title: Negative pretransplant serostatus for Toxoplasma gondii is associated with impaired survival after heart transplantation.
abstract: Chronic Toxoplasma gondii infection is known to trigger potentially adverse immunoregulatory changes, but limited data exist on long-term implications for heart transplant (HTX) recipients. We evaluated the risk of all cause mortality regarding T. gondii serostatus prior to HTX. Pre-HTX T. gondii serostatus was obtained in 344 recipients and 294 donors. Mean age was 52.1 +/- 10.2 years and mean follow-up time after HTX was 5.7 (+/-5.5, median 3.5) years. All seronegative patients received prophylaxis with pyrimethamine/sulfomethoxazole or cotrimoxazol for 6 months after transplantation. Multivariate survival analysis adjusted for diabetes mellitus, pre-HTX renal function, recipient age, type of primary immunosuppression (i.e. HTX before 2001), cytomegalovirus (CMV) high-risk status, ischemic time, and number of treated rejection episodes was performed. Overall, 190 recipients (55.2% of total) were seronegative and 154 (44.8% of total) were seropositive for T. gondii prior to HTX. One hundred and fifty-two recipients died during follow-up (44.2% of total). Negative recipient Toxoplasma serostatus was associated with a significantly higher risk of all-cause mortality (P = 0.0213). Recipient T. gondii serostatus did not influence the number of cellular or humoral rejection episodes. Analyses of specific causes of death showed a trend toward a higher number of infection-related deaths in the seronegative subgroup (P = 0.13). No statistically significant effects of T. gondii donor/recipient seropairing, or seroconversion were observed. Negative preoperative serostatus for T. gondii in HTX recipients appears to be an independent risk factor associated with increased all-cause mortality. The cause of impaired survival in Toxoplasma seronegative recipients is currently unclear; possible explanations include an alteration of immune-reactivity/-regulation or adverse effects of prophylactic medication.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. andreas.doesch@med.uni-heidelberg.de
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ammon
authors.forename: Mathias
authors.initials: M
authors.lastname: Konstandin
authors.forename: Sultan
authors.initials: S
authors.lastname: Celik
authors.forename: Arnt
authors.initials: A
authors.lastname: Kristen
authors.forename: Lutz
authors.initials: L
authors.lastname: Frankenstein
authors.forename: Susanne
authors.initials: S
authors.lastname: Müller
authors.forename: Falk-Udo
authors.initials: FU
authors.lastname: Sack
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dengler
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000150:complications / Q000628:therapy; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D057234:Preoperative Period; D016016:Proportional Hazards Models; D014122:Toxoplasma / Q000378:metabolism*; D014123:Toxoplasmosis / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D018664:Interleukin-12; D007371:Interferon-gamma