History

Most cases of primary amebic meningoencephalitis (PAM) involve a history of exposure to fresh warm water. Patients with PAM generally present with a history of bathing in a pond or lake 2-6 days prior to the onset of symptoms of meningeal irritation.

The index of suspicion should be increased in children and young adults who have a history of recently swimming in freshwater lakes, ponds, and pools. Isolated cases of PAM have followed bathing in tap and hot water.

Clusters of cases of PAM have been documented during the summer months when freshwater sources are warm. The higher temperature during the hot summer months facilitates the growth of N fowleri.

Physical

The physical signs of PAM are similar to those of bacterial meningitis, as follows:

Fever (high temperature up to 40°C)
Alteration in taste (ageusia) or smell (parosmia)
Sudden-onset headache (usually frontal or bitemporal)
Nausea, vomiting, or both
Stiff neck
Photophobia (later in the course of illness)
Positive Kernig and Brudzinski signs
Mental status changes
Hallucinations
Physical findings associated with encephalitis and eventual herniation (cranial nerve palsies, seizures, coma)
Rapid onset of coma and death (within 2 wk)

Causes

PAM is caused by infection with the ameba N fowleri. In 2009, another free-living amoebae, Paravahlkampfia francinae, has been reported to cause PAM.^[31]

Complications

PAM typically is fatal. Death is due to pulmonary edema or cardiorespiratory arrest within a week of appearance of the first symptoms. Persistent seizures may occur in patients who have otherwise recovered.

