- Email: [email protected]
Parasitic Infection in Renal Transplant Recipients
INFECTIONS
Parasitic Infection in Renal Transplant Recipients C. Valar, E. Keitel, R.L. Dal Prá, D. Gnatta, A.F. Santos, P.D. Bianco, T.C.T. Sukiennik, K.L. Pegas, A.E. Bittar, K.T. Oliveira, and V.D. Garcia ABSTRACT The purpose of this study was to evaluate the prevalence of symptomatic parasitic infections in adult renal transplant recipients. We retrospectively analyzed a sample of 657 adult renal transplant recipients performed from January 2001 to December 2005 for immunosuppression protocol, clinical manifestations, parasite diagnosis, treatments, and outcomes. The prevalence of symptomatic parasitosis infections was 2.4% (16/657). None of the infected patients received cyclosporine in their immunosuppression protocol. Most of the infections were caused by Strongyloids stercoralis (n ⫽ 11), followed by Giardia lamblia (n ⫽ 3), Toxoplasma gondii (n ⫽ 1), and Trypanosoma cruzi: (n ⫽ 1). Strongyloides stercoralis was the most frequent agent, causing three cases of hyperinfection including one fatal case. With the new immunosuppressive regimes there must be a suspicion of parasitic infection to avoid the diagnostic delay that can be fatal. Strategies, including empiric treatment for S. stercoralis, must be considered.
A
BOUT 340 PARASITIC species infect more than 3 billion people worldwide with varying morbidity and mortality.1 Infections cause significant morbidity and mortality among immunosupressed hosts. Acquisition of infection, clinical severity, and outcome of a parasitic disease depend on innate and acquired host immunity as well as on the parasite’s own response against the host when the infection is established. The incidence and prevalence of parasitic infections in transplant recipients is unknown; only a few patients are symptomatic.2 Only 5% of known humanpathogenic parasitic infections have been reported in transplant recipients. This certainly does not represent the true prevalence because only those infections that cause significant morbidity would be expected to find their way into the literature.1 Since the use of cyclosporine (CsA) has become a cornerstone in prophylactic immunosuppresion, this syn0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.01.025 460
drome has become exceedingly rare, owing to the strong parasiticidal effect of the drug against a wide range of organisms, as documented in mice and humans.1,3 The new immunosuppresive drugs used to prevent graft rejection have lead to an increase in parasitic infections in renal
From the Nephrology Service-Renal and Pancreas Transplant Unit (C.V., E.K., R.L.D.P., D.G., A.F.S., P.D.B., A.E.B., K.T.O., V.D.G.); Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (E.K.); Infectious Diseases Control Unit (T.C.T.S.); and Pathology Laboratory (K.L.P.), Complexo Hospitalar Santa Casa de Porto Alegre, Brazil. Address reprint requests to Valter Duro Garcia, Av. Independência, 155. HDVS - 6° andar. Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, RS-Brazil 90025090. E-mail: [email protected] © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 460 – 462 (2007)
PARASITIC INFECTION IN RENAL RECIPIENTS
461
transplant recipients. The purpose of our study was to evaluate the prevalence of symptomatic parasitosis infections in adult renal transplant recipients with request to the immunosupression protocol, diagnosis, treatment, and outcome. METHODS We retrospectively analyzed a sample of 657 renal transplant recipients performed from January 2001 to December 2005. The evaluated variables were imunosuppression, clinical manifestation, diagnosis of parasites, treatment, and outcomes.
