Naegleria fowleri 98 Percent Fatal a Comprehensive Survey

Sai Samadhan Shirsath¹, Vaishanavi Samadhan Shirsath², Rahul Tanaji Bhopale³

¹Matoshri Institute of Pharmacy Dhanore, Tal Yeola, Dist.: Nashik.

²SND Babhulgaon, Tal: Yeola, Dist.: Nashik.

³Yashwant Redekar College of Pharmacy At: Nesari.

*Corresponding Author E-mail: saishirsath06@gmail.com

Abstract:

Naegleria fowleri, colloquially termed the "brain-eating amoeba," presents a formidable public health concern due to its astonishingly high fatality rate of 98%. This abstract provides a thorough examination of the various aspects surrounding Naegleria fowleri, encompassing its morphology, life cycle, transmission routes, clinical manifestations, diagnostic methods, treatment strategies, and preventive measures. Naegleria fowleri, an amoeboid protist, thrives in warm freshwater environments, predominantly in regions with elevated temperatures. Infections occur when contaminated water enters the nasal passages, leading to primary amebic meningoencephalitis (PAM), an acute and often fatal condition affecting the central nervous system. The clinical course of PAM is rapid, with symptoms escalating from initial flu-like manifestations to severe neurological impairment within days. Diagnosis of PAM remains challenging, relying on specialized laboratory techniques such as polymerase chain reaction (PCR) and immunofluorescence assays. Despite efforts to develop effective treatments, mortality rates remain alarmingly high, emphasizing the critical importance of preventive measures. Avoiding freshwater activities in warm, stagnant water bodies, utilizing nose clips or plugs during water-related activities, and ensuring proper disinfection of recreational water sources are key strategies in mitigating the risk of the risk of Naegleria fowleri infections and reducing its devastating impact on public health.

KEYWORDS: Naegleria Fowleri, Brain-Eating Amoeba, Primary Amebic Meningoencephalitis, Freshwater Environments, Prevention.

INTRODUCTION:

Naegleria fowleri, a microscopic free-living amoeba, presents a significant public health concern due to its capacity to cause primary amebic meningoencephalitis (PAM), a rare but almost always fatal infection of the brain. This introduction aims to provide a comprehensive overview of Naegleria fowleri, exploring its transmission, habitat, temperature preferences, and feeding habits.

Naegleria fowleri is unique among pathogens, primarily infecting humans when contaminated water enters the nasal passages, leading to a devastating journey to the brain where it wreaks havoc on brain tissue. Instances of infection commonly occur during recreational water activities in warm freshwater environments such as lakes, rivers, and hot springs. Moreover, religious practices involving nasal cleansing and sinus rinsing with contaminated tap water have also been linked to infections.

This amoeba thrives in warm environments, displaying a preference for temperatures reaching up to 115°F (46°C). Although most infections occur during the warmer months of July, August, and September, Naegleria fowleri can persist in water temperatures above 80°F. It is noteworthy that even in cooler water temperatures, the amoeba may still reside in lake or river sediment, posing a risk to unsuspecting individuals.

In terms of sustenance, Naegleria fowleri sustains itself by preying on other small organisms like bacteria, commonly found in the sediment of freshwater bodies. This feeding behavior underscores the amoeba's adaptability to various environmental niches, further complicating efforts to mitigate its impact on public health.

Understanding the habitat preferences, transmission routes, and dietary habits of Naegleria fowleri is paramount in developing effective preventive measures and treatment strategies to combat the devastating consequences of PAM. Through enhanced knowledge and awareness, we can strive towards minimizing the risk posed by this heat-loving amoeba and safeguarding public health worldwide.^1,2,3

Treatment for Naegleria fowleri infections, particularly primary amebic meningoencephalitis (PAM), remains challenging due to its rapid progression and high fatality rate. However, several approaches have been attempted in efforts to improve outcomes:

Figure 1 Microscopic view of nagleria

Treatment for Brain Eating Amoeba:

1. Antimicrobial Agents: While no specific drug has been established as a definitive cure for PAM, some antimicrobial agents have shown potential efficacy against Naegleria fowleri. Notably, drugs like amphotericin B and miltefosine have been used in combination therapy to combat the infection. These drugs work by disrupting the cell membrane of the amoeba, ultimately leading to its death. However, their effectiveness in treating PAM remains limited, and survival rates remain low.

