Here What You need to know About the Brain Eating Amoeba!

Introduction

Credits to CDC

You might have heard about the brain eating viruses and parasites in many zombie and horror movies which is their basic theme where their movie revolves around about. But guess what they theme is of movies is kind of getting real. The Brain eating parasite which could harm us human does exists in our world!

What is this brain eating amoeba?

Credits to CDC

This brain eating parasite is actually an amoeba which is member of genus Percolozoa. Now what is this Percolozoa ? The Percolozoa are a specific category of Excavata — Excavata is like a big family of microscopic living things, and they have some properties like morphological and genetic characteristics in common. One thing is that many of them have a special groove or dent on one side of their cell. This family includes various tiny organisms with different shapes and ways of living. Some of them are called diplomonads, parabasalids, and Euglenozoa, which itself has groups like kinetoplastids and euglenids. (Don’t worry, I am not going any further in detail because it is very complicated to make understand.) They're all part of this larger family called Excavata. They lack colour and photosynthetic capabilities. This group comprise of many similar numerous organisms which are capable of transforming themselves into amoeboid, flagellate, and cyst phases.

Credits to CDC

It is a free living brain eating amoeba called — “Naegleria Fowleri” which was named after Malcolm Fowler who described the initial cases of it. It has gained tremendous media attention in the past few years due to its increasing public cases.

Where is Naegleria Fowleri found ?

Credits to Ms. Radhika Gharpure

This brain-eating amoeba — Naegleria Fowleri, is typically found in warm freshwater environments such as lakes, hot springs, and soil. But it can live in pipes, hot springs, spas and pools if they are not treated properly. It survives in temperatures ranging from 25 to 46 degrees Celsius (77 to 115 degrees Fahrenheit). Afterwards, I will also tell some surprising fact about it too. The warmer the environment, the better is its growth as it lives warm environment. Thus, in summers, we all will have highest chances of getting affected by them.

What is the life cycle of Naegleria Fowleri?

The brain eating amoeba – Naegleria fowleri develops in three stages in its whole life cycle :

1. Cyst
2. Trophozoites
3. flagellated forms

What happens when you brain eating amoeba?

First of all, Naegleria Fowleri does not even wants to consume your brain. It just enters through our nose when one plays in dirty source of water in search of its preys i.e., tiny bacteria. After entering in the nose, our immune system greets its well-meaningly, our defence mechanism tries to identify the treat and thus destroy it there once and for all. But unfortunately for us humans, N. Fowleri is good at hiding itself. Thus, resulting in not even detected by radar of our immune system.

Credits to CDC

As the amoeba pass through the mucosa  – the slime filled with chemical which kills all the invaders that protects your nasal cavity, it finds the nerve cells that are connected to the brain. These nerve cells transmit all the information they catch to the olfactory bulb ­– it is also called as the centre of smell of our brain. To do their jobs, these release various different kinds of chemicals and decode them  using special receptors. One of these chemicals is acetylcholine. Now, the real danger closes in, N. Fowleri happens to have receptors that recognize acetylcholine. Thus, tends to attract that chemical like a magnet and a metal.

Credits to Wikipedia

Thus, these deadly amoeba follows the chemical signals and proceed towards our brain. It is then greeted by our second line of defence – Neutrophils which are the suicide warriors of our immune systems. But individually, they stand no chance against N. Fowleri as these amoebas are a pretty large buffed fighters. Neutrophils will now swarm the intruder and try to kill it by vomiting chemicals or ripping parts of them off. But as N. fowleri is not at all a solo hunter and neutrophils slow them down.

They still follow the olfactory nerves and reach their final destination:  Our Brain. This process takes from 1 day to more than a week to occur and you won’t even notice a thing until the amoeba reach the olfactory bulb. Now, our brain cells are all helpless and as they release these wonderful chemical – acetylcholine which this amoebas love. N. Fowleri massacres our brain cells using various attacks like ripping holes into our cells in its contact and consume the dead nerve pieces. Now, the amoeba will develop many suckers called as food cups and will now rip large bits out of our brain cells as they are still alive. Things escalate quickly as our immune system tries to kills these invaders. But our immune system is not an intelligent fighter. It will attack like destroying a whole country just to kill some bandits. Immune system will try to attack these brain eating amoeba by all means from Neutrophil to eating them alive.

But N. Fowleri has became too powerful now as it swallows, disarms and destroys any chemical attack done on it. Our body will catch a high fever to stop them but as N. Fowleri is resistant to heat, it does nothing. As the war wages, our body send fluid to the brain for inflammation purpose and the brain expands. At a points, as our skull restrict it from expanding, the brain will start shrinking which disables our brainstem which control stuffs like breathing. The fatality rate is 97% and within a week, the patient dies.

What symptoms do our body shows if it gets contaminated by this brain-eating amoeba (N. fowleri) ?

