Advertisement

International Journal of Hematology

, Volume 104, Issue 6, pp 729–740 | Cite as

Clinical characteristics and computed tomography findings of pulmonary toxoplasmosis after hematopoietic stem cell transplantation

  • Masahiko SumiEmail author
  • Kazumi Norose
  • Kenji Hikosaka
  • Hiroko Kaiume
  • Wataru Takeda
  • Takehiko Kirihara
  • Taro Kurihara
  • Keijiro Sato
  • Toshimitsu Ueki
  • Yuki Hiroshima
  • Hiroshi Kuraishi
  • Masahide Watanabe
  • Hikaru Kobayashi
Original Article

Abstract

The prognosis of pulmonary toxoplasmosis, including disseminated toxoplasmosis involving the lungs, following hematopoietic stem cell transplantation (HSCT) is extremely poor due to the difficulties associated with early diagnosis and the rapidly progressive deterioration of multiorgan function. In our institution, we identified nine cases of toxoplasmosis, representing incidences of 2.2 and 19.6 % among all HSCT recipients and seropositive HSCT recipients, respectively. Of the patients with toxoplasmosis, six had pulmonary toxoplasmosis. Chest computed tomography (CT) findings revealed centrilobular, patchy ground-glass opacities (n = 3), diffuse ground-glass opacities (n = 2), ground-glass opacities with septal thickening (n = 1), and marked pleural effusion (n = 1). All cases died, except for one with suspected pulmonary toxoplasmosis who was diagnosed by a polymerase chain reaction assay 2 days after the onset of symptoms. In pulmonary toxoplasmosis, CT findings are non-specific and may mimic pulmonary congestion, atypical pneumonia, viral pneumonitis, and bronchopneumonia. Early diagnosis and treatment is crucial for overcoming this serious infectious complication. Pulmonary toxoplasmosis should be considered during differential diagnosis in a recipient with otherwise unexplained signs of infection and CT findings with ground-glass opacities, regardless of the distribution.

