Due to my curiosity, I've done some light research about how people are going about managing Naegleria fowleri and treating patients who have the amoeba in their system. However, some articles have stated that the use of the drug, miltefosine, kills naegleria fowleri--and therefore, have used the drug on patients infected. My concern is that if people continue to use the drug to combat Naegleria fowleri, wouldn't the amoeba gain resistance to miltefosine over time and prove to be ineffective as treatment?
The CDC has the following recommendations:
Clinicians: For 24/7 diagnostic assistance, specimen collection guidance, shipping instructions, and treatment recommendations, please contact the CDC Emergency Operations Center at 770-488-7100. More detailed guidance is under Information for Public Health & Medical Professionals.
https://www.cdc.gov/parasites/naegleria/treatment.html
Fortunately, there is no risk that Naegleria fowleri could become resistant to miltefosine, since (i) N.fowleri is not transmitted from people to people, i.e., miltefosine treated cases would not in any way transmit those drug-exposed ameba to other people/hosts as a requirement of development of drug resistance and (ii) since N.fowleri in its natural environment (fresh water etc.) would not be pre-exposed to miltefosine and hence could not develop any drug exposure-driven development of drug resistance. N.fowleri is a common environmental fresh water amoeba in lake shores etc. of warmer climates worldwide and human infections are a 'freak accident' not related to any regular parasitic life cycle of this pathogenic ameba that would be required for drug resistance as seen in other parasites or bacteria.
Theoretically it is possible. The use if miltefosine extends beyond that if Naegleria - it is the only approved oral agent for the treatment of Leishmaniasis, and is used (rarely) to treat metronidazole-resistant Trichomonas, refractory Chaga's disease, other free-living amoeba like Balamuthia and Acanthamoeba. It has also been found to effective against more hardly strains of Candida species and Plasmodium falciparum - so its use is broad-spectrum, anti-amoebic, anti-protozoal, anti-fungal.. Leishmaniasis is the more common indication - it is endemic in nearly 100 countries, has an incidence of over 1 million cases every year, and 350 million people at risk of the disease. Its potential use therefore is actually pretty significant. Miltefosine is unfortunately, not excluded from the development of resistance. In recent years there has been an increasing trend in treatment failures and relapses in patients with Leishmaniasis and the mechanism of resistance has been found to be altered aminophospholipid/miltefosine transporter (MT), so inward translocation of the drug is defective.
There are several possibilities for resistance development:
(i) environmental exposure due to the increased use to the drug
(ii) genetically transferable antibiotic resistance: cross-species genetic transfer by way of capsids (or a similar model)
(iii) the inherent symbiont nature of amoeba of facilitating genetic transfer between bacteria could be a risk factor - amoeba are the genetic "melting pots" after all
(iv) the gene-switching ability of amoeba by utilisation of the genetic material of endosymbiotic bacteria
(v) increased habitat availability with rising temperatures
(vi) dilution of the salinity of sea water by melting glaciers again increases potential habits
(vii) flagellate-empty hypothesis: Naegleria thrives when competition posed by thermosensitive fauna is eliminated, so thermal pollution, again contributes to its abundance by removing resource competitor
(viii) other animals have also been found to be susceptible to Naegleria, including rodents, sheep, cattle and tapirs. These could serve as potential reservoirs, and the thermostability may allow for their survival of cooking and be acquired from consumption of infected meat as well (sheep/goat brain is commonly eaten in some regions).
(ix) The advent of multi-drug resistant superbugs and the role they could play in horizontal gene transfer needs to be considered
(x) Changing trends in infectious disease epidemiology - there is a change in the infection patterns globally, with previously rare diseases becoming more frequently seen - these "Emerging Infectious Diseases" are an excellent model to study the effect of the ecological changes we have set in motion. This group of diseases includes Zika, Ebola, SARS, Chikungunya. The environmental changes that have taken place and are continuing to take place favour the thermophilic amoeba - it very well could become an emerging infectious disease.
Of course these are mostly theoretical, but drug resistance itself was a theory until the first cases of penicillinase producing bacteria were discovered hardly a decade after the introduction of penicillin..
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