Hazardous Waters: Lessons From a Brain-Eating Amoeba

Hazardous Waters: Lessons From a Brain-Eating Amoeba

July 19, 2022 0 By Jennifer Walker

Earlier this month, officials closed access to a lake in Iowa’s Lake of Three Fires State Park and started testing its water after a swimmer there developed primary amoebic meningoencephalitis (PAM).

Tragically, the patient faced daunting odds. Of 154 people who suffered PAM in the U.S. between 1962 and 2021, only four survived; in people infected between 1962 and 2008, the case-fatality rate was 99%.

On July 15, The Des Moines Register reported the swimmer’s death, citing the onset of PAM after infection from Naegleria fowleri, also known as the “brain-eating amoeba.” Yet, there have also been remarkable saves from this dreaded disease. Broader education about the disease and efforts to prevent infection in the first place can help stop this killer in its tracks.

Two Perilous Amoebae

Two years after graduating from medical school, I attended the London School of Hygiene & Tropical Medicine and immersed myself in parasites. I was especially drawn to single-celled protozoa with unique modes of locomotion from cilia and flagella to propulsive pseudopods.

Back then, N. fowleri was a mere footnote compared with Entamoeba histolytica, another parasite with pseudopods. First shown in 1875 to sicken experimentally-infected dogs, E. histolytica continues to this day to burrow into intestinal tissue causing dysentery, and to sometimes perforate colons and invade distant organs. Thankfully, we now have simple, effective treatments, and with better sanitation, there’s also reason to believe its global burden will fall. Nonetheless, since many people still ingest food and water laced with human feces, E. histolytica continues to annually afflict roughly 50 million people and kill 100,000 worldwide.

Now consider E. histolytica‘s far-rarer kin, a “free-living amoeba” that enters humans not through their mouth but through their nose. Distinctly thermophilic, N. fowleri inhabits freshwater lakes, rivers, ponds, hot springs, and unchlorinated swimming pools whose ambient temperatures range from 37 to 45 degrees Celsius. Finally, when viewed through a microscope, its 15-25 um trophozoite (feeding stage) is scarily motile.

First reported in Australia in 1965, infections due to N. fowleri have now occurred in numerous countries and are sometimes linked to nasal rinsing with Neti pots as well as recreational water activities such as swimming, diving, splashing, or water skiing. Fortunately, most colonized people never fall ill. In a luckless few, however, the amoebae breach nasal linings, crawl through the cribriform plate and enter the brain, where they rapidly destroy tissue.

Killing a Killer

What constitutes modern treatment for PAM? In short: multi-drug cocktails containing agents not unlike those that once rescued a 9-year-old girl in California. This successfully treated patient received care from a long-time friend and colleague.

“At first, we thought she was doomed,” said Jack Edwards, MD, emeritus chief of the Division of Infectious Disease at Harbor-University of California Los Angeles (UCLA) Medical Center, when we recently spoke about the 9-year-old girl who, days before falling ill, had visited Deep Creek Hot Springs in California’s San Bernardino County, then experienced headaches, nausea, and lethargy progressing to coma.

Upon transfer to Harbor-UCLA Medical Center, the patient had sky-high intrathecal pressure, and her cerebrospinal fluid (CSF) contained numerous neutrophils as well as actively motile cells consistent with N. fowleri. That’s when Edwards and others began a cocktail of intravenous, intrathecal, and oral drugs. Her regimen contained two intravenous and intrathecal anti-fungals — amphotericin B and miconazole — plus rifampin and sulfasoxazole as well as phenytoin to control seizures and dexamethasone to lower intracranial pressure.

This regimen not only saved the girl’s life but prevented long-term damage. To the best of my colleague’s knowledge, she has no neurologic sequelae 40 years later.

Today, amphotericin is still a mainstay. In fact, three recent survivors of PAM received both high-dose intravenous and intrathecal amphotericin deoxycholate plus fluconazole, rifampin, azithromycin, miltefosine, and dexamethasone. Having said that, clinicians who suspect PAM in a patient under their care should contact the CDC Emergency Operations Center (770-488-7100) for 24/7 assistance in all decisions around diagnosis and treatment.

Anticipating Infection, Spreading the Word

When I think about PAM, what strikes me as grievous is not just its terrible prognosis, but failing to suspect it early enough to (possibly) alter its outcome. This sometimes occurs because medical providers lack knowledge. In other cases, a lab tech can miss N. fowleri‘s motile trophozoites unless he or she performs an immediate wet mount of centrifuged CSF following lumbar puncture.

Failing to diagnose PAM may also mean we never answer a critical question: Are cases now rising due to environmental warming and increasingly contaminated water?

If I were teaching undergrads, I would be tempted to say “yes,” despite insufficient data to confirm this hypothesis. But new reports might also help back me up. For example, many recent cases of PAM have affected men in the sub-Indian continent who have neither splashed nor swum but who have performed nasal ablution. This practice may explain most of the 146 cases of PAM that occurred in Karachi, Pakistan between 2008 and 2019. In addition, as Pakistani experts stated in their 2020 publication in Lancet Infectious Diseases, “Extended summers and prolonged humid conditions due to climate change provide an ideal environment for amoebas to flourish in bodies of water.”

So, what can be done to lessen PAM’s threat? Among other thoughts: how about widespread education targeting schoolkids, parents, and frontline physicians; posting more warnings at hot springs and other high-risk recreational settings; and using chlorine to disinfect and eliminate biofilms in certain water systems, as happened in Louisiana.

Of course, individual actions remain the final line of defense. Looking back on my days in London, I’m thankful I learned enough to become mindful. A decade later, at a beautiful thermal pool in Australia’s Northern Territory, this struck me anew. Yes, I enjoyed its warm, aquamarine waters fringed by tropical palms, but while others splashed and dunked, I never submerged my face.

Claire Panosian Dunavan, MD, is a professor of infectious diseases at the David Geffen School of Medicine at UCLA and a past president of the American Society of Tropical Medicine and Hygiene.