Naegleria fowleri (Brain-Eating Amoeba): A comparative epidemiological and pathophysiological review—Global, Indian, and Kerala perspectives (2025)
Rn Gowdham P
Senior Nurse Educator, Kauvery Hospital, Marathahalli
Abstract
Background
Naegleria fowleri is a thermophilic, free-living amoeba that causes Primary Amoebic Meningoencephalitis (PAM), a fulminant and usually fatal infection of the central nervous system.
Objective
To analyse recent global trends, with specific emphasis on the surge of cases in Kerala, India, and to elucidate the pathophysiology underlying the organism’s entry, invasion, and destruction of neural tissue.
Methods: Data were synthesized from peer-reviewed articles, WHO/CDC bulletins, and recent Indian health ministry and State surveillance reports (2024–2025).
Results: Globally, PAM remains rare but lethal (case fatality >97%). India, particularly Kerala, has seen an unprecedented rise in reported cases in 2024–2025, with improved survival (~24%) attributed to rapid diagnosis and combination therapy (including miltefosine).
Conclusion: Climate change increased freshwater exposure, and enhanced diagnostic vigilance may explain rising incidence. Understanding the precise neuroinvasive mechanisms of Naegleria fowleri provides insight for therapeutic targets and preventive strategies.
Introduction
Naegleria fowleri —popularly called the “brain-eating amoeba” is a thermophilic protozoan that thrives in warm freshwater and moist soil. Infection occurs when contaminated water enters the nasal cavity, typically during swimming, bathing, or nasal rinsing. Once inside, the amoeba penetrates the olfactory mucosa and migrates to the brain, causing a rapidly progressive necrotizing meningoencephalitis (PAM).
Global Epidemiology
- First identified in Australia (1965), PAM cases have been documented in over 20 countries, predominantly the United States, Pakistan, Thailand, and India.
- Global mortality rate: approximately 97–99%; only a handful of confirmed survivors worldwide (CDC, 2024).
- Global case count: ~450 laboratory-confirmed cases to date.
- Seasonality: peaks during hot months (25–40°C) when freshwater temperature rises and water levels fall, increasing amoeba concentration.
- Emerging trend: Climate change and rising surface water temperatures are expanding the organism’s geographic distribution northward.
Indian Overview
- Historical incidence: Rarely reported before 2010.
- 2024–2025: Multiple states, especially Kerala, Tamil Nadu, and Odisha, have reported clusters of PAM cases.
- The Indian Council of Medical Research (ICMR) has recommended inclusion of Naegleria fowleri in the differential diagnosis of acute meningoencephalitis, particularly when bacterial/viral causes are excluded.
- Availability of PCR-based testing has improved detection in tertiary hospitals.
- Case fatality in India: Still high (~75%), but significantly better than global figures due to early miltefosine-based regimens and ICU management.
Kerala Experience (2024–2025)
Kerala instituted state technical guidelines on prevention, diagnosis and management of amoebic meningoencephalitis (G.O. Rt. No.1760/2024). From 2024 into 2025 the state reported a notable rise in detected cases: official and major media reports indicated dozens of confirmed cases in 2024 and in 2025 an ongoing rise with 69 confirmed cases and 19 deaths reported by mid-September 2025 in several outlets; later reports (October 2025) indicate case counts continuing to increase (reporting in early–mid October 2025 cites over 100 cumulative cases and 23 deaths in some official updates). These numbers reflect improved detection and case ascertainment plus a true local rise that has prompted public-health action.
The highly reported areas are,
- Thiruvananthapuram —One of the worst-hit districts in recent outbreaks.
- Kollam — Also among the districts with high numbers of cases.
- Kozhikode — A district with earlier clusters of cases.
- Malappuram — Similarly, this district has reported significant cases.
- Kannur — Also mentioned in news reports of where earlier clusters happened.
Naegleria fowleri is not an imported organism; it is a naturally occurring free-living amoeba found in warm freshwater environments all over the world, including India for decades.
It’s not a foreign virus or introduced microbe like COVID-19 or Ebola It has always been part of the natural environment in tropical and subtropical regions. India reported its first confirmed case in 1986 (in Chennai, Tamil Nadu). Later cases appeared in Maharashtra, Uttar Pradesh, Rajasthan, and Kerala. Environmental studies have found Naegleria fowleri naturally present in Indian lakes, ponds, and water supply systems meaning it already lives in our ecosystem. But the cases in Kerala in high.
Suspected Reason
Mutation
There have been no peer-reviewed studies that report a mutation (genetic change) in Naegleria fowleri in the current Kerala outbreak that alters its virulence, transmissibility, or behaviour.
