The Hidden Risk of Toxoplasmosis in the Expanding Immunomodulated Host Population: A Call for Guidelines and Registries in Patients on Biologics, Small Molecules, and Cellular Therapies

Targeted immunotherapies with biologics, small molecules, and CAR T-cell therapies have revolutionized treatment across autoimmune, chronic inflammatory, oncologic, and transplant-related conditions. However, they have also expanded the population of patients susceptible to opportunistic infections. Toxoplasma gondii (T. gondii), a globally prevalent parasite, has emerged as an underrecognized pathogen in this immunomodulated host population. Toxoplasmosis, in such patients, can occur either through reactivation of a chronic/latent/past infection or from an acute/primary infection and may be severe and even fatal. We present here the recommendations for such patients from the Remington Lab, the National Reference Center for Toxoplasmosis in the US. Screening for Toxoplasma infections is needed at baseline prior to starting targeted immunotherapy to identify seropositive patients who would benefit from prophylaxis or pre-emptive strategies and seronegative patients who would benefit from measures to prevent primary/acute infections. Prompt diagnosis of Toxoplasma disease (toxoplasmosis) with molecular tools (T. gondii PCR and/or agnostic metagenomics next-generation sequencing), and prompt initiation of anti-Toxoplasma therapy, can be lifesaving and prevent permanent neurocognitive sequelae and vision loss. The immunomodulatory effects of these therapies persist for several months after discontinuation, thereby extending the window of vulnerability. T. gondii-seropositive women are at increased risk of vertical transmission, even if targeted immunotherapy was discontinued several months before conception. We make a call for education, guidelines, prospective registries, targeted research, and addition of toxoplasmosis risk in the Warnings section of drug leaflets (and particularly so for T. gondii-seropositive women who intend to conceive after having been on targeted immunotherapies).