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Original Article Arousal of a New, Life-Taking Threat to the World….. Fowleri!! Somia Gul* and Umaima Alam

Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan

ABSTRACT Objective: Since we are living in the city near the cost shore and we

have got a marine life as well along with the humans living in Karachi, A newly introduced life threatening Marine ‘’ should be brought into special considerations. Health officials have disclosed the news that this about 144 lives has been claimed in different countries all over the world by this deadly water borne (Primary amoebic ). Method: The major object of this study was to know how many people actually know about this lethal protist and what amount of victims we have of this brutal organism. A general survey was conducted among 100 people belonging to various categories of our society in Karachi. The type of participants we got included Students, Teachers, working men and women, local citizens and old age people who watch news on a regular basis with great interest. Results: Our results showed us that most of the people in Karachi have some kind of perception regarding Naegleria and the major

source of information was found to be Media and television. But none of them knew about the symptoms that appear after inhalation of this amoeba which creates greater chances of of our people. Conclusion: Since Naegleria fowleri enters through the nose and invades the CNS where it starts Tissue , due to which it is known as ‘the brain-eating amoeba’. This brute has been causing frequent of people around the world since the year 1962 and Address for its first victim belonged to Czechoslovakia. Since the organism is not Correspondence so common worldwide that’s why people do not pay much attention towards it but number of deaths associated with it is increasing day Faculty of Pharmacy, by day throughout the world which is becoming a major cause of Jinnah University for concern for our safety and health. The report highlights the major Women, Karachi, causes and symptoms of PAM so that people should have awareness Pakistan. about the fatal outcomes, this organism causes. E-mail: drsomi1983 @yahoo.com Keywords: life-taking threat, Naegleria fowleri, .

American Journal of Phytomedicine and Clinical Therapeutics www.ajpct.org Somia et al______ISSN 2321 – 2748

INTRODUCTION The major rationale of this whole autopsied in Virginia in the year of 1937 and study and research is the rapidly increasing positive results of this infection PAM were number of deaths in Pakistan which is obtained4. The studies and researches we caused by this brutal organism i.e. Naegleria performed showed us that more than 144 Fowleri, and all of the information cases have been confirmed in a variety of mentioned below was collected through countries since the year of 1965. And various articles, research papers, ebooks, finally, in 1966, Fowler termed the infection books etc. N. Fowleri, a new threat to the resulting from N. Fowleri primary amoebic world, is an amoeba that is usually found in meningoencephalitis (PAM) so that the fresh water and soil1. The organism belongs disease can be distinguished from other to the group of Perocolozoa or Central Nervous System disorders which Heterolobosea and is supposed to be a free- may be caused by other organisms such as living, thermophilic i.e Temperature loving Entamoeba Histolytica1. form of protist and is usually present in Almost all of the researchers, warmer environment of ponds, lakes, rivers scientists and physicians working on this etc. The organism is also supposed to be deadly brute, have supported the fact that the present in soil, warm water discharges assassin invades and attacks the human which are produced from the industrial nervous system. The infection and plants and may also be present in swimming availability of this organism is not so pools in which chlorination is not done common but if this amoeba gets inside the properly and has greater risks of human body it always result to death of the contamination. It is popularly known as victim. The is estimated at ‘Brain-eating Amoeba’2. There is no 98%1.Usually, the major source of evidence of this organism living in salt inhalation this organism is via swimming. If water1. a person loves diving and he inadvertently The question arises that when and by aspirates water through his nostrils then the whom this Ameoba was discovered. With amoeba enters through the nose and travels the help of various historical reports we to brain where it starts invading the brain have reviewed, it has been revealed that the cells by performing tissue necrosis and death first discovery of this lethal disease which is of the individual may occur within a few Primary Ameobic Meningoencephalitis, days and sometimes even in few hours. It caused by Naegleria was done by the may also be present in well-waters so famous physicians M. Fowler and R. F. children have the greater tendency of Carter in , in the year of attaining this infection during bathing as 19653. This amoebic protozoan complete its their immune system is not so strong which life cycle in two stages, in which one phase may fight against such type of organisms. [3] is completed in the environment they are Also, the major source of entering of N. living whilst the second phase is completed fowleri into our nose is through ritual in a human body. The first time when this ablutions (wuzoo) performed by our adults amoeba was discovered was when a death as a part of our religious practices5. took place in the year of 1961 due to this Researchers have documented that infection. Soon after, a death was reported the organism goes through three stages in its from U.S in the year of 1962 and the person life cycle: amoeboid trophozite stage (in this got infected was a common dweller in phase the mode of nutrition for amoeba is Florida. Before that, tissue samples were bacteria and the mode of replication is via

