Sex as a risk factor for occurrence and severity of infectious and parasitic diseases in dogs: Protocol for a systematic review.

Biological sex is an important risk factor for the occurrence and severity of infectious and parasitic diseases. Although various studies and reviews have described sex differences in infectious diseases of humans, wildlife and laboratory animals, there has been little focus on biological sex as a risk factor for infectious and parasitic diseases of domestic animals. We aim to identify and synthesise evidence in dogs for the hypothesis that biological sex and gonadectomy status are determinants of occurrence and severity of disease across taxa of pathogens. This systematic review follows the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. We will search Web of Science, Scopus and PubMed for peer-reviewed studies published in English from database inception through 2021. All study designs for infectious and parasitic diseases of dogs will be included. This review will include the outcomes prevalence or incidence of infection or disease; and severity of disease as measured by case-fatality, time to death or recovery, hospitalisation time, pathogen burden (e.g. viral load or parasitaemia) or relevant clinicopathological parameters. Two reviewers will jointly assess the first 500 records from all three databases. Subsequently, one reviewer will screen the remaining records, and then the second reviewer will verify all records excluded by the first reviewer. Full-texts of all included records will be retrieved and assessed for eligibility by the first review author, and then the second author will review those records excluded by the first author. The risk of bias in individual studies will be assessed using the Risk of Bias Assessment tool for Nonrandomized Studies. We will synthesise the information from the studies and present this as a narrative in the text. The findings will be presented by outcome type and also grouped by pathogen type. Evidence on sex-specific effects will expand our understanding of infectious disease pathogenesis and underlying mechanisms, and this may be of importance in implementation of disease control interventions.