By Dr. Faisal Ali
The victimization of ease by disease has always remained the bête noire of human beings since the birth of humanity. The forays of medical luminaries for bringing respite against portending vagaries of Naegleria Fowleri never panned out even in 21st century. In order to flicker amusement in the eyes of the affected people, the curtailment of this amoeba should be made the primary objective by the comity of nations.
The term Naegleria Fowleri is derived from the name of F-P-O Nagler, an early 20th century bacteriologist while Fowleri is emanated from the name of Malcoln Fowler, an Australian physician. In 1966, Fowler termed the infection of human brain resulting from Naegleria Fowleri as Primary Amoebic Meningoencephalitis (PAM). This brain eating amoeba is present in fresh water and soil. The Trophozoite is the vegetative stage of Naegleria Fowleri which is found in the Cerebrospinal Fluid (CSF) and tissues of the infected humans.
Naegleria Fowleri enters the nasal cavity of human beings when contaminated water is inhaled or splashed into nose. The Trophozoites then disrupt the olfactory mucosa, invade the Cribriform Plate and ascend via Olfactory nerves into the brain. The organism then begins to feast on the cells of the brain by means of Amoebostome. It becomes pathogenic and causes Primary Amoebic Meningoencephalitis (PAM). Headache, fever, nausea and vomiting are the initial signs and symptoms of Naegleria Fowleri infection which are followed by neck stiffness, seizures, altered mental status, hallucinations and coma. Cranial nerve palsies especially that of third, fourth and sixth cranial nerves can also transpire in this disease. The laboratory confirmation can be carried out by finding motile Naegleria trophozoites in wet mounts of freshly obtained Cerebrospinal fluid (CSF).
Other investigations include Naegleria Fowleri Nucleic Acid tests in CSF or biopsy tissue using PCR, Naegleria Fowleri antigen tests in CSF or Biopsy tissue using Immunohistochemistry (IHC) and Culture of Naegleria Fowleri. The flushing of the Cribriform Plate with saline using a device can also be used to obtain Naegelria Fowleri for diagnostic PCR and microscopic viewing . The CSF R/E of the infected person mirrors that of bacterial meningitis that is why this infection most often leads to a false diagnosis. Pathologic examination reveals hemorrhagic necrosis of the brain tissue which is most often prominent in Olfactory Bulbs and marked Leptomeningitis.
The deathly scenes produced by this dreadful amoeba can be seen throughout the planet. In Pakistan, Seven cases were registered as confirmed victims of Naegleria Fowleri in initial months of 2015. Thirty five cases were reported in United States of America (USA) between 1998 and 2009. Between 1968 and 1978, eight fatal cases of PAM occurred in New Zealand after the victims had been swimming in geothermal water at locations between Taupo and Matamata, in the Waikato Region. The infections of this amoeba have also been described in children from Australia after exposure to water transported through overland pipes. Currently, there is no licensed vaccine or specific drug to beat the perils in the affected regions. Amphotericin B and Rifampicin are the regimens of choice in clinical practice along with therapeutic hypothermia.
The Centers for Diseases Control and Prevention (CDC) recommends Miltefosine which has shown promising results against Naegleria Fowleri. A study in mice models has ferreted out Chlorpromazine to have the best therapeutic activity against Naegleria, both in vitro and vivo. A novel macrolide, Corifungin is also observed to have a higher efficacy against the brain eating amoeba than Amphotericin B. The department of Biological and Biomedical sciences of Aga Khan University Karachi experimented Digoxin and Procyclidine in vitro against the implicated amoeba which revealed more than 95% potent amoebicidal effects. Furthermore, the same institution highlighted the transcribrial route for administering drugs against naegleriasis.
In the arena of vaccination, the nfa1 DNA vaccination against Naegleria Fowleri using a viral vector is the subject of interest. Hence more uniform efforts are required in the international arena to formulate and certify a standard treatment for evolving an ephemeral life for this amoeba.
Elimination of the brain eating amoeba demands both long term and short term plans. Minimizing the risk and scale of infection, a paradigm of ideal chlorination of swimming pools and water reservoirs should be made a prodigious affair throughout the globe. Research should be carried out for developing a tool which can prevent the sucking apparatus of amoebostome which is involved in the consummation of cells. One of the potential factors in the motility of Naegleria Fowleri is the protein coded by nfa1 gene. The discovery of drugs which can inhibit the expression of nfa1 gene shall be quantum leap in therapeutic arena.
Chlorpromazine is hitherto known to have inhibitory effects on both nfa1 and Mp2CL5 genes. The nfa1 gene and nfa1 protein have been knocked down with the help of synthetic double-stranded RNA of nfa1 gene in vitro. For that reason, The RNA interference (RNAi) technique needs further exploration for in vivo availability in the future. Blocking the process of Promitosis which is a means of multiplication for this organism especially in the ventricles of the brain can also lead to a therapeutic breakthrough. To fathom the mystery of the real role of Cell Mediated Immunity in resistance to naegleriasis, the immunologists and microbiologists must come forward for a solution to this quagmire.
Lastly, studies should also be conducted to observe any therapeutic role of Naegleria Fowleri in management of Brain tumors. Access to get unique treatment has been upheld as a sacrosanct by every humanitarian charter and ideology. In order to make the earth as a safe haven for humanity, the whole world must step forward to make the future free from gory incidents in other parts of our planet.
- The writer is the medical graduate of Xi’An Jiaotong University, China. Can be reached at [email protected]