toxoplasmosis is a zoonotic disease of worldwide distribution , with a high incidence in certain countries . humans are usually infected through ingestion of oocysts that are present in contaminated water or soil , or by eating undercooked meat with tissue cysts . although the typical course of acute infection is a benign febrile syndrome in healthy patients , severe disease occurs in hosts with immune system impairment , including transplant and aids patients . transplant recipients who are seronegative for toxoplasma gondii are at particular risk of developing a severe toxoplasmosis infection upon receipt of an organ from a seropositive donor . in this study , we studied six cases of t. gondii myocarditis following heart transplantation before routine use of pyrimethamine prophylaxis in our institution . we performed a retrospective study of all cases of t. gondii infections in adult patients who had received an orthotopic cardiac transplant at our institution from may 1968 to january 2011 . the heart institute ( incor - hcfmusp ) is a tertiary cardiology care hospital in so paulo , brazil , with a heart transplant program that was founded in 1964 . until 1996 starting with the 112th heart transplant , oral pyrimethamine 75  mg / day was used for seronegative transplant recipients whose donors were seropositive or unknown . this regimen was given from the first day after transplant and was maintained until the 100th day after transplant . we diagnosed toxoplasmosis by analyzing the histology of endomyocardial biopsies and/or necropsies , in which toxoplasma infection was determined by morphology using hematoxylin and eosin , and immunohistochemistry using commercially available polyclonal rabbit antibody against t. gondii ( produced by chemicon international , inc . during the study period , 436 adult heart transplants were performed , and six patients ( 1.3% ) developed t. gondii infection / reactivation in the postoperative period . all infections / reactivations occurred before 1996 , and none of the patients received pyrimethamine prophylaxis . demographic and clinical information are described in table 1 , and examples of histological examination are in figures 1 and 2 . two patients ( 33.3% ) presented with disseminated toxoplasmosis infection , and all patients ( 100% ) had myocarditis . five patients ( 83.3% ) were toxoplasma seronegative before transplant and one patient did not have before transplant serology available . median time for toxoplasma infection onset was 131 days ( mean = 69 days , range 21534 ) following transplantation . after 1996 , we did not observe any additional cases of t. gondii infection / reactivation . t. gondii primary infection / reactivation after solid organ transplantation is a serious complication , due to the high mortality rate after disseminated disease . following transplant , the parasitic infection is clearly related to the type and duration of suppressive therapy . in a multicenter , matched - case control study , the frequency of toxoplasmosis was significantly higher in heart recipients compared to the kidney and liver recipients . a negative serostatus prior to transplantation was the only independent risk factor for toxoplasmosis ( odds ratio = 15.12 [ 95% confidence interval , 2.3796.31 ] ; p = .004 ) . patients receiving heart transplants have a higher risk of developing t. gondii - induced  myocarditis when compared with other solid organ transplants . reviewed tissue - invasive toxoplasmosis in noncardiac solid organ transplant recipients ( kidney , liver , small bowel , and pancreas ) and found that in 52 cases , 44 ( 85% ) patients had disseminated disease , while only 19% developed myocarditis . patients with toxoplasmosis after heart transplantation have myocarditis that may cause allograph dysfunction in 75% ; disseminated disease occurs in nearly 45% of them . mortality due to toxoplasma infection is also high . in a kidney transplant patient cohort with 31 cases of toxoplasmosis , 20 patients ( 64.5% ) died . in our study , we observed 50% mortality among the six infected patients . death in most reported cases has been related to a delay in diagnosis and targeted treatment . endomyocardial biopsy ( emb ) is a reliable way to identify and track rejection following heart transplantation , and in some cases , emb may show the presence of infectious organisms , including toxoplasma pseudocysts . toxoplasma - related myocarditis has a fugacious exudative or neutrophilic component occurring when the myocyte ruptures following toxoplasma proliferation . this fugacious component becomes mononuclear shortly after rupture , which results in an increasingly