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CDC at Work: Naegleria fowleri


Naegleria fowleri Program

CDC created the national Free-living Ameba (FLA) Laboratory in 1978, which has become a national and global leader for diagnostic expertise and clinical guidance. As a national resource for health departments and clinicians, CDC’s FLA laboratory diagnoses most Naegleria fowleri infections in the U.S. In 1989, CDC began formally tracking Naegleria fowleri infections as part of the national Waterborne Disease and Outbreak Surveillance System (WBDOSS) 1. The CDC WBDOSS surveillance system and FLA laboratory track and assist with infections caused by Naegleria fowleri, Balamuthia mandrillaris, Acanthamoeba, and Sappinia.

The CDC Naegleria fowleri program focuses on five main areas to better understand and combat this disease:

  1. Providing 24/7 diagnostic expertise and clinical guidance to health professionals
  2. Tracking, investigating, and reporting infections and disease outbreaks
  3. Leading CDC health promotion and communication activities
  4. Testing the efficacy of promising drugs against the ameba in the laboratory setting
  5. Developing new methods for detection of Naegleria fowleri in clinical and environmental samples (for example, in water)

Progress is being made in all five areas of the program:

  1. Providing 24/7 diagnostic services, clinical guidance, and an investigational drug to health professionals.
    1. Assisting health professionals in diagnosing most infections in the U.S. as well as giving international assistance 2-11.
    2. Consulting with physicians across the world to provide clinical guidance on treatment of Naegleria fowleri infections 7,8,12-15.
    3. Providing the promising investigational drug, miltefosine, to clinicians, which contributed to the first US survivors of infection in 35 years 16.
    4. Created extensive informational packets for immediate use by treating physicians.
    5. Demonstrated that Naegleria fowleri can also infect other animals such as cows 17 and tapirs 18.
    6. Co-discovered the non-pathogenic species Naegleria dunnbackei while investigating PAM deaths 19.
  2. Tracking, investigating, and reporting infections and disease outbreaks.
    1. Collecting tracking data on PAM infections in the United States as part of WBDOSS since 1989 and summarized every 2 years in CDC MMWR Surveillance Summaries.
    2. Developing standardized information collection and investigation tools for investigators.
    3. Completed an extensive retrospective research effort in 2007 with the Council for State and Territorial Epidemiologists (CSTE) to identify every reported U.S. infection and abstract all known information on the infections. After verification by all affected states, this database has become the national Naegleria fowleri infection database for use in tracking all future infections 5, 20.
    4. Co-sponsored a CSTE Position Statement 21 that established standardized case definitions for Naegleria fowleri and other FLA infections to improve future reporting of infections.
    5. Assessing the potential for climate-related changes to the geographical range of the organism and associated infections.
    6. Investigating the who, what, where, and why of primary amebic meningoencephalitis (PAM) infections to better understand the occurrence of disease, sources of infection and risk factors to potentially develop prevention recommendations in the future 2-11, 20, 22.
  3. Leading CDC health promotion and communication activities.
    1. Write and manage all content and web development for CDC’s Naegleria fowleri website.
    2. Answer all public and media inquiries regarding Naegleria fowleri infections.
    3. Make presentations to and create educational materials for public health, laboratory, and medical professionals to educate them about the disease, diagnosis, treatment, and prevention efforts 23-30.
  4. Testing the efficacy of promising drugs against the ameba in the laboratory setting.
    1. The FLA laboratory has tested numerous drugs 31 against the ameba in the laboratory including the investigational drug miltefosine. It is a breast cancer and anti-leishmania drug that has shown in vitro (in laboratory culture) and animal model ameba-killing activity against Naegleria fowleri 32. Miltefosine has also been used successfully to treat infections with the free-living amebae Balamuthia and Acanthamoeba 32.
  5. Developing new methods for detection of Naegleria fowleri in clinical and environmental samples.
    1. The FLA laboratory developed specific antibodies directed against Naegleria fowleri and used these to develop an indirect fluorescence antibody test (IFA). This test has become the “gold standard” for Naegleria fowleri testing. The technology has been transferred to laboratories around the world 33, 34.
    2. The diagnostics laboratory in CDC’s Division of Parasitic Diseases and Malaria developed a CLIA-certified laboratory polymerase chain reaction (PCR) test for simultaneously detecting Naegleria, Balamuthia, and Acanthamoeba DNA in clinical specimens 35. This test is now considered the equivalent of the “gold standard” IFA test.
    3. CDC’s Molecular Diagnostics laboratory in the Waterborne Disease Prevention Branch has developed new methods to better understand genetic variation in Naegleria fowleri isolates to better understand whether different isolates differ in the severity or course of illness they cause 36.
    4. The FLA Laboratory is collaborating with an international group of researchers to obtain the complete genetic code for Naegleria fowleri. This information could yield information important for treatment and detection of the ameba. Comparing the sequence with other Naegleria species may give an understanding of why Naegleria fowleri infects humans while other Naegleria species do not.
    5. CDC’s Environmental Microbiology Laboratory in the Waterborne Disease Prevention Branch has sampled lake water using traditional methods. It is now developing an advanced method for the detection of Naegleria in water samples from lakes and rivers. This will allow CDC and others to test and potentially quantitate Naegleria in natural waters. This should facilitate future research into the ecology of Naegleria to help us understand where and why Naegleria grows and potentially assist in predicting areas of increased risk for swimming. No such predictions can be made at this time with current detection technology.

