Acanthamoeba, Naegleria, and Balamuthia in Transplant Patients: An Emerging Threat

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Free-living amoebae (FLA) are ubiquitous in the environment. Although they rarely cause infection in humans, when they do so, the infection is often severe and diagnosed late. The three most clinically relevant genera of FLA are Acanthamoeba spp., Naegleria fowleri, and Balamuthia mandrillaris. An increasing body of literature points to these organisms as potential disease-causing agents in immunocompromised and transplant patients, particularly with regard to donor-derived infections. This chapter will review the salient features, diagnostic modalities, and therapeutic recommendations of these infections in transplant patients.


Naegleria fowleri Acanthamoeba Balamuthia mandirllaris Primary amebic meningoencephalitis Granulomatous amebic encephealitis Donor-derived infection 



The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.


  1. 1.
    La Hoz RM, Morris MI, Infectious Diseases Community of Practice of the American Society of Transplantation. Tissue and blood protozoa including toxoplasmosis, Chagas disease, leishmaniasis, Babesia, Acanthamoeba, Balamuthia, & Naegleria in solid organ transplant recipients – guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation. Clin Transplant. 2019;33:e13546.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Wolfe CR, Ison MG, The ASTIDCoP. Donor-derived infections: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33:e13547.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Siddiqui R, Khan NA. Biology and pathogenesis of Acanthamoeba. Parasit Vectors. 2012;5:6.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Szentmary N, Daas L, Shi L, Laurik KL, Lepper S, Milioti G, et al. Acanthamoeba keratitis – clinical signs, differential diagnosis and treatment. J Curr Ophthalmol. 2019;31(1):16–23.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Centers for Disease Control and Prevention. Acanthamoeba keratitis multiple states, 2005–2007. MMWR Morb Mortal Wkly Rep. 2007;56(21):532–4.Google Scholar
  6. 6.
    Barete S, Combes A, de Jonckheere JF, Datry A, Varnous S, Martinez V, et al. Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant patient. Emerg Infect Dis. 2007;13(5):736–8.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Brondfield MN, Reid MJ, Rutishauser RL, Cope JR, Tang J, Ritter JM, et al. Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: case report and review of the literature. Transpl Infect Dis. 2017;19(2):e12661.
  8. 8.
    Harrison WT, Lecky B, Hulette CM. Fatal granulomatous amebic encephalitis in a heart transplant patient: clinical, radiographic, and autopsy findings. J Neuropathol Exp Neurol. 2018;77(11):1001–4.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Kutner A, Aldrich M, Patel S, Kang JJ, Amin B, Mann R, et al. Acanthamoeba endophthalmitis during treatment for cutaneous disease in a renal transplant patient. Transpl Infect Dis. 2018;20(2):e12843.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Salameh A, Bello N, Becker J, Zangeneh T. Fatal granulomatous amoebic encephalitis caused by Acanthamoeba in a patient with kidney transplant: a case report. Open Forum Infect Dis. 2015;2(3):ofv104.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Breland M, Beckmann N. Amebic osteomyelitis in an immunocompromised patient. Radiol Case Rep. 2016;11(3):207–11.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Satlin MJ, Graham JK, Visvesvara GS, Mena H, Marks KM, Saal SD, et al. Fulminant and fatal encephalitis caused by Acanthamoeba in a kidney transplant recipient: case report and literature review. Transpl Infect Dis. 2013;15(6):619–26.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Mutreja D, Jalpota Y, Madan R, Tewari V. Disseminated Acanthamoeba infection in a renal transplant recipient: a case report. Indian J Pathol Microbiol. 2007;50(2):346–8.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Steinberg JP, Galindo RL, Kraus ES, Ghanem KG. Disseminated acanthamebiasis in a renal transplant recipient with osteomyelitis and cutaneous lesions: case report and literature review. Clin Infect Dis. 2002;35(5):e43–9.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Afshar K, Boydking A, Ganesh S, Herrington C, McFadden PM. Rapidly fatal disseminated acanthamoebiasis in a single lung transplant recipient. Ann Transplant. 2013;18:108–11.