2. Adjunctive Therapies: In addition to antimicrobial agents, adjunctive therapies are often employed to manage symptoms and support the body's immune response. These may include corticosteroids to reduce inflammation in the brain, anticonvulsants to control seizures, and osmotic agents to reduce intracranial pressure. While these therapies may improve patient comfort and alleviate some symptoms, they do not directly target the underlying infection.

3. Experimental Treatments: Given the severity of PAM and the lack of effective treatments, researchers are continuously exploring novel therapeutic approaches. Experimental treatments, such as combination drug therapies, immunotherapy, and novel antimicrobial agents, are being investigated in preclinical and clinical settings. These treatments aim to enhance the efficacy of existing drugs or target specific mechanisms involved in Naegleria fowleri infection.⁴

Despite these efforts, the prognosis for PAM remains poor, with the majority of cases resulting in death within days to weeks of symptom onset. Early recognition of symptoms, prompt initiation of treatment, and supportive care are crucial in maximizing the chances of survival. However, prevention remains the most effective strategy for mitigating the risk of Naegleria fowleri infection.

As for the pharmacology of Naegleria fowleri, it involves understanding the mechanisms of action of antimicrobial agents used in treatment and their interactions with the amoeba. Antimicrobial agents like amphotericin B and miltefosine exert their effects by disrupting the integrity of the cell membrane, leading to leakage of cellular contents and ultimately cell death. Additionally, research into the pharmacokinetics and pharmacodynamics of these drugs aims to optimize dosing regimens and improve treatment outcomes. Despite ongoing research efforts, further elucidation of the pharmacology of Naegleria fowleri and the development of targeted therapeutic agents are needed to address this formidable pathogen effectively.⁶

Source of infection and Risk Factors:

Naegleria fowleri, a heat-loving amoeba commonly found in warm freshwater environments worldwide, poses a grave threat to human health as it is the causative agent of primary amebic meningoencephalitis (PAM), a nearly always fatal disease of the central nervous system. Despite its microscopic size, this amoeba's impact is substantial, with only a handful of survivors among the 157 reported PAM cases in the United States from 1962 to 2022. Alarmingly, the majority of infections cluster in southern-tier states, notably Texas and Florida, and affect males and children disproportionately, possibly reflecting the prevalence of water activities more common among young boys.

Naegleria fowleri's preference for warm environments underscores its ubiquitous presence in various water sources, including lakes, rivers, hot springs, and poorly maintained swimming pools, where it thrives by feeding on bacteria and other microbes. Although infections historically concentrated in warmer regions, recent occurrences in northern states suggest its expanding range. Notably, infections have also been associated with recreational water activities beyond lakes and rivers, such as hot springs and canals.

While the primary mode of transmission is through nasal exposure to contaminated water during activities like swimming, rare cases have been linked to contaminated tap water used for nasal irrigation or religious practices. Once inhaled, the amoeba migrates to the brain along the olfactory nerve, causing extensive tissue destruction. Despite concerns, there is no evidence of transmission through water vapor or aerosol droplets.

The potential transmission of Naegleria fowleri via organ transplantation highlights additional complexities. While organ recipients from infected donors have not contracted PAM, the presence of the amoeba in non-brain tissues suggests a possible transmission route, albeit the risk remains uncertain. This underscores the importance of careful risk assessment in transplant decisions, balancing the benefits of immediate transplantation against the potential risks associated with donor-derived infections.

Overall, understanding Naegleria fowleri's habitat preferences, transmission routes, and associated risks is crucial for implementing effective preventive measures and informing public health strategies to mitigate its devastating impact on human health. Continued research is imperative to address gaps in knowledge and develop targeted interventions to combat this formidable pathogen.^7,8,9

INDIAN CASE:

