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Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (>?80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a subset of infected individuals is incompletely understood, but individual host differences including genetic factors and immune responses have been proposed. We sought to identify genetic risk factors that are associated with more severe disease outcomes for both viruses in order to shed light on possible shared mechanisms of resistance and potential therapeutic interventions. METHODS:We applied a search strategy using four major databases (Medline, PubMed, Embase, and Global Health) to find all known genetic associations identified to date with dengue or West Nile virus disease. Here we present a review of our findings and a meta-analysis of genetic variants identified. RESULTS:We found genetic variations that are significantly associated with infections of these viruses. In particular we found variation within the OAS1 (meta-OR?=?0.83, 95% CI: 0.69-1.00) and CCR5 (meta-OR?=?1.29, 95% CI: 1.08-1.53) genes is significantly associated with West Nile virus disease, while variation within MICB (meta-OR?=?2.35, 95% CI: 1.68-3.29), PLCE1 (meta-OR?=?0.55, 95% CI: 0.42-0.71), MBL2 (meta-OR?=?1.54, 95% CI: 1.02-2.31), and IFN-? (meta-OR?=?2.48, 95% CI: 1.30-4.71), is associated with dengue disease. CONCLUSIONS:Despite substantial heterogeneity in populations studied, genes examined, and methodology, significant associations with genetic variants were found across studies within both diseases. These gene associations suggest a key role for immune mechanisms in susceptibility to severe disease. Further research is needed to elucidate the role of these genes in disease pathogenesis and may reveal additional genetic factors associated with disease severity.

SUBMITTER: Cahill ME

PROVIDER: S-EPMC6014009 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis.

Cahill Megan E ME Conley Samantha S DeWan Andrew T AT Montgomery Ruth R RR

BMC infectious diseases 20180622 1

<h4>Background</h4>Dengue and West Nile viruses are highly cross-reactive and have numerous parallels in geography, potential vector host (Aedes family of mosquitoes), and initial symptoms of infection. While the vast majority (> 80%) of both dengue and West Nile virus infections result in asymptomatic infections, a minority of individuals experience symptomatic infection and an even smaller proportion develop severe disease. The mechanisms by which these infections lead to severe disease in a s ...[more]

PMID: 29929468

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Project description:BackgroundFlavivirus diseases such as dengue fever (DENV), West Nile virus (WNV), Zika and yellow fever represent a substantial global public health concern. Preexisting chronic conditions such as cardiovascular diseases, diabetes, obesity, and asthma were thought to predict risk of progression to severe infections.ObjectiveWe aimed to quantify the frequency of chronic comorbidities in flavivirus diseases to provide an estimate for their prevalence in severe and non-severe infections and examine whether chronic diseases contribute to the increased risk of severe viral expression.MethodsWe conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic and grey literature databases to identify studies reporting prevalence estimates of comorbidities in flavivirus diseases. Study quality was assessed with the risk of bias tool. Age-adjusted odds ratios (ORs) were estimated for severe infection in the presence of chronic comorbidities.ResultsWe identified 65 studies as eligible for inclusion for DENV (47 studies) and WNV (18 studies). Obesity and overweight (i.e., BMI> 25 kg/m2, prevalence: 24.5%, 95% CI: 18.6-31.6%), hypertension (17.1%, 13.3-21.8%) and diabetes (13.3%, 9.3-18.8%) were the most prevalent comorbidities in DENV. However, hypertension (45.0%, 39.1-51.0%), diabetes (24.7%, 20.2-29.8%) and heart diseases (25.6%, 19.5-32.7%) were the most prevalent in WNV. ORs of severe flavivirus diseases were about 2 to 4 in infected patients with comorbidities such as diabetes, hypertension and heart diseases. The small number of studies in JEV, YFV and Zika did not permit estimating the prevalence of comorbidities in these infections.ConclusionHigher prevalence of chronic comorbidities was found in severe cases of flavivirus diseases compared to non-severe cases. Findings of the present study may guide public health practitioners and clinicians to evaluate infection severity based on the presence of comorbidity, a critical public health measure that may avert severe disease outcome given the current dearth of clear prevention practices for some flavivirus diseases.

Project description:BACKGROUND:West Nile Virus (WNV), a member of the genus Flavivirus, is one of the most widely distributed arboviruses in the world. Despite some evidence for circulation of WNV in countries summarized by the World Health Organization as the Eastern Mediterrian Regional Office (EMRO), comprehensive knowledge about its epidemiology remains largely unknown. This study aims to provide a concise review of the published literature on WNV infections in the Eastern Mediterranean Regional Office of WHO (EMRO). METHODOLOGY/PRINCIPAL FINDINGS:A systematic review of WNV prevalence studies on humans, animals and vectors in the EMRO region was performed by searching: Web of Science, Science Direct, Scopus, PubMed, Embase and Google Scholar. Finally, 77 citations were included, comprising 35 seroprevalence studies on general population (24460 individuals), 15 prevalence studies among patients (3439 individuals), 22 seroprevalence studies among animals (10309 animals), and 9 studies on vectors (184242 vector species). Of the 22 countries in this region, five had no data on WNV infection among different populations. These countries include Kuwait, Bahrain, Oman, Syria and Somalia. On the other hand, among countries with available data, WNV-specific antibodies were detected in the general population of all investigated countries including Djibouti (0.3-60%), Egypt (1-61%), Iran (0-30%), Iraq (11.6-15.1%), Jordan (8%), Lebanon (0.5-1%), Libya (2.3%), Morocco (0-18.8%), Pakistan (0.6-65.0%), Sudan (2.2-47%), and Tunisia (4.3-31.1%). WNV RNA were also detected in patient populations of Iran (1.2%), Pakistan (33.3%), and Tunisia (5.3% -15.9%). WNV-specific antibodies were also detected in a wide range of animal species. The highest seropositivity rate was observed among equids (100% in Morocco) and dogs (96% in Morocco). The highest seroprevalence among birds was seen in Tunisia (23%). In addition, WNV infection was detected in mosquitoes (Culex, and Aedes) and ticks (Argas reflexus hermanni). The primary vector of WNV (Culex pipiens s.l.) was detected in Djibouti, Egypt, Iran and Tunisia, and in mosquitoes of all these countries, WNV was demonstrated. CONCLUSIONS:This first systematic regional assessment of WNV prevalence provides evidence to support the circulation of WNV in the EMRO region as nearly all studies showed evidence of WNV infection in human as well as animal/vector populations. These findings highlight the need for continued prevention and control strategies and the collection of epidemiologic data for WNV epidemic status, especially in countries that lack reliable surveillance systems.

Dataset Information

Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis.

Publications

Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis.

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