Weird science: Brain-eating amoeba

There’s a new medical mystery that reminds medical researchers of the early days of AIDS: brain-eating amoeba.

Remember when Legionnaire’s disease (Philadelphia Flu) first started unfolding? It raised a lot of interesting questions.

Why Philadelphia? Why US veterans? What was causing it? Why hadn’t it happened previously? How could it be stopped? What could we do to treat it?

Actually, upon investigation, all of those answers were uncovered in a relatively short time. It was caused by a bacterium, living in the water supply at the host hotel of the Legionnaire’s convention. It was susceptible to an antibiotic that we already had available. It had been around causing pneumonias previously but never so many in such a short time and never so well publicized (see Pontiac Fever).

Trophozoite of N. fowleri in CSF, from the CDC.

Trophozoite of N. fowleri in CSF, from the CDC.

Then AIDS happened. The causative organism was harder to identify (viruses often are). It was devastating, causing protean symptoms: skin and visceral cancers (Kaposi’s sarcoma), opportunistic infections like Pneumocystis carinii (now jiroveci) pneumonia, thrush, encephalitis, tuberculosis and others. It rapidly led to death. No effective drugs were available. How it was spread was unclear at first. It would take decades of research and public health investigations to develop treatments, isolate and identify the organism, slow its spread, educate people. And the work still continues in all of those areas.

Now there’s a “new” disease that is also incompletely understood. It’s rare, very rare. It has a very high fatality rate. Its mechanism of transmission is suspected. Until recently, no effective drug was available. While it’s not as multifaceted as AIDS, it still raises a very interesting question – why are some people stricken and others not?

You may have read some things about the “brain-eating amoeba,” Naegleria fowleri, and how it causes Primary Amebic Meningoencephalitis (PAM). Some other amebas can cause similar disease, B. mandrillaris and Acanthamoeba spp., but Naegleria is the one to focus on here.

Naegleria has several species, but, so far, only fowleri has been implicated in causing PAM. These amebas are micricroscopic, motile and found in warm water. Most patients who get PAM die. Fortunately, there haven’t been many cases of PAM. In the past 10 years, only about three dozen cases of PAM have been diagnosed in the US. All were fatal. But, as awareness of the disease spreads, more cases may come to light. And men, often younger men, get PAM more often than women. Interestingly, symptoms can mimic the type of meningitis that can decimate men who have sex with men.

Location of Naegleria

Naegleria have been found in warm waters (lakes, streams, hot springs), warm-water outflow from industrial and manufacturing plants, inadequately chlorinated swimming pools, soil and may be found in warm water supplies in homes in the US, Australia and other countries. Naegleria infection is more common in states in the southern US, but, during summer as temperatures rise, infections can be seen in northern states, as well. The infection occurs when water contaminated with these amebas gets up into the nose. Two people are known to have gotten PAM after using neti pots to cleanse their sinuses. The remainder of the cases have been associated with swimming and diving. One child even got PAM from playing in a water filled ditch.

But how do the amebas get into the brain? Why are boys and young men more commonly infected? Can it be treated?

How Infection Starts

NOTE: Naegleria and PAM can NOT be acquired through drinking water contaminated with Naegleria. Only when the Naegleria-contaminated water enters the nose can infection occur.

Naegleria are commonly found in lakes, rivers and streams, yet infection is extremely rare. Well over 99.9999% of people don’t get Naegleria when swimming in waters where these amebas have been found. Boys and young men are thought to get it more often because they may be more active in swimming and diving games, and stir up the bottom sediment in lakes and streams. However, that is conjecture, not proven. But tens of millions of people swim in warm waters outdoors every year and don’t get the disease.

Naegleria_fowleri_lifecycle_stages

Some of the stages of the life cycle of Naegleria fowleri, via the CDC.

