Toxoplasmosis in Transplant Recipients

Europe, 2010-2014

Florence Robert-Gangneux; Valeria Meroni; Damien Dupont; Françoise Botterel; José M. Aguado Garcia; Marie-Pierre Brenier-Pinchart; Isabelle Accoceberry; Hamdi Akan; Isabella Abbate; Katia Boggian; Fabrizio Bruschi; Jordi Carratalà; Miruna David; Lubos Drgona; Olgica Djurković-Djaković; Maria Carmen Farinas; Francesca Genco; Effrossyni Gkrania-Klotsas; Andreas H. Groll; Edward Guy; Cédric Hirzel; Nina Khanna; Özgür Kurt; Lia Monica Junie; Tiziana Lazzarotto; Oscar Len; Nicolas J. Mueller; Patricia Munoz; Zoi Dorothea Pana; Emmanuel Roilides; Tijana Stajner; Christian van Delden; Isabelle Villena; Hervé Pelloux; Oriol Manuel

Disclosures

Emerging Infectious Diseases. 2018;24(8):1497-1504. 

In This Article

Results

Participating Centers, Transplantation Activity, and Case Notification

Overall, 46 centers from 11 countries (1–10 centers/country) participated in the survey; countries represented were France, Germany, Greece, Italy, Romania, Serbia, Slovakia, Spain, Switzerland, Turkey, and the United Kingdom (online Technical Appendix, https://wwwnc.cdc.gov/EID/article/24/8/18-0045-Techapp1.pdf). Responses indicated that 5 countries (Switzerland, Slovakia, Turkey, Greece and the United Kingdom) report toxoplasmosis cases in a national database.

During 2010–2014, the mean annual number (range) of allo-HSCT procedures reported per country was 1,016 (13–1,900) and of auto-HSCT was 1,524 (14–3,078) (online Technical Appendix). Regarding SOT recipients, the mean annual number (range) of transplantations was 155 (10–420) for heart, 1,286 (55–3,074) for kidney, and 622 (35–1,241) for liver. The cumulative annual transplant activity among the responding centers reached a total of 1,089 allo-HSCT and 1,168 auto-HSCT (26 centers) and, for SOT, 394 heart (26 centers), 2,566 kidney (35 centers), and 1,455 liver (26 centers) transplants.

Pretransplant Serologic Screening for Toxoplasmosis

Although serologic screening of HSCT donors is not mandatory, all responding countries reported that they were performing this screening. Screening of allo-HSCT recipients was performed in all countries except Slovakia (mandatory in 4 countries), whereas screening of auto-HSCT recipients was performed regularly (4 countries), inconstantly (5 countries), or not at all (1 country). Overall, of 26 responding centers, 24 centers screened allo-HSCT and 17 screened auto-HSCT recipients for Toxoplasma antibodies before transplantation.

Serologic screening of solid organ donors (heart, kidney, or liver) was performed in all countries, although screening was reportedly mandatory in only 7 countries (France, Greece, Italy, Romania, Slovakia, Switzerland, and Turkey). At most centers, SOT recipients were screened (24/26 liver, 31/35 kidney, and 25/26 heart).

Anti-toxoplasma Chemoprophylaxis Practices and Follow-up

Virtually all allo-HSCT recipients received cotrimoxazole chemoprophylaxis, whether primarily targeting Pneumocystis or Toxoplasma. At the 24 responding centers, cotrimoxazole was usually prescribed for >6 months despite the lack of official guidelines at 11 (46%) centers. The preferred regimen at 60% of centers was 960 mg 3 times a week but ranged from 480 mg 2 times a week to 1,920 mg 3 times a week. Auto-HSCT patients at 73% of centers received cotrimoxazole, administered mostly for 3 or 6 months. Serologic follow-up was reported by 2 allo-HSCT centers and PCR-based follow-up by 4.

For heart transplant recipients, 24 (92%) of 26 centers stated that they gave cotrimoxazole prophylaxis (3 months to lifelong), and 10 (43%) of 23 centers implemented serologic follow-up for Toxoplasma 2 and 4 times per year, particularly in cases of serologic mismatch (D+/R–). The most frequently prescribed regimen was 960 mg of cotrimoxazole 3 times a week or 480 mg daily. Although anti-Pneumocystis prophylaxis was implemented at 29 (83%) of 35 kidney and 17 (65%) of 26 liver transplant centers for 3–12 months, specific recommendations regarding toxoplasmosis chemoprophylaxis in this population were reported by only 4 countries (France, Greece, Spain, Turkey). The most frequently used regimen was cotrimoxazole at 480 mg daily (50% of kidney and 40% of liver transplant centers). Serologic monitoring of D+/R– patients was reportedly performed at 6 kidney and 5 liver transplant centers.