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promitosis which is a type of binary fission floor of cranium and finally enters into the and the organism proliferates but its nuclear brain via neuroepithelium, and there it membrane remains intact), if the environ- extends a special and unique apparatus from mental conditions become unfavorable for its cell surface for the purpose of sucking, the amoeba as the ionic concentrations or and begins to consume cells of the brain temperature gets low, then the trophozoites imperceptibly, turning into a real pathogenic will be transformed into the flagellated stage organism leading to the infection Primary and reverts back when the conditions Ameobic Meningoencephalitis (PAM or become favorable for them. But if the PAME) 2. After the patient got hit by this environmental conditions become highly life-taking amoeba, the major symptoms that unfavorable for them then they encyst their develops initially appears within 5 days of selves. The pathogenic form of this amoeba exposure or it may take a few weeks to be which is usually found in the CSF is the prominent enough to notice. In the trophozoite form. Just like other , beginning of this infection patient suffers Naegleria Fowleri’s mode of locomotion is through changes in smell or taste which then also via pseudopodia6. While their mode of progress to , , loss of appetite nutrition is of two types, they may be and and finally the major feeding on bacteria if they are in symptoms appears as confusions, semi trophozoidal and free-living state; whilst if consciousness or coma. Physical the trophozoites are present inside the examination shows fever and a stiff neck human body, they get their nutrition by (meningismus)7. As we have discussed engulfing RBCs and WBCs and performs above that it is a Central Nervous System destruction of tissues3. The feasible period disorder so for further examination spinal for the growth of this organism is during tap should be performed in which spinal summer months as it is thermophilic in fluid will be examined to check whether the nature. In the popular press, Naegleria amoeba is present or not. A patient may also fowleri is intermittently called the brain- go through some of the newer tests available eating amoeba, and meningoencephalitis is which includes the PRC i.e. Polymerase sometimes referred to as Naegleriasis4. Chain Reaction technology to detect Literature survey revealed the amoebic DNA in the spinal fluid1.Chutatip pathways of N. Fowleri through which it Siripanth revealed in his research journal performs major destruction in our brain Amphizoic amoebae: pathogenic free-living cells. If the individual is freshly been that the organism N. Fowleri can exposed to fresh water, swimming pools, be easily detected with the help of its life lakes, ponds or contaminated tap water cycle as the amoeba goes through three containing this brutal protist, then the first stages of its life cycle which firstly includes and major path of entering into human body the stage, trophozoidal stage and is via nose. N. Fowleri majorly pathogenies the cystic stage. It has also been discovered the Central Nervous System. The olfactory that around 10% of Naegleria species were mucosa and the present in found to be of Naegleria Fowleri in the the nasal tissues allows penetration of this human environment9. This life-taking specie organism which starts causing necrosis and can also be analyzed experimentally. hemorrhaging of the nasal tissues and cells Literature shows that if one needs to and moves forward by causing destruction perform experimental analysis on N. Fowleri of the olfactory bulbs. From there, the then this organism can be artificially grown amoeba climbs along the nerve fibers via the by preparing a medium which may consists

