Abstract
BACKGROUND: Some common infections are associated with poorer age-related health outcomes; however, findings are limited to a small number of pathogens and frequently inconclusive. This study aimed to expand the range of pathogens investigated in relation to frailty and mortality in older age. METHODS: We investigated relationships between seropositivity for 18 viruses, bacteria and protozoa with concurrent frailty and prospective mortality in middle-aged and older adults within two UK population-based cohorts: UK Biobank (N = 9427; aged 40-70 years) and Medical Research Council National Survey of Health and Development (N = 1791; aged 60-65 years). Multiplex serological assays were used to identify seropositivity for each pathogen and frailty was assessed using a frailty index measuring the accumulation of age-related health deficits. Mortality was determined from linked administrative records. RESULTS: Adjusting for sex, age, income and education, previous infection with Toxoplasma gondii ((β = 0.77%; 95% CI, 0.42-1.11) and Helicobacter pylori (0.63%; 95% CI, 0.28-0.97) were associated with higher frailty equivalent to 3.8 or 3.1 years of aging, as was inflammation-weighted pathogen burden (0.41%/SD, 95% CI, 0.25-0.57; 0.42%/SD, 95% CI, 0.26-0.58). Previous infection with Chlamydia trachomatis, human herpes simplex virus 1 and cytomegalovirus were associated with increased frailty after adjustment for sex and age, although relationships were confounded by socioeconomic circumstances. No common infections were robustly associated with mortality. CONCLUSIONS: Our results indicate that infection with H. pylori and T. gondii, and the combined burden of infection may detrimentally impact ageing health. These pathogens may warrant targeting beyond current clinical measures to mitigate the development of frailty.