Parasitic Infections in Solid Organ Transplantation

Abstract

As organ transplantation is carried out more regularly around the world and immigration and travel to and from developing countries becomes more common, infections with parasitic diseases are more frequently identified in recipients of organ transplantation. This increase in identification of parasitic infection and recognition of new infections being transmitted through organ transplantation presents the transplant community with new issues regarding donor and recipient screening, as well as, management of infections posttransplantation. Although recent years show an increase in the number of published papers on parasitic infections in transplant recipients it still remains the most understudied of all infections related to organ transplantation with very few prospective trials and no randomized studies that can be accounted for in this field. Recommendations are based primarily on expert opinion (III) unless otherwise stated. Since publication of the last update of these guidelines in 2009, Balamuthia has been identified as a protozoa transmitted through organ transplantation. Guidelines from several groups have provided recommendations on the management of Trypanosoma cruzi infection in the transplant setting. Some helpful new insights on the risks of strongyloides infection and updates on treatment have been published. Slowly, some new treatment options for parasitic diseases are being developed (most are not currently FDA approved) and newer diagnostic assays for parasitic infections are being developed. Parasitic diseases may affect transplant recipients as a result of either recrudescence of latent infections in the previously infected recipient or “de novo” infection by means of natural infection or transmission by transplanted organ into a naïve recipient. The incidence of parasitic infection is expected to grow in solid organ transplant (SOT) recipients due to multiple factors:•Many geographic areas where parasitic infections are prevalent now have active organ transplant programs.•Donors and recipients from endemic areas, with latent or asymptomatic infections, are sometimes referred to transplant centers in Western countries.•Some patients from developed countries undergo transplantation in endemic areas (“transplant tourism”) and return home with either donor derived or naturally acquired infection(s).•Immigrants to Western countries, unaware of their infectious status, are accepted for organ donation without further evaluation for diseases that are prevalent in their countries of origin.•With the recent increase in leisure tourism, transplant recipients travel to endemic areas and enhance their risk of exposure.•The decrease in cyclosporine-based immunosuppressive regimens and the increased use of newer drugs that lack the antiparasitic effects of cyclosporine metabolites may result in higher rates of parasitic infection. Toxoplasmosis is a zoonotic illness due to infection with the protozoa Toxoplasma gondii. Infection in transplant recipients can occur through ingestion of contaminated food or water, after receiving an infected allograft, or by reactivation of latent infection. Cardiac transplant recipients who are seronegative for toxoplasmosis and receive an organ from a seropositive donor have a 57–75% risk of developing symptomatic infection without prophylaxis, usually within 3 months after transplantation (1Wreghitt TG Hakim M Gray JJ et al.Toxoplasmosis in heart and heart and lung transplant recipients.J Clin Pathol. 1989; 42: 194-199Crossref PubMed Google Scholar,2Luft BJ Naot Y Araujo FG Stinson EB Remington JS Primary and reactivated toxoplasma infection in patients with cardiac transplants. Clinical spectrum and problems in diagnosis in a defined population.Ann Intern Med. 1983; 99: 27-31Crossref PubMed Google Scholar). Latent infection in the donor myocardium during cardiac transplantation is the most common method of donor transmission, although it has been transmitted through transplantation of other organs (3Fernandez-Sabe N Cervera C Farinas MC et al.Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: A matched case-control study.Clin Infect Dis. 2012; 54: 355-361Crossref PubMed Scopus (97) Google Scholar,4Campbell AL Goldberg CL Magid MS Gondolesi G Rumbo C Herold BC First case of toxoplasmosis following small bowel transplantation and systematic review of tissue-invasive toxoplasmosis following noncardiac solid organ transplantation.Transplantation. 2006; 81: 408-417Crossref PubMed Scopus (60) Google Scholar). However, among noncardiac, SOT-related cases of toxoplasmosis are more varied in origin (4Campbell AL Goldberg CL Magid MS Gondolesi G Rumbo C Herold BC First case of toxoplasmosis following small bowel transplantation and systematic review of tissue-invasive toxoplasmosis following noncardiac solid organ transplantation.Transplantation. 2006; 81: 408-417Crossref PubMed Scopus (60) Google Scholar). Toxoplasmosis gondii infection occurs worldwide but it is more common in patients from endemic regions, including France and the moist tropical areas of Latin America and sub-Saharan Africa, when the prevalence may approach 90%. In the United States, 10–40% of people are seropositive for T. gondii (5Israelski DM Chmiel JS Poggensee L Phair JP Remington JS Prevalence of Toxoplasma infection in a cohort of homosexual men at risk of AIDS and toxoplasmic encephalitis.J Acquir Immune Defic Syndr. 1993; 6: 414-418PubMed Google Scholar,6Roghmann MC Faulkner CT Lefkowitz A Patton S Zimmerman J Morris Jr., JG Decreased seroprevalence for Toxoplasma gondii in Seventh Day Adventists in Maryland.Am J Trop Med Hyg. 1999; 60: 790-792Crossref PubMed Google Scholar). Risk factors for primary infection include ingestion of cysts in under cooked meat or contaminated soil, contact with oocysts in feline feces, maternal-fetal transmission, or via blood or SOT (7Kotton CN Zoonoses in solid-organ and hematopoietic stem cell transplant recipients.Clin Infect Dis. 2007; 44: 857-866Crossref PubMed Scopus (101) Google Scholar). Water-borne transmission of T. gondii has been considered uncommon but has been reported (8Dubey JP Toxoplasmosis—A waterborne zoonosis.Vet Parasitol. 2004; 126: 57-72Crossref PubMed Scopus (471) Google Scholar). A large review of 15 800 SOT recipients at one center found 22 cases of toxoplasmosis disease. Notably, 90% of recipients were seronegative at the time of transplant. Morbidity was high, and the crude mortality rate was 3/22 (13.6%; Ref. 3Fernandez-Sabe N Cervera C Farinas MC et al.Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: A matched case-control study.Clin Infect Dis. 2012; 54: 355-361Crossref PubMed Scopus (97) Google Scholar). Transplant patients with toxoplasmosis can present with fever, myocarditis, lymphadenopathy, hepatosplenomegaly and meningitis, brain abscess, chorioretinitis, pneumonitis, hepatitis, pancytopenia or disseminated disease. Symptoms often present within 3 months posttransplant, however, later presentations can be seen, particularly after discontinuation of chemoprophylaxis (3Fernandez-Sabe N Cervera C Farinas MC et al.Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: A matched case-control study.Clin Infect Dis. 2012; 54: 355-361Crossref PubMed Scopus (97) Google Scholar,4Campbell AL Goldberg CL Magid MS Gondolesi G Rumbo C Herold BC First case of toxoplasmosis following small bowel transplantation and systematic review of tissue-invasive toxoplasmosis following noncardiac solid organ transplantation.Transplantation. 2006; 81: 408-417Crossref PubMed Scopus (60) Google Scholar,9Martina MN Cervera C Esforzado N et al.Toxoplasma gondii primary infection in renal transplant recipients. Two case reports and literature review.Transpl Int. 2011; 24: e6-e12Crossref PubMed Scopus (54) Google Scholar). Definitive diagnosis requires the identification of tachyzoites on histopatholoy of tissue, seroconversion or amplification of toxoplasma DNA by PCR of infected tissues (10Montoya JG Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis.J Infect Dis. 2002; 185: S73-S82Crossref PubMed Scopus (344) Google Scholar). The presence of multiple ring-enhancing