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of 2% Bacto-Casitone (Difco) and 10% may also be used for the detection of N. fresh horse serum dissolved in distilled Fowleri in CSF. Studies from the literature water. [10]. As we have already discoursed surveys have showed that so far, the most that inflammatory reactions are produced in effective treatment for Primary Amoebic the brain thus, the host inflammatory Meningoencephalitis (PAM) is through the response and polymorphonuclear cell lysis administration of amphotericin B12,13. The contribute to a great extent to the central results of another study supported previous nervous system tissue damage and in this finding that not only , but, way the amoeba invades our CNS11. one of its derivative i.e. methyl ester of Taking the treatment in amphotericin B is also proved to be a really consideration, best choice would be effective agent against this organism. A lot amphotericin B through intravenous of combinations have been administered in administration5. For the achievement of order to achieve the best results for better results, it has been seen that treatment of this disease but amongst all of instillation of amphotericin B through I/V them amphotericin B along with and then also through I/C i.e. intrathecally minocyclines or amphotericin B plus (directly into the brain) improves the tetracyclines showed synergism14. In Britain, condition of the patient rapidly8. two children were infected by PAM due to After observing some of the case muddy, puddle soil and they also survived studies present in various research articles, it and recovered by the treatment of has been showed that, so far the best Amphotericin B15. One of the literature treatment of PAM was done of a 9-year-old reports also showed a case of a Chinese girl whose disease was diagnosed in early whose CSF was taken and N. fowleri was stages, with the help of intravenous and detected positively in it and successful intrathecal administration of amphotericin results were obtained when a regular 6-week B, intravenous and intrathecal course of amphotericin B was administered and oral rifampin, this treatment provided along with and chloramphenicol the patient a healthy recovery by having and brain drainage was also only some of the minor neurologic performed16. But Amphotericin B was a ramifications. [10]In another research journal, toxic antibiotic which may cause harms to it was reported that a 25-year-old Indian boy other organs of the body so a new survived by a successful treatment exploration was performed in which consisting of amphotericin B, rifampicin, Chlorpromazine, Amphotericin B and and for 4 weeks, along with were administered together in ventriculoperitoneal shunt for obstructive mice and the survival rates increased up to hydrocephalous. The child was kept under 75%. Thus, Chlorpromazine had so far, treatment for about 8 months and finally he much better therapeutic activity against recovered from all the neurologic disorders PAM17. Additionally, a disquisition has which may occur as a consequence of PAM. proven that has both in vitro [11]. Current research shows intranasal and in vivo activity versus N. Fowleri18. administration of Cry1Ac protoxin alone or When further investigations for the in combination with amoebic lysates vaccination of N. fowleri were performed it increases protection against Naegleria was suggested by the researchers that nfa1 Fowleri meningoencephalitis in mice2. vaccination might prove to be an effective Another method comprising of method for treatment of N. Fowleri indirect immunofluorescence techniques infection19. Desferrioxamine B and

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rhodotorulic acid are supposed to be iron- advise to use freshly, boiled, sterilized or chelating agents of microbial origin, and it filtered water and sewerage water should be has been launched that they exert a avoided for drinking purposes. Also during pronounced inhibitory effect on pathogenic ritual ablutions (wuzoo) nasal area should be specie of Naegleria at microgram levels20. cleaned properly, thus, all of the actions Dilemma is that, many of the doctors, through which there are chances of pharmacists, pathologists and laboratorians inhalation of water inside our body like are still unaware about this free living brutal brushing teeth, gargling etc. should be done organism and the symptoms that appear after with proper measures and cleanliness should inhalation of N. Fowleri21. In Thailand, be a major factor to be concerned about. around 5 cases of N. fowleri were Furthermore, children should be completely reported and around 4 of the 5 cases were informed about this fatal organism so that males and none of them were exposed to the they avoid swimming the contaminated common sources which proves that amoebas pools and rain water, in order to spread can travel from one source to another [22]. It awareness among the people, government was also noticed in a research work, that, in should launch various campaigns by Thailand there was fortunately a non-lethal pharmacists, clinicians and doctors who may case, and the author emphasized in his advice to people and make them aware article that a dose regimen comprising of about all the precautionary measures they short doses of amphotericin B for a prolong must take to be safe from the consequences period of time is much more effective as of Primary Amoebic Meningoencephalitis. compared to larger doses of the drug for a The major purpose of this research work is short period of time to achieve immediate to make the people aware about the recovery from PAM2324. outcomes of this deadly organism, and all of The focus of this article is mainly the studies and cases that are highlighted in allied on the fact, that people are utterly this paper are taken from the authentic incognizant regarding to the mortal journals and articles. organism N. fowleri and unfortunately, 2 lives has been claimed in Karachi this year METHODOLOGY due to same reason, which is a very big and dangerous threat for the people of our The survey was conducted among country. So it is our responsibility to spread 100 people belonging to various categories consciousness about this deadly slayer and of our society in Karachi including students, keep our society aware about the life- teachers, working men and women, local threatening dangers that this organism can citizens of our society and old age people produce. The objective of this research who watch news regularly with great paper would be succeeded if health officials interest. Mostly socially active people were will make some good efforts for the selected for our survey as their general betterment of people’s health. Likewise, knowledge is comparatively higher than the from now on, the locals of Pakistan should simple wives. Also, media has been get complete understanding of PAM disease covering quite a few times about N. Fowleri and its causative agent, and they should start that is why people who watch news taking some precautionary measures by regularly gave a better and positive response keeping in consideration their children’s than the people who are not updated. The healthy and sound future. In fact, for the study that we conducted is based on general betterment of or people, doctors constantly questions regarding Naegleria Fowleri, which included what they know about this

