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. More detailed guidance is under Information for Public Health & Medical Professionals.
Clinicians: CDC no longer provides miltefosine for treatment of free-living ameba infections. Miltefosine is now commercially available. Please visit impavido.com for more information on obtaining miltefosine in the United States. If you have a patient with suspected free-living ameba infection, please contact the CDC Emergency Operations Center at 770-488-7100 to consult with a CDC expert.
Primary Amebic Meningoencephalitis (PAM) is treated with a combination of drugs, often including amphotericin B, azithromycin, fluconazole, rifampin, miltefosine, and dexamethasone. These drugs are used because they are thought to have activity against Naegleria fowleri and have been used to treat patients who survived. Miltefosine is the newest of these drugs and has shown ameba-killing activity against free-living amebae, including Naegleria fowleri, in the laboratory1, 2, 3. Miltefosine has also been used to successfully treat patients infected with Balamuthia4 and disseminated Acanthamoeba infection5.
Although most cases of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri infection in the United States have been fatal (150/154 in the U.S.)6, 7, there have been five documented survivors in North America: one in the U.S. in 19788, 9, one in Mexico in 200310, two additional survivors from the U.S. in 2013 5, 6, and one from the U.S. in 2016. 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 infections13.
After 35 years without a Naegleria survivor in the United States, during the summer of 2013, two 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 of amphotericin B, fluconazole, rifampin, azithromycin, and dexamethasone within 36 hours. She also received the investigational drug miltefosine 7-9 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 hypothermia11.
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 amphotericin B, fluconazole, rifampin, azithromycin, miltefosine, and dexamethasone but was diagnosed and treated several days after his symptoms began. Cooling of the body below normal body temperature was not used12.
In the summer of 2016, a 16-year-old boy was reported as the 4th U.S. PAM survivor. This patient was diagnosed within hours of presentation to the hospital and was treated with the same protocol used for the 12-year-old 2013 survivor. This patient also made a full neurologic recovery and returned to school.
- Kaminsky R. Miltefosine Zentaris. Curr Opin Investig Drugs. 2002;3:550-4.
- Schuster FL, Guglielmo BJ, Visvesvara GS. In-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: Balamuthia mandrillaris, Acanthamoeba, and Naegleria fowleri. J Eukaryot Microbiol. 2006;53:121-6.
- 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.
- 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.
- Aichelburg AC, Walochnik J, Assadian O, Prosch H, Steuer A, Perneczky G, Visvesvara GS, Aspöck H, Vetter N. Successful treatment of disseminated Acanthamoeba infection with miltefosine. [PDF – 4 pages] Emerg Infect Dis. 2008;14:1743-6.
- 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.
- Gharpure R, Bliton J, Goodman A, Ali IKM, Yoder J, Cope JR. Epidemiology and Clinical Characteristics of Primary Amebic Meningoencephalitis Caused by Naegleria fowleri: A Global Review | Clinical Infectious Diseases | Oxford Academic (oup.com). Clin Inf Dis. 2021;73(1):e19-e27.
- 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.
- Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba, Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol. 2007;50:1-26.
- 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.
- Linam WM, Ahmed M, Cope JR, Chu C, Visvesvara GS, da Silva AJ, Qvarnstrom Y, Green J. Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis. Pediatrics. 2015; 135: e744–8.
- Cope JR, Conrad DA, Cohen N, Cotilla M, DaSilva A, Jackson J, Visvesvara GS. 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;62:774-6.
- John DT, John RA. Cytopathogenicity of Naegleria fowleri in mammalian cell cultures. Parasitol Res. 1989;76:20-5.