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References
  1. Herwaldt BL, Craun GF, Stokes SL, Juranek DD. Waterborne-disease outbreaks, 1989-1990. [PDF - 22 pages] MMWR Surveill Summ. 1991;40:1-21.
  2. Yoder JS, Straif-Bourgeois S, Roy SL, Moore TA, Visvesvara GS, Ratard RC, Hill V, Wilson JD, Linscott AJ, Crager R, Kozak NA, Sriram R, Narayanan J, Mull B, Kahler AM, Schneeberger C, da Silva AJ, Beach MJ. Deaths from Naegleria fowleri associated with sinus irrigation with tap water: a review of the changing epidemiology of primary amebic meningoencephalitis. Clin Infect Dis. 2012;1-7.
  3. Lopez C, Budge P, Chen J, Bilyeu S, Mirza A, Custodio H, Irazuzta J, Visvesvara G, Sullivan KJ. Primary amebic meningoencephalitis: a case report and literature review. Pediatr Emerg Care. 2012 Mar;28(3):272-6.
  4. Kemble SK, Lynfield R, DeVries AS, Drehner DM, Pomputius WF 3rd, Beach MJ, Visvesvara GS, da Silva AJ, Hill VR, Yoder JS, Xiao L, Smith KE, Danila R. Fatal Naegleria fowleri infection acquired in Minnesota: possible expanded range of a deadly thermophilic organism. Clin Infect Dis. 2012;54:805-9.
  5. CDC. Primary amebic meningoencephalitis--Arizona, Florida, and Texas, 2007. MMWR Morb Mortal Wkly Rep. 2008;57:573-7.
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  7. Shakoor S, Beg MA, Mahmood SF, Bandea R, Sriram R, Noman F, et al. Primary amebic meningoencephalitis caused by Naegleria fowleri, Karachi, Pakistan. [PDF - 4 pages] Emerg Infect Dis. 2011:17;258-61.
  8. Cogo PE, Scagli M, Gatti S, Rossetti F, Alaggio R, Laverda AM, Zhou L, Xiao L, Visvesvara GS. Fatal Naegleria fowleri meningoencephalitis, Italy. Emerg Infect Dis. 2004 Oct;10(10):1835-7.
  9. CDC. Primary amebic meningoencephalitis—Georgia, 2002. MMWR Morb Mortal Wkly Rep. 2003;52(40):962-4.
  10. CDC. Primary amebic meningoencephalitis—North Carolina, 1991. MMWR Morb Mortal Wkly Rep. 1992;41(25):437-40.
  11. CDC. Primary amebic meningoencephalitis—California, Florida, New York. MMWR Morb Mortal Wkly Rep. 1978;27:343-4.
  12. Vargas-Zepeda J, Gomez-Alcala AV, Vasquez-Morales JA, Licea-Amaya L, De Jonckheere JF, Lores-Villa F. Successful treatment of Naegleria PAM using IV amphotericin B, fluconazole, and rifampin. Arch Med Research 2005;36:83-6.
  13. Schuster FL, Visvesvara GS. Free-living opportunistic and non-opportunistic pathogens of humans and animals. Int J Parasitiol 2004;34:1001-27.
  14. Schuster FL, Visvesvara GS. Opportunistic amebae: challenges in prophylaxis and treatment. Drug Resistance Updates 2004;7:41-51.
  15. Seidel J, Harmatz P, Visvesvara GS, Cohen A, Edwards J, Turner J. Successful treatment of primary amebic meningoencephalitis. New Engl J Med 1982;306:346-8.
  16. CDC. Investigational drug available directly from CDC for the treatment of infections with free-living amebae. MMWR Morb Mortal Wkly Rep. 2013;62(33):666.
  17. Visvesvara GS, De Jonckheere JF, Sriram R, Daft B. Isolation and molecular typing of Naegleria fowleri from the brain of a cow that died of primary amebic meningoencephalitis. J Clin Microbiol. 2005;43:4203-4.
  18. Lozano-Alarcón F, Bradley GA, Houser BS, Visvesvara GS. Primary amebic meningoencephalitis due to Naegleria fowleri in a South American tapir. Vet Pathol. 1997 May;34(3):239-43.
