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Host Genetic Susceptibility to Enteric Viruses: A Systematic Review and Metaanalysis.

ABSTRACT: Norovirus and rotavirus are prominent enteric viruses responsible for severe acute gastroenteritis disease burden around the world. Both viruses recognize and bind to histo-blood group antigens, which are expressed by the fucosyltransferase 2 (FUT2) gene. Individuals with a functional FUT2 gene are termed "secretors." FUT2 polymorphisms may influence viral binding patterns and, therefore, may influence host susceptibility to infection by these viruses.We performed a systematic review of the published literature on this topic. Data were abstracted and compiled for descriptive analyses and metaanalyses. We estimated pooled odds ratios (ORs) for infection using random-effects models.We found that secretors were 9.9 times (95% confidence interval [CI], 3.9-24.8) as likely to be infected with genogroup II.4 noroviruses and 2.2 times as likely to be infected with genogroup II non-4 noroviruses (95% CI, 1.2-4.2) compared with nonsecretors. Secretors were also 26.6 times more susceptible to infections from P[8]-type rotaviruses compared with nonsecretors (95% CI, 8.3-85.0).Our analyses indicate that host genetic susceptibility to norovirus and rotavirus infection may be strain specific. As strain distribution and the proportion of genetic phenotypes vary in different countries, future studies should focus on differences in susceptibility among various ethnicities. Knowledge of innate susceptibility to rotavirus and norovirus can lead to improved understanding of both vaccine performance and individual risk of disease.

SUBMITTER: Kambhampati A

PROVIDER: S-EPMC4679673 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Host Genetic Susceptibility to Enteric Viruses: A Systematic Review and Metaanalysis.

Kambhampati Anita A Payne Daniel C DC Costantini Veronica V Lopman Benjamin A BA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20151026 1

<h4>Background</h4>Norovirus and rotavirus are prominent enteric viruses responsible for severe acute gastroenteritis disease burden around the world. Both viruses recognize and bind to histo-blood group antigens, which are expressed by the fucosyltransferase 2 (FUT2) gene. Individuals with a functional FUT2 gene are termed "secretors." FUT2 polymorphisms may influence viral binding patterns and, therefore, may influence host susceptibility to infection by these viruses.<h4>Methods</h4>We perfor ...[more]

PMID: 26508510

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Project description:BACKGROUND:The recent SARS-CoV-2 pandemic raises many scientific and clinical questions. One set of questions involves host genetic factors that may affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work has been conducted on other coronaviruses that affect different species. OBJECTIVES:We aimed to review the literature on host genetic factors related to coronaviruses, with a systematic focus on human studies. METHODS:We conducted a PubMed-based search and analysis for articles relevant to host genetic factors in coronavirus. We categorized articles, summarized themes related to animal studies, and extracted data from human studies for analyses. RESULTS:We identified 1,187 articles of potential relevance. Forty-five studies were related to human host genetic factors related to coronavirus, of which 35 involved analysis of specific genes or loci; aside from one meta-analysis on respiratory infections, all were candidate-driven studies, typically investigating small number of research subjects and loci. Multiple significant loci were identified, including 16 related to susceptibility to coronavirus (of which 7 identified protective alleles), and 16 related to outcomes or clinical variables (of which 3 identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Of the other studies, 28 involved both human and non-human host genetic factors related to coronavirus, 174 involved study of non-human (animal) host genetic factors related to coronavirus, 584 involved study of non-genetic host factors related to coronavirus, including involving immunopathogenesis, 16 involved study of other pathogens (not coronavirus), 321 involved other studies of coronavirus, and 18 studies were assigned to the other categories and removed. KEY FINDINGS:We have outlined key genes and loci from animal and human host genetic studies that may bear investigation in the nascent host genetic factor studies of COVID-19. Previous human studies to date have been limited by issues that may be less impactful on current endeavors, including relatively low numbers of eligible participants and limited availability of advanced genomic methods.