Keywords

Toxoplasma gondii Pulmonary toxoplasmosis Disseminated toxoplasmosis Stem cell transplantation 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004;363:1965–76.CrossRefPubMedGoogle Scholar
  2. 2.
    Saadatnia G, Golkar M. A review on human toxoplasmosis. Scand J Infect Dis. 2012;44:805–14.CrossRefPubMedGoogle Scholar
  3. 3.
    Hakko E, Ozkan HA, Karaman K, Gulbas Z. Analysis of cerebral toxoplasmosis in a series of 170 allogeneic hematopoietic stem cell transplant patients. Transpl Infect Dis. 2013;15:575–80.CrossRefPubMedGoogle Scholar
  4. 4.
    Miyagi T, Itonaga H, Aosai F, Taguchi J, Norose K, Mochizuki K, et al. Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two case reports and review of the literature. Transpl Infect Dis. 2015;17:593–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Martino R, Maertens J, Bretagne S, Rovira M, Deconinck E, Ullmann AJ, et al. Toxoplasmosis after hematopoietic stem cell transplantation. Clin Infect Dis. 2000;31:1188–95.CrossRefPubMedGoogle Scholar
  6. 6.
    de Medeiros BC, de Medeiros CR, Werner B, Loddo G, Pasquini R, Bleggi-Torres LF. Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases. Transpl Infect Dis. 2001;3:24–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Chandrasekar PH, Momin F. Disseminated toxoplasmosis in marrow recipients: a report of three cases and a review of the literature. Bone Marrow Transplant. 1997;19:685–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Bautista G, Ramos A, Forés R, Regidor C, Ruiz E, de Laiglesia A, et al. Toxoplasmosis in cord blood transplantation recipients. Transpl Infect Dis. 2012;14:496–501.CrossRefPubMedGoogle Scholar
  9. 9.
    Schmidt M, Sonneville R, Schnell D, Bigé N, Hamidfar R, Mongardon N, et al. Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study. Clin Infect Dis. 2013;57:1535–41.CrossRefPubMedGoogle Scholar
  10. 10.
    Goebel WS, Conway JH, Faught P, Vakili ST, Haut PR. Disseminated toxoplasmosis resulting in graft failure in a cord blood stem cell transplant recipient. Pediatr Blood Cancer. 2007;48:222–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Sing A, Leitritz L, Roggenkamp A, Kolb HJ, Szabados A, Fingerle V, et al. Pulmonary toxoplasmosis in bone marrow transplant recipients: report of two cases and review. Clin Infect Dis. 1999;29:429–33.CrossRefPubMedGoogle Scholar
  12. 12.
    Pappas G, Roussos N, Falagas ME. Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol. 2009;39:1385–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Derouin F, Pelloux H, ESCMID Study Group on Clinical Parasitology. Prevention of toxoplasmosis in transplant patients. Clin Microbiol Infect. 2008;14:1089–101.CrossRefPubMedGoogle Scholar
  14. 14.
    Mulanovich VE, Ahmed SI, Öztürk T, Khokhar FA, Kontoyiannis DP, de Lima M. Toxoplasmosis in allo-SCT patients: risk factors and outcomes at a transplantation center with a low incidence. Bone Marrow Transplant. 2011;46:273–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Martino R, Bretagne S, Einsele H, Maertens J, Ullman AJ, Parody R, et al. Early detection of Toxoplasma infection by molecular monitoring of Toxoplasma gondii in peripheral blood samples after allogeneic stem cell transplantation. Clin Infect Dis. 2005;40:67–78.CrossRefPubMedGoogle Scholar
  16. 16.
    Sakikawa M, Noda S, Hanaoka M, Nakayama H, Hojo S, Kakinoki S, et al. Anti-Toxoplasma antibody prevalence, primary infection rate, and risk factors in a study of toxoplasmosis in 4,466 pregnant women in Japan. Clin Vaccine Immunol. 2012;19:365–7.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Goto K, Kurita M, Masuhara N, Iijima Y, Saeki K, Ohno S. The prevalence of Toxoplasma antibody in patients with various ocular diseases in central Japan. Graefes Arch Clin Exp Ophthalmol. 1996;234:493–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Matsuo Y, Takeishi S, Miyamoto T, Nonami A, Kikushige Y, Kunisaki Y, et al. Toxoplasmosis encephalitis following severe graft-vs.-host disease after allogeneic hematopoietic stem cell transplantation: 17 yr experience in Fukuoka BMT group. Eur J Haematol. 2007;79:317–21.CrossRefPubMedGoogle Scholar
  19. 19.
    Sumi M, Aosai F, Norose K, Takeda W, Kirihara T, Sato K, et al. Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients. Int J Hematol. 2013;98:214–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Gajurel K, Dhakal R, Montoya JG. Toxoplasma prophylaxis in haematopoietic cell transplant recipients: a review of the literature and recommendations. Curr Opin Infect Dis. 2015;28:283–92.CrossRefPubMedGoogle Scholar
  21. 21.
    Robert-Gangneux F, Sterkers Y, Yera H, Accoceberry I, Menotti J, Cassaing S, et al. Molecular diagnosis of toxoplasmosis in immunocompromised patients: a 3-year multicenter retrospective study. J Clin Microbiol. 2015;53:1677–84.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Burg JL, Perelman D, Kasper LH, Ware PL, Boothroyd JC. Molecular analysis of the gene encoding the major surface antigen of Toxoplasma gondii. J Immunol. 1988;141:3584–91.PubMedGoogle Scholar
  23. 23.