  19. Visvesvara GS, De Jonckheere JF, Marciano-Cabral F, Schuster FL. Morphologic and molecular identification of Naegleria dunnebackei n. sp. isolated from a water sample. J Eukaryot Microbiol. 2005;52:523-31.
  20. Yoder JS, Eddy BA, Visvesvara GS, Capewell L, Beach MJ. The epidemiology of primary amoebic meningoencephalitis in the USA, 1962-2008. Epidemiol Infect. 2010;138:968-75.
  21. Council for State and Territorial Epidemiologists (CSTE). Case Definitions for Non-notifiable Infections Caused by Free-living Amebae (Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp.) [PDF - 10 pages]. Infectious Disease Committee. 2012.
  22. CDC. Primary amebic meningoencephalitis associated with ritual nasal rinsing — St. Thomas, U.S. Virgin Islands, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(45):903.
  23. Visvesvara G, Yoder J, Beach MJ. (2012) Primary amebic meningoencephalitis Chapter 73, pgs 442-7. In: Netter's Infectious Diseases, Eds. Yong EC, Stevens DL. Elsevier Saunders. Philadelphia, PA.
  24. Visvesvara G. Pathogenic and opportunistic free-living amebae. In: Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D, editors. Manual of Clinical Microbiology. 10 ed. Washington, DC: ASM Press; 2011. p. 2139-48.
  25. Visvesvara G, Roy S, Maguire J. Pathogenic and opportunistic free-living amebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia pedata. In: Guerrant R, Walker D, Weller P, editors. Tropical Infectious Diseases: Principles, Pathogens and Practice: Expert Consult. 3 ed: WB Saunders Company; 2011. p. 1-9, e1-e2.
  26. Visvesvara GS. Free-living amebae as opportunistic agents of human disease. [PDF - 13 pages] J Neuroparasitol. 2010;1.
  27. Visvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis. 2010 Dec;23(6):590-4.
  28. Visvesvara GS. Parasite Culture: Acanthamoeba and Naegleria spp. In: Garcia LS, editor. Clinical Microbiology Procedures Handbook. 3rd ed. Washington, DC: ASM Press;2010.
  29. Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol and Med Microbiol. 2007;50:1–26.
  30. Visvesvara GS. Pathogenic and Opportunistic Amebae. Manual of Clinical Microbiology, 9th ed. Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Washington DC: ASM Press. 2007. p. 2082-91.
  31. Schuster FL, Visvesvara GS. Opportunistic amebae: challenges in prophylaxis and treatment. Drug Resistance Updates 2004;7:41-51.
  32. Schuster FL, Guglielmo BJ, Visvesvara GS. In-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. J Eukaryot Microbiol. 2006;53:121-6.
  33. Visvesvara GS, Peralta MJ, Brandt FH, Wilson M, Aloisio C, Franko E. Production of monoclonal antibodies to Naegleria fowleri, agent of primary amebic meningoencephalitis. J Clin Microbiol. 1987;25:1629-34.
  34. Visvesvara GS, Healy GR. Comparative antigenic analysis of pathogenic and free-living Naegleria species by the gel diffusion and immunoelectrophoresis techniques. Infect Immunity. 1975;11:95-108.
  35. 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.
  36. Zhou L, Sriram R, Visvesvara GS, Xiao L. Genetic variations in the internal transcribed spacer and mitochondrial small subunit rRNA gene of Naegleria spp. J Eukaryot Microbiol. 2003;50 Suppl:522-6.

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