The method of infection is as follows. The contaminated water gets into the nose while swimming, diving or playing in water containing Naegleria. The amebas get to the top part of the nose, separated from the brain by a thin section of bone called the cribiform plate. There are multiple openings in the skull that allow for nerves and blood vessels to enter and leave the brain. The cribiform plate has a number of tiny holes. The reason is so that tiny nerve fibers of the olfactory nerve (Cranial Nerve I) can exit the brain and be able to sense odors brought into the nose. The olfactory nerve detects odors and sends that information to the brain. The amebas probably gain entry to the brain here. Perhaps, in the affected patients, these holes in the cribiform aren’t tightly plugged by the exiting nerve rootlets and dura mater and the amebas crawl into the brain that way. Or the amebas may actually be able to penetrate the nerve cells and follow them into the brain. Or digest their way through the nerves and dura. Perhaps there are extra holes that don’t have rootlets in place. Maybe there is a defect in the nerve structure that allows the amebas access. Perhaps the affected patients have some type of immune deficiency that allows the amebas to more easily enter their central nervous systems.

It’s difficult to know because some of these things can only be observed at autopsy or in research done on primates. These are tiny holes, tiny nerves and tiny amebas. The average Naegleria is about 8-30 microns in size. An average red blood cell is about 7-8 microns in diameter For reference, the diameter of a human hair is about 90-100 microns. In the brain, the amebas destroy and eat brain tissue. That in itself, causes some damage. However, the immune system also responds and causes even more destruction.

Symptoms

As mentioned previously, the symptoms can mimic bacterial meningitis (like meningococcal meningitis) that was causing an outbreak in men who have sex with men, HIV positive men and men meting other men at bars or by using smartphone apps. The symptoms are: headache, fever, anorexia, nausea, vomiting, stiff neck, seizures, hallucinations, confusion/altered mental status and coma. Symptoms appear from 1-7 days after exposure to contaminated water and death occurs about 7-12 days after symptoms start.

Diagnosis

It is difficult to make the diagnosis since the symptoms are so closely related to bacterial meningitis, which is much more common. And, since the is is a rare condition, most patients and physicians don’t think of PAM in the diagnosis. The amebas can be seen in cerebrospinal fluid or in tissue specimens or from biopsies. Naegleria infections tend to occur during the warmer months, especially when water levels are lower.

Prevention

When swimming, use nose clips, don’t stir up sediment, keep the head out of the water, do not irrigate nose or sinuses with unsterile solutions. Again, Naegleria infection and subsequent PAM, do not occur from drinking Naegleria containing water.

Treatment

Several drugs have been tried in the past. A few drug combinations have seemed to work in a few cases.

Miltefosine, a drug that is used to treat a different kind of parasite infection, is showing promise in treating PAM. Currently, there are two children with PAM in US hospitals, both have received miltefosine treatment. One seems to be recovering. The other seems to no longer be infected with Naegleria, however he has suffered extensive brain damage and the eventual outcome may still be fatal.

As knowledge of this infection spreads, more interest is being generated in studying it – much like with Legionnaire’s disease and AIDS. More researchers, physicians and members of the public are becoming aware of it.

Unfortunately, with the sequester, government research money is decreasing, and an “orphan” disease like this may not get the funding it needs for additional study. Also, pharmaceutical companies are not interested in developing drugs that will only benefit a handful of patients. However, since miltefosine is used to treat another disease, perhaps other anti-parasite drugs, already available might be useful in treating PAM.


Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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  • EdHandy

    I’ve always been told “never use well water” without boiling (I’m a very long time irrigator); I don’t have any idea what level of filtration would be adequate if any. As for the proper temperature, with the plastic bottles 120ml, you can microwave them; for room temperature water, 20 seconds in my fairly powerful microwave, 25 at my in-laws’ rather weaker one… drop a couple of seconds on a fairly hot day.

  • Rob Dowdy

    Translation: “Apropos of nothing, here’s something randomly gay.”

  • discus_sucks_ass

    inaccurate as hell too

  • Monoceros Forth

    Oof, good point. Leaves a bad taste, doesn’t it?

  • http://www.rebeccamorn.com/mind BeccaM

    Thanks for the advice, I appreciate it. I think I’ll go the boiling water route. My neti-pot is made of stainless steel, so sterilization isn’t a problem — in fact, I do that regularly with anti-bacterial soap, then an alcohol wash, and finally rinsing with filtered water. I can add a boiling water regime to that as well.

  • http://www.rebeccamorn.com/mind BeccaM

    We have a private well that runs through multiple filtration systems, including reverse osmosis.

  • discus_sucks_ass

    stopped reading at paragraph 8, last line.

  • EdHandy

    I’m fairly sure that if you live in a municipality that uses chlorine or chloramine to purify the water that should be adequate to kill Naegleria. (This is the upside to the reason you have to be careful about what municipal water is purified with if you keep fish.)

