Free-living amoebae (FLA) namely Naegleria fowleri, Acanthamoeba, and Balamuthia mandrillaris, albeit rare, are increasingly being reported to cause infections. FLA infections have distinct clinical presentations. While all of the above-mentioned parasites cause disease of the central nervous system (CNS), Acanthamoeba (genotypes 1–22) also cause keratitis, cutaneous and mucosal infections.[1,2] Acanthamoeba spp. and B. mandrillaris lead to granulomatous amoebic encephalitis (GAE) with a subacute or chronic course and very high mortality, while N. fowleri causes primary amoebic meningoencephalitis (PAM), characterized by an acute and fatal progression.[2,3,4] FLA infections are a diagnostic challenge due to nonspecific symptoms and limited laboratory capabilities. Granulomatous amoebic encephalitis presents a broad differential diagnosis owing to its subacute or chronic nature, encompassing various CNS infections, fungal diseases, parasitic infections, and even neoplasms. Conversely, the rapid onset of primary amoebic meningoencephalitis narrows the differential, necessitating concurrent consideration of bacterial or viral etiologies.[5] However, FLAs are considered only when the other causes have been ruled out or when a treatment regimen fails to show any clinical improvement. Host susceptibility factors such as malnutrition, diabetes, or immunocompromise contribute to FLA pathogenesis.[5] FLA’s presence in water, soil, and hospital environments complicates eradication efforts. Moreover, FLA can act as carriers for pathogens like Legionella. Pseudomonas, Vibrio, etc., enhancing their dissemination. These pathogens residing inside amoebae, escape the host immune responses while also acquiring virulence factors and becoming more pathogenic and drug resistant.[2]
Imaging modalities such as computed tomography scans and magnetic resonance imaging can localize lesions but are not diagnostic for GAE or PAM. Cerebrospinal fluid (CSF) analysis often yields nonspecific findings, may not identify the causative agent, and fails to pinpoint the specific pathogen as an etiological agent. Direct examination of motile trophozoites in CSF samples can aid in diagnosis. The CSF can be inoculated onto an Escherichia coli coated non nutrient agar plate to grow Acanthamoeba or Naegleria. However, Balamuthia fails to grow on this medium and can be grown at 35°C–37°C on monkey kidney cells with fetal bovine serum.[1,2] The introduction of molecular tests has improved the detection of infectious agents and has paved the way for the detection of new or rare pathogens.[2,5,6] Molecular diagnosis using pan-FLA primers or inclusion of these amoebae in encephalitis/meningitis panel is warranted. Despite enhanced awareness, diagnostics, and clinical suspicion, the actual prevalence likely surpasses reported cases.
Administration of an early and specific therapy has the potential to improve the outcome and prognosis. Treatment involves specific antiparasitic therapy alongside management of raised intracranial pressure and associated symptoms. The general rule is the use of various combinations of antimicrobials, including azoles, amphotericin B, benzimidazole derivatives, pyrimidine derivatives, miltefosine, and macrolides by parenteral route.[5,7]
Health education is crucial for disease prevention, especially regarding FLA transmission routes, such as swimming in freshwater and nasal irrigation practices. The route of transmission in the case of GAE due to Acanthamoeba and Balamuthia is either through skin breaches or through nasal rote, while that for Naegleria is through nasal route commonly in warmer climates by swimming in recreational water, use of neti pots, or nasal ablution for religious purposes.[2]
Studies from India have identified FLA in environmental specimens.[8,9] Incidents of FLA-related CNS infections have been documented across various Indian regions, emphasizing the need for heightened vigilance and research in this domain. A study by Puthanpurayil et al.,[10] published in the July 2024–December 2024 issue of Tropical Parasitology, describes two cases of PAM and GAE from Kerala that succumbed to infection. Research on new antiamoebic agents is essential, as no regimen has demonstrated 100% efficacy against these diseases.
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