A 5-month-old infant was admitted to paediatric department with a two-day history of fever, decreases breast feeding, vomiting, and abnormal body movements. His birth history as well as developmental history was uneventful. The child was immunized up to date. The mother had no signs of mastitis. The child was apparently asymptomatic until two-days prior to admission, and then presented with decreased breast feeding, continuous high-grade fever, and two episodes of vomiting following semisolid feed which contained food particles which was neither bile nor blood stained. On the day of admission, mother noticed tonic-clonic movements which was limited to lower limb initially and gradually involved the whole body. After that episode, the child had continuous unsteadiness of trunk and neck. On admission, his weight was 6.2 kg, temperature 38◦C, heart rate 140 beats/min, respiratory rate 60 breaths/min, blood pressure 106/70 mmHg, and SpO2 was 100% at room temperature. CNS examination revealed bulging and tensed anterior fontanelle with positive Kernig’s sign and presence of nystagmus. White blood cell count was 17,700 cells/cumm with 89% polymorphonuclear cells. Provisional diagnosis of acute bacterial meningitis was made, and the child was put empirically on Inj. Ceftriaxone 250 mg TID and Inj. Amikacin 50 mg BD with anticonvulsants and antiedema measures. Lumbar puncture was done, and CSF was sent for microbiological and cytological analysis. CSF was clear, and biochemical analysis showed glucose concentration of 5 mg/dL (Normal value 40–85 mg/dL), 2 proteins concentration of 731 mg/dL (Normal value 15– 45 mg/dL), and chloride ions concentration of 105 mEq/mL. CSF counts revealed a total WBC count of 990/cumm (normal value < 5/cumm) with predominantly lymphocytes. No bacteria or fungal elements were seen on Gram stain. Bacterial culture was sterile. Microscopic examination of wet CSF preparation showed motile trophozoite of free living amoeba which was suggestive of Naegleria fowleri (Figures 1 and 2). Final diagnosis of PAM was made, and therapy with IV amphotericin B 3 mg and IV ceftazidime 300 mg was started, but his condition deteriorated and was taken home by his relatives in a moribund condition against medical advice and subsequently died.

Successful Treatments for Primary Amoebic Meningoencephalitis (PAM):

Treatment for primary amoebic meningoencephalitis (PAM), caused by the Naegleria fowleri amoeba, often involves using a combination of medications. These medications, like amphotericin B, azithromycin, fluconazole, rifampin, miltefosine, and dexamethasone, are thought to be effective against the amoeba. Miltefosine, the newest addition to these medications, has shown promise in laboratory tests for killing Naegleria fowleri and has been used successfully to treat patients with other amoebic infections.

Though PAM has historically had a high fatality rate in the United States, with only a handful of survivors, there have been a few documented cases of successful treatment. In one instance, a 12-year-old girl was diagnosed with PAM quickly after falling ill and received prompt treatment with a combination of medications, including miltefosine. Additionally, her brain swelling was aggressively managed by cooling her body below normal temperature. This girl made a full recovery and was able to return to school.

Another child, an 8-year-old boy, also survived PAM, although he experienced lasting brain damage. He received similar treatment to the girl but was diagnosed and treated later, after his symptoms had already started.

In 2016, a 16-year-old boy became the fourth documented survivor of PAM in the United States. He was diagnosed shortly after arriving at the hospital and received the same treatment as the girl in 2013. Like her, he also made a complete recovery and was able to return to school.

These cases highlight the importance of early diagnosis and treatment in improving the chances of survival from PAM. Additionally, the use of new medications like miltefosine and innovative approaches like therapeutic hypothermia shows promise in treating this devastating disease.^10,11

In a retrospective analysis spanning several decades, cases of primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri were examined, shedding light on both treatment outcomes and demographic factors. Here is a summary of the cases:

· 1971: Pan and Ghosh reported two cases, a 3-year-old male and a 5-month-old male, both of whom had contact with water. They were successfully treated with a combination of amphotericin B, sulphadiazine, streptomycin, and dexamethasone, resulting in a cure.

· 1998: Singh et al. documented an 8-year-old male who did not have contact with water. The patient was treated with amphotericin B and rifampicin and was cured.

· 2002: Shenoy et al. reported a case involving a 4-month-old male with water contact who unfortunately died despite treatment with amphotericin B.

· 2002: Jain et al. described a 26-year-old female without water contact who was successfully treated with amphotericin B and rifampicin.

· 2005: Hebbar et al. documented a 5-month-old male with water contact who died despite treatment with amphotericin B, chloramphenicol, and metronidazole.

· 2006: Tungikar et al. reported a case involving a 30-year-old male without water contact who died despite treatment with cefotaxime, amikacin, metronidazole, and azithromycin.

· 2008: Kaushal et al. described a 36-year-old male with water contact who died despite treatment with amphotericin B, rifampicin, and ceftazidime.

· Present Case: Vinay et al. documented a 5-month-old male without water contact who unfortunately died despite treatment with amphotericin B and ceftazidime.

Prevention of Naegleria fowleri infection, commonly known as the "brain-eating amoeba," primarily revolves around minimizing exposure to contaminated water sources. Here are some key preventive measures:

1. Avoidance of Warm Freshwater: Limit exposure to warm freshwater environments such as lakes, rivers, and hot springs, especially during the warmer months when the amoeba is more prevalent.