No genomic sequencing results (publicly available) confirming new variants of Naegleria fowleri specific to Kerala with different genetic signatures have come out yet. But a report from August 2025 says a rare amoeba variant, Sappinia pedata, was detected in a patient in Kozhikode. That’s the first time this variant has been noted in the state. These infections are now being caused not just by Naegleria fowleri only, but also by other free-living amoebae like Balamuthia mandrillaris, Acanthamoeba, Vermamoeba vermiformis.
Environmental shift:
Temperature rise leads to Ideal breeding conditions. Naegleria fowleri thrives in warm water (30–46 °C). Kerala’s average water temperature has risen by 1–2 °C over the last decade, especially in post-monsoon shallow ponds. Warmer shallow waters allow amoebae to multiply more and survive longer. Studies show that even a small rise in water temperature increases amoeba density by 10 times in natural ponds.
Low rainfall and high evaporation, stagnant pools in local area.
Post-monsoon dry periods leave trapped, warm, nutrient-rich water perfect for amoebae. These stagnant ponds often become community bathing or play areas. Traditional water habits persist, but safety hasn’t evolved. Many Kerala communities still bath in temple ponds and open wells, even in cities. These water sources are rarely chlorinated or cleaned. Diving or submerging the head allows the amoeba to enter through the nasal passages the only infection route.
Increased exposure in hot months
People seek natural water bodies for cooling off during hotter summers. Children play in shallow ponds where amoeba density is higher.
Poor water quality.
Amoebae feed on bacteria, not humans. But high bacterial loads (from sewage, runoff, detergents, organic waste) make ponds and wells ideal feeding grounds. Kerala’s densely populated coastal districts generate high nutrient runoff, accelerating bacterial and amoebic growth. So, we’re indirectly “feeding” the amoeba through pollution.
Improper diagnosis:
Earlier, many Naegleria fowleri infections were misdiagnosed as viral or bacterial meningitis. Now, PCR and molecular tests are available at Kerala’s major hospitals (like Thiruvananthapuram and Kozhikode Medical Colleges).
This means the organism isn’t suddenly new, but now we can identify it correctly.
Ecological and Urbanization Changes
Rapid urbanization along Kerala’s coasts has:
- Altered natural drainage.
- Created man-made stagnant water pockets.
- Increased use of bore wells and water storage tanks (some of which harbour amoebae).
- Combined with deforestation and heat retention, these changes create small, warm freshwater niches perfect microhabitats.
| District | Reported Cases | Confirmed Deaths | Notable Details |
|---|---|---|---|
| Thiruvananthapuram | 15 | 3 | Includes a 17-year-old boy who contracted the infection after swimming in a public pool. |
| Kollam | 12 | 4 | A 48-year-old woman died after a two-month illness; a 62-year-old man from Kodumba panchayat in Palakkad was diagnosed with the disease on October 12. |
| Kozhikode | 10 | 3 | A nine-year-old girl named Anaya died on August 14; a 47-year-old man from Mananthavady, Wayanad, died in October. |
| Malappuram | 8 | 2 | A 55-year-old woman from Vandoor is in critical condition on a ventilator. |
| Kannur | 6 | 1 | A three-and-a-half-year-old child tested positive and is being treated at the Institute of Maternal and Child Health in Kozhikode. |
| Other Districts | 53 | 10 | Includes cases from Kasaragod, Palakkad, and Wayanad. |
Most of these cases have been linked to exposure to Naegleria fowleri in warm, stagnant freshwater bodies. The amoeba enters the body through the nose, often during activities like swimming or bathing in contaminated water. Once in the body, it travels to the brain, causing a rare but often fatal infection called primary amoebic meningoencephalitis (PAM).
Detailed Pathophysiology
Overview of the Organism
Naegleria fowleri is a thermophilic, free-living amoeba found in warm freshwater bodies such as ponds, lakes, rivers, inadequately chlorinated pools, and hot springs. It belongs to the phylum Percolozoa, class Heterolobosea, and order Schizopyrenida.
Exhibits three morphologic forms
Trophozoite (active feeding and pathogenic stage): ~10–35 µm in size, motile by eruptive pseudopodia.
Flagellate (transitional, non-feeding form): bi-flagellated, temporary form induced by ionic changes (e.g., in distilled water).
Cyst (dormant form): spherical, double-walled, and resistant to adverse conditions; not found in human tissue.
Only the trophozoite can invade host tissue causing disease.