  • http://adgitadiaries.com/ karmanot

    What whatever, never, never swim in the Nile. :-)

  • Bill_Perdue

    Thanks

  • KLG

    No. Naegleria is a protozoan (single-cell eukaryote). It is endemic in the US, mostly in the South, though two cases have been reported in Minnesota. It multiplies best in very warm fresh water. Dengue is caused by a virus carried by mosquitos. As the range of the vector increases with a warmer climate you can expect more Dengue and similar diseases in the US.

  • KLG

    This is not new, nor is it a medical mystery. Naegleria fowleri-induced encephalitis has been known for a long time. According to CDC, 128 cases have been confirmed from 1962-2012. Almost all of them were in people who had gone swimming in very warm fresh water (shallow lakes or farm ponds) or who were diving or water skiing in warm lakes. According to Yoder et al. (2012) two (2) people have become infected using contaminated water for nasal irrigation. Both died. Take-home message: Don’t put dirty water up your nose.

    Although Naegleria fowleri is a scary organism, stop with the medical horror stories. They do not help your credibility, and this comes from a long-time reader.

  • Bill_Perdue

    Did this come from the tropics like Dengue fever?

  • docsterx

    Naegleria is susceptible to some other drugs like: amphotericin B, rifampin, orindazol, miconazol, sulisoxazole, or chloramphenicol and voriconazole to a degree. Almost all patients get treated with a cocktail of several of these drugs.

    One problem may be that PAM isn’t suspected or diagnosed early enough to start treatment in time. There have been < 150 cases diagnosed in the US in the last several dozen years, but many, many more cases of non-N. fowleri meningitis (e.g. meningococcal meningitis, seen in children and gay males).

  • Zharre

    Oh! From room temperature, I microwave for 30 seconds. (However, I then carry the glass I microwaved the water in into the bathroom, pour it into the neti pot, then mix the saline packet in, so it does cool down a bit from the moment I take it out of the microwave.)

  • docsterx

    nicho, distilled water isn’t necessarily sterile. Unless the distillate water is collected in a sterile fashion and tested to be sure that it’s sterile, you can’t be sure. But, since it was boiled, it should be free from live Naegleria.

    Becca, boil the tap water for 3 minutes and let cool. If the material that the neti pot is made from can stand it, rinse with the boiled water while still steaming. Let it stand for several minutes (~7), then discard water. Let neti pot dry completely before next use. Again, if neti pot can stand it, boil it for three minutes and let cool and dry. Then add previously boiled water. Make sure that neti pot and water are cool before instilling water into your nose.

    Or, if available without an Rx in New Mexico, go to a surgical pharmacy/wound care store and get “sterile water for irrigation, USP” a 2L bottle costs about $7. If you need an Rx for it, I’m sure your doctor would write it for you as soon as you explain the reason

  • http://www.americablog.com/ Naja pallida

    Seems to me the primary reason why the fatality rate with this sort of thing is so high is the old “when you hear hoof beats, think horses, not zebras” mentality that is instilled in physicians. Coupled with the all too familiar problem of treating symptoms, instead of doing the work to determine the underlying cause of a condition. All of the common/early symptoms are the same as countless other potential conditions. By the time a diagnostician could get around to determining there even is an amoebic infection, it is far too late for adequate treatment. As patients we’re instilled with the belief that every doctor is Gregory House or Doug Ross, always going above and beyond to figure something out and make sure they get it right for their patient, just in the nick of time… but the reality is so very far from that. I don’t even know how we begin to address it. Taking the profit out of health care would be a nice start, but that’s a whole different conversation.

    I’m curious about the various *azole drugs used for other amoebic infections, many of which are ubiquitous and relatively cheap, are they not effective on Naegleri? I know you’d have to have something that crosses the blood-brain barrier, but metronidazole – probably the most common amebicide/antiprotozoal out there I believe does. Of course, that still wouldn’t treat the end result, but being relatively inexpensive, with minimal side effects, if infection was suspected, could be given prophylactically without too much concern? Dunno, I’m not a doctor… just spit-balling. :)

  • http://www.rebeccamorn.com/mind BeccaM

    Yeah, but I’m talking “how do I bring the temperature up to what I can tolerate in my sinuses?” I guess there’s always the microwave, just have to figure out how long, etc.

