Naegleria fowleri – the organism that eats you from within

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Parasitic behaviour, by definition, is when organisms benefit from the deterioration of others – whether it be through extraction of their resources, theft of their nutrients, or any other method of siphoning the ingredients of life from the hosts they live in. Perhaps the most terrifying example to humans is the one of Naegleria fowleri, an amoeba that has the ability to consume our brains from within if infected – causing almost imminent death within two weeks.

Primary Amebic Meningoencephalitis (PAM) - Naegleria fowleri ...
A visualisation of N.fowleri, taken from https://www.cdc.gov/parasites/naegleria/index.html

The first case of Primary Amoebic Meningoencephalitis (PAM) as a result of this pathogen was recorded in 1962, in Florida – although there has been evidence that N.fowleri was present in tissues from the early 20th century. Naming of the organism derives from the scientist who identified it, Malcolm Fowler, who named it in 1965 in Australia. It has been reported that from 1964 – 2014, there were 260 cases globally – of which 11 people survived.[1]

Naegleria fowleri is not exactly a parasite, per say. There are many terms to define it, with it primarily being a free-living pathogenic protozoa, which means it is a single celled organism that does not require another organism to survive, (disqualifying it from classification as a parasite) that has the capability to cause disease[1]. It is thermophilic, which means that the main areas it is found in are freshwater bodies and soil that are at higher temperatures (optimally surviving at 35-45 degrees Celsius). The organism is also defined as an amphizoic amoeba, which means it can live freely in the aforementioned areas as well as a host, in this case humans. Geographically, they are ubiquitous, although the temperatures do restrict them especially with their breeding.[2]

Pathogen & Environment | Naegleria fowleri | CDC
The typical life cycle of Naegleria Fowleri, taken from https://www.cdc.gov/parasites/naegleria/pathogen.html

The typical life cycle of N. fowleri consists of three stages; a cyst stage, a trophozoite stage and a flagellate stage. One of the most interesting things about the organism is that it can change its phenotype depending on the environment: in favourable conditions, it manifests in the trophozoite stage, which is the infectious stage (as well as the reproductively active stage)[1]. The flagellate stage is temporarily used for moderate conditions, and the cyst stage is typically dormant and reserved for the worse conditions, so that the organism can survive until more preferable environmental conditions arise – thus these two stages are non-feeding and non-reproductive. The trophozoite N.fowleri can infiltrate the body when humans swim in water containing it, passing up through the nasal cavity and through the olfactory epithelium – then using our own nerves as a method of transport directly to the brain, where the infection starts. This allows the pathogen to bypass the protection that other routes have, essentially taking the path of least resistance. Interestingly, it cannot infect us through our mouths, nor through our lungs – evidence has shown that penetration of the respiratory epithelium is rare.[3]

This entry into our brains is what causes the onset of PAM – the disease which is so fatal to us. Carrying a mortality rate of over 97%, infection ensues a variety of symptoms – severe inflammation, high cranial pressure, vomiting, nausea, frontal headaches, and fevers.[2] The cerebral edoema (inflammation) is the primary cause of death, as it gradually restricts brain function – to the point where the rest of the bodily functions are also restricted, leading to death. In addition, small cups on the organism itself allow it to feed on brain material as well. Headaches, fevers, nausea and vomiting are the presenting symptoms, which make diagnosing PAM more difficult, as it shares these symptoms with bacterial meningitis.[4] As a result, the diagnosis often comes too late for any treatments to be administered, and combined with the already extreme mortality rate survival is nothing short of a miracle. Only a specific laboratory test of cerebrospinal fluid will reveal the organism present, which confirms the diagnosis – this only happens before death in 27% of cases.[2]

Amphotericin B - Wikipedia
The formula for amphotericin-B, which allows it to target cell membranes, taken from https://en.wikipedia.org/wiki/Amphotericin_B

Treatment consists of multi-drug therapy, with the primary drug being amphotericin-B. This targets the cell membrane of the organism, binding to a specific chemical (ergosterol) to depolarize and alter the permeability of the membrane, causing death. This alone does not work, due to the toxic side-effects of amphotericin-B (when applied intravenously or intrathecally, 80% of patients develop toxicity as it binds to human cells) as well as the need for other drugs.[5]The majority of the survivors were administered multiple drugs – including other antifungals such as fluconazole, antibacterials such as rifampin and steroids to control the extreme inflammation.[6]

While these treatments work in a few cases, there is evidently a need for new methods and drugs that can offer a more reliable solution to this problem. Clinicians in areas that have N.fowleri are advised to consider water exposure two weeks prior to onset, and increasing the availability of the cerebrospinal fluid test in these areas would help to accelerate diagnoses. More research has to be carried out into anti-parasitic drugs – which can be used more reliably and with less side effects. However, the difficulty in diagnosing this means some thought is being given to strategies focused on preventative measures, and the improvement of the immune system. But for now, Naegleria fowleri remains a danger that if contracted, is practically a death sentence.


References

  1. Jahangeer M, Mahmood Z, Munir N, et al. Naegleria fowleri: Sources of infection, pathophysiology, diagnosis, and management; a review. Clin Exp Pharmacol Physiol. 2020;47(2):199-212. doi:10.1111/1440-1681.13192
  2. Cope JR, Ali IK. Primary Amebic Meningoencephalitis: What Have We Learned in the Last 5 Years?. Curr Infect Dis Rep. 2016;18(10):31. doi:10.1007/s11908-016-0539-4
  3. Moseman EA. Battling brain-eating amoeba: Enigmas surrounding immunity to Naegleria fowleri. PLoS Pathog. 2020;16(4):e1008406. Published 2020 Apr 23. doi:10.1371/journal.ppat.1008406
  4. https://www.cdc.gov/parasites/naegleria/illness.html, Page last reviewed: April 4, 2019
  5. Noor A, Preuss CV. Antifungal Membrane Function Inhibitors (Amphotericin B) [Updated 2020 Apr 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482327/
  6. Naegleria fowleri: Pathogenesis, Diagnosis, and Treatment OptionsEddie Grace, Scott Asbill, Kris VirgaAntimicrobial Agents and Chemotherapy Oct 2015, 59 (11) 6677-6681; DOI: 10.1128/AAC.01293-15

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