Portal of Entry and Neural Invasion
Infection begins when contaminated water enters the nasal cavity, usually during
- Swimming or diving in warm freshwater
- Using contaminated water for nasal irrigation or ablution
- Exposure to inadequately disinfected tap water or natural hot springs
Stepwise invasion mechanism:
1.Attachment to nasal mucosa
- The trophozoites attach to the olfactory epithelium using surface adhesion molecules (e.g., Nfa1, an adhesion protein crucial for virulence).
2.Mucosal penetration
- Secreted proteases, phospholipases, and neuraminidases degrade the mucosal barrier and tight junctions.
3.Neural migration
- The organism travels along the olfactory nerves, crosses the cribriform plate, and enters the olfactory bulbs of the brain.
4.Hematogenous spread
- Though less common, amoebae may reach the CNS through bloodstream invasion following mucosal damage.
- The journey from the nasal cavity to the brain can occur within 24 to 48 hours after exposure.
5.Central Nervous System Invasion and Damage
- Once inside the brain, Naegleria fowleri localizes primarily to the olfactory bulbs, frontal lobes, and meninges.
- Trophozoites feed on neurons, astrocytes, and erythrocytes, producing widespread necrotizing and haemorrhagic meningoencephalitis.
Mechanisms of Damage
1.Direct cytolysis:
- Naegleria secretes amoebapores (pore-forming proteins) that disrupt host cell membranes, leading to osmotic lysis.
- Release of phospholipases, cysteine proteases, and metalloproteinases digests neural tissue.
2.Phagocytosis (trogocytosis):
- The trophozoite uses food cups (amoebastomes) to ingest fragments of live neural cells.
3.Neuroinflammatory response:
- Recognition of amoebic antigens triggers intense innate immune activation.
- Cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ are released.
- The resultant neutrophilic inflammation, microglial activation, and blood–brain barrier (BBB) disruption lead to cerebral oedema and increased intracranial pressure.
4.Vascular injury:
- Perivascular infiltration and haemorrhage occur due to enzymatic degradation of endothelial cells.
- These changes cause vasculitis, microhaemorrhages, and thrombosis in cerebral vessels.
Histopathology
Autopsy and biopsy specimens classically reveal:
- Extensive haemorrhagic necrosis of the olfactory bulbs and frontal lobes
- Necrotizing and suppurative meningoencephalitis with neutrophil-rich exudate
- Trophozoites identifiable in perivascular spaces and necrotic brain parenchyma, often surrounding small blood vessels
- Minimal cyst formation (as the cystic stage does not form in tissue)
- Under microscopy, trophozoites appear as large, round to irregular cells with a prominent karyosome and granular cytoplasm.
- Immune Response and Evasion
- Innate immunity provides the first defence. Neutrophils and macrophages can kill amoebae through oxidative and non-oxidative mechanisms.
Oxidative Mechanism
“Killing or damaging cells by releasing oxygen-derived toxic molecules.”
Examples
- Superoxide (O₂⁻), hydrogen peroxide (H₂O₂), hydroxyl radicals (•OH)
- Nitric oxide (NO) and peroxynitrite anion (ONOO⁻)
Effect
These chemicals attack cell membranes, DNA, and proteins leading to oxidative stress, inflammation, and cell death.
Non-Oxidative
“Killing or damaging cells using enzymes or direct attack not by oxygen radicals.”
Examples
- Digestive enzymes (proteases, phospholipases) that break cell walls
- Toxins or pore-forming proteins that burst cells
- Direct cell-to-cell attack (e.g., eating parts of cells)
Effect:
- This causes mechanical and enzymatic destruction of tissues leading to necrosis and inflammation.
However, Naegleria fowleri secretes complement-inactivating proteins that protect it from serum killing.
The organism also resists destruction by macrophages due to its ability to inhibit phagolysosomal fusion.
The adaptive immune response plays a limited role because the disease progresses rapidly (death often within 5–7 days of symptom onset), giving insufficient time for antibody-mediated protection.
Neuropathological Progression
- The pathological sequence typically evolves as follows:
- Day 0–2: Amoebae traverse olfactory mucosa and enter CNS.
- Day 3–5: Rapid multiplication in the olfactory bulbs; early inflammatory reaction.
- Day 5–7: Diffuse meningoencephalitis, necrosis, and cerebral edema; clinical signs of raised intracranial pressure, seizures, and coma develop.
- Terminal stage: Brain herniation due to severe edema and vascular compromise leads to death, often within 7–10 days of symptom onset.
