Potential risk factors associated with human alveolar echinococcosis: Systematic review and meta-analysis

<div><p>Background</p><p>Human alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of <i>Echinococcus multilocularis</i>. AE is commonly associated with a long incubation period that may last for more than ten years. The objective of this systematic literature review was to identify and summarize the current knowledge on statistically relevant potential risk factors (PRFs) associated with AE in humans.</p><p>Methodology/Principal findings</p><p>Six bibliographic databases were searched, generating a total of 1,009 publications. Following the removal of duplicate records and the exclusion of papers that failed to meet the criteria of a previously agreed <i>a priori</i> protocol, 23 publications were retained; however, 6 of these did not contain data in a format that allowed their inclusion in the meta-analysis. The remaining 17 publications (6 case-control and 11 cross-sectional studies) were meta-analysed to investigate associations between AE and PRFs. Pooled odds ratios (OR) were used as a measure of effect and separately analysed for case-control and cross-sectional studies. In the case-control studies, the following PRFs for human AE showed higher odds of outcome: “dog ownership”, “cat ownership”, “have a kitchen garden”, “occupation: farmer”, “haymaking in meadows not adjacent to water”, “went to forests for vocational reasons”, “chewed grass” and “hunting / handling foxes”. In the cross-sectional studies, the following PRFs showed higher odds of outcome: “dog ownership”, “play with dogs”, “gender: female”, “age over 20 years”, “ethnic group: Tibetan”, “low income”, “source of drinking water other than well or tap”, “occupation: herding” and “low education”. Our meta-analysis confirmed that the chance of AE transmission through ingestion of food and water contaminated with <i>E</i>. <i>multilocularis</i> eggs exists, but showed also that food- and water-borne PRFs do not significantly increase the risk of infection.</p><p>Conclusions/significance</p><p>This systematic review analysed international peer-reviewed articles that have over the years contributed to our current understanding of the epidemiology of human AE. The identification of potential risk factors may help researchers and decision makers improve surveillance and/or preventive measures that aim at decreasing human infection with <i>E</i>. <i>multilocularis</i>. More primary studies are needed to confirm potential risk factors and their role in the epidemiology of human AE.</p></div

Estimated test accuracies for <i>E. multilocularis</i> and <i>E. granulosus</i>.

<p>Estimated test accuracies (posterior means) for <i>E. multilocularis</i> and <i>E. granulosus</i> and their 95% credibility intervals in the final model with <i>Taenia</i> co-infection as a covariate on prevalence.</p

Effect of <i>Taenia</i> co-infection on prevalence of <i>E. multilocularis.</i>

<p>Using a Bayesian latent-class model, prevalence of <i>E. multilocularis</i> in <i>Taenia</i> test-negative dogs was estimated at 12.2% (95% credible intervals 7.6–18.9%), and in <i>Taenia</i> test-positive dogs was estimated at 22.3 (95% credible intervals 8.2–47.7%). <i>Taenia</i> co-infection was found to be a significant covariate with <i>E. multilocularis</i> infection (odds ratio 2.06, 95% credible intervals 1.07–3.9). In the figure the posterior distributions of the prevalence of <i>E. multilocularis</i> with (blue) and without (red) <i>Taenia</i> co-infection are shown.</p

Key findings on the highly statistically significant (p<0.01) potential risk factors associated with human cystic echinococcosis (CE) derived from the meta-analysis of case-control (C-c) and cross-sectional (C-s) studies.

<p>In blue: possible vertical and horizontal interventions aimed at decreasing or interrupting the transmission of CE to humans.</p

Analysis of factors associated with seropositivity to <i>E. granulosus</i> in inhabitants of the Limarí province.

<p>Analyses were carried out with Fisher exact test. p<0.1 was considered significant.</p><p>Analysis of factors associated with seropositivity to <i>E. granulosus</i> in inhabitants of the Limarí province.</p

Meta-analysis of potential and protective risk factors identified in case-control studies on human alveolar echinococcosis.

<p>Meta-analysis of potential and protective risk factors identified in case-control studies on human alveolar echinococcosis.</p

Estimated test accuracies with specificities of copro-PCR alone or with purge fixed to 1.

<p>Estimated test accuracies (posterior means) for <i>E. multilocularis</i> and <i>E. granulosus</i> and their 95% credibility intervals if the specificity of the copro-PCR alone or in addition to the specificity of the purge is fixed to 1.</p