RESULTS
The prevalence of symptomatic parasitosis was 2.4% (16/ 657). Among the infected recipients (n ⫽ 16), the mean age was 44.3 ⫾ 12.9 years. Nine patients were male. Twelve patients received induction therapy (75%). Fourteen were recipients of deceased donor kidneys. None received CsA in the immunosupressive protocol: other combinations included tacrolimus, mycophenolate, rapamycin, azathioprine, and prednisone. The distribution of parasites, clinical manifestation, site of parasite identification, and the treatment and outcome of the patients are shown in Table 1. Three patients in our series showed Strongyloides hyperinfection syndrome. The first patient had initial symptoms at 67 days after renal transplantation. S. stercoralis organisms were identified by a duodenal biopsy; the treatment was thiabendazole. She died due to sepsis 17 days after the first symptoms. The second patient showed nonspecific symptoms at 54 days after transplantation. Bronchoalveolar lavage fluid revealed multiple S. stercoralis organisms. He received thiabendazole, ivermectin, and metronidazole to treat the infection. Blood cultures were positive for grampositive cocci. He presented recurrent infection. The third patient displayed S. stercoralis in the sputum. He received treatment with thiabendazole and had complete recovery. All three patients received induction therapy and were recipients of deceased donor organs. The other eight patients infected by S. stercoralis had a good treatment response; one patient presented with recurrent infection. The patient with toxoplasmosis had a sero-
logic diagnosis that confirmed the infection among the differential diagnostic entities for persistent pyrexia. Serologic testing for Toxoplasma gondii antibodies were positive before the renal transplantation. The recrudescence of a dormant infection explained this infection. The subject had a good response to sulphadiazine/pyrimethamine. Three patients with giardiasis presented as diarrhea illnesses. Giardia lamblia was isolated by a fresh stool. They were treated with metronidazole (two patients) and albendazole (one patient). The Trypanossoma cruzi infection had an usual neurologic presentation. The diagnosis was reached by a biopsy of central nervous system lesion. Benzonidazole was used with success. Immunosuppression is most pronounced from month 1 to month 6; infection is most often due to common bacterial pathogens or opportunistic pathogens present in the environment or host.13 Thirteen of 16 patients showed their first symptoms in this period. The other three patients showed the parasitological symptoms seven months after the kidney transplant. None of 16 patients were under CsA regime. DISCUSSION
Most parasite infections are characterized by low morbidity. They can exist in a transplant recipient without important clinical sequel.1 Among 657 renal transplant recipients, only 16 patients showed symptoms and had a confirmed diagnosis. Most infections were caused by Strongyloides stercoralis; the main symptoms were gastrointestinal. This is a helmintic parasite endemic to tropical and subtropical areas. The cycle of autoinfection can perpetuate in healthy hosts, causing chronic or subclinical infections that may persist for decades without an adverse event.4,5 However, in immunocompromised hosts S. stercoralis may cause a frequently fatal hyperinfection or disseminated disease.4 – 6 Strongyloides hyperinfection syndrome occurs when the normal life cycle of S. stercoralis infestation is augmented in humans, resulting in a massive infection of the gastrointestinal tract, circulation, and lung.6 Corticosteroid therapy and malnutrition may change the host parasite relationship, resulting in hyperinfection and dissemination.4,7–9
Table 1. Characteristics of Parasitic Infection in Renal Transplant Recipients Parasites
Total Number of Patients Infected
Strongyloides stercoralis
11
Symptoms
n
Gastrointestinal Pulmonary Pruritus
8 2 1
Site of Parasitic Identification
n
Treatment
n
Outcome
n
8
Ivermectin Thiabendazole Albendazole Albendazole/ Thiabendazole Metronidazole Albendazole Sulfadiazine/ pyrimethamine Benzonidazole
1 8 4 1
Hyperinfection (2 recover and 1 death) Recurrent infection
3
2 1 1
Complete recover
3
Complete recover
1
1
Complete recover
1
Giardia lamblia
3
Gastrointestinal
3
Stool fresh Bronchoalveolar lavage fluid Sputum Duodenal biopsy Stool fresh
Toxoplasma gondii
