Treatment

Although most cases of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri infection in the United States have been fatal (139/143 in the U.S., ¹), there have been five well-documented survivors in North America: one in the U.S. in 1978 ^{2, 3}, one in Mexico in 2003 ⁴, 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 infections ⁷.

Recently an investigational breast cancer and anti-leishmania drug, miltefosine ⁸, 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 ^{9, 10,}. Miltefosine has also been used to successfully treat patients infected with Balamuthia ¹¹ and disseminated Acanthamoeba infection ¹². 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, 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 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 hypothermia ⁵.

The 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 ⁶.

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.

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. 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.
6. 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(6):774-6.
7. John DT, John RA. Cytopathogenicity of Naegleria fowleri in mammalian cell cultures. Parasitol Res. 1989;76:20-5.
8. Kaminsky R. Miltefosine Zentaris. Curr Opin Investig Drugs. 2002;3(4):550-4.
9. 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(2):121-6.
10. 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.
11. 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.
12. 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(11):1743-6.