Negative pretransplant serostatus forToxoplasma gondiiis associated with impaired survival after heart transplantation

Abstract

Summary 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.

Toxoplasma gondii Exposure in the Heart Transplant Recipient

“…With a median of 5.5 years of follow-up, the authors noted that Toxoplasma seropositivity was associated with increased mortality even after adjustment for potential confounders including age, hypertension, smoking status, and serum creatinine. This is in stark contrast to the results of a study by Doesch et al in 2010, in which 344 heart transplant recipients transplanted between 1989 and 2008 at the University of Heidelberg in Germany were examined (4). With a median of 5.7 years of follow-up, the authors noted that Toxoplasma seronegativity was associated with increased mortality even after adjustment for potential confounders including age, serum creatinine, cytomegalovirus serostatus, diabetes, ischemic time, azathioprine versus mycophenolate mofetil immunosuppression, and number of treated rejection episodes.…”

Toxoplasma gondii Serostatus Is Not Associated With Impaired Long-Term Survival after Heart Transplantation

“…Searching for an explanation of the contradictory results of the studies of Arora et al ( 1 ) and Doesch et al ( 2 ) and our study, we demonstrated several differences between the studies. A summary is presented in Table 5.…”

“…However, oral folinic acid administration prevents the negative side effects of a pyrimethamine-sulfadiazine regimen in most cases. This study, as well as the studies by Arora et al ( 1 ) and Doesch et al ( 2 ), did not identify a difference in mortality between Toxoplasma seronegative recipients that received the heart of a seropositive versus a seronegative donor, suggesting that the antibiotic prophylactic drugs given to Toxoplasma mismatch recipients (D+/R-) do not negatively affect outcome.…”

Comparison of serologic status of Toxoplasma gondii infection in pre‐ and post‐heart transplantation in a pediatric population: A preliminary study

“…19 This result supports the idea of importance of prophylactic anti-toxoplasma treatment among these cases.Thus, clinicians should be well-informed about the risk of T gondii infection in patients receiving heart transplant. In another study by Doesch et al,20 from 344 heart transplant adults, 55.2% were seronegative and 44.8% were seropositive before transplantation. In the long-term follow-up, 152 of them died.…”