1
Pyrexia
1
Serology
1
Trypanossoma cruzi
1
Neurologic
1
Biopsy of Central nervous system lesion
1
3
2
462
Disseminated strongyloidiasis is asymptomatic in the majority of individuals. Examination of a stool sample should be mandatory for all patients on long-term immunosuppressive therapy to prevent the disease’s morbidity and mortality.7,8,10 S. stercoralis is one of most difficult parasitic infections to diagnose. The parasitological methods have low sensivity even when repeated several times. They must be performed on fresh stools, rarely a standard procedure in hospital clinical laboratories.5,9 Paula et al showed the value of an indirect immunofluorescence antibody test and enzyme-linked immunosorbent assay to detect IgG and IgM antibodies to diagnose human strongyloidiasis among immunocompromised hosts. This assay contributed to the establishment of the diagnosis of this parasitosis and the possibility of early treatment. A useful evaluation may involve a combination of tests; for example, serology, serial examination, and differential white blood cell count. Otherwise unexplained eosinophilia should prompt an evaluation for occult parasitic infection, including strongyloidiasis. Unfortunately, eosinophilia is not a common finding because corticosteroids depress cell-mediated immunity.4,7 Posttransplant toxoplasmosis has been reported most frequently with heart transplants, but it remains a rare but significant pathogen in renal transplant recipients.1,11 There are few reports in the literature regarding giardiasis in immunocompromised hosts and no reports on the effect of the drugs cell-mediated immunity on the outcome of Giardia infections humans. De novo Trypanosoma cruzi infections have been reported1 and cerebral infections in patients with acquired immunodeficiency syndrome, but it is rare in renal transplant recipents.12 Immunosuppression breaks the balance between the agent and the host in the chronic phase of disease. It is known that cyclosporine has antiparasitic actions in vitro toward malaria and schistosomiasis. It has reduced the incidence of strongyloidiasis in renal transplant recipients. However, this effect was not described with other infectious agents.13,14 The mechanism of action is unclear. In laboratory models CsA reduces survival, growth, or fecundity in a wide range of protozoans and helminths.15 In conclusion, parasitic and protozoan infections remain a challenge in diagnosis because immunocompromised hosts are usually asymptomatic and the blood cell count can
VALAR, KEITEL, DAL PRÁ ET AL
be normal. The suspicion of a parasite infection must be kept in mind to avoid a diagnostic delay that can be fatal. With the new imunosuppressive strategies, empiric treatment and advances in the diagnosis, especially for S. stercoralis, should be considered in transplant patients. REFERENCES 1. Barsoum RS: Parasitic infections in organ transplantation. Exp Clin Transplant 2:258, 2004 2. Thom K, Forrest G: Gastrointestinal infections in immunocompromised hosts. Curr Opin Gastroenterol 22:18, 2006 3. Cunningham GA, Grubb WB, Mendis AH, et al: Murine strongyloidiasis: the effects of cyclosporin A and thiabendazole administered singly and in combination. Int J Parasitol 25:533, 1995 4. Schaeffer MW, Buell JF, Gupta M, et al: Strongyloides hyperinfection syndrome after heart transplantation: case report and review of the literature. J Heart Lung Transplant 23:905, 2004 5. de Paula FM, de Castro E, Goncalves-Pires M, et al: Parasitological and immunological diagnoses of strongyloidiasis in immunocompromised and non-immunocompromised children at Uberlandia, State of Minas Gerais, Brazil. Rev Inst Med Trop Sao Paulo 42:51, 2000 6. Ribeiro LC, Júnior Rodrigues ENA, Silva MD, et al: Púrpura em pacientes com estrongiloiase disseminada. Revista da Sociedade Brasileira de Medicina Tropical 38:255, 2005 7. Salluh JI, Bozza FA, Pinto TS, et al: Cutaneous periumbilical purpura in disseminated strongyloidiasis in cancer patients: a pathognomonic feature of potentially lethal disease? Braz J Infect Dis 9:419, 2005 8. Reddy IS, Swarnalata G: Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: report of two cases. Indian J Dermatol Venereol Leprol 71:38, 2005 9. Lewthwaite P, Gill GV, Hart CA, et al: Gastrointestinal parasites in the immunocompromised. Curr Opin Infect Dis 18: 427, 2005 10. Keiser PB, Nutman TB: Strongyloides stercoralis in the