Case Report
Acanthamoeba-Induced LETM Mimicking NMOSD: A Rare Case Scenario
https://doi.org/10.21203/rs.3.rs-8385294/v1
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We report a unique case of Acanthamoeba-induced longitudinally extensive transverse myelitis in a pregnant woman without classical epidemiologic risk factors. Cerebrospinal fluid (CSF) wet-mount microscopy and DNA PCR confirmed Acanthamoeba spp. Coinfections with Aspergillus spp. and tuberculous meningitis were also identified, highlighting the 'Trojan horse’ phenomenon.
Acanthamoeba
longitudinally extensive transverse myelitis
hypoglycorrhachia
free-living amoebae
NMOSD
Aspergillus
Mycobacterium
FLA PCR
wet mount
trophozoite
Trojan horse
genetic melting pot
Free-living amoeba (FLA) are ubiquitous protozoa causing devastating central nervous system (CNS) infections. Naegleria fowleri infections manifest as fulminant primary amoebic meningoencephalitis (PAM) while Acanthamoeba and Balamuthia mandrillaris result in subacute/chronic CNS infections manifesting as granulomatous amoebic encephalitis (GAE), typically in immunocompromised individuals1.Though infarction of the spinal cord is documented, acanthamoebic myelitis is rare2. Longitudinally extensive transverse myelitis (LETM) has not yet been reported.
We report a case of Acanthamoeba-induced LETM in a pregnant woman, masquerading as neuromyelitis optica spectrum disorder (NMOSD), complicated by co-infections.
A 25-year-old primigravida (26 weeks of gestation) was referred to our obstetrics wing with a two-week history of progressive bilateral lower limb weakness. Initial MRI spine showed myelitis involving D2-D4 segments. Detailed etiologic evaluation was unyielding. With an initial diagnosis of seronegative NMOSD, she was treated with IV methylprednisolone and immunoglobulin. Other symptoms were limited to mild headaches.
Despite treatment, weakness progressed (grade II to 0), and the patient developed bilateral papilledema and lateral rectus palsy. CSF study showed lymphocytic pleocytosis (92 cells/cmm), with normal glucose and protein (58 mg/dl and 48 mg/dl respectively). Four sessions of plasma exchange were done. Following fetal bradycardia, emergency LSCS was done at 34 weeks of gestation.
In view of clinical deterioration despite immunomodulation, mild hypoglycorrhachia (CSF:Serum ratio 0.55) and elevated opening pressure (56 cm H2O); workup for infectious etiologies was repeated. MRI study of the brain and MR venogram were normal, while the spinal cord showed diffuse enlargement (from cervicomedullary junction to conus) with patchy enhancement (Fig. 1). CSF wet mount showed motile trophozoites (Fig. 2a), and DNA PCR tested positive for Acanthamoeba spp (Fig. 2b). Anti-amoebic therapy (amphotericin B, miltefosine, voriconazole, cotrimoxazole, and azithromycin) was initiated but later modified due to transaminitis.
Subsequently; CSF culture grew Aspergillus (culture positive, species unidentified) and Mycobacterium tuberculosis (Fig. 3a, b). Intraventricular CSF Gene Xpert (CBNAAT) was also positive. Persistent elevated intracranial pressure (> 55 cm of H2O) necessitated external ventricular drain placement. Despite maximal support, including modified ATT and intraventricular amphotericin B, she succumbed 9 weeks after symptom onset
She belonged to a rural household with access to borewell and municipal water supplies. She had a habit of dipping feet into a fish tank at home (fish spa) Other than that exposure to stagnant water or soil was lacking. PCR of a water sample from her house tested positive for Balamuthia and Paravahlkampfia spp.
This case represents a novel presentation of Acanthamoeba infection as LETM in a pregnant woman, expanding the spectrum beyond GAE. The complex immune modulation in pregnancy, with controlled shift towards tolerance and TH2-like responses, increases susceptibility to opportunistic infections3. Although GAE has been reported in immunocompetent individuals also, disseminated disease and GAE is far more common in immunocompromised individuals, especially those with HIV, malnutrition, diabetes, kidney failure, cirrhosis, steroid use, chemotherapy, lymphoproliferative disorders, solid or bone marrow transplants, and agammaglobulinemia1.
