Toxoplasma gondii IgG Serointensity Is Positively Associated With Frailty

Abstract

Background: Persistent inflammation related to aging ("inflammaging") is exacerbated by chronic infections and contributes to frailty in older adults. We hypothesized associations between Toxoplasma gondii (T. gondii), a common parasite causing an oligosymptomatic unremitting infection, and frailty, and secondarily between T. gondii and previously reported markers of immune activation in frailty.

Methods: We analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) serointensity was measured with an enzyme-linked immunosorbent assay. The Fried criteria were used to define frailty status. Validated translations of Mini-Mental State Examination, Geriatric Depression Scale, and the Charlson Comorbidity Index were used to evaluate confounders. Previously analyzed biomarkers that were significantly associated with frailty in both prior reports and the current study, and also related to T. gondii serointensity, were further accounted for in multivariable logistic models with frailty as outcome.

Results: In T. gondii-seropositives, there was a significant positive association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for multiple successive confounders. Among biomarkers linked with frailty, kynurenine/tryptophan and soluble tumor necrosis factor receptor II were positively associated with T. gondii serointensity in seropositives (p < .05). Associations with other biomarkers were not significant.

Conclusions: This first reported association between T. gondii and frailty is limited by a cross-sectional design and warrants replication. While certain biomarkers of inflammaging were associated with both T. gondii IgG serointensity and frailty, they did not fully mediate the T. gondii-frailty association.

Keywords: Chronic toxoplasmosis; Inflammaging; Kynurenine to tryptophan ratio; sTNF-RII.

Figure 1.

Members of the Felidae family are the only known definitive hosts for Toxoplasma gondii (domestic cats and their relatives). The cat’s waste contains unsporulated oocysts➊. Oocysts normally only shed for 1–3 weeks; however, they can shed in huge numbers. Oocysts take 1–5 days to sporulate in the environment and become infective. After consuming contaminated soil, water, or plant matter in nature, intermediate hosts (such as birds and rodents) get infected➋. In the digestive tract, oocysts quickly change into tachyzoites after being consumed. These tachyzoites ride dendritic cells and monocytes to settle in muscle and neural tissue, where they become tissue cyst bradyzoites➌. Cats become infected after consuming intermediate hosts harboring tissue cysts➍. Cats may also become infected directly by ingestion of sporulated oocysts, just as any warm-blooded intermediate host➎. There are several ways humans can get infected: (a) consuming raw or undercooked meat containing tissue cysts➏; (b) consuming food or water contaminated with cat excrement or by exposure to oocysts in soil or changing a cat’s litter box, in conjunction to poor hand hygiene➐; (c) organ transplantation or blood transfusion➑; and (d) devastatingly for the fetus, from the pregnant mother during gestation, transplacentally➒. The parasites create tissue cysts in the human host, most frequently in the skeletal muscle, heart, brain, and eyes; these cysts may last the entirety of the host’s life. Serology is typically used for diagnosis, though stained biopsy specimens may show tissue cysts as well➓. Toxoplasma gondii DNA in amniotic fluid can be uncovered using molecular techniques like PCR to diagnose congenital infections⓫. [Based on: https://www.cdc.gov/parasites/toxoplasmosis/biology.html (accessed on October 7, 2022)].