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organism and how do they know. A 25 years, 10% of them was of 35 years and questionnaire containing common questions above, 15% were the old age people ranging about N. Fowleri was distributed among the in between 60-75 years whilst 10% of common people and also generalized teenagers of 20 years and below were interviews were taken from the people involved. It has been examined from our belonging to different age groups. The reports that mostly people had some survey was scrutinized using common perceptions of water borne infections and a language. People were questioned in a major quantity were also familiar with N. manner that whether they like swimming fowleri but still if any symptoms appear during summers or not, do they take any related to the disease, they do not pay much precautions while doing so and also, their attention towards it and do not consult to their familiarity to any water borne disease or doctors which could bring a very hazardous specifically N. Fowleri was inquired. situation in their lives as the disease is completely fatal and survival rates are Statistical analysis extremely low. Government should start The survey results are expressed in organizing some awareness campaigns so that percentages in order to compare ratios of the the common dwellers of our country would people who know about the deadly water become more conscious and protective about borne infections that can cause serious their children’s life and it might save some of threats to our lives. (See figure 1.) the innocent lives. The distribution of N. Fowleri In Fig 2, Total data for 112 people has infections throughout the world are described been investigated for observing the as shown in Fig 2. Results are investigated epidemiology of N. fowleri throughout the from authentic references and researches. world. Among them 16 cases were reported from Czechoslovakia, 8 people were RESULTS proclaimed from New Zealand, 22 victims were of Pakistan, a girl was broadcasted from Survey reports have showed that most United Kingdom, major distribution of this of the people like to swim during summers disease was observed to be found in United but they do not pay any attention towards the States, 9 lives were taken from Virginia, 20 important precautions they should take. fatal cases were reported from India, 2 patient Familiarity to the was not belonged to Louisiana while one of them as low as expected, in fact, most of the people were from Vietnam. The result shows that, surveyed, already knew about N. fowleri greater number of victims was found to be infection, and media proved to be the major habitants of United States and after that source of information for them, but dilemma Pakistan is on the main target of this brutal has been inspected that people do not consult organism. So our locals should get beware of to doctors if any of the symptoms like it. headache, nausea, stiff neck appear after they have dived in water. We also came to know DISCUSSION that people were really interested to cognize more about the infection and they wanted the Naegleria Fowleri is an amoebic government to start some campaigns so that parasite usually found in fresh water. It is alertness could be spread amongst them. supposed to be most active during summer From the data of Fig 1, 100 common months as it has also been found near warm people were surveyed in a report, 65% of water discharges, swimming pools and even whom were taken from the age between 20- the accumulated rain water. The organism

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does not live in the presence of salt. It is positive for the infection, doctors used to aspirated through the nasal cavity and travels prefer Amphotericin B as the first choice of to the brain where it starts tissue necrosis and treatment for them. Then some of the research hemorrhaging, so ultimately it is known as findings showed that Amphotericin B along ‘Brain-eating Amoeba’. It is one of the best with other drugs can produce greater examples of microbes that complete their life therapeutic effect. But Amphotericin B was a cycle in the environment as well as inside the toxic antibiotic so researches testified that human body. The parasite goes through three Chlorpromazine had also a great therapeutic stages of its life cycle i.e. cyst, trophozoite activity with less adverse effects to other and the flagellate stage. It is the trophozoite organs. Vaccine development for this disease form that causes human diseases. It mainly is still on progress but by far, researches attacks the human nervous system and revealed that nfa-1 gene can be used as a produces lethal effects. vaccination for N. fowleri infection. The disease produced by this deadly PAM has a greater prominence in amoeba is known as ‘Primary Ameba males rather than females with a ratio of 3:1. Meningoencephalitis’. M. Fowler and R.F The organism has no prominent attraction Carter were the first discoverers of this according to the sex of the individual, but the organism in the year 1965 in Australia. only reason we have found so far is that there Epidemiology of PAM was initiated from is a greater chance of exposure of males to the Czechoslovakia between the years of 1962 contaminated water and environment rather and 1965 because of bathing in indoor than females. Also children are at a greater swimming pools. And after that, the slayer risk of being swindled by the organism has taken so many lives of innocent people all because they are greatly exposed to the over the world, finally, a girl got survival of contaminated pools, rain water etc. One more this life-taking disease in 2013 in United factor is considered which depends on the States, when the doctors lowered her porosity of cribriform plate i.e. the cribriform temperature to 93 F. The survival rates of this plate in children and young individuals in disease are extremely low as just 2 among found to be more porous as compared to the 128 people have survived so far. Signs and adults that is the reason they are more likely symptoms produced by this brute initiates to be victimized by this lethal organism. So, from severe headache, nausea, , neck children and young individuals who have stiffness and then it leads to the secondary recently bathed in swimming pools or hot symptoms including , hallucina- water must be tested completely to diagnose tions, lack of attention, , and . the presence of this organism. PAM has also As soon as the symptoms starts appearing in a been reported via tap and hot water patient of PAM, immediate diagnosis could domestically and some cases of PAM has also be performed in a lab, simply by preparing an been documented via fresh water during artificial liquid axenic media in which agar summer months when the sources of sewage solution is poured with no nutrients in it on a water are usually warm. Number of cases petri dish and it is coated with a layer of have been reported till now but the actual bacteria. A drop of the CSF sample to be reason that why this amoeba attack some analyzed is dropped over the plate. If the CSF specific individual and others are not affected is victimized by N. Fowleri then the agar will by it is still cannot be identified. But to take be cleared off in thin tracks as the organism in precautionary measures especially during its trophozoite stage will be feeding over the summer months should be highly considered bacteria. If god forbid, diagnosis proves to be in order to keep yourself and your family safe