Workup

Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED). Parasites — Naegleria fowleri — Primary Amebic Meningoencephalitis (PAM) — Amebic Encephalitis. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/parasites/naegleria/index.html. 2017 Feb 28 (last reviewed May 3, 2023); Accessed: September 20, 2023.
Yadav D, Aneja S, Dutta R, Maheshwari A, Seth A. Youngest survivor of naegleria meningitis. Indian J Pediatr. 2013 Mar. 80(3):253-4. [QxMD MEDLINE Link].
Schuster FL. Cultivation of pathogenic and opportunistic free-living amebas. Clin Microbiol Rev. 2002 Jul. 15(3):342-54. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Primary amebic meningoencephalitis--Arizona, Florida, and Texas, 2007. MMWR Morb Mortal Wkly Rep. 2008 May 30. 57(21):573-7. [QxMD MEDLINE Link].
Parija SC. Textbook of Medical Parasitology. Protozoology and Helminthology. 4 ed. New Delhi: All India Publishers and Distributers; 2013.
Cervantes-Sandoval I, Serrano-Luna Jde J, Garcia-Latorre E, Tsutsumi V, Shibayama M. Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion. Microbiology. 2008 Dec. 154(Pt 12):3895-904. [QxMD MEDLINE Link].
Jung SY, Kim JH, Song KJ, Lee YJ, Kwon MH, Kim K. Gene silencing of nfa1 affects the in vitro cytotoxicity of Naegleria fowleri in murine macrophages. Mol Biochem Parasitol. 2009 May. 165(1):87-93. [QxMD MEDLINE Link].
Yoder JS, Eddy BA, Visvesvara GS, Capewell L, Beach MJ. The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-2008. Epidemiol Infect. 2010 Jul. 138(7):968-75. [QxMD MEDLINE Link].
CDC. Parasites-Naegleria fowleri-Primary Amoebic Meningoencephalitis (PAM)- Amebic Encephalitis. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/parasites/naegleria/index.html. May 3, 2023; Accessed: August 28, 2023.
Yoder JS, Straif-Bourgeois S, Roy SL, Moore TA, Visvesvara GS, Ratard RC. Primary amebic meningoencephalitis deaths associated with sinus irrigation using contaminated tap water. Clin Infect Dis. 2012 Nov. 55(9):e79-85. [QxMD MEDLINE Link].
Jamerson M, Remmers K, Cabral G, Marciano-Cabral F. Survey for the presence of Naegleria fowleri amebae in lake water used to cool reactors at a nuclear power generating plant. Parasitol Res. 2009 Apr. 104(5):969-78. [QxMD MEDLINE Link].
Marciano-Cabral F, Jamerson M, Kaneshiro ES. Free-living amoebae, Legionella and Mycobacterium in tap water supplied by a municipal drinking water utility in the USA. J Water Health. 2010 Mar. 8(1):71-82. [QxMD MEDLINE Link].
Laseke I, Korte J, Lamendella R, Kaneshiro ES, Marciano-Cabral F, Oerther DB. Identification of Naegleria fowleri in warm ground water aquifers. J Environ Qual. 2010 Jan-Feb. 39(1):147-53. [QxMD MEDLINE Link].
Kaushal V, Chhina DK, Ram S, Singh G, Kaushal RK, Kumar R. Primary amoebic meningoencephalitis due to Naegleria fowleri. J Assoc Physicians India. 2008 Jun. 56:459-62. [QxMD MEDLINE Link].
Khanna V, Khanna R, Hebbar S, Shashidhar V, Mundkar S, Munim F. Primary Amoebic Meningoencephalitis in an Infant due to Naegleria fowleri. Case Rep Neurol Med. 2011. 2011:782539. [QxMD MEDLINE Link].
Shakoor S, Beg MA, Mahmood SF, Bandea R, Sriram R, Noman F. Primary amebic meningoencephalitis caused by Naegleria fowleri, Karachi, Pakistan. Emerg Infect Dis. 2011 Feb. 17(2):258-61. [QxMD MEDLINE Link].
Herriman R. Sindh Naegleria fowleri death toll reaches a dozen in 2015. Outbreak News Today. 2015.
Phu NH, Hoang Mai NT, Nghia HD, Chau TT, Loc PP, Thai le H. Fatal consequences of freshwater pearl diving. Lancet. 2013 Jan 12. 381(9861):176. [QxMD MEDLINE Link].
Ithoi I, Ahmad AF, Nissapatorn V, Lau YL, Mahmud R, Mak JW. Detection of Naegleria species in environmental samples from Peninsular Malaysia. PLoS One. 2011. 6(9):e24327. [QxMD MEDLINE Link].
Tung MC, Hsu BM, Tao CW, Lin WC, Tsai HF, Ji DD. Identification and significance of Naegleria fowleri isolated from the hot spring which related to the first primary amebic meningoencephalitis (PAM) patient in Taiwan. Int J Parasitol. 2013 May 9. [QxMD MEDLINE Link].
Ozçelik S, Coskun KA, Yunlu O, Alim A, Malatyali E. The prevalence, isolation and morphotyping of potentially pathogenic free-living amoebae from tap water and environmental water sources in Sivas. Turkiye Parazitol Derg. 2012. 36(4):198-203. [QxMD MEDLINE Link].
Shin HJ, Im KI. Pathogenic free-living amoebae in Korea. Korean J Parasitol. 2004 Sep. 42(3):93-119. [QxMD MEDLINE Link].
Chomba M, Mucheleng'anga LA, Fwoloshi S, Ngulube J, Mutengo MM. A case report: primary amoebic meningoencephalitis in a young Zambian adult. BMC Infect Dis. 2017 Aug 1. 17 (1):532. [QxMD MEDLINE Link].
Vargas-Zepeda J, Gomez-Alcala AV, Vasquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lares-Villa F. Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin. Arch Med Res. 2005 Jan-Feb. 36(1):83-6. [QxMD MEDLINE Link].
Rai R, Singh DK, Srivastava AK, Bhargava A. Primary amebic meningoencephalitis. Indian Pediatr. 2008 Dec. 45(12):1004-5. [QxMD MEDLINE Link].
Gautam PL, Sharma S, Puri S, Kumar R, Midha V, Bansal R. A rare case of survival from primary amebic meningoencephalitis. Indian J Crit Care Med. 2012 Jan. 16(1):34-6. [QxMD MEDLINE Link].
