Brain-eating amoeba

by Mark Thoma, MD 

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.

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.

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.