difficult differential diagnosis of rejection . therefore , in some cases , the lymphoid infiltrate may not be caused by transplant rejection . in addition , the pseudocysts are often present in non - inflamed myocardial tissue , that is , when there is no myocyte rupture and the microorganism remains hidden from the immune system and may go unnoticed , even by a very experienced pathologist . this occurred in one case in our series of patients , where the review of a biopsy showed a small toxoplasma pseudocyst present in a non - inflamed area of the myocardial sample . the use of t. gondii immunohistochemistry could help with the differential diagnosis of seronegative patients with suspected acute rejections ( figures 1 and 2 ) . consequently , we would like to caution the pathologist to be careful in their interpretation of tissue samples , considering the difficulty in visualizing toxoplasma pseudocysts , as well as the difficulty in differentiating the diagnosis of rejection when inflammation is induced . in our series , five of six toxoplasma infection presented as cardiac failure without fever . in the first months following cardiac transplant , this clinical situation could be misdiagnosed as acute rejection , resulting in increased immunosuppression and inadvertent favor of t. gondii infection . although the combination of pyrimethamine and sulfadiazine is the most effective regimen in the prevention of t. gondii infection , monotherapy with pyrimethamine has been suggested after heart transplantation for prophylaxis [ 8 , 9 ] . other transplant programs that have been successful in preventing toxoplasma infection include the use of trimethoprim / sulfamethoxazole ( cotrimoxazole ) during the post transplant period [ 1012 ] . cotrimoxazole is systematically used following kidney or liver transplants to prevent opportunistic infections , such as pneumocystosis , but there is no consistent evidence for its efficacy following heart transplantation . in a review of two transplant programs in the usa , baran et al . found no evidence of toxoplasmosis postheart transplantation and proposed that p. jiroveci prophylaxis with cotrimoxazole is sufficient to prevent toxoplasmosis infection / reactivation . our heart transplant program does not recommend routine prophylaxis with cotrimoxazole for pneumocystosis prevention . in areas with a high prevalence of toxoplasmosis ( 50%80% in adults ) , such as in brazil , there is a low number of seronegative patients receiving heart transplants , and the prophylaxis could be individualized . considering the adverse events related to universal p. jiroveci prophylaxis with cotrimoxazole ( i.e. , skin rashes or nephrotoxicity ) and the low risk of pneumocystosis , we adopted the use of pyrimethamine as toxoplasma prophylaxis in seronegative recipients . we did not observe any incidents of t. gondii reactivation ( igg - positive recipients ) in 43 years of cardiac transplant experience . in conclusion , toxoplasmosis in heart allographs was more frequent among seronegative heart recipients , and oral pyrimethamine was highly effective for the prevention of t. gondii infection in this population .
toxoplasma gondii primary infection / reactivation after solid organ transplantation is a serious complication , due to the high mortality rate following disseminated disease . 
 we performed a retrospective study of all cases of t. gondii infections in 436 adult patients who had received an orthotopic cardiac transplant at our institution from may 1968 to january 2011 . 
 six patients ( 1.3% ) developed t. gondii infection / reactivation in the post - operative period . 
 all infections / reactivations occurred before 1996 , when no standardized toxoplasmosis prophylactic regimen or co - trimoxazole prophylaxis was used . 
 starting with the 112th heart transplant , oral pyrimethamine 75  mg / day was used for seronegative transplant recipients whose donors were seropositive or unknown . 
 two patients ( 33.3% ) presented with disseminated toxoplasmosis infection , and all patients ( 100% ) had myocarditis . 
 five patients ( 83.3% ) were seronegative before transplant and one patient did not have pre - transplant serology available . 
 median time for infection onset was 131 days following transplantation . 
 three patients ( 50% ) died due to toxoplasmosis infection . 
 after 1996 , we did not observe any additional cases of t. gondii infection / reactivation . in conclusion , 
 toxoplasmosis in heart allographs was more frequent among seronegative heart recipients , and oral pyrimethamine was highly effective for the prevention of t. gondii infection in this population .