CDC at Work | Naegleria fowleri | CDC

CDC at Work | Naegleria fowleri | CDC

CDC at Work: Naegleria fowleri

Stories from the Field

 

• Protecting public water systems and the public fromNaegleria fowleri (brain-eating ameba) infections  [PDF - 8 pages]– Page 2, National Center for Emerging and Zoonotic Infectious Diseases Accomplishments 2013
• Louisiana wrestles “brain-eating ameba”– Page 10, National Public Health Information Coalition News, January/February 2014

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 nationalWaterborne 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 ofNaegleria 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-leishmaniadrug 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 fowleriisolates 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

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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.
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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 ofNaegleria 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.
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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.
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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 ofAcanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri. J Clin Microbiol. 2006;44(10):3589-95.
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