% and 78.8% of the human populations lived within 5?km of these areas in Denmark, Norway and Sweden.ConclusionThe model suggests that increasing temperatures in the future may expand tick distribution geographically in northern Europe, but this may only affect a small additional proportion of the human population.
| S-EPMC6402176 | biostudies-literature
Project description:Background:The lethality of endometrioid endometrial cancer (EEC) is primarily attributable to advanced-stage diseases. We sought to develop a biomarker model that predicts EEC surgical stage at the time of clinical diagnosis. Results:PSES was significantly correlated with surgical stage in the TCGA cohort (P < 0.0001) and in the validation cohort (P = 0.0003). Even among grade 1 or 2 tumors, PSES was significantly higher in advanced than in early stage tumors in both the TCGA (P = 0.005) and MD Anderson Cancer Center (MDACC) (P = 0.006) cohorts. Patients with positive PSES score had significantly shorter progression-free survival than those with negative PSES in the TCGA (hazard ratio [HR], 2.033; 95% CI, 1.031 to 3.809; P = 0.04) and validation (HR, 3.306; 95% CI, 1.836 to 9.436; P = 0.0007) cohorts. The ErbB signaling pathway was most significantly enriched in the PSES proteins and downregulated in advanced stage tumors. Methods:Using reverse-phase protein array expression profiles of 170 antibodies for 210 EEC cases from TCGA, we constructed a Protein Scoring of EEC Staging (PSES) scheme comprising 6 proteins (3 of them phosphorylated) for surgical stage prediction. We validated and evaluated its diagnostic potential in an independent cohort of 184 EEC cases obtained at MDACC using receiver operating characteristic curve analyses. Kaplan-Meier survival analysis was used to examine the association of PSES score with patient outcome, and Ingenuity pathway analysis was used to identify relevant signaling pathways. Two-sided statistical tests were used. Conclusions:PSES may provide clinically useful prediction of high-risk tumors and offer new insights into tumor biology in EEC.
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