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from any lethal hazards caused by this of occurrence of more deaths from this fatal amoeba. slayer will increase gradually. Since primary amebic meningoen- This report highlights basic cephalitis is a rare disease, and people are not information about the fatal N. fowleri and much informed about the disease and the emergence of its infection in a megacity. One that appear after of the major reasons for sudden increasing inhalation of N. Fowleri are not known by the death rates due to N. Fowleri are the climatic people, so our health care providers and changes which have badly affected the especially our pharmacists must be well environment and people are being more prone informed about each and everything regarding to this disease. A worldwide survey must be PAM, its signs and symptoms and also the conducted to identify the reason of this rise in treatment so that they may answer the PAM cases. And also, the research work at a patient’s queries. Furthermore, it is their greater extent must be performed for its responsibility to spread awareness amongst treatment and development of vaccination if people, and for that, they should organize we really want to save the world from hazards informative campaigns regarding the of this organism. precautionary measures people must take to be safe from N. Fowleri25. REFERENCES

CONCLUSION 1. Mary D. Nettleman, MD, MS, MACP, Charles Patrick Davis, MD, PhD (2011) Naegleria Fowleri is the only specie Naegleria Fowleri. of its Genus Naegleria, which causes serious 2. http://en.wikipedia.org/wiki/Naegleria_fowle lethal infections to human brain. It is not ri. really common worldwide, that is the reason 3. Fowler M & Carter RF people do not pay much attention in spreading (1965) Acute pyogenic probably knowledge and awareness about it. The result due to sp.: a preliminary of our survey has reported an increase of N. report. Br Med J. 2:740–742. 4. Santos Neto, J.G. American Journal of Fowleri PAM cases in the world and Clinical Pathology. 1970; vol 54: pp 737- especially in Pakistan. Also various cases 742. have been reported till now. Most cases were 5. Yadav D, Aneja S, Dutta R, Maheshwari A, associated with freshwater swimming while Seth A. Youngest survivor of naegleria ritual ablution (wuzoo) has also been a major meningitis. Indian J Pediatr. Mar 2013; factor for acquiring this disease as N. fowleri 80(3):253-4. [Medline]. enters through the nostrils by aspiration and 6. Kaushal V, Chhina DK, Ram S, Singh this has been the major route of acquiring this G, Kaushal RK, Kumar R. Department of infection. This shows that threat is increasing Microbiology Primary amoebic meningoen- day by day and many of the karachiites are at cephalitis due to Naegleria Fowleri. greater risk of having this lethal disease. So PMID:18822627. 7. Yadav D, Aneja S, Dutta R, Maheshwari A, our locals should become more concerned Seth A. Youngest survivor of naegleria about it, and pay attention towards taking the meningitis. Indian J Pediatr. Mar 2013; precautionary measures they usually ignore. 80(3):253-4. [Medline]. And also our government should take some 8. Vinay Khanna, Ruchee Khanna, Shrikiran powerful decisions about sewage water we Hebbar, V. Shashidhar, Sunil Mundkar, use, and make it sure to be clearly purified FrenilMunim, Karthick Annamalai, Deepak and free from Naegleria. Otherwise, chances Nayak, and Chiranjay Mukhopadhayay. Case Reports in Neurological Medicine. Primary

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25. Centers for Disease Control and Prevention. Morb Mortal Wkly Rep. 2008; 57(21):573- Primary amebic meningoencephalitis-- 577. Accessed August 19, 2011. Arizona, Florida, and Texas, 2007. MMWR

90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Yes No

AWARENESS RATES OF N.FOWLERI IN OUR COMMUNITY

Figure 1. Survey reports of N. fowleri

Distribution of N.Fowleri throughout the World

Czechoslovakia

New Zealand Pakistan United Kingdom United States Virginia India

Figure 2. Epidemiology of N. Fowleri

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