Clinical symptoms and signs of infection with N. fowleri typically manifest within 2 to 8 days of exposure, although some cases have been reported within 24 hours. Despite the absence of specific indicators for N. fowleri infection, the most common symptoms include :

·       Severe headache

·       Fever

·       Chills

·       Positive Brudzinski sign (It is the inflammation of the tissues surrounding the brain and spinal cord)

·       Positive Kernig sign (It is the extension of the knees beyond 135 degrees)

·       Photophobia

·       Confusion

·       Seizures

·       Coma

Moreover, some rare cases have shown cardiac rhythm (irregular heartbeats) abnormalities and myocardial necrosis (heart attack). Of particular significance, an association has been observed between increased intracranial pressure and cerebral spinal fluid (CSF) pressure, directly correlating with fatalities. CSF analysis has revealed varying colour abnormalities, transitioning from grey in the early stages of infection to red in late-stage disease due to a significant increase in red blood cells. Additionally, elevated concentrations of polymorphonuclear cells – a type of white blood cells (up to 26,000mm³) and the presence of trophozoites in the CSF (detected using trichrome or Giemsa stain) have been noted. Magnetic resonance imaging (MRI) of the brain frequently has shown abnormalities in different regions, including the midbrain and subarachnoid space.

What are the treatments for this amoeba ?

Due to the rarity of cases of N. fowleri infections in humans, there have been no clinical trials conducted to date that gives us  the information about the effectiveness of one treatment regimen over another. Information on the efficacy of medications is primarily derived from case reports or laboratory studies conducted in vitro (The term "vitro" refers to studies or experiments conducted outside of a normal living organism, typically in a controlled laboratory environment , test tube or a glass). Amphotericin B is widely acknowledged as a commonly used medication for treating N. fowleri infection, supported by in vitro studies and documented in several case reports. Other anti-infectives reported in case studies include fluconazole, miconazole, miltefosine, azithromycin, and rifampin. Additionally, various agents, such as hygromycin, rokitamycin, clarithromycin, erythromycin, roxithromycin, and zeocin, have been examined either in vitro or in vivo for potential efficacy.

According to the research paper by Grace E, Asbill S and Virga K. I have explained two of them here as follows but I will recommend you all to take a look at their research papers for more information :

Amphotericin B

Credits to Wikipedia

One of the recommended medications is Amphotericin B which is effective against N. fowleri with a minimal amoebicidal concentration ­of 0.01 μg/ml. Minimal amoebicidal concentration is the lowest concentration of any drug or substance that is required to kill amoebas, such as Naegleria fowleri, in a laboratory environment. However, in vitro studies indicated that a concentration of at least 0.1 μg/ml was required to suppress over 90% of growth, and 0.39 μg/ml was necessary for complete amoeba proliferation suppression. The MICs (Minimum inhibitory concentrations) of amphotericin B to kill 100% of organisms in in vitro studies was found to be 0.78 μg/ml.

Studies in mice infected with N. fowleri demonstrated that a daily dose of 7.5 mg/kg of body weight of amphotericin B is needed to improve survival. In adults, recommended intravenous doses range from 0.25 to 1.5 mg/kg/day, while paediatric patients are advised doses between 0.5 to 0.7 mg/kg/day. The recommended duration of amphotericin B therapy for treating N. fowleri is 10 days. The Centres for Disease Control and Prevention (CDC) suggests the use of conventional amphotericin B over the liposomal formulation or amphotericin B methyl ester due to significantly higher MIC against N. fowleri. For intravenous therapy, the CDC recommends doses of 1.5 mg/kg/day in two divided doses for 3 days, followed by 1 mg/kg/day once daily for an additional 11 days (totalling 14 days). Intrathecal amphotericin B should also use the conventional formulation, with a recommended dose of 1.5 mg/day for 2 days, followed by 1 mg/day for an additional 8 days (totalling 10 days).

While amphotericin B is the primary drug for treating primary amoebic meningoencephalitis (PAM) – It is a fatal infection caused in central nervous system by Naegleria fowleri , it is associated with multiple side effects, including kidney failure. Corifungin, described as a new drug entity, has shown promising in vivo efficacy in a mouse model of PAM, surpassing amphotericin B at equivalent dosing. Corifungin's increased aqueous solubility (--100 mg/ml) is believed to contribute to its enhanced physical boosts. However, human studies showing these therapeutic benefits such as improved blood-brain barrier penetration and reduced renal toxicity have not been reported.

Miltefosine

Credits to Wikipedia

In 2013, two patients who were infected with N. fowleri managed to survive following treatment with miltefosine drug, showing us its promising outcomes when an early diagnosis is made. Miltefosine is a phospholipid with an attached choline, categorized as an Alkyl phosphocholine. Miltefosine's reported mechanism of action involves inhibitory action against protein kinase B (PKB or Akt), making it of interest as an anticancer agent due to its impact on cell survival.