lesions in the basal ganglia or cerebrum on neuro-imaging, especially in the presence of anti-Toxoplasma IgG seropositivty, is suggestive of CNS toxoplasmosis and is sufficient to start presumptive treatment. Stem cell transplant recipients often show a variable enhancement pattern, with the lesion enhancement inversely correlated with the severity of immunosuppression; the radiographic appearance in SOT recipients has not been well described (11Ionita C Wasay M Balos L Bakshi R MR imaging in toxoplasmosis encephalitis after bone marrow transplantation: Paucity of enhancement despite fulminant disease.AJNR Am J Neuroradiol. 2004; 25: 270-273PubMed Google Scholar). Brain biopsy should be considered in nonresponding patients, as the radiographic differences with other infections or malignancies are neither sufficiently specific nor sensitive. Cerebrospinal fluid (CSF) may have a mild mononuclear pleocytosis and/or an elevated protein. Identification of toxoplasma DNA by PCR in the CSF of patients with HIV/AIDS has a high specificity (96–100%) but the sensitivity is more limited (52–98%; Refs. 12Joseph P Calderon MM Gilman RH et al.Optimization and evaluation of a PCR assay for detecting toxoplasmic encephalitis in patients with AIDS.J Clin Microbiol. 2002; 40: 4499-4503Crossref PubMed Scopus (0) Google Scholar, 13Mesquita RT Ziegler AP Hiramoto RM Vidal JE Pereira-Chioccola VL Real-time quantitative PCR in cerebral toxoplasmosis diagnosis of Brazilian human immunodeficiency virus-infected patients.J Med Microbiol. 2010; 59: 641-647Crossref PubMed Scopus (0) Google Scholar, 14Cinque P Scarpellini P Vago L Linde A Lazzarin A Diagnosis of central nervous system complications in HIV-infected patients: Cerebrospinal fluid analysis by the polymerase chain reaction.Aids. 1997; 11: 1-17Crossref PubMed Scopus (0) Google Scholar). Rarely tachyzoites can be seen on centrifuged CSF samples after Giemsa staining (10Montoya JG Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis.J Infect Dis. 2002; 185: S73-S82Crossref PubMed Scopus (344) Google Scholar). Myocarditis may present with heart failure; the diagnosis is made by seeing tachyzoites on myocardial biopsy. Chorioretinitis often presents with scotoma, blurred vision, pain or photophobia. On fundoscopic examination raised, yellow-white, cottony lesions in a nonvascular distribution (unlike the perivascular exudates of CMV retinitis) are seen and vitreal inflammation may be present. Pulmonary disease often presents with fever, dyspnea and nonproductive cough, and reticulonodular infiltrates on chest imaging. This pattern of disease may be indistinguishable from Pneumocystis jiroveci pneumonia but toxoplasma tachyzoites are identified in bronchoalveolar lavage (BAL) fluid. Although rare, cutaneous toxoplasmosis has been seen after hematopoietic stem cell transplantation (15Vidal CI Pollack M Uliasz A del Toro G Emanuel PO Cutaneous toxoplasmosis histologically mimicking graft-versus-host disease.Am J Dermatopathol. 2008; 30: 492-493Crossref Scopus (0) Google Scholar). Optimal treatment after SOT has not been well studied. However, an extensive literature exists on treatment of toxoplasmosis in patients with HIV/AIDS, which serves as a guide for treatment of the transplant population. The drugs routinely used in the treatment of toxoplasmosis treat the proliferative form (tachyzoites) found during the acute phase of infection but do not eradicate the encysted form of the parasite. Treatment for active toxoplasmosis includes induction therapy with pyrimethamine (plus leucovorin) and sulfadiazine to combat the tachyzoites, followed by chronic suppressive therapy (secondary prophylaxis) to prevent recrudescence of disease (16Kaplan JE Benson C Holmes KH Brooks JT Pau A Masur H Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.MMWR Recomm Rep. 2009; 58 (quiz CE1–4.): 1-207Google Scholar). Induction therapy is usually given for at least six weeks depending on response to therapy. Chronic suppressive therapy in HIV/AIDS patients is usually provided as reduced doses of the induction therapy until reconstitution of the patient’s immune system. A similar strategy is appropriate in transplant recipients, however because the transplant population requires life-long immune suppression, chronic suppressive therapy with reduced toxicity medication, such as trimethoprim/sulfamethoxazole (TMP/SMX) may be considered (Refs. 17Beraud G Pierre-Francois S Foltzer A et al.Cotrimoxazole for treatment of cerebral toxoplasmosis: An observational cohort study during 1994–2006.Am J Trop Med Hyg. 2009; 80: 583-587Crossref PubMed Scopus (62) Google Scholar,18Torre D Casari S Speranza F et al.Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group.Antimicrob Agents Chemother. 1998; 42: 1346-1349Crossref PubMed Google Scholar; see Table 1).Table 1:Therapy for common parasitic infections in SOT recipientsOrganismPreferred therapyAlternative therapyBlood and tissue protozoaBabesiaAtovaquone 750 mg (pediatric: 20 mg/kg/dose) po bid plus azithromycin 600 mg (pediatric 12 mg/kg) a day (if able to take oral medications) to ≥2 weeks beyond clearance of parasitemia (≥6 weeks minimum total treatment; Ref. 123Krause PJ Lepore T Sikand VK et al.Atovaquone and azithromycin for the treatment of babesiosis.N Engl J Med. 2000; 343: 1454-1458Crossref PubMed Scopus (274) Google Scholar)Clindamycin 600 mg (pediatric: 20–40 mg/kg/day divided) po tid or 1.2 g IV q12 hours plus quinine 650 mg (pediatric: 30 mg/kg/day divided) po tid (or quinidine IV) to ≥2 weeks beyond clearance of parasitemia (≥6 weeks minimum total treatment; Ref. 123Krause PJ Lepore T Sikand VK et al.Atovaquone and azithromycin for the treatment of babesiosis.N Engl J Med. 2000; 343: 1454-1458Crossref PubMed Scopus (274) Google Scholar)LeishmaniaVisceral diseaseLiposomal amphotericin B given 3 mg/kg IV on days 1 through 5, 14, and 21.Amphotericin B deoxycholate 1.0 mg/kg daily for 15–20 days OR pentavalent antimony compoundConsider secondary prophylaxis with intermittent dosing in patients at high-risk for relapseConsider secondary prophylaxis with intermittent dosing in patients at high-risk for relapseCutaneous or mucocutaneous diseaseA pentavalent antimony compound (stibogluconate or meglumine antimoniate) at 20 mg/kg IV/IM daily. Duration: cutaneous disease, 21 days and mucocutaneous disease, 28 daysLiposomal amphotericin B, amphotericin B deoxycholate, miltefosine, paromomycin, pentamidine, and fluconazole can be considered based on species and availabilityToxoplasma gondiiInduction therapy: Pyrimethamine 200 mg po x1 then 50 mg (<60 kg) to 75 mg (≥60 kg) (pediatric 2 mg/kg/day) PO daily plus sulfadiazine 1.0 (<60 kg) to 1.5 gm (≥ 60 kg) (pediatric 100–200 mg/kg/day divided) PO q6h plus leucovorin 10–25 mg PO daily for at least 6 weeksInduction therapy: Pyrimethamine (same dosing as preferred therapy) plus clindamycin 600 mg IV/PO q6h OR TMP-SMX (10 mg/kg TMP-50 mg/kg SMX) IV/PO divided BID OR Atovaquone 1500 mg PO BID plus either pyrimethamine and leucovorin (same dosing as preferred therapy) or sulfadiazine (sameChronic suppressive therapy: Pyrimethamine 25 mg (< 60 kg) to 50 mg (≥ 60 kg) PO daily plus sulfadiazine 2.0 gm (< 60 kg) to 4.0 gm (≥ 60 kg) PO daily (in 2–4 divided doses) plus leucovorin 10–25 mg PO dailydosing as preferred therapy) OR azithromycin 900–1200 mg PO daily plus pyrimethamine and leucovorin (same dosing as preferred therapy)Chronic suppressive therapy: Pyrimethamine (same dosing as preferred therapy) plus clindamycin 600 mg PO q8h OR TMP-SMX 1 DS tab q12h OR atovaquone 750 mg PO q6–12h +/- either pyrimethamine and leucovorin (same dosing as preferred therapy) or sulfadiazine (same dosing as preferred therapy) OR azithromycin 900–1200 mg PO daily plus pyrimethamine and leucovorin (same dosing as preferred therapy)Trypanosoma cruziBenznidazole* 5–7 mg/kg/day (pediatric<12 years: 10 mg/kg) divided bid for 60 daysNifurtimox* 8–10 mg/kg/day divided three times daily for 90 days (pediatric: 1–10 years: 15–20 mg/kg /day divided qid; 11–16 years: 12.5–15 mg /kg/day divided qid)Intestinal protozoaBlastocystis hominisNitazoxanide 500 mg po bid for 3 days (pediatric: 12–47 months 100 mg/dose