immunocompromised population. Clin Microbiol Rev 17:208, 2004 11. Wulf MW, van Crevel R, Portier R, et al: Toxoplasmosis after renal transplantation: implications of a missed diagnosis. J Clin Microbiol 43:3544, 2005 12. Yoo TW, Mlikotic A, Cornford ME, et al: Concurrent cerebral American trypanosomiasis and toxoplasmosis in a patient with AIDS. Clin Infect Dis 39:e30, 2004 13. Walker M, Zunt JR: Parasitic central nervous system infections in immunocompromised hosts. Clin Infect Dis 40:1005, 2005 14. Fiorelli AI, Stolf NA, Honorato R, et al: Later evolution after cardiac transplantation in Chagas’ disease. Transplant Proc 37:2793, 2005 15. Matsuzawa K, Nakamura F, Abe M, et al: Immunosuppressive and antiparasitic effects of cyclosporin A on Hymenolepis nana infection in mice. Int J Parasitol 28:579, 1998
Parasitic Infection in Renal Transplant Recipients C. Valar, E. Keitel, R.L. Dal Prá, D. Gnatta, A.F. Santos, P.D. Bianco, T.C.T. Sukiennik, K.L. Pegas, A.E. Bittar, K.T. Oliveira, and V.D. Garcia ABSTRACT The purpose of this study was to evaluate the prevalence of symptomatic parasitic infections in adult renal transplant recipients. We retrospectively analyzed a sample of 657 adult renal transplant recipients performed from January 2001 to December 2005 for immunosuppression protocol, clinical manifestations, parasite diagnosis, treatments, and outcomes. The prevalence of symptomatic parasitosis infections was 2.4% (16/657). None of the infected patients received cyclosporine in their immunosuppression protocol. Most of the infections were caused by Strongyloids stercoralis (n ⫽ 11), followed by Giardia lamblia (n ⫽ 3), Toxoplasma gondii (n ⫽ 1), and Trypanosoma cruzi: (n ⫽ 1). Strongyloides stercoralis was the most frequent agent, causing three cases of hyperinfection including one fatal case. With the new immunosuppressive regimes there must be a suspicion of parasitic infection to avoid the diagnostic delay that can be fatal. Strategies, including empiric treatment for S. stercoralis, must be considered.
A
BOUT 340 PARASITIC species infect more than 3 billion people worldwide with varying morbidity and mortality.1 Infections cause significant morbidity and mortality among immunosupressed hosts. Acquisition of infection, clinical severity, and outcome of a parasitic disease depend on innate and acquired host immunity as well as on the parasite’s own response against the host when the infection is established. The incidence and prevalence of parasitic infections in transplant recipients is unknown; only a few patients are symptomatic.2 Only 5% of known humanpathogenic parasitic infections have been reported in transplant recipients. This certainly does not represent the true prevalence because only those infections that cause significant morbidity would be expected to find their way into the literature.1 Since the use of cyclosporine (CsA) has become a cornerstone in prophylactic immunosuppresion, this syn0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.01.025 460
drome has become exceedingly rare, owing to the strong parasiticidal effect of the drug against a wide range of organisms, as documented in mice and humans.1,3 The new immunosuppresive drugs used to prevent graft rejection have lead to an increase in parasitic infections in renal
From the Nephrology Service-Renal and Pancreas Transplant Unit (C.V., E.K., R.L.D.P., D.G., A.F.S., P.D.B., A.E.B., K.T.O., V.D.G.); Fundação Faculdade Federal de Ciências Médicas de Porto Alegre (E.K.); Infectious Diseases Control Unit (T.C.T.S.); and Pathology Laboratory (K.L.P.), Complexo Hospitalar Santa Casa de Porto Alegre, Brazil. Address reprint requests to Valter Duro Garcia, Av. Independência, 155. HDVS - 6° andar. Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, RS-Brazil 90025090. E-mail: [email protected] © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 460 – 462 (2007)
PARASITIC INFECTION IN RENAL RECIPIENTS
461
transplant recipients. The purpose of our study was to evaluate the prevalence of symptomatic parasitosis infections in adult renal transplant recipients with request to the immunosupression protocol, diagnosis, treatment, and outcome. METHODS We retrospectively analyzed a sample of 657 renal transplant recipients performed from January 2001 to December 2005. The evaluated variables were imunosuppression, clinical manifestation, diagnosis of parasites, treatment, and outcomes.