While ongoing studies aim to determine miltefosine's absolute bioavailability in humans, evidence indicates favourable (≥80%) oral bioavailability in rodents and dogs. Miltefosine shows both passive and active transport mechanisms following oral administration, with over 95% plasma protein binding and wide tissue distribution in rodent models, concentrating in organ tissues like the lung, adrenal glands, spleen, and liver. Although the penetration of miltefosine into the central nervous system (CNS) remains challenging to rationalize due to its permanently charged nature, its demonstrated efficacy in N. fowleri infection suggests some level of penetration. However, specific studies on miltefosine concentrations in the brain and the compromise of the blood-brain barrier in infected patients have not been described.

Metabolism studies on human subjects are still lacking, but evaluations against a large superfamily of proteins – Cytochrome P-450 (CYP450) isoforms suggest low risk for drug-drug interactions. In vitro efficacy studies against N. fowleri indicate many benefits in treatment, with concentrations of 40 μg considered mobocratic (representing the MIC) and concentrations of 55 μg considered amoebicidal (representing the minimum amoebicidal concentration). The CDC has made miltefosine available on a need basis through an investigational new drug (IND) protocol for infections caused by free-living amoebas, including N. fowleri. Recommended miltefosine doses are 50 mg orally two to three times daily (based on body weight), with a maximum dose of 1.5 mg/kg/day for a total treatment duration of 28 days.

How to prevent this brain-eating amoeba?

Here are some ways to stay safe from N. Fowleri :

1.     Experts have advised to avoid swimming in freshwater bodies like rivers, lakes and ponds, especially in the times of summer.

2.     If such activities cannot be avoided, it is recommended to avoid jumping into the body of water, splashing, or submerging their heads under the water in order to avoid this deadly amoeba from entering the nasal passages.

3.     Individuals are also recommended to use nose clips to avoid fatal situations like this.

4.     If anybody wants to perform physical activities in water bodies, consider doing them in cleaned and filtered pools rather than in freshwater bodies.

5.     CDC recommends treating water for sinus rinsing by either boiling or filtering the water using a filter with pores of 1 μm or smaller.

Survivor Cases

Here is the information of patients that caught Naegleria fowleri infection that has been documented worldwide. Four of these survivors were in North America, comprising three cases in the United States and one in Mexico. The first case of N. fowleri survival in North America occurred in the United States in 1978 (published in 1982). It involved a 9-year-old girl who had been swimming in Deep Creek Hot Springs in the San Bernardino National Forest on two separate occasions. The treatment protocol included intravenous and intrathecal administration of conventional amphotericin B and miconazole, along with oral rifampin, intravenous dexamethasone, and oral phenytoin.

In 2004, a survivor was reported in Mexico, where a 10-year-old boy developed N. fowleri infection a week after swimming in an irrigation canal. The patient successfully underwent treatment with intravenous amphotericin B for 14 days, combined with rifampin and fluconazole for one month. Discharged on day 23 of therapy, the brain computed tomography showed no evidence of infection.

The two more U.S. cases occurred in 2013. The first involved a 12-year-old girl diagnosed with N. fowleri infection seven days after visiting a water park near Little Rock, Arkansas. Treatment commenced on the same day as her emergency department presentation, incorporating amphotericin B (intravenously and intrathecally), miltefosine, fluconazole, rifampin, dexamethasone, and azithromycin. The patient made a full recovery following treatment. The second 2013 case involved an 8-year-old male in the United States, treated with a combination of intrathecal and intravenous amphotericin B, rifampin, fluconazole, dexamethasone, azithromycin, and miltefosine. Although the patient survived the infection, he experienced brain damage secondary to the prolonged infection, and medically induced hypothermia, used in the previous case, was not employed.

The latest case was reported back in 2023 in India where a 15 year old boy in the state of Kerala died due to the rare infection – “Primary Amoebic Meningoencephalitis (PAM)” caused by N. Fowleri.

Conclusion

So, while concluding this blog, we can say that Naegleria Fowleri is rare deadly amoeba that can do serious brain damage in case of humans. But as seen from the below data, only an average of approximately 2.75 people are affected by it every year by the reports conducted by CDC.

Credits to CDC

Credits to CDC

The treatments are not yet been developed for it as not much research is conducted on it. Thus, avoiding swimming in open water sources should be avoided. Recent cases of N. Fowleri were also discussed here.

References : Here, I am giving credits to the websites which I took and shared all this precious information from. Also, the above information is been collected from many research papers and from various experts making it verified and correct. I would recommend you all to visit their sites and surf them for deeper information and knowledge :

1. General Information  | Naegleria fowleri | CDC. (n.d.). https://www.cdc.gov/parasites/naegleria/general.html
2. Grace, Eddie, Scott Asbill, and Kris Virga. "Naegleria fowleri: pathogenesis, diagnosis, and treatment options." Antimicrobial agents and chemotherapy 59.11 (2015): 6677-6681.
3. Wikipedia contributors. (2024d, March 3). Naegleria fowleri. Wikipedia. https://en.wikipedia.org/wiki/Naegleria_fowleri

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