Sood A, Chauhan S, Chandel L, Jaryal SC. Prompt diagnosis and extraordinary survival from Naegleria fowleri meningitis: a rare case report. Indian J Med Microbiol. 2014 Apr-Jun. 32 (2):193-6. [QxMD MEDLINE Link].
John DT, John RA. Cytopathogenicity of Naegleria fowleri in mammalian cell cultures. Parasitol Res. 1989. 76 (1):20-5. [QxMD MEDLINE Link].
Diaz J. Seasonal primary amebic meningoencephalitis (PAM) in the south: summertime is PAM time. J La State Med Soc. 2012 May-Jun. 164(3):148-50, 152-5. [QxMD MEDLINE Link].
Cabanes PA, Wallet F, Pringuez E, Pernin P. Assessing the risk of primary amoebic meningoencephalitis from swimming in the presence of environmental Naegleria fowleri. Appl Environ Microbiol. 2001 Jul. 67(7):2927-31. [QxMD MEDLINE Link].
Visvesvara GS, Sriram R, Qvarnstrom Y, Bandyopadhyay K, Da Silva AJ, Pieniazek NJ, et al. Paravahlkampfia francinae n. sp. masquerading as an agent of primary amoebic meningoencephalitis. J Eukaryot Microbiol. 2009 Jul-Aug. 56 (4):357-66. [QxMD MEDLINE Link].
da Rocha-Azevedo B, Tanowitz HB, Marciano-Cabral F. Diagnosis of infections caused by pathogenic free-living amoebae. Interdiscip Perspect Infect Dis. 2009. 2009:251406. [QxMD MEDLINE Link].
Parija SC, Dinoop K, Venugopal H. Management of granulomatous amebic encephalitis: Laboratory diagnosis and treatment. Trop Parasitol. 2015 Jan-Jun. 5 (1):23-8. [QxMD MEDLINE Link].
Schuster FL. Cultivation of pathogenic and opportunistic free-living amebas. Clin Microbiol Rev. 2002 Jul. 15 (3):342-54. [QxMD MEDLINE Link].
Sohn HJ, Kang H, Seo GE, Kim JH, Jung SY, Shin HJ. Efficient Liquid Media for Encystation of Pathogenic Free-Living Amoebae. Korean J Parasitol. 2017 Jun. 55 (3):233-238. [QxMD MEDLINE Link].
Reveiller FL, Cabanes PA, Marciano-Cabral F. Development of a nested PCR assay to detect the pathogenic free-living amoeba Naegleria fowleri. Parasitol Res. 2002. 88:443-50.
Marciano-Cabral F, MacLean R, Mensah A, LaPat-Polasko L. Identification of Naegleria fowleri in domestic water sources by nested PCR. Appl Environ Microbiol. 2003 Oct. 69(10):5864-9. [QxMD MEDLINE Link].
Johnson PE, Deromedi AJ, Lebaron P, Catala P, Havens C, Pougnard C. High throughput, real-time detection of Naegleria lovaniensis in natural river water using LED-illuminated Fountain Flow Cytometry. J Appl Microbiol. 2007 Sep. 103(3):700-10. [QxMD MEDLINE Link].
Flores BM, Garcia CA, Stamm WE, Torian BE. Differentiation of Naegleria fowleri from Acanthamoeba species by using monoclonal antibodies and flow cytometry. J Clin Microbiol. 1990 Sep. 28(9):1999-2005. [QxMD MEDLINE Link].
Madarova L, Trnkova K, Feikova S, Klement C, Obernauerova M. A real-time PCR diagnostic method for detection of Naegleria fowleri. Exp Parasitol. 2010 Sep. 126(1):37-41. [QxMD MEDLINE Link].
Visvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis. 2010 Dec. 23(6):590-4. [QxMD MEDLINE Link].
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 Oct. 44 (10):3589-95. [QxMD MEDLINE Link].
Cárdenas-Zúñiga R, Silva-Olivares A, Villalba-Magdaleno JA, Sánchez-Monroy V, Serrano-Luna J, Shibayama M. Amphotericin B induces apoptosis-like programmed cell death in Naegleria fowleri and Naegleria gruberi. Microbiology. 2017 Jul. 163 (7):940-949. [QxMD MEDLINE Link].
Kim JH, Jung SY, Lee YJ, Song KJ, Kwon D, Kim K. Effect of therapeutic chemical agents in vitro and on experimental meningoencephalitis due to Naegleria fowleri. Antimicrob Agents Chemother. 2008 Nov. 52(11):4010-6. [QxMD MEDLINE Link].
Investigational Drug Available Directly from CDC for the Treatment of Infections with Free-Living Amebae. MMWR Morb Mortal Wkly Rep. 2013 Aug 23. 62(33):666. [QxMD MEDLINE Link].
Grace E, Asbill S, Virga K. Naegleria fowleri: pathogenesis, diagnosis, and treatment options. Antimicrob Agents Chemother. 2015 Nov. 59 (11):6677-81. [QxMD MEDLINE Link]. [Full Text].
Debnath A, Tunac JB, Galindo-Gomez S, Silva-Olivares A, Shibayama M, McKerrow JH. Corifungin, a new drug lead against Naegleria, identified from a high-throughput screen. Antimicrob Agents Chemother. 2012 Nov. 56(11):5450-7. [QxMD MEDLINE Link].
Garcia A, Goni P, Cieloszyk J, Fernandez MT, Calvo-Beguería L, Rubio E. Identification of free-living amoebae and amoeba-associated bacteria from reservoirs and water treatment plants by molecular techniques. Environ Sci Technol. 2013 Apr 2. 47(7):3132-40. [QxMD MEDLINE Link].
Carrasco-Yepez M, Rojas-Hernandez S, Rodriguez-Monroy MA, Terrazas LI, Moreno-Fierros L. Protection against Naegleria fowleri infection in mice immunized with Cry1Ac plus amoebic lysates is dependent on the STAT6 Th2 response. Parasite Immunol. 2010 Sep-Oct. 32(9-10):664-70. [QxMD MEDLINE Link].
Kim JH, Lee SH, Sohn HJ, Lee J, Chwae YJ, Park S. The immune response induced by DNA vaccine expressing nfa1 gene against Naegleria fowleri. Parasitol Res. 2012 Dec. 111(6):2377-84. [QxMD MEDLINE Link].
Herriman R. California reports 7th ever Naegleria fowleri case in Inyo County woman. Outbreak News Today. 2015.