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Walia R, Montoya JG, Visvesvera GS, Booton GC, Doyle RL. A case of successful treatment of cutaneous Acanthamoeba infection in a lung transplant recipient. Transpl Infect Dis. 2007;9(1):51–4.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Duarte AG, Sattar F, Granwehr B, Aronson JF, Wang Z, Lick S. Disseminated acanthamoebiasis after lung transplantation. J Heart Lung Transplant. 2006;25(2):237–40.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Vernon SE, Acar BC, Pham SM, Fertel D. Acanthamoeba infection in lung transplantation: report of a case and review of the literature. Transpl Infect Dis. 2005;7(3–4):154–7.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Morrison AO, Morris R, Shannon A, Lauer SR, Guarner J, Kraft CS. Disseminated Acanthamoeba infection presenting with cutaneous lesions in an immunocompromised patient: a case report, review of histomorphologic findings, and potential diagnostic pitfalls. Am J Clin Pathol. 2016;145(2):266–70.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Voshtina E, Huang H, Raj R, Atallah E. Amebic encephalitis in a patient with chronic lymphocytic leukemia on Ibrutinib therapy. Case Rep Hematol. 2018;2018:6514604.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Nampoothiri RV, Malhotra P, Jain A, Batra N, Gupta K, Saj F, et al. An unusual cause of central nervous system infection during acute myeloid leukemia induction chemotherapy: Acanthamoeba brain abscess. Indian J Hematol Blood Transfus. 2018;34(1):153–5.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Coven SL, Song E, Steward S, Pierson CR, Cope JR, Ali IK, et al. Acanthamoeba granulomatous amoebic encephalitis after pediatric hematopoietic stem cell transplant. Pediatr Transplant. 2017;21(8):e13060.
  23. 23.
    Epperla N, Olteanu H, Hamadani M. Think outside the box: Acanthamoeba encephalitis following autologous haematopoietic stem cell transplantation. Br J Haematol. 2016;175(5):758.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Juan A, Alonso L, Olive T, Navarro A, Sulleiro E, Sanchez de Toledo J, et al. Successful treatment of sinusitis by Acanthamoeba in a pediatric patient after allogeneic stem cell transplantation. Pediatr Infect Dis J. 2016;35(12):1350–1.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Akpek G, Uslu A, Huebner T, Taner A, Rapoport AP, Gojo I, et al. Granulomatous amebic encephalitis: an under-recognized cause of infectious mortality after hematopoietic stem cell transplantation. Transpl Infect Dis. 2011;13(4):366–73.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Abd H, Saeed A, Jalal S, Bekassy AN, Sandstrom G. Ante mortem diagnosis of amoebic encephalitis in a haematopoietic stem cell transplanted patient. Scand J Infect Dis. 2009;41(8):619–22.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Kaul DR, Lowe L, Visvesvara GS, Farmen S, Khaled YA, Yanik GA. Acanthamoeba infection in a patient with chronic graft-versus-host disease occurring during treatment with voriconazole. Transpl Infect Dis. 2008;10(6):437–41.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Peman J, Jarque I, Frasquet J, Alberola C, Salavert M, Sanz J, et al. Unexpected postmortem diagnosis of Acanthamoeba meningoencephalitis following allogeneic peripheral blood stem cell transplantation. Am J Transplant. 2008;8(7):1562–6.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Castellano-Sanchez A, Popp AC, Nolte FS, Visvesvara GS, Thigpen M, Redei I, et al. Acanthamoeba castellani encephalitis following partially mismatched related donor peripheral stem cell transplantation. Transpl Infect Dis. 2003;5(4):191–4.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Feingold JM, Abraham J, Bilgrami S, Ngo N, Visvesara GS, Edwards RL, et al. Acanthamoeba meningoencephalitis following autologous peripheral stem cell transplantation. Bone Marrow Transplant. 1998;22(3):297–300.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Cope JR, Roy S, Ali I. Oral Abstract 865. Acanthamoeba Disease Associated with the Practice of Nasal Rinsing in Immunocompromised Patients. IDWeek 2018; October 4, 2018; San Francisco, CA2018.Google Scholar
  32. 32.
    Fowler M, Carter RF. Acute pyogenic meningitis probably due to Acanthamoeba sp.: a preliminary report. Br Med J. 1965;2(5464):740–2.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Butt CG. Primary amebic meningoencephalitis. N Engl J Med. 1966;274(26):1473–6.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Lam C, He L, Marciano-Cabral F. The effect of different environmental conditions on the viability of Naegleria fowleri amoebae. J Eukaryot Microbiol. 2019;66:752.PubMedCrossRefGoogle Scholar