Project description:Viruses, which are transmitted mainly via the digestive tract, are responsible for the high morbidity and mortality of diseases, particularly in low-income countries. Although several studies have established the prevalence and characterization of various enteric viruses in Burkina Faso, to date, no aggregate data have been released. Our objective was to describe the available data on the prevalence and circulating genotypes of enteric pathogen viruses responsible for human infections in Burkina Faso by carrying out a systematic review and meta-analysis. Potentially relevant studies were identified by a search of PubMed, ScienceDirect, Google Scholar, university libraries and by a manual search of the reference lists of identified studies. The search with no restrictions on language or age was limited to studies conducted only in Burkina. Study selection, data extraction, and methodological quality of the included studies were performed independently by two investigators. Heterogeneity between studies was assessed using the Cochrane Q test and I2 test statistics based on the random effects model. Comprehensive meta-analysis (CMA 3.7) was employed to compute the pooled prevalence of pathogens identified in the studies. Forty-three (43) studies reporting 4,214 diagnosed cases in all aged human populations were selected. Overall, 72.6% of the pathogens diagnosed were gastroenteritis, and 27.2% were entero-transmissible hepatitis viruses. Rotavirus was the most common cause of human viral gastroenteritis, accounting for 27.7% (95% CI: 20.9 - 35.8) of the cases, followed by norovirus (16% (95% CI: 12.25 - 20.6)) and sapovirus (11.2% (95% CI: 6.2 - 19.4)). In terms of human entero-transmissible infections, hepatitis A virus (HAV) was the most prevalent (52% [95% CI: 14.2-87.7] of total antibodies), followed by hepatitis E virus (HEV) (28.3% [95% CI: 17.7-42]). This study highlights the substantial burden of viral enteric infections and highlights the need for more molecular epidemiological studies to improve preventive measures against these viruses.

Project description:RationaleExtracorporeal life support (ECLS) for acute respiratory failure has increased as a result of technological advancements and promising results from recent studies as compared with historical trials.ObjectivesSystematically review the effect of ECLS compared with mechanical ventilation on mortality, length of stay, and adverse events in respiratory failure.MethodsData sources included were MEDLINE, EMBASE, and CENTRAL (through to October 2013). Any randomized controlled trial (RCT) or observational study comparing ECLS to mechanical ventilation in adults was used. Two authors independently abstracted the data. Our primary outcome was mortality. Secondary outcomes included intensive care unit length of stay, hospital length of stay, and adverse events. A sensitivity analysis was performed restricted to RCTs and quasi-RCTs, and a number of predefined subgroups were identified to explore heterogeneity.Measurements and main resultsTen studies (four RCTs, six observational studies, 1,248 patients) were included. There was no significant difference in hospital mortality with ECLS as compared with mechanical ventilation (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.79-1.33; I(2) = 77%). When restricted to venovenous ECLS studies of randomized trials and quasi-randomized trials (three studies; 504 patients), there was a decrease in mortality with ECLS compared with mechanical ventilation (RR, 0.64; 95% CI, 0.51-0.79; I(2) = 15%). There were insufficient study-level data to evaluate most secondary outcomes. Bleeding was significantly greater in the ECLS group (RR, 11.44; 95% CI, 3.11-42.06; I(2) = 0%). In the H1N1 subgroup (three studies; 364 patients), ECLS was associated with significantly lower hospital mortality (RR, 0.62; 95% CI, 0.45-0.8; I(2) = 25%).ConclusionsECLS was not associated with a mortality benefit in patients with acute respiratory failure. However, a significant mortality benefit was seen when restricted to higher-quality studies of venovenous ECLS. Patients with H1N1-acute respiratory distress syndrome represent a subgroup that may benefit from ECLS. Future studies are needed to confirm the efficacy of ECLS as well as the optimal configuration, indications, and timing for adult patients with respiratory failure.

Dataset Information

Host Genetic Susceptibility to Enteric Viruses: A Systematic Review and Metaanalysis.

Publications

Host Genetic Susceptibility to Enteric Viruses: A Systematic Review and Metaanalysis.

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