  • Zharre

    Boiling water for a few minutes yourself will sterilize it (and kill the amoeba, if it is present), and is what is recommended for neti pot usage. I boil filtered tap water and put it in a sealed container to cool down prior to use.

  • nicho

    I buy a two-gallon container of distilled water at the supermarket for not much money at all. (I’m cheap). But you also can just boil some water and put it in a clean container. I’ve done that too.

  • nicho

    It’s important to note that the people who got the amoeba from using Neti pots were using plain tap water — and not distilled water or sterilized water, as the instruction clearly state.

  • nicho

    Legionnaires outbreaks in the recent past have come from a variety of sources — decorative fountains in hotel lobbies, the misters at the produce section at grocery stores, a hot tub display in a big-box hardware store, hot tubs on a luxury cruise ship infecting passengers eating at an outdoor cafe below, a fountain at a flower show in Europe.

    You can find sources anywhere you can find a plume of mist from standing water. A lot of cases occur outdoors because of the plume that comes from the air conditioning cooling tanks — which is what happened in Philadelphia.

    It’s ironic that in this no-smoking age, when office workers are forced to huddle in the streets to slake their addiction, they’re put directly in the path of these AC cooling tank plumes coming from the top of the building – -and since smokers are more susceptible, well . . . .

  • Jim Olson

    Zomboebas?

  • http://www.rebeccamorn.com/mind BeccaM

    Crap… I use the neti pot to try to keep my sinuses clear (hayfever allergies, prone to sinus infection).

    Mark: Do you have a recommendation for how to do this safely, at the proper temperature (straight up cold water is brutal), without the expense of having to buy sterile distilled water? I’m happy to use filters, but I loathe the entire ‘bottled water’ craze, too.

  • http://adgitadiaries.com/ karmanot

    OMG, it all brings up twenty years of plague horror.

  • Hue-Man

    Since my childhood – post-polio but we all got chickenpox, mumps, and both types of measles – the public in the West have been lured into a false sense of security that pharma has won the battle of human disease. IMHO, this complacency has led to reduced public investment on basic research, public health investments to detect and prevent disease, the abuse/misue of important drugs like antibiotics (scare yourself by looking up what treatments remain for emerging antibiotic-resistant strains of TB), and the anti-vaccination tinhats. (I’ll save the rant about tropical diseases that Westerners ignore but which will soon re-emerge as climate change moves the “tropics” into the American South and Southern Europe.)

    The Legionnaires outbreak in Quebec City last summer is a case study: “Since the outbreak began in July [2012], 180 cases have been reported. Thirteen people have died.” “Public-health authorities say they have identified the source of Quebec City’s outbreak of legionnaires’ disease: an office building in the provincial capital.” http://www.theglobeandmail.com/news/national/source-of-quebec-city-legionnaires-disease-identified/article4556068/

  • TheOriginalLiz

    zombie amoeba … mmmmm…brains….

  • nicho

    HIV, like Legionnaires, has — and had — been around for a long time before being identified. In fact, I had a cousin who, in retrospect, died of AIDS in the early ’70s. All the things she went though at the time were completely consistent with what we saw with AIDS a decade later. But the doctors at the local hospital were mystified. They’d never seen anything like this before and there was nothing in the literature. We found out later that her boyfriend at the time was an IV drug user,

    It was only when we began seeing clusters that the disease was identified. If you remember, HIV came to light when a nurse at CDC became alarmed at the number of requests for a drug to treat pneumocystis that started coming from San Francisco.

    Legionnella is fairly ubiquitous. If you took random samples of standing water from all sources today, you would find Legionnella in about 60-65 percent of them. Many of us come in contact with it — and we can fight it off without any ill effect. Most susceptible are the elderly, smokers, and those with immune systems that are otherwise compromised — which pretty much described the Legionnaires attending the convention in Philly. This is why you saw a cluster, and that’s why the disease was identified.

    Even today, if you were to go to the ER with pneumonia, they would simply treat the pneumonia without any further investigation. However, if a group of people from your apartment building or your office were to come down with it, they would start looking for Legionnella. No one knows how many cases of Legionnaires disease there are today — probably over 100,000 a year. And no one knows how many deaths, unless they occur in a cluster.

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