RESULTS
The prevalence of symptomatic parasitosis was 2.4% (16/ 657). Among the infected recipients (n ⫽ 16), the mean age was 44.3 ⫾ 12.9 years. Nine patients were male. Twelve patients received induction therapy (75%). Fourteen were recipients of deceased donor kidneys. None received CsA in the immunosupressive protocol: other combinations included tacrolimus, mycophenolate, rapamycin, azathioprine, and prednisone. The distribution of parasites, clinical manifestation, site of parasite identification, and the treatment and outcome of the patients are shown in Table 1. Three patients in our series showed Strongyloides hyperinfection syndrome. The first patient had initial symptoms at 67 days after renal transplantation. S. stercoralis organisms were identified by a duodenal biopsy; the treatment was thiabendazole. She died due to sepsis 17 days after the first symptoms. The second patient showed nonspecific symptoms at 54 days after transplantation. Bronchoalveolar lavage fluid revealed multiple S. stercoralis organisms. He received thiabendazole, ivermectin, and metronidazole to treat the infection. Blood cultures were positive for grampositive cocci. He presented recurrent infection. The third patient displayed S. stercoralis in the sputum. He received treatment with thiabendazole and had complete recovery. All three patients received induction therapy and were recipients of deceased donor organs. The other eight patients infected by S. stercoralis had a good treatment response; one patient presented with recurrent infection. The patient with toxoplasmosis had a sero-
logic diagnosis that confirmed the infection among the differential diagnostic entities for persistent pyrexia. Serologic testing for Toxoplasma gondii antibodies were positive before the renal transplantation. The recrudescence of a dormant infection explained this infection. The subject had a good response to sulphadiazine/pyrimethamine. Three patients with giardiasis presented as diarrhea illnesses. Giardia lamblia was isolated by a fresh stool. They were treated with metronidazole (two patients) and albendazole (one patient). The Trypanossoma cruzi infection had an usual neurologic presentation. The diagnosis was reached by a biopsy of central nervous system lesion. Benzonidazole was used with success. Immunosuppression is most pronounced from month 1 to month 6; infection is most often due to common bacterial pathogens or opportunistic pathogens present in the environment or host.13 Thirteen of 16 patients showed their first symptoms in this period. The other three patients showed the parasitological symptoms seven months after the kidney transplant. None of 16 patients were under CsA regime. DISCUSSION
Most parasite infections are characterized by low morbidity. They can exist in a transplant recipient without important clinical sequel.1 Among 657 renal transplant recipients, only 16 patients showed symptoms and had a confirmed diagnosis. Most infections were caused by Strongyloides stercoralis; the main symptoms were gastrointestinal. This is a helmintic parasite endemic to tropical and subtropical areas. The cycle of autoinfection can perpetuate in healthy hosts, causing chronic or subclinical infections that may persist for decades without an adverse event.4,5 However, in immunocompromised hosts S. stercoralis may cause a frequently fatal hyperinfection or disseminated disease.4 – 6 Strongyloides hyperinfection syndrome occurs when the normal life cycle of S. stercoralis infestation is augmented in humans, resulting in a massive infection of the gastrointestinal tract, circulation, and lung.6 Corticosteroid therapy and malnutrition may change the host parasite relationship, resulting in hyperinfection and dissemination.4,7–9
Table 1. Characteristics of Parasitic Infection in Renal Transplant Recipients Parasites
Total Number of Patients Infected
Strongyloides stercoralis
11
Symptoms
n
Gastrointestinal Pulmonary Pruritus
8 2 1
Site of Parasitic Identification
n
Treatment
n
Outcome
n
8
Ivermectin Thiabendazole Albendazole Albendazole/ Thiabendazole Metronidazole Albendazole Sulfadiazine/ pyrimethamine Benzonidazole
1 8 4 1
Hyperinfection (2 recover and 1 death) Recurrent infection
3
2 1 1
Complete recover
3
Complete recover
1
1
Complete recover
1
Giardia lamblia
3
Gastrointestinal
3
Stool fresh Bronchoalveolar lavage fluid Sputum Duodenal biopsy Stool fresh
Toxoplasma gondii
1
Pyrexia
1
Serology
1
Trypanossoma cruzi
1
Neurologic
1
Biopsy of Central nervous system lesion
1
3
2
462