Incidence and Clinical Presentation of Toxoplasmosis

Overall, during the 5-year study period, 87 cases of Toxoplasma infection in transplant patients (58 HSCT, 29 SOT) were reported from 15 centers in 8 countries (online Technical Appendix). Severe manifestations (cerebral toxoplasmosis, disseminated toxoplasmosis, pulmonary toxoplasmosis) were more frequently observed (42 [48%] patients) than were mild manifestations (ocular toxoplasmosis, fever; 14 [16%] patients). A total of 31 (36%) patients had no apparent clinical signs. Asymptomatic episodes occurred mainly among HSCT recipients (81%) and were diagnosed mostly on the basis of a positive PCR (84%). Symptomatic HSCT recipients most often had disseminated (10/33, 30%) or cerebral (11/33, 33%) toxoplasmosis; these cases accounted for 60% of all cases of disseminated and 85% of cerebral toxoplasmosis (Table 1).

For the 87 reported cases, PCR was the most helpful diagnostic tool (77 [89%] cases), followed by imaging (32 [37%] cases) and serology (28 [32%] cases) (Table 1). PCR was reportedly positive for 100% of patients with cerebral and 90% with pulmonary toxoplasmosis (Table 1).

Pretransplantation Toxoplasma serologic test results for donor and recipient were available for 70 of the 87 patients (46 HSCT and 24 SOT). Toxoplasmosis occurred in the main groups at risk: in 35 (76%) of 46 D–/R+ HSCT recipients and 11 (46%) of 24 D+/R– SOT recipients (Table 2). Overall, 35 patients (18 HSCT and 17 SOT recipients) received chemoprophylaxis (Table 3). Only 4 (36%) of 11 D+/R– SOT recipients received chemoprophylaxis, but for all of them toxoplasmosis occurred after discontinuation of prophylaxis (data not shown). Overall, toxoplasmosis was diagnosed after the end of prophylaxis for 17 recipients (9 HSCT and 8 SOT). For 9 HSCT and 5 SOT recipients, toxoplasmosis occurred during chemoprophylaxis (Table 3). Of these, 13 (93%) were asymptomatic: 1 kidney, 1 heart, and 11 HSC transplant recipients (Table 1). The proportion of mismatched cases (D+/R–) did not differ according to organ type (Table 4).

The mean time between transplantation and toxoplasmosis diagnosis was shorter among patients with pulmonary toxoplasmosis (p<0.05) (Table 1) than among patients with other types of disease manifestation. For seropositive recipients, the mean time to toxoplasmosis onset was short (<4 months after transplantation) compared with that for seronegative recipients (>4 years) (Table 2). Furthermore, the time to disease onset after transplantation was shorter among HSCT patients than SOT recipients (p<0.0001) (Table 4). The incidence of toxoplasmosis differed among the responding countries but seemed to not be linked to the seroprevalence in the country (online Technical Appendix).

Risk Factors for Death

Survival rates differed significantly between HSCT and SOT recipients (p<0.001) (Table 5). The 2-month survival rate was significantly poorer for patients with cerebral (38%) or pulmonary (50%) toxoplasmosis (p<0.001) (Table 1). Survival rates were also poorer for seropositive patients (p<0.05 at 2 months and p<0.001 at 6 months) (Table 5), mainly consisting of HSCT patients (Table 2). Of note, the percentage of asymptomatic patients who survived 6 months (58%) was similar to that of patients with pulmonary (50%) or disseminated (53%) toxoplasmosis (Table 1). A lower percentage of HSCT and liver transplant recipients survived at 2 and 6 months after diagnosis; deep site-associated toxoplasmosis was diagnosed for only half of them (Table 4). The survival rates for HSCT (38%) and liver transplant (50%) recipients with toxoplasmosis were significantly lower than those for the general HSC (84%) and liver transplant (75%) populations (p<0.05) (Table 4).

Transplant recipients in whom toxoplasmosis developed were less likely to survive if they were not receiving chemoprophylaxis before or at onset of disease (p<0.05 at 2 months and p<0.01 at 6 months after disease onset) (Table 5); this finding was particularly common among SOT recipients (p<0.05) (Table 3). However, despite chemoprophylaxis, the outcome remained poorer for HSCT patients than for SOT patients (Table 3, Table 5).

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