Negative pretransplant serostatus for Toxoplasma gondii is associated with impaired survival after heart transplantation.
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.
Doesch
Andreas O
AO
Department of Cardiology, University of Heidelberg, Heidelberg, Germany. andreas.doesch@med.uni-heidelberg.de
Ammon
Kerstin
K
Konstandin
Mathias
M
Celik
Sultan
S
Kristen
Arnt
A
Frankenstein
Lutz
L
Müller
Susanne
S
Sack
Falk-Udo
FU
Katus
Hugo A
HA
Dengler
Thomas J
TJ
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
D018664:Interleukin-12; D007371:Interferon-gamma