Disseminated strongyloidiasis is asymptomatic in the majority of individuals. Examination of a stool sample should be mandatory for all patients on long-term immunosuppressive therapy to prevent the disease’s morbidity and mortality.7,8,10 S. stercoralis is one of most difficult parasitic infections to diagnose. The parasitological methods have low sensivity even when repeated several times. They must be performed on fresh stools, rarely a standard procedure in hospital clinical laboratories.5,9 Paula et al showed the value of an indirect immunofluorescence antibody test and enzyme-linked immunosorbent assay to detect IgG and IgM antibodies to diagnose human strongyloidiasis among immunocompromised hosts. This assay contributed to the establishment of the diagnosis of this parasitosis and the possibility of early treatment. A useful evaluation may involve a combination of tests; for example, serology, serial examination, and differential white blood cell count. Otherwise unexplained eosinophilia should prompt an evaluation for occult parasitic infection, including strongyloidiasis. Unfortunately, eosinophilia is not a common finding because corticosteroids depress cell-mediated immunity.4,7 Posttransplant toxoplasmosis has been reported most frequently with heart transplants, but it remains a rare but significant pathogen in renal transplant recipients.1,11 There are few reports in the literature regarding giardiasis in immunocompromised hosts and no reports on the effect of the drugs cell-mediated immunity on the outcome of Giardia infections humans. De novo Trypanosoma cruzi infections have been reported1 and cerebral infections in patients with acquired immunodeficiency syndrome, but it is rare in renal transplant recipents.12 Immunosuppression breaks the balance between the agent and the host in the chronic phase of disease. It is known that cyclosporine has antiparasitic actions in vitro toward malaria and schistosomiasis. It has reduced the incidence of strongyloidiasis in renal transplant recipients. However, this effect was not described with other infectious agents.13,14 The mechanism of action is unclear. In laboratory models CsA reduces survival, growth, or fecundity in a wide range of protozoans and helminths.15 In conclusion, parasitic and protozoan infections remain a challenge in diagnosis because immunocompromised hosts are usually asymptomatic and the blood cell count can
VALAR, KEITEL, DAL PRÁ ET AL
be normal. The suspicion of a parasite infection must be kept in mind to avoid a diagnostic delay that can be fatal. With the new imunosuppressive strategies, empiric treatment and advances in the diagnosis, especially for S. stercoralis, should be considered in transplant patients. REFERENCES 1. Barsoum RS: Parasitic infections in organ transplantation. Exp Clin Transplant 2:258, 2004 2. Thom K, Forrest G: Gastrointestinal infections in immunocompromised hosts. Curr Opin Gastroenterol 22:18, 2006 3. Cunningham GA, Grubb WB, Mendis AH, et al: Murine strongyloidiasis: the effects of cyclosporin A and thiabendazole administered singly and in combination. Int J Parasitol 25:533, 1995 4. Schaeffer MW, Buell JF, Gupta M, et al: Strongyloides hyperinfection syndrome after heart transplantation: case report and review of the literature. J Heart Lung Transplant 23:905, 2004 5. de Paula FM, de Castro E, Goncalves-Pires M, et al: Parasitological and immunological diagnoses of strongyloidiasis in immunocompromised and non-immunocompromised children at Uberlandia, State of Minas Gerais, Brazil. Rev Inst Med Trop Sao Paulo 42:51, 2000 6. Ribeiro LC, Júnior Rodrigues ENA, Silva MD, et al: Púrpura em pacientes com estrongiloiase disseminada. Revista da Sociedade Brasileira de Medicina Tropical 38:255, 2005 7. Salluh JI, Bozza FA, Pinto TS, et al: Cutaneous periumbilical purpura in disseminated strongyloidiasis in cancer patients: a pathognomonic feature of potentially lethal disease? Braz J Infect Dis 9:419, 2005 8. Reddy IS, Swarnalata G: Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: report of two cases. Indian J Dermatol Venereol Leprol 71:38, 2005 9. Lewthwaite P, Gill GV, Hart CA, et al: Gastrointestinal parasites in the immunocompromised. Curr Opin Infect Dis 18: 427, 2005 10. Keiser PB, Nutman TB: Strongyloides stercoralis in the immunocompromised population. Clin Microbiol Rev 17:208, 2004 11. Wulf MW, van Crevel R, Portier R, et al: Toxoplasmosis after renal transplantation: implications of a missed diagnosis. J Clin Microbiol 43:3544, 2005 12. Yoo TW, Mlikotic A, Cornford ME, et al: Concurrent cerebral American trypanosomiasis and toxoplasmosis in a patient with AIDS. Clin Infect Dis 39:e30, 2004 13. Walker M, Zunt JR: Parasitic central nervous system infections in immunocompromised hosts. Clin Infect Dis 40:1005, 2005 14. Fiorelli AI, Stolf NA, Honorato R, et al: Later evolution after cardiac transplantation in Chagas’ disease. Transplant Proc 37:2793, 2005 15. Matsuzawa K, Nakamura F, Abe M, et al: Immunosuppressive and antiparasitic effects of cyclosporin A on Hymenolepis nana infection in mice. Int J Parasitol 28:579, 1998