Clinical Spectrum, Radiological Findings, and Outcomes of Severe Toxoplasmosis in Immunocompetent Hosts: A Systematic Review

Abstract

Background: Accumulating evidence suggests that toxoplasmosis in immunocompetent hosts can be severe and life-threatening.

Methods: We performed a systematic review of severe toxoplasmosis cases in immunocompetent patients to gain insight into the epidemiology, clinical characteristics, radiological findings, and outcomes of these cases. We classified severe toxoplasmosis as cases with the symptomatic involvement of target organs (the lungs, central nervous system (CNS), and heart), disseminated disease, prolonged disease (>3 months), or a fatal outcome. Our primary analysis focused on cases published from 1985-2022 to avoid confounding with cases in AIDS patients.

Results: We identified 82 pertinent articles (1985-2022) with a total of 117 eligible cases; the top five countries for these cases were French Guiana (20%), France (15%), Colombia (9%), India (9%), and Brazil (7%). Overall, 44% (51/117) of cases had pulmonary involvement, 39% (46/117) CNS, 31% (36/117) cardiac, 24% (28/117) disseminated disease, 2% (2/117) had prolonged disease, and 8% (9/117) of patients died. More than one organ was involved in 26% (31/117) of cases. Eighty-four percent (98/117) of cases occurred in the context of a recent acute primary Toxoplasma infection; for the remaining, the exact timing of infection was unclear. Genotyping data were very sparse. Among those reporting genotyping data, 96% (22/23) were caused by atypical non-type II strains; one case was caused by a type-II strain. Only half of the cases reported risk factors. The most common risk factors were eating raw/undercooked meat or eating game meat (47% (28/60)), drinking untreated water (37% (22/60)), or living in a toxoplasmosis high-prevalence area (38% (23/60)). For the 51 pulmonary cases, the main clinical presentation was pneumonia or pleural effusions in 94% (48/51) and respiratory failure in 47% (24/51). For the 46 CNS cases, the main clinical presentation was encephalitis in 54% (25/46), meningitis in 13% (6/46), focal neurologic findings in 24% (11/46), cranial nerve palsies in 17% (8/46), Guillain-Barre syndrome or Miller Fisher syndrome in 7% (3/46), and Brown-Sequard syndrome in 2% (1/46) of cases; more than one clinical manifestation could also be present. Among the 41 CNS cases reporting the CNS imaging findings, 68% (28/41) had focal supratentorial lesions and 7% (3/41) had focal infratentorial lesions. Brain abscess-like/mass-like lesions were seen in 51% (21/41) of cases. For the 36 cardiac cases, the main clinical presentation was myocarditis in 75% (27/36), pericarditis in 50% (18/36), heart failure and/or cardiogenic shock in 19% (7/36), and cardiac arrhythmias in 22% (8/36); more than one manifestation could also be present. Illness was critical in 49% (44/90) of cases intensive care unit care was needed in 54% (29/54) of cases among those reporting this information, and 9 patients died.

Conclusion: The diagnosis of severe toxoplasmosis in immunocompetent hosts can be challenging. Toxoplasmosis should be considered in the differential diagnosis of immunocompetent patients presenting with severe illness of unclear etiology with pulmonary, cardiac, CNS, or multiorgan involvement/failure, or prolonged febrile illness, even in the absence of common exposure risk factors or common manifestations of toxoplasmosis (e.g., fever, mononucleosis-like illness, lymphadenopathy, and chorioretinitis). Fatal outcomes can also rarely occur in immunocompetent patients. Prompt initiation of anti-Toxoplasma treatment can be lifesaving.

Keywords: CNS toxoplasmosis; cardiac toxo-plasmosis; disseminated toxoplasmosis; fatal toxoplasmosis; immunocompetent host; pulmonary toxoplasmosis; severe toxoplasmosis.

Figure 1

Search strategy 1: (toxoplasmosis OR toxoplasma gondii OR t.gondii) AND (severe OR fatal OR lethal OR disseminated OR fulminant OR multisystem OR muti-organ OR shock) AND (immunocompetent OR non immunocompromised OR not immunocompromised OR healthy). Filters: Human. Search Date: 22 August 2022. Search strategy 2: (toxoplasmosis OR toxoplasma gondii OR t.gondii OR toxoplasm*) AND (pulmonary OR lung OR myocarditis OR myopericarditis OR encephalitis OR brain OR cerebral OR central nervous system OR intracrania* OR intra-cranial OR seizures OR mental status changes OR myelopathy OR spinal cord OR acute disseminated encephalomyelitis OR ADEM OR hemophagocytic OR hepatitis OR nephritis OR nephrotic OR myositis OR pyomyositis OR complications OR atypical OR unusual) AND (immunocompetent OR non immunocompromised OR not immunocompromised OR healthy OR without immunosupression) Filters: Human. Search Date: 22 August 2022. Search strategy 3: (toxoplasmosis OR toxoplasma gondii OR t.gondii OR toxoplasm*) AND (pulmonary OR lung OR myocarditis OR myopericarditis OR encephalitis OR brain OR cerebral OR central nervous system OR intracrania* OR intra-cranial OR seizures OR mental status changes OR myelopathy OR spinal cord OR acute disseminated encephalomyelitis OR ADEM OR hemophagocytic OR hepatitis OR nephritis OR nephrotic OR myositis OR pyomyositis OR complications OR atypical OR unusual) AND (child (ti) OR adult (ti) OR woman (ti) OR patient(ti)) Filters: Human. Search Date: 22 August 2022. Search strategy 4: ((toxoplasmosis OR toxoplasma gondii OR t.gondii OR toxoplasma*) AND (pulmon* (ti) OR chest (ti) OR cardiac(ti) OR cardio*(ti) OR intensive care(ti) OR intubat*(ti) OR respiratory failure(ti) OR respiratory support(ti) OR neurol* (ti) OR neur* (ti) OR liver(ti) OR renal(ti) OR kidney(ti))) NOT search strategy #1, OR #2 OR #3.

Figure 2

Countries where infections likely occurred (when information was missing, we imputed the country of authors, marking the country with an *).