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Clinicians: For 24/7 diagnostic assistance, specimen collection guidance, shipping instructions, and treatment recommendations, please contact the CDC Emergency Operations Center at 770-488-7100.

Clinicians: CDC now has an investigational drug called miltefosine available for treatment of free-living ameba (FLA) infections caused by Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba species. If you have a patient with suspected FLA infection, please contact the CDC Emergency Operations Center at 770-488-7100 to consult with a CDC expert regarding the use of this drug.


Although most cases of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri infection in the United States have been fatal (129/132 in the U.S., 1), there have been four well-documented survivors in North America: one in the U.S. in 1978 2, 3, one in Mexico in 2003 4, and two additional survivors from the U.S. in 2013. It has been suggested that the original U.S. survivor’s strain of Naegleria fowleri was less virulent, which contributed to the patient’s recovery. In laboratory experiments, the original U.S. survivor’s strain did not cause damage to cells as rapidly as other strains, suggesting that it is less virulent than strains recovered from other fatal infections 5.

Recently an investigational breast cancer and anti-leishmania drug, miltefosine 6, has shown some promise in combination with some of these other drugs. Miltefosine has shown ameba-killing activity against free-living amebae, including Naegleria fowleri, in the laboratory 7, 8. Miltefosine has also been used to successfully treat patients infected with Balamuthia 9 and disseminated Acanthamoeba infection 10. CDC now has a supply of miltefosine for treatment of Naegleria fowleri infection 11. If you are a clinician and have a patient with suspected Naegleria or other free-living ameba infection, please contact the CDC Emergency Operations Center at 770-488-7100 to consult with a CDC expert regarding the use of this drug. 

After 35 years without a Naegleria survivor in the United States, during the summer of 2013, 2 children with Naegleria fowleri infection survived. The first, a 12-year-old girl, was diagnosed with PAM approximately 30 hours after becoming ill and was started on the recommended treatment within 36 hours. She also received the investigational drug miltefosine 6-8 and her brain swelling was aggressively managed with treatments that included cooling the body below normal body temperature (therapeutic hypothermia). This patient made a full neurologic recovery and returned to school. Her recovery has been attributed to early diagnosis and treatment and novel therapeutics including miltefosine and hypothermia.

A second child, an 8-year-old male, is also considered a PAM survivor, although he has suffered what is likely to be permanent brain damage. He was also treated with miltefosine but was diagnosed and treated several days after his symptoms began. Cooling of the body below normal body temperature was not used.

References

  1. 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.
  2. Seidel JS, Harmatz P, Visvesvara GS, Cohen A, Edwards J, Turner J. Successful treatment of primary amebic meningoencephalitis. N Engl J Med. 1982;306:346-8.
  3. 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;50:1-26.
  4. 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 Res. 2005;36:83-6.
  5. John DT, John RA. Cytopathogenicity of Naegleria fowleri in mammalian cell cultures. Parasitol Res. 1989;76:20-5.
  6. Kaminsky R. Miltefosine Zentaris. Curr Opin Investig Drugs. 2002;3:550-4.
  7. 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.
  8. Kim JH, Jung SY, Lee YJ, Song KJ, Kwon D, Kim K, Park S, Im KI, Shin HJ. Effect of therapeutic chemical agents in vitro and on experimental meningoencephalitis due to Naegleria fowleri. [PDF - 7 pages] Antimicrob Agents Chemother. 2008;52:4010-16.
  9. Martínez DY, Seas C, Bravo F, Legua P, Ramos C, Cabello AM, Gotuzzo E. Successful treatment of Balamuthia mandrillaris amoebic infection with extensive neurological and cutaneous involvement. Clin Infect Dis. 2010;51:e7-11.
  10. Aichelburg AC, Walochnik J, Assadian O, Prosch H, Steuer A, Perneczky G, Visvesvara GS, Aspöck H, Vetter N. Successful treatment of disseminated Acanthamoeba sp. infection with miltefosine. [PDF - 4 pages] Emerg Infect Dis. 2008;14:1743-6.
  11. 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.
 
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