  35. 35.
    Siddiqui R, Ali IKM, Cope JR, Khan NA. Biology and pathogenesis of Naegleria fowleri. Acta Trop. 2016;164:375–94.PubMedCrossRefGoogle Scholar
  36. 36.
    Cope JR, Ali IK. Primary amebic meningoencephalitis: what have we learned in the last 5 years? Curr Infect Dis Rep. 2016;18(10):31.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Yoder JS, Eddy BA, Visvesvara GS, Capewell L, Beach MJ. The epidemiology of primary amoebic meningoencephalitis in the USA, 1962–2008. Epidemiol Infect. 2010;138(07):968–75.PubMedCrossRefGoogle Scholar
  38. 38.
    Capewell LG, Harris AM, Yoder JS, Cope JR, Eddy BA, Roy SL, et al. Diagnosis, clinical course, and treatment of primary amoebic meningoencephalitis in the United States, 1937–2013. J Pediatric Infect Dis Soc. 2015;4(4):e68–75.PubMedCrossRefGoogle Scholar
  39. 39.
    Matanock A, Mehal JM, Liu L, Blau DM, Cope JR. Estimation of undiagnosed Naegleria fowleri primary amebic meningoencephalitis, United States(1). Emerg Infect Dis. 2018;24(1):162–4.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Roy SL, Metzger R, Chen JG, Laham FR, Martin M, Kipper SW, et al. Risk for transmission of Naegleria fowleri from solid organ transplantation. Am J Transplant. 2014;14(1):163–71.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Visvesvara GS, Martinez AJ, Schuster FL, Leitch GJ, Wallace SV, Sawyer TK, et al. Leptomyxid ameba, a new agent of amebic meningoencephalitis in humans and animals. J Clin Microbiol. 1990;28(12):2750–6.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Cope JR, Landa J, Nethercut H, Collier SA, Glaser C, Moser M, et al. The epidemiology and clinical features of Balamuthia mandrillaris disease in the United States, 1974–2016. Clin Infect Dis. 2019 68(11):1815–1822.Google Scholar
  43. 43.
    Maritschnegg P, Sovinz P, Lackner H, Benesch M, Nebl A, Schwinger W, et al. Granulomatous amebic encephalitis in a child with acute lymphoblastic leukemia successfully treated with multimodal antimicrobial therapy and hyperbaric oxygen. J Clin Microbiol. 2011;49(1):446–8.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Epperla N, Olteanu H, Hamadani M. Think outside the box: Acanthamoeba encephalitis following autologous haematopoietic stem cell transplantation. Br J Haematol. 2016;175:758.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Ong TYY, Khan NA, Siddiqui R. Brain-eating amoebae: predilection sites in the brain and disease outcome. J Clin Microbiol. 2017;55(7):1989–97.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Qvarnstrom Y, Visvesvara GS, Sriram R, da Silva AJ. Multiplex real-time PCR assay for simultaneous detection of Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri. J Clin Microbiol. 2006;44(10):3589–95.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Yokoe D, Casper C, Dubberke E, Lee G, Munoz P, Palmore T, et al. Safe living after hematopoietic cell transplantation. Bone Marrow Transplant. 2009;44(8):509–19.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Smalley HK, Anand N, Buczek D, Buczek N, Lin T, Rajore T, et al. Assessment of risk for transplant-transmissible infectious encephalitis among deceased organ donors. Transpl Infect Dis. 2018;20(5):e12933.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Bennett WM, Nespral JF, Rosson MW, McEvoy KM. Use of organs for transplantation from a donor with primary meningoencephalitis due to Naegleria fowleri. Am J Transplant. 2008;8(6):1334–5.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Kramer MH, Lerner CJ, Visvesvara GS. Kidney and liver transplants from a donor infected with Naegleria fowleri. J Clin Microbiol. 1997;35(4):1032–3.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Avery RK, Michaels MG, Practice ASTIDCo. Strategies for safe living following solid organ transplantation – guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33:e13519.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Farnon EC, Kokko KE, Budge PJ, Mbaeyi C, Lutterloh EC, Qvarnstrom Y, et al. Transmission of Balamuthia mandrillaris by organ transplantation. Clin Infect Dis. 2016;63(7):878–88.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Centers for Disease Control and Prevention (CDC). Balamuthia mandrillaris transmitted through organ transplantation – Mississippi, 2009. MMWR Morb Mortal Wkly Rep. 2010;59(36):1165–70.Google Scholar
  54. 54.
    Centers for Disease Control and Prevention (CDC). Notes from the field: transplant-transmitted Balamuthia mandrillaris – Arizona, 2010. MMWR Morb Mortal Wkly Rep. 2010;59(36):1182.Google Scholar