The diagnostic dilemma stemmed from the subacute onset and lymphocytic pleocytosis, with repeated CSF CBNAAT and autoimmune evaluations yielding negative results. The combination of fulminant intracranial pressure elevation, mild hypoglycorrhachia, and absence of an alternate etiology—features noted during the recent outbreak of Acanthamoeba CNS infections in Kerala, India—ultimately guided the diagnosis in this patient.
Diagnostic Challenges
Amoebic trophozoites are best appreciated on fresh, unfixed samples at room temperature and may be mistaken for macrophages4.Standard light microscopy lacks the resolution to clearly distinguish the spiculated appearance5..Amoebic load and trophozoite movements may also be variable, and repeated testing may be required5. Thus, microbiological identification of acanthamoeba is tedious in resource-limited settings.
For our patient, the diagnosis was based on the species-specific 18S rRNA PCR method, developed by the molecular diagnostics division of The State Public Health Lab, Kerala, India. DNA extraction was performed using the Roche MagNA Pure automated nucleic acid extraction system and the amoebae were detected by single plex real-time TaqMan PCR; using the previously published primers and probes targeting the 18S rRNA gene for
Additionally, a newly designed TaqMan probe was used for Vermamoeba vermiformis.
The concentrations of primers and probes were maintained as previously published, and assays amplified using Quant Studio 5 real time PCR system (Applied Biosystems). The primer used for acanthamoeba spp. was 18S_F 5’-CCC AGA TCG TTT ACC GTG AA-3’, Aca 18S_R 5’-TAA ATA TTA ATG CCC CCA ACT ATC C-3’ and probe was 18S_P 5’-FAM-CTG CCA CCG AAT ACA TTA GCA TGG-BHQ1-3’. Positive and negative controls were included in each run. Using this method, the presence of Acanthamoeba spp. was confirmed in our patient's CSF sample.
Therapeutic Challenges
The treatment of nervous system infections by Acanthamoeba spp. is also challenging due to endosymbiosis9. The endosymbionts include bacteria like Campylobacter jejuni, Escherichia coli, Legionella, Rickettsiales, Listeria, yeasts, giant viruses, algae, and protozoa 9. There is evidence that Acanthamoeba can harbor atypical mycobacteria and even Mycobacterium tuberculosis10.
Acanthamoeba can act as a “trojan horse” for microorganisms, which force their entry into amoebae, resist amoeba-mediated killing, and are hence protected by acanthamoeba’s ability to resist extreme temperatures, pH, and osmolarity11,12. Acanthamoeba is also used as a reservoir, and several organisms in environmental niches can multiply inside the trophozoites12. Failure to identify the Aspergillus species in our patient may be because it is unrepresented in the MALDI-TOF database due to its environmental origin.
Acanthamoeba also exhibits a “genetic melting pot” phenomenon whereby exchange of genetic material between intracellular bacteria leads to the development of virulence traits13. The genome of intra-amoeba microorganisms is significantly larger than that of their relatives which also suggest this.13
Public Health Challenges
The patient's only documented water exposure was through fish-spa activities and household water use, without traditional high-risk behaviours such as swimming in warm freshwater bodies or exposure to contaminated soil. This profile indicates that epidemiologic links may be more diverse and ubiquitous than previously recognized. Early molecular testing for FLA should be integrated into diagnostic algorithms for atypical neurological presentations, especially in resource-limited settings where these amoebae may be more prevalent in water systems.
The manuscript is original, and has been submitted to the Emerging Infectious Diseases; a publication of CDC (manuscript number: EID-25-1853). We declare no conflicts of interest.
Written informed consent was obtained from relative of the patient. Human Ethics Committee of Government Medical College Thiruvananthapuram, Kerala, India has approved the original study (HEC NO:27/16/2025/MCT) from which this data has been taken as specified in the protocol
Use of AI tools: used Grammarly to check the grammar and improve readability.
Informed consent for publication of this case report was obtained from the patient's husband following the patient's death. As the legal next of kin, the husband provided written consent for the use of clinical data and publication of this case. All efforts have been made to maintain patient confidentiality and anonymity.
The authors declare potential competing interests as follows: We declare no conflicts of interest
Fig 1: Timeline of Patient Care for Acanthamoeba-Induced LETM
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