Cases of brain eating amoeba in India: Primary amoebic meningoencephalitis clinical features and pathogenesis

Primary amoebic meningoencephalitis (PAM), or ‘brain-eating amoeba’ is caused by a free-living protozoa called Naegleria fowleri. It is, though notably uncommon, a condition that carries a high mortality risk [1]. In Kerala, India, the first reported case of PAM in 2024 was on May 21, involving a five-year-old girl. The second case, reported on June 25, involved a 13-year-old girl. Two additional cases were reported in July, involving two fourteen-year-old boys, making it to a total of four cases in Kerala this year. All four children affected by the disease passed away [2]. The five-year-old girl bathed in a local river four days prior with four other children [3].

The organism has been detected in every country except Antarctica. Worldwide, between 1965 and 2018, a total of 381 PAM cases were reported in international literature and to the CDC, and the number of reported cases increased by 1.6 % each year from 1965 to 2016 [4]. Previous literature has concluded that, as the officially reported cases of N. fowleri are an underestimation, quantifying the true burden of the disease stands to be difficult [1].

N. fowleri is named after Malcolm Fowler, who described the earliest reported cases of N. fowleri PAM in 1965 in Australia. It is a eukaryotic amoeba that best grows in thermophilic environments with temperatures as high as 45 °C [5]. Forty-seven species of Naegleria have been discovered so far, and only N. fowleri has been shown to cause PAM [1]. N. fowleri grows in freshwater that is contaminated with soil. The amoeba's life cycle consists of three forms: cyst, trophozoite, and flagellate, and it enters humans in the reproductive form, the trophozoite [5]. With low food resources or other environmental factors that do not accommodate its survival, the amoeba in trophozoite form can switch to the flagella form and return to trophozoite form when the conditions are ideal [5].

Around the world, the organism thrives in freshwater lakes, hot water springs, poorly chlorinated pools, and other bodies of water that rapidly fluctuate in temperature due to thermal pollution [5]. Infection with N. fowleri occurs when freshwater enters the nasal cavity under pressure, such as during diving or swimming, following the use of a neti pot with amoeba-infested water, or during religious ablution. Drinking contaminated water does not transmit the disease. Following inoculation, the amoeba penetrates the olfactory mucosa and respiratory epithelium, then enters through the cribriform plate into the central nervous system [5]. The result is extensive cortical hemorrhage, tissue necrosis, and edema of the brain tissue, with the olfactory bulb and cerebellum being the most affected parts. The duration of incubation varies between 1 and 14 days [5].

The clinical features of N. fowleri PAM may resemble those of bacterial meningitis, thus rendering an initial diagnosis difficult [5]. Initial symptoms include nausea, vomiting, fever, headaches, and lethargy. With the rapid progression of the disease, more severe symptoms of confusion, neck stiffness, photophobia, seizures, and cranial nerve abnormalities develop. In most cases, the disease subsequently progresses to coma and death [5].

The diagnosis should be suspected in cases of meningitis or meningoencephalitis with a history of recent freshwater exposure. CSF analysis shows low to normal glucose levels, elevated protein and polymorphonuclear cells, and high CSF pressures, which may reach as high as 600 mmHg [5]. The Gram staining and cultures may fail to isolate the organism as they are normally destroyed during the fixation procedure. Wet mounts, hematoxylin, eosin (H&E), periodic acid Schiff (PAS), Giemsa-Wright staining, or modified trichrome stains allow successful visualization of the organism [5]. A definitive diagnosis is made through immunohistochemistry (IHC), indirect immunofluorescence, polymerase chain reaction, or next-generation sequencing [4]. The most widely used medication is amphotericin B. Other medications used in the treatment include miltefosine, azoles (fluconazole, voriconazole), azithromycin, and rifampin. Another recently employed treatment that shows a promising prognosis is controlled hypothermia [5].

The high fatality rate of N. fowleri-associated PAM warrants frequent health promotional activities at high-risk areas to educate the public regarding protective habits for those going into contact with freshwater bodies. The public should be urged not to engage in water-based activities near warm, stagnant water and to pinch the nose or use a nose clip during water-based activities. They should be advised to avoid diving and jumping into stagnant freshwater and to keep their heads above the water level when swimming in freshwater and untreated thermal bodies of water [1].

CRediT authorship contribution statement

Mariyam Niusha Naseer: Formal analysis, Methodology, Validation, Visualization, Writing – original draft, Writing – review & editing. Kannan Subbaram: Conceptualization, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing. Razana Faiz: Investigation, Supervision, Writing – original draft, Writing – review & editing. Zeba Un Naher: Methodology, Supervision, Writing – original draft, Writing – review & editing. Punya Laxmi Manandhar: Methodology, Supervision, Writing – original draft, Writing – review & editing. Sheeza Ali: Investigation, Methodology, Supervision, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Patricia Schlagenhauf