bid)Metronidazole 1.5 grams x 1 daily for 10 days OR Iodoquinol 650 g po tid x 20 days, OR TMP/SMX DS bid x 7 daysCryptosporidiumNitazoxanide 500 mg po bid x 14 days (same as for HIV+)Paromomycin or azithromycin; consider combination therapy(pediatric: 12–47 months of age, 100 mg PO bid 4–11 years of age, 200 mg PO bid ≥12 years of age – see adult dosing)Reduce immunosuppression if possibleCyclosporaTMP/SMX DS qid x 10 days then tid (pediatric: TMP 5 mg/kg/SMX 25 mg/kg/day divided bid)Ciprofloxacin 500 mg po bid x 7 days, then three times a week x 2 weeksEntamoeba histolyticaMetronidazole 750 mg (pediatric 35–50 mg/kg/day divided) po tid x 10 days OR Tinidazole 2 gram (pediatric >3 years 50 mg/kg) po once daily x 3 days followed byNitazoxanide: intestinal amoebiasis: 500 mg po bid x 3 days and for extraintestinal (hepatic) amoebiasis 500 mg po bid x 10 days followed by paromomycin or iodoquinol as per preferred therapyParomomycin 500 mg (pediatric 25–35 mg/kg/day divided) potid x 7 days OR Iodoquinol 650 mg po (pediatric 30–40 mg/kg/day divided) tid x 20 days to eliminate cysts.GiardiaTinidazole 2 gram x 1, or Nitazoxanide 500 mg po bid x 3 days (pediatric: 12–47 months 100 mg PO bid 4–11 years 200 mg PO bid ≥12 years—see adult dosing)Metronidazole 500–750 mg po (pediatric 15–30 mg/kg/day divided) tid x 5 days; OR Paromomycin 500 mg po qid x 7 days; refractory disease: Metronidazole 750 mg tid plus quinacrine 100 mg tid both for 3 weeksCystoisospora belliImmunocompromised host: TMP/SMX DS qid x 10 days then bid x 3 weeks (same as for HIV+) (pediatric: TMP 5 mg/kg/SMX 25 mg/kg/day divided bid)Ciprofloxacin 500 mg po bid x 7 days OR pyrimethamine 75 mg po a day with folinic acid 10 mg a day for 14 daysMicrosporidiaAlbendazole 400 mg (Pediatric 15 mg/kg/day divided) po bid x 3 weeks or Fumagillin 200 mg po tidHelminthsStrongyloidesIvermectin 200 microgram/kg/day x 2 days; repeat in 2 weeks (3 mg tablets) (longer for hyperinfection)Albendazole 400 mg po bid x 10–14 days (longer for hyperinfection)Hyperinfection: Treat until document clearance – then 7–14 days longerOff-Label alternatives if oral therapy not an option:HTLV-1 co-infection: Treat until document clearance – then 7–14 days longer. Expect persistent infection. Monitor and retreat as needed.(a) Per rectum ivermectin(b) Subcutaneous ivermectinSchistosomaPraziquantel 20 mg/kg/dose po bid x 1 day if S. hematobium or S. mansoni)Oxamniquine and artemether (anti-malarial)Praziquantel 20 mg/kg/dose po tid x 1 day if S. japonicum or S. mekongiEchinococcusAlbendazole 400 mg po bid (pediatric 15 mg/kg/day divided bid) for 1–6 months plus possible surgery or PAIR procedure)Off-Label preprocedure or presurgical use:albendazole (+/- praziquantel in combination) to reduce the chance of secondary seedingTherapy for Common Parasites.Note: There are no prospective trials for any regimen in transplantation. Very few drugs interactions with standard transplant-related medications have been reported, and may be underappreciated.•In the United States, these drugs must be obtained from the Centers for Disease Control at 404–639-3670 (emergency after hours 404–639-2888).•Pediatric doses are included where available. Open table in a new tab Therapy for Common Parasites. Note: There are no prospective trials for any regimen in transplantation. Very few drugs interactions with standard transplant-related medications have been reported, and may be underappreciated.•In the United States, these drugs must be obtained from the Centers for Disease Control at 404–639-3670 (emergency after hours 404–639-2888).•Pediatric doses are included where available. Pretransplant screening for prior toxoplasmosis exposure is generally done before heart transplant, and is less frequently done before other organ transplants. One retrospective cohort study of 1006 SOT recipients at a single center identified a pretransplant Toxoplasma seroprevalence rate of 13% in donors and 18% in recipients, with an incidence of Toxoplasma donor-recipient mismatch of 10%, of whom only 39% of mismatched recipients received TMP/SMX prophylaxis. Only four patients seroconverted, of whom two had received prophylaxis, and there were no cases of clinical disease (19Gourishankar S Doucette K Fenton J Purych D Kowalewska-Grochowska K Preiksaitis J The use of donor and recipient screening for toxoplasma in the era of universal trimethoprim sulfamethoxazole prophylaxis.Transplantation. 