In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 16, No. 2 ( 2022-2-10), p. e0010116-
Abstract:
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. Methodology/ Principal findings 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 log 10 PFU) and route of inoculation. The final model reduced the heterogeneity substantially (I^2 38.9, df 265), explaining 54% of the variability. Conclusion/ Significance 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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0010116
DOI:
10.1371/journal.pntd.0010116.g001
DOI:
10.1371/journal.pntd.0010116.g002
DOI:
10.1371/journal.pntd.0010116.g003
DOI:
10.1371/journal.pntd.0010116.g004
DOI:
10.1371/journal.pntd.0010116.g005
DOI:
10.1371/journal.pntd.0010116.g006
DOI:
10.1371/journal.pntd.0010116.g007
DOI:
10.1371/journal.pntd.0010116.g008
DOI:
10.1371/journal.pntd.0010116.g009
DOI:
10.1371/journal.pntd.0010116.t001
DOI:
10.1371/journal.pntd.0010116.t002
DOI:
10.1371/journal.pntd.0010116.s001
DOI:
10.1371/journal.pntd.0010116.s002
DOI:
10.1371/journal.pntd.0010116.s003
DOI:
10.1371/journal.pntd.0010116.s004
DOI:
10.1371/journal.pntd.0010116.s005
DOI:
10.1371/journal.pntd.0010116.s006
DOI:
10.1371/journal.pntd.0010116.s007
DOI:
10.1371/journal.pntd.0010116.s008
DOI:
10.1371/journal.pntd.0010116.s009
DOI:
10.1371/journal.pntd.0010116.s010
DOI:
10.1371/journal.pntd.0010116.s011
DOI:
10.1371/journal.pntd.0010116.r001
DOI:
10.1371/journal.pntd.0010116.r002
DOI:
10.1371/journal.pntd.0010116.r003
DOI:
10.1371/journal.pntd.0010116.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2429704-5
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