Mouse models of Japanese encephalitis virus infection: A systematic review and meta-analysis using a meta-regression approach.



Bharucha, Tehmina ORCID: 0000-0002-6772-2855, Cleary, Ben ORCID: 0000-0001-6989-3255, Farmiloe, Alice ORCID: 0000-0002-6979-4369, Sutton, Elizabeth ORCID: 0000-0001-8028-7694, Hayati, Hanifah ORCID: 0000-0002-2733-8410, Kirkwood, Peggy ORCID: 0000-0001-5809-8627, Al Hamed, Layal ORCID: 0000-0003-0059-9247, van Ginneken, Nadja, Subramaniam, Krishanthi S, Zitzmann, Nicole
et al (show 2 more authors) (2022) Mouse models of Japanese encephalitis virus infection: A systematic review and meta-analysis using a meta-regression approach. PLoS neglected tropical diseases, 16 (2). e0010116 - ?.

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Abstract

<h4>Background</h4>Japanese encephalitis (JE) virus (JEV) remains a leading cause of neurological infection across Asia. The high lethality of disease and absence of effective therapies mean that standardised animal models will be crucial in developing therapeutics. However, published mouse models are heterogeneous. We performed a systematic review, meta-analysis and meta-regression of published JEV mouse experiments to investigate the variation in model parameters, assess homogeneity and test the relationship of key variables against mortality.<h4>Methodology/ principal findings</h4>A PubMed search was performed up to August 2020. 1991 publications were identified, of which 127 met inclusion criteria, with data for 5026 individual mice across 487 experimental groups. Quality assessment was performed using a modified CAMARADES criteria and demonstrated incomplete reporting with a median quality score of 10/17. The pooled estimate of mortality in mice after JEV challenge was 64.7% (95% confidence interval 60.9 to 68.3) with substantial heterogeneity between experimental groups (I^2 70.1%, df 486). Using meta-regression to identify key moderators, a refined dataset was used to model outcome dependent on five variables: mouse age, mouse strain, virus strain, virus dose (in log10PFU) and route of inoculation. The final model reduced the heterogeneity substantially (I^2 38.9, df 265), explaining 54% of the variability.<h4>Conclusion/ significance</h4>This is the first systematic review of mouse models of JEV infection. Better adherence to CAMARADES guidelines may reduce bias and variability of reporting. In particular, sample size calculations were notably absent. We report that mouse age, mouse strain, virus strain, virus dose and route of inoculation account for much, though not all, of the variation in mortality. This dataset is available for researchers to access and use as a guideline for JEV mouse experiments.

Item Type: Article
Uncontrolled Keywords: Animals, Humans, Mice, Encephalitis Virus, Japanese, Encephalitis, Japanese, Disease Models, Animal
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 05 Apr 2022 15:21
Last Modified: 05 Oct 2022 20:11
DOI: 10.1371/journal.pntd.0010116
Open Access URL: https://doi.org/10.1371/journal.pntd.0010116
URI: https://livrepository.liverpool.ac.uk/id/eprint/3152183