  55. 55.
    Gupte AA, Hocevar SN, Lea AS, Kulkarni RD, Schain DC, Casey MJ, et al. Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management. Am J Transplant. 2014;14(6):1417–24.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Sparkes T, Lemonovich TL, Practice ASTIDCo. Interactions between anti-infective agents and immunosuppressants – guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33:e13510.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Aichelburg AC, Walochnik J, Assadian O, Prosch H, Steuer A, Perneczky G, et al. Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine. Emerg Infect Dis. 2008;14(11):1743–6.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Centers for Disease Control and Prevention. Investigational drug available directly from CDC for the treatment of infections with free-living amebae. MMWR Morb Mortal Wkly Rep. 2013;62(33):666.Google Scholar
  59. 59.
    Cope JR, Conrad DA, Cohen N, Cotilla M, DaSilva A, Jackson J, et al. Use of the novel therapeutic agent miltefosine for the treatment of primary amebic meningoencephalitis: report of 1 fatal and 1 surviving case. Clin Infect Dis. 2016;62(6):774–6.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Seijo Martinez M, Gonzalez-Mediero G, Santiago P, Rodriguez De Lope A, Diz J, Conde C, et al. Granulomatous amebic encephalitis in a patient with AIDS: isolation of Acanthamoeba sp. Group II from brain tissue and successful treatment with sulfadiazine and fluconazole. J Clin Microbiol. 2000;38(10):3892–5.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol. 2007;50(1):1–26.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Singhal T, Bajpai A, Kalra V, Kabra SK, Samantaray JC, Satpathy G, et al. Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials. Pediatr Infect Dis J. 2001;20(6):623–7.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Slater CA, Sickel JZ, Visvesvara GS, Pabico RC, Gaspari AA. Brief report: successful treatment of disseminated Acanthamoeba infection in an immunocompromised patient. N Engl J Med. 1994;331(2):85–7.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Schuster FL, Visvesvara GS. Free-living amoebae as opportunistic and non-opportunistic pathogens of humans and animals. Int J Parasitol. 2004;34(9):1001–27.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Linam WM, Ahmed M, Cope JR, Chu C, Visvesvara GS, da Silva AJ, et al. Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis. Pediatrics. 2015;135(3):e744–8.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Colon BL, Rice CA, Guy RK, Kyle DE. Phenotypic screens reveal posaconazole as a rapidly acting amebicidal combination partner for treatment of primary amoebic meningoencephalitis. J Infect Dis. 2019;219(7):1095–103.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Laurie MT, White CV, Retallack H, Wu W, Moser MS, Sakanari JA, et al. Functional assessment of 2,177 U.S. and international drugs identifies the quinoline nitroxoline as a potent amoebicidal agent against the pathogen Balamuthia mandrillaris. MBio. 2018;9(5):e02051.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Tan SK, Gajurel K, Tung C, Albers G, Deresinski S, Montoya JG, et al. Fatal Acanthamoeba encephalitis in a patient with a total artificial heart (syncardia) device. Open Forum Infect Dis. 2014;1(2):ofu057.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Wang Q, Li J, Ji J, Yang L, Chen L, Zhou R, et al. A case of Naegleria fowleri related primary amoebic meningoencephalitis in China diagnosed by next-generation sequencing. BMC Infect Dis. 2018;18(1):349.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Basavaraju SV, Kuehnert MJ, Zaki SR, Sejvar JJ. Encephalitis caused by pathogens transmitted through organ transplants, United States, 2002–2013. Emerg Infect Dis. 2014;20(9):1443–51.PubMedPubMedCentralCrossRefGoogle Scholar

Authors and Affiliations

  1. 1.Division of Infectious Diseases, Department of MedicineMontefiore Medical Center and Albert Einstein College of MedicineBronxUSA
  2. 2.Division of Pediatric Infectious Diseases, Department of PediatricsMontefiore Medical Center and Albert Einstein College of MedicineBronxUSA
  3. 3.Waterborne Disease Prevention BranchNational Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionAtlantaUSA

Section editors and affiliations

  • Camille Nelson Kotton
    • 1
  1. 1.Infectious Diseases DivisionHarvard University Medical SchoolBostonUSA

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