2. Nasal Protection: When participating in water-related activities, use nose clips or hold your nose shut to prevent water from entering the nasal passages, where Naegleria fowleri can enter the body.

3. Proper Swimming Pool Maintenance: Ensure that swimming pools, hot tubs, and water parks are adequately maintained and chlorinated. Proper chlorination can effectively kill Naegleria fowleri and reduce the risk of infection.

4. Avoiding Submerging the Head: Refrain from submerging the head or diving into warm freshwater bodies where the amoeba may be present.

5. Avoiding Activities in Stagnant Water: Minimize activities in stagnant or poorly flowing water bodies where Naegleria fowleri is more likely to proliferate.

6. Use of Nose Rinse Devices: If using devices like neti pots for nasal irrigation, ensure that only sterile, distilled, or previously boiled water is used to prevent exposure to contaminated water sources.

7. Educational Awareness: Educate individuals, especially those residing in regions where Naegleria fowleri infections have been reported, about the risks associated with warm freshwater activities and the importance of preventive measures.

By following these preventive measures and exercising caution when engaging in water-related activities, individuals can reduce their risk of Naegleria fowleri infection and minimize the potential for this rare but serious disease.^12,13,14

Naegleria fowleri In North Indian Region:

Naegleria fowleri the causative agent of Primary Amoebic Meningoencephalitis, is ubiquitously distributed worldwide in various warm aquatic environments and soil habitats. The present study reports on the presence of Naegleria spp. in various water bodies present in Rohtak and Jhajjar district, of state Haryana, India. A total of 107 water reservoirs were screened from summer till autumn (2012 and 2013). In order to isolate Naegleria spp. from the collected water samples, the water samples were filtered and the trapped debris after processing were transferred to non-nutrient agar plates already seeded with lawn culture of Escherichia coli. Out of total 107 water samples, 43 (40%) samples were positive by culture for free living amoeba after incubation for 14 days at 37°C. To identify the isolates, the ITS1, 5.8SrDNA and ITS2 regions were targeted for PCR assay. Out of total 43 positive samples, 37 isolates were positive for Naegleria spp. using genus specific primers and the most frequently isolated species was Naegleria australiensis. Out of 37 Naegleria spp. positive isolates, 1 isolate was positive for Naegleria fowleri. The sequence analysis revealed that the Naegleria fowleri strain belonged to Type 2.¹⁵

DRUG DISCOVERY FOR PAM:

Use of nanotechnology:

Since nanomaterials-based drug delivery systems may improve the pharmacokinetics and pharmacodynamics of cargo drugs, nanoparticles gained much attention in the drug discovery study. Silver, gold and iron oxide are considered as the most common metal carriers for nanoparticle-based drug delivery systems. Both currently available drugs and natural products can be conjugated with nanoparticles to enhance the activity of the compounds. Silver nanoparticle conjugation was performed with amphotericin B and fluconazole and the conjugated nanoparticles were tested for their activity against N. fowleri. While silver nanoparticles conjugation enhanced amebicidal activity of amphotericin , conjugated fluconazole exhibited limited activity . Future animal efficacy study is required to confirm if this increased amebicidal activity of conjugated amphotericin B in vitro translates to a better delivery of the drug in the animal model and improved efficacy in vivo.

Synthesis and testing of novel azoles and quinazolinones:

Considering that azoles are antifungals and demonstrate wide range antimicrobial properties, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against N. fowleri. One indazole and one tetrazole compound showed moderate activity at 50 µM concentration based on the documented antifungal activities of quinazolinones, 34 novel arylquinazolinones were also synthesized and tested for activities on N. fowleri. A relatively higher concentration of these compounds inhibited the growth of the trophozoites Further improvement of these compounds will be required to achieve increased potency.^16,17,18

CONCLUSION:

Naegleria infections, though rare, pose a significant threat to human health. With primary amoebic meningoencephalitis being the most severe outcome, the disease demands prompt diagnosis and treatment. While cases have been documented globally, particularly in warmer regions, research on effective treatments remains ongoing. Advances in understanding the pathogenesis and therapeutic interventions offer hope for improved management and outcomes. Vigilance, early detection, and collaboration between medical professionals and researchers are essential in combating this potentially deadly infection.

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Received on 11.05.2024 Modified on 18.05.2024

Research J. Science and Tech. 2024; 16(2):163-168.

DOI: 10.52711/2349-2988.2024.00024