2008; 85: 980-985Crossref PubMed Scopus (0) Google Scholar). These data suggest that in transplant centers with low Toxoplasma seroprevalence, routine screening in SOT donors and recipients might not be necessary, particularly in the era of routine TMP/SMX prophylaxis. In areas of high seroprevalence, routine screening may be indicated. The routine use of TMP/SMX for post-SOT prophylaxis has decreased the risk of toxoplasmosis (20Orr KE Gould FK Short G et al.Outcome of Toxoplasma gondii mismatches in heart transplant recipients over a period of 8 years.J Infect. 1994; 29: 249-253Abstract Full Text PDF PubMed Scopus (0) Google Scholar, 21Baden LR Katz JT Franck L et al.Successful toxoplasmosis prophylaxis after orthotopic cardiac transplantation with trimethoprim-sulfamethoxazole.Transplantation. 2003; 75: 339-343Crossref PubMed Scopus (0) Google Scholar, 22Baran DA Alwarshetty MM Alvi S et al.Is toxoplasmosis prophylaxis necessary in cardiac transplantation? Long-term follow-up at two transplant centers.J Heart Lung Transplant. 2006; 25: 1380-1382Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 23Munoz P Arencibia J Rodriguez C et al.Trimethoprim-sulfamethoxazole as toxoplasmosis prophylaxis for heart transplant recipients.Clin Infect Dis. 2003; 36: 932-933Crossref PubMed Scopus (0) Google Scholar) and is currently the most common prophylaxis against this parasite. Multiple studies support the efficacy of primary prophylaxis with TMP/SMX, although the optimal dose and duration of TMP/SMX remains unclear. Many studies showed successful prophylaxis using TMP/SMX (160 mg of TMP, 800 mg of SMX) thrice weekly for varying durations (range 3 months to lifelong; Refs. 21Baden LR Katz JT Franck L et al.Successful toxoplasmosis prophylaxis after orthotopic cardiac transplantation with trimethoprim-sulfamethoxazole.Transplantation. 2003; 75: 339-343Crossref PubMed Scopus (0) Google Scholar, 22Baran DA Alwarshetty MM Alvi S et al.Is toxoplasmosis prophylaxis necessary in cardiac transplantation? Long-term follow-up at two transplant centers.J Heart Lung Transplant. 2006; 25: 1380-1382Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 23Munoz P Arencibia J Rodriguez C et al.Trimethoprim-sulfamethoxazole as toxoplasmosis prophylaxis for heart transplant recipients.Clin Infect Dis. 2003; 36: 932-933Crossref PubMed Scopus (0) Google Scholar). In patients with HIV/AIDS, TMP/SMX (160 mg of TMP, 800 mg of SMX) one tablet daily is recommended as first line prophylaxis (16Kaplan JE Benson C Holmes KH Brooks JT Pau A Masur H Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.MMWR Recomm Rep. 2009; 58 (quiz CE1–4.): 1-207Google Scholar). Reports of toxoplasmosis in high-risk patients after stopping prophylaxis have been described (24Keogh A Macdonald P Richens D Harvison A Spratt P Mini-dose trimethoprim with sulphamethoxazole prevents pneumocystis and toxoplasmosis infections after heart transplantation.Transplant Proc. 1992; 24: 2263PubMed Google Scholar). An alternative to TMP-SMX that has been well studied in patients with HIV/AIDS is dapsone plus pyrimethamine (plus leucovorin; Refs. 25Girard PM Landman R Gaudebout C et al.Dapsone-pyrimethamine compared with aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia and toxoplasmosis in HIV infection. The PRIO Study Group.N Engl J Med. 1993; 328: 1514-1520Crossref PubMed Scopus (0) Google Scholar, 26Podzamczer D Salazar A Jimenez J et al.Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine for the simultaneous primary prophylaxis of Pneumocystis pneumonia and toxoplasmosis in patients infected with HIV.Ann Intern Med. 1995; 122: 755-761Crossref PubMed Scopus (0) Google Scholar, 27Opravil M Hirschel B Lazzarin A et al.Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus-infected patients.Clin Infect Dis. 1995; 20: 531-541Crossref PubMed Google Scholar). Atovaquone with or without pyrimethamine (plus leucovorin) has not been well studied but is considered a likely effective alternative regimen as well (16Kaplan JE Benson C Holmes KH Brooks JT Pau A Masur H Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.MMWR Recomm Rep. 2009; 58 (quiz CE1–4.): 1-207Google Scholar). Some transplant centers have reported using pyrimethamine with or without sulfadiazine for prophylaxis of toxoplasmosis infection in high-risk cardiac recipients (22Baran DA Alwarshetty MM Alvi S et al.Is toxoplasmosis prophylaxis necessary in cardiac transplantation? Long-term follow-up at two transplant centers.J Heart Lung Transplant. 2006; 25: 1380-1382Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar,23Munoz P Arencibia J Rodriguez C et al.Trimethoprim-sulfamethoxazole as toxoplasmosis prophylaxis for heart transplant recipients.Clin Infect Dis. 2003; 36: 932-933Crossref PubMed Scopus (0) Google Scholar,28Montoya JG Giraldo LF Efron B et al.Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center.Clin Infect Dis. 2001; 33: 629-640Crossref PubMed Scopus (235) Google Scholar). To avoid primary infection, transplant recipients should avoid contact with undercooked meat, soil, water or animal feces that might contain toxoplasmosis cysts. •All heart transplant candidates and donors should be tested for Toxoplasma IgG pretransplant.•The benefit of screening nonheart transplant recipients and donors is not well established but could be considered in high prevalence areas. •Acute toxoplasma infection can be identified by histopathological results, seroconversion, or molecular testing (PCR).•Initiation of empiric therapy (particularly of CNS infection) should be considered based on clinical and radiographic findings manifestations while awaiting results. •Pyrimethamine plus sulfadiazine is recommended as first-line therapy of acute toxoplasmosis infection.•Chronic suppressive therapy after induction therapy is recommended. •Among toxoplasma seropositive heart transplant recipients and seronegative heart transplant recipients receiving organs from seropositive donors, prophylaxis against toxoplasma infection is recommended with TMP/SMX. The optimal dose and duration of prophylaxis posttransplant has not been determined, but many transplant centers give life-long prophylaxis with TMP/SMX double strength (160 mg of TMP, 800 mg of SMX) one tab three times weekly or TMP/SMX single strength (80 mg of TMP, 400 mg of SMX) one tab daily. Chagas disease is caused by the protozoan parasite, T. cruzi and infection is transmitted to humans primarily by contaminated feces of a triatomine insect vector (29Rodriques Coura J de Castro SL A critical review on Chagas disease chemotherapy.Mem Inst Oswaldo Cruz. 2002; 97: 3-24Crossref PubMed Google Scholar). However, T. cruzi infection has also been transmitted by blood transfusion, infected mother to fetus, oral ingestion, and organ transplantation. Chagas disease is endemic in most Latin-American countries where 8–9 million people are currently living with infection and 2–5 million people have Chagasic cardiomyopathy. Because of recent immigration it is estimated that between 0.3 and 1 million T. cruzi infected people are living in the United States (30Hotez PJ Dumonteil E Woc-Colburn L et al.Chagas disease: “The new HIV/AIDS of the Americas.”.PLoS Negl Trop Dis. 2012; 6: e1498Crossref PubMed Scopus (0) Google Scholar, 31Rodriguez-Hernandez MJ Ruiz-Perez-Pipaon M Canas E Bernal C Gavilan F Strongyloides stercoralis hyperinfection transmitted by liver allograft in a transplant recipient.Am J Transplant. 2009; 9: 2637-2640Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 32Bern C Montgomery SP An estimate of the burden of Chagas disease in the United States.Clin Infect Dis. 2009; 49: e52-e54Crossref PubMed Scopus (442) Google Scholar). Human disease has two distinct phases: the acute phase and the chronic infection. In the normal host, the acute disease usually resolves spontaneously even if untreated; but witho