Invasion of the Brain Eaters

by Julia Canick

Meet 12-year-old Kali Hardig. Until recently, Kali was an average girl, and certainly no medical marvel. But that all changed in July 2013, when she became the third documented survivor in North America of Naegleria fowleri.¹

Naegleria fowleri aren’t your typical invaders of the central nervous system. They can cross the blood-brain barrier and destroy the brain in a matter of days—but, unlike other parasites, which enter the body through methods like bug bites and accidental oral ingestion, these amoebas take the road less traveled: the nose.²

Naegleria fowleri are single-celled amoeba found in warm freshwater.² Upon human inhalation of contaminated water, the parasites pass through the olfactory epithelium and travel along nerves that extend from the nose to the brain, where they end up in the olfactory bulb, bathed in cerebrospinal fluid.³ From there, they can enter the brain, where they digest neurons in less than a day.² They do this by producing pore-forming proteins that lyse mammalian cells on contact and by secreting enzymes that degrade mammalian tissue.⁴ This infection is also known as primary amoebic meningoencephalitis (PAM), and can cause death one to eighteen days after symptoms arise.²

About five days after infection, initial PAM symptoms, such as nausea, fever, and vomiting, begin. The later symptoms include confusion, lack of attention, seizures, and hallucinations.² The amoeba causes death soon after; though it is not evolutionary advantageous for Naegleria fowleri, human beings are a dead-end host for the parasite.

Perhaps the most disconcerting aspect of the parasite isn’t its mechanism of invasion, but its evasion of the immune response. The parasite is resistant to cytokines, which are some of the cells involved in triggering the body’s response to a foreign pathogen. N. fowleri may even use cytokine inflammation against the body of the host to worsen the disease. They are also resistant to the complement system, which helps antibodies and phagocytes clear pathogens from a host; N. fowleri can synthesize surface proteins that protect them against complement-mediated lysis.⁴

The amoebae actually thrive best when they are in their pathogenic state, in the human body. When in the infectious state, they are able to migrate and divide more quickly than they can when in water.⁴ Naegleria fowleri’s ability to infect and spread quickly gives it a whopping 97% fatality rate;² Kali recently became the third survivor, out of 133 infected individuals.

Kali Hardig’s story is nothing short of a miracle. After swimming in several bodies of water, she developed a fever, head pain, and drowsiness.¹ Her parents quickly drove her to the hospital, where a staining technique demonstrated the presence of amoebae in Kali. The doctors knew they had to act quickly, given the pathogen’s relatively short time window for survival. Doctors took multiple measures to treat her: they lowered her body temperature to reduce swelling and herniation¹ and administered a combination of medications,⁵ including miltefosine, a drug that has been used to combat cancer. The key factor, however, was almost certainly the immediate detection of the amoeba;⁵ often, individuals don’t know about the infection until it’s too late.

Kali survived the infection, but others weren’t quite as lucky. This past August, Michael John Riley, Jr. encountered the parasite when he was swimming in a state park; he died within days.⁶ Others who have encountered the pathogen have shared similar fates.

Though infection is extremely rare, Naegleria fowleri are relatively common in the environment and were recently found in two water systems in Louisiana.⁷ Luckily, ingesting the amoeba orally is completely harmless; the only way to contract illness from N. fowleri is through the nose.² Though scientists are working to find a drug that acts quickly enough to combat the infection, it is most pragmatic to focus on disease prevention. According to the Center for Disease Control, the best prevention is to avoid swimming in warm freshwater that is untreated, and to exercise caution with neti pots, ritual nasal rinsing, and public drinking water.² Humans can’t contract the infection from a properly cleaned and maintained, disinfected pool, or by drinking infested water; the best prevention is to avoid inhaling water that could contain the parasite.

Since the body’s immune response is part of what contributes to the parasite’s lethality, researchers are searching for a two-step treatment: immunosuppressive drugs, followed by drugs that combat PAM.⁸ The most successful medication has been miltefosine, the aforementioned cancer drug, but researchers are on the hunt for other treatments.² The inflammatory response triggered by the body ends up backfiring and doing more harm than good; immunosuppression would counter this inflammation and buy more time for the patient. Then, drugs that attack primary amoebic meningoencephalitis could be able to treat and, hopefully, eradicate the infection from the individual.

As N. fowleri continues to pop up in the news, scientists are understanding more and more about what they are capable of. As we come to understand more about this amoeba, we will be able to think up better ways to treat it.

Julia Canick ‘17 is a junior in Adams House, concentrating in Molecular and Cellular Biology.

Works Cited

1. Main, D. How A 12-Year-Old Survived A Brain-Eating Amoeba Infection. Newsweek, Feb. 22, 2015. http://www.newsweek.com/how12-year-old-survived-brain-eating-amoeba-infection-308427 (accessed Oct. 4, 2015).
2. Centers for Disease Control and Prevention. http://www.cdc.gov/parasites/naegleria/ (accessed Oct. 4, 2015).
3. Kristensson, K. Nature Rev Neurosci. 2011, 12, 345-347.
4. Marciano-Cabral, F.; Cabral, G.A. FEMS Immunol Med Microbiol, 2007, 51, 243-259.
5. Linam, W. M. et al. Pediatrics 2015, 135, e744-e748.
6. Yan, H. Brain-Eating Amoeba Kills 14-Year-Old Star Athlete. CNN, Aug. 31, 2015. http://www. cnn.com/2015/08/31/health/brain-eating-amoeba-deaths/ (accessed Oct. 4, 2015).
7. Brain-Eating Amoeba Found In Another Louisiana Water System. CBS News, Aug. 18, 2015. http://www.cbsnews.com/news/brain-eating-amoeba-found-in-another-louisiana-water-system/ (accessed Oct. 4, 2015).
8. Rivas, A. Suppressing Immune System Might Save People Infected By Brain-Eating Amoeba Naegleria Fowleri. Medical Daily, May 16, 2015. http://www.medicaldaily.com/suppressing-immune-system-might-save-people-infected-brain-eating-amoeba-naegleria-333686 (accessed Oct. 4, 2015).