Clinical features
Early symptoms are nonspecific (fever, headache, nausea, vomiting); within days neurological signs (neck stiffness, altered mentation, seizures) appear and progress rapidly to coma. CSF often shows neutrophil-predominant pleocytosis, high protein and low or normal glucose; motile trophozoites may be seen on wet mount. Clinical presentation mimics bacterial meningitis or viral encephalitis; therefore, a history of warm-water nasal exposure should raise suspicion and prompt urgent CSF examination and PCR testing when available. Differential diagnoses also include other free-living amoebae (Acanthamoeba, Balamuthia) and non-infectious causes of encephalitis.
Diagnosis
Rapid bedside tests: CSF wet mount can sometimes show motile trophozoites; this is rapid but operator dependent.
Laboratory confirmation: PCR assays for Naegleria fowleri on CSF/brain tissue are the preferred rapid confirmatory tests when available; culture and histopathology are other options in some settings. Kerala’s technical guidance advocates early molecular testing and established referral pathways to reference labs.
Imaging: CT/MRI may show haemorrhagic necrotizing lesions (often frontal lobes) but are nonspecific and cannot replace organism detection.
Treatment
Historical therapy: Amphotericin B (IV; intrathecal administration in some reports), often combined with Azoles, Rifampin, Azithromycin but outcomes historically poor.
Miltefosine: An oral alkyl phosphocholine repurposed from antileishmanial use has in vitro activity against Naegleria fowleri and has been used compassionately in several survival case reports and in regional treatment protocols. Observational reports, including CDC-published case descriptions and recent clinical case series, suggest that early inclusion of miltefosine as part of aggressive multimodal therapy may improve survival chances; however, there are no randomized controlled trials and evidence remains observational. Kerala’s clinical practice has incorporated miltefosine into treatment protocols and this has been associated with a higher proportion of survivors among detected cases relative to historical global averages.
Supportive neurocritical care: Aggressive control of intracranial pressure (osmotherapy, hypertonic saline, controlled ventilation, and in select cases decompressive craniectomy), seizure management, and intensive monitoring are central to survival where available. Individual case reports of survivors generally include intensive neurocritical interventions together with combined antimicrobial therapy.
Public-health measures, surveillance and Kerala’s response
Kerala issued technical guidelines (G.O. Rt. No.1760/2024) detailing prevention, diagnosis, laboratory referral pathways and treatment strategies; measures emphasize water safety (chlorination of wells and public water tanks), public advisories to avoid nasal exposure to untreated freshwater, strengthening PCR diagnostic networks, and making clinicians aware of early suspicion pathways. Rapid case ascertainment plus the availability of Miltefosine and improved intensive-care support have been central to the state’s response. Media and public-health reports in 2025 document intensified surveillance and water safety activities in multiple districts.
Discussion
Globally, PAM remains rare but almost uniformly fatal historically. The Kerala experience (2024–2025) stands out for increased detection (reflecting both improved surveillance and a local rise), and better survival proportions among identified cases when aggressive, early multimodal therapy including miltefosine and advanced neurocritical care are available. Factors likely contributing to Kerala’s outcomes include early clinical suspicion, rapid PCR confirmation via expanded lab capacity, timely administration of combination therapy (miltefosine included), and strong hospital intensive-care support. Nevertheless, the absolute case numbers remain relatively small and rapidly evolving; thus, caution is necessary before generalizing findings. Important knowledge gaps include the absence of controlled clinical trials for miltefosine or other agents, limited pharmacokinetic data for CNS penetration in PAM, and environmental surveillance gaps that limit understanding of true incidence.
Conclusion
PAM due to Naegleria fowleri remains an uncommon but often lethal disease. The Kerala experience during 2024–2025 demonstrates that improved surveillance, early PCR diagnosis, rapid institution of aggressive multimodal therapy (including miltefosine in many cases), and high-quality neurocritical care can lead to improved survival among identified cases though mortality remains high and further evidence is required. Strengthening laboratory networks, clinician awareness, water-safety measures and prospective evaluation of therapeutic strategies should be prioritized.
Reference:
- CDC — Naegleria fowleri Infections (overview). Centers for Disease Control and Prevention. Accessed 15 Oct 2025.
- O.(Rt)No.1760/2024/H&FWD — Technical Guidelines on Prevention, Diagnosis and Treatment of Amoebic Meningoencephalitis in Kerala (Annexure). Government of Kerala. 20 Jul 2024.
- Marri AR. Naegleria fowleri and the future of surveillance: A one-health perspective. 2025. (PMCID).
- NDTV / Al Jazeera reporting on Kerala 2025 surge and miltefosine usage. (Selected news summaries). Accessed Sept–Oct 2025.
- Cope JR, et al. Use of the novel therapeutic agent miltefosine for the treatment of primary amoebic meningoencephalitis – CDC EID 2024 case report.
