Survivors of Acanthamoeba Granulomatous Encephalitis in Children: A Case Series and Review of Literature

To the Editors: Granulomatous amebic encephalitis (GAE) is a rare but often fatal central nervous system (CNS) infection, primarily affecting immunocompromised individuals, although it can also occur in immunocompetent children. It is caused by free-living amebae, including Balamuthia mandrillaris and Acanthamoeba species.1,2 GAE progresses insidiously, often mimicking other chronic CNS infections, such as bacterial and tubercular meningitis, resulting in frequent misdiagnosis and treatment delays. The global mortality rate for CNS infections exceeds 90%.2,3 Cerebrospinal fluid (CSF) microscopy, polymerase chain reaction (PCR) and magnetic resonance imaging (MRI) are vital for distinguishing GAE from other CNS infections. We report 2 survivors of GAE caused by Acanthamoeba species. A 2-month-old male infant presented with a 6-day history of fever, vomiting, refusal to feed, noisy breathing, cough, abnormal body movements, lethargy and a bulging anterior fontanel. CSF analysis indicated lymphocytic pleocytosis, elevated protein and motile organisms resembling Acanthamoeba, with PCR confirming Acanthamoeba species (Figure, Supplemental Digital Content 1, https://links.lww.com/INF/G557). MRI revealed multiple thick-walled ring-enhancing lesions in the bilateral gangliocapsular region alongside meningeal enhancement (Figure A, B, Supplemental Digital Content 2, https://links.lww.com/INF/G557). Treatment included 24-week course of fluconazole, trimethoprim-sulfamethoxazole and rifampicin, resulting in a negative CSF-PCR after 4 weeks. Follow-up showed partial resolution of lesions but noted global developmental delay and MRI findings of bilateral caudate nucleus atrophy (Figure C–F, Supplemental Digital Content 2, https://links.lww.com/INF/G557). Similarly, a 16-year-old boy with low-grade fever and persistent headache (following pond water exposure) was diagnosed with tubercular meningitis. His MRI showed moderate obstructive hydrocephalus and a ring-enhancing lesion, with repeat CSF analysis identifying motile Acanthamoeba. He underwent a 24-week oral therapy regimen and ventriculoperitoneal shunt, achieving complete neurological recovery by 4 months, despite a persistent ring-enhancing lesion, which later resolved on follow-up MRIs (Figure, Supplemental Digital Content 3, https://links.lww.com/INF/G557). A systematic review by Ahmad Zamzuri et al4 highlights the chronic nature of Acanthamoeba infections compared to the acute and fatal Naegleria fowleri infections. Treatment regimens, based on survivor case studies, involve combination therapies including azoles (fluconazole and ketoconazole), antibiotics (rifampicin and trimethoprim-sulfamethoxazole) and antiparasitic agents (miltefosine).5 Potassium hydroxide mount (KOH) and Indian Ink staining provide crucial diagnostic insights, enabling timely diagnosis and early treatment, as shown in the present cases. A review of literature from 1960 to 2025 identified 46 pediatric GAE cases (Tables, Supplemental Digital Content 4 and 5, https://links.lww.com/INF/G557). Two-thirds were from India and the United States. Notably, 87% were immunocompetent, yet most were initially misdiagnosed. Diagnosis was mainly via CSF or PCR; 17% were diagnosed postmortem. There were 24 deaths (52%) and 21 survivors (46%). Of the 29 children receiving targeted therapy, the survival rate was 66%. The present cases were treated with azoles, miltefosine (for the adolescent boy), trimethoprim-sulfamethoxazole and rifampicin over 6 months, reinforcing the benefits of early suspicion, timely diagnostics and aggressive therapy. This case series emphasizes the importance of clinical suspicion, diagnostic advancements, treatment duration, follow-up (every 4 weeks) and neurologic outcomes, with the adolescent boy achieving recovery and the infant facing global developmental delay. Overall, this series contributes to growing evidence that GAE in children, although rare, is treatable, necessitating timely diagnostics and aggressive therapy for at least 6 months, as developing brains are particularly vulnerable to sequelae and delays.