    Burg JL, Grover CM, Pouletty P, Boothroyd JC. Direct and sensitive detection of a pathogenic protozoan, Toxoplasma gondii, by polymerase chain reaction. J Clin Microbiol. 1989;27:1787–92.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Mikita K, Maeda T, Ono T, Miyahira Y, Asai T, Kawana A. The utility of cerebrospinal fluid for the molecular diagnosis of toxoplasmic encephalitis. Diagn Microbiol Infect Dis. 2013;75:155–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Sumi M, Hata S, Sato K, Fujikawa Y, Shimizu I, Ueki T, et al. Severe pulmonary toxoplasmosis mimicking viral pneumonitis after a third allogeneic stem cell transplantation in a man with acute lymphoblastic leukemia. Intern Med. 2012;51:2943–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Kurihara T, Sumi M, Kaiume H, Takeda W, Kirihara T, Sato K, et al. Successful treatment of disseminated toxoplasmosis after cord blood transplantation by early diagnosis. Rinsho Ketsueki. 2016;57:736–41.PubMedGoogle Scholar
  28. 28.
    Döring M, Cabanillas Stanchi KM, Feucht J, Queudeville M, Teltschik HM, Lang P, Feuchtinger T, et al. Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients. Ann Hematol. 2016;95:311–23.CrossRefPubMedGoogle Scholar
  29. 29.
    Duband S, Cornillon J, Tavernier E, Dumollard JM, Guyotat D, Péoc’h M. Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy. Transpl Infect Dis. 2008;10:372–4.CrossRefPubMedGoogle Scholar
  30. 30.
    Segall L, Moal MC, Doucet L, Kergoat N, Bourbigot B. Toxoplasmosis-associated hemophagocytic syndrome in renal transplantation. Transpl Int. 2006;19:78–80.CrossRefPubMedGoogle Scholar
  31. 31.
    Karras A, Thervet E, Legendre C, Groupe Coopératif de transplantation d’Ile de France. Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004;77:238–43.CrossRefPubMedGoogle Scholar
  32. 32.
    Janka GE, Lehmberg K. Hemophagocytic syndromes—an update. Blood Rev. 2014;28:135–42.CrossRefPubMedGoogle Scholar
  33. 33.
    Volanakis JE. Human C-reactive protein: expression, structure, and function. Mol Immunol. 2001;38:189–97.CrossRefPubMedGoogle Scholar
  34. 34.
    Suzuki Y, Rani S, Liesenfeld O, Kojima T, Lim S, Nguyen TA, et al. Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice. Infect Immun. 1997;65:2339–45.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Heegaard PM, Stockmarr A, Piñeiro M, Carpintero R, Lampreave F, Campbell FM, et al. Optimal combinations of acute phase proteins for detecting infectious disease in pigs. Vet Res. 2011;42:50.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Birgisdóttir A, Asbjörnsdottir H, Cook E, Gislason D, Jansson C, Olafsson I, et al. Seroprevalence of Toxoplasma gondii in Sweden, Estonia and Iceland. Scand J Infect Dis. 2006;38:625–31.CrossRefPubMedGoogle Scholar
  37. 37.
    Mese S, Ozekinci T, Atmaca S. Investigation of correlation between Toxoplasma gondii IgG positivity and Hs-CRP. Scand J Infect Dis. 2007;39:922.CrossRefPubMedGoogle Scholar
  38. 38.
    Albrecht H, Skörde J, Arasteh K, Heise W, Stellbrink HJ, Grosse G, et al. Disseminated toxoplasmosis in AIDS patients–report of 16 cases. Scand J Infect Dis. 1995;27:71–4.CrossRefPubMedGoogle Scholar
  39. 39.
    Costalonga EC, Melo NC, Rodrigues CE, Sette LH, Ianhez LE. The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients. Clin Transplant. 2009;23:710–5.CrossRefPubMedGoogle Scholar
  40. 40.
    Escuissato DL, Gasparetto EL, Marchiori E, Rocha Gde M, Inoue C, Pasquini R, et al. Pulmonary infections after bone marrow transplantation: high-resolution CT findings in 111 patients. AJR Am J Roentgenol. 2005;185:608–15.CrossRefPubMedGoogle Scholar
  41. 41.
    Pomeroy C, Filice GA. Pulmonary toxoplasmosis: a review. Clin Infect Dis. 1992;14:863–70.CrossRefPubMedGoogle Scholar
  42. 42.
    Campagna AC. Pulmonary toxoplasmosis. Semin Respir Infect. 1997;12:98–105.PubMedGoogle Scholar
  43. 43.
    Escuissato DL, de Aguiar RO, Gasparetto EL, Müller NL. Disseminated toxoplasmosis after bone marrow transplantation: high-resolution CT appearance. J Thorac Imaging. 2004;19:207–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Marchiori E, Escuissato DL, Gasparetto TD, Considera DP, Franquet T. “Crazy-paving” patterns on high-resolution CT scans in patients with pulmonary complications after hematopoietic stem cell transplantation. Korean J Radiol. 2009;10:21–4.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Nash G, Kerschmann RL, Herndier B, Dubey JP. The pathological manifestations of pulmonary toxoplasmosis in the acquired immunodeficiency syndrome. Hum Pathol. 1994;25:652–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Parker GA, Langloss JM, Dubey JP, Hoover EA. Pathogenesis of acute toxoplasmosis in specific-pathogen-free cats. Vet Pathol. 1981;18:786–803.CrossRefPubMedGoogle Scholar
  47. 47.
    Mendorf A, Klyuchnikov E, Langebrake C, Rohde H, Ayuk F, Regier M, et al. Atovaquone for prophylaxis of toxoplasmosis after allogeneic hematopoietic stem cell transplantation. Acta Haematol. 2015;134:146–54.CrossRefPubMedGoogle Scholar
  48. 48.
    Osthoff M, Chew E, Bajel A, Kelsey G, Panek-Hudson Y, Mason K, et al. Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient. Transpl Infect Dis. 2013;15:E14–9.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Masahiko Sumi
    • 1
    Email author
  • Kazumi Norose
    • 2
  • Kenji Hikosaka
    • 2
  • Hiroko Kaiume
    • 1
  • Wataru Takeda
    • 1
  • Takehiko Kirihara
    • 1
  • Taro Kurihara
    • 1
  • Keijiro Sato
    • 1
  • Toshimitsu Ueki
    • 1
  • Yuki Hiroshima
    • 1
  • Hiroshi Kuraishi
    • 3
  • Masahide Watanabe
    • 4
  • Hikaru Kobayashi
    • 1
  1. 1.Department of HematologyNagano Red Cross HospitalNagano CityJapan
  2. 2.Department of Infection and Host Defense, Graduate School of MedicineChiba UniversityChibaJapan
  3. 3.Respiratory DivisionNagano Red Cross HospitalNagano CityJapan
  4. 4.Department of PathologyNagano Red Cross HospitalNagano CityJapan

Personalised recommendations