Media Gallery

Hematoxin and eosin (H&E)-stained photomicrograph (125X) that shows the cytoarchitectural histopathology found in a case of primary amoebic meningoencephalitis (PAM), caused by Naegleria gruberi. Courtesy of the US Centers for Disease Control and Prevention and Dr. George R. Healy.

of 1

Author

Subhash Chandra Parija, MD, MBBS, PhD, DSc, FRCPath Professor Emeritus, National Academy of Medical Sciences, India; Former Director, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India

Subhash Chandra Parija, MD, MBBS, PhD, DSc, FRCPath is a member of the following medical societies: Indian Academy of Tropical Parasitology, Indian Association of Biomedical Scientists, Indian Association of Medical Microbiologists, Indian Association of Pathologists and Microbiologists, Indian Medical Association, Indian Society for Parasitology, National Academy of Medical Sciences (India), Royal College of Pathologists

Disclosure: Nothing to disclose.

Coauthor(s)

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Thomas M Kerkering, MD, FACP, FIDSA Professor of Medicine with Tenure, Division of Infectious Diseases, Virginia Tech Carilion School of Medicine; Adjunct Professor, Department of Population Studies, Masters of Public Health Program, Virginia Tech University, School of Veterinary Medicine

Thomas M Kerkering, MD, FACP, FIDSA is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Human and Animal Mycology, Medical Society of Virginia, Roanoke Academy of Medicine, Virginia Infectious Diseases Society, Wilderness Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Additional Contributors

Daniel R Lucey, MD, MPH, MD, MPH

Daniel R Lucey, MD, MPH, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Barnett Gibbs, MD Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences

Disclosure: Nothing to disclose.

Diane H Johnson, MD Assistant Director, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine

Diane H Johnson, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Women's Association, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.