Fatal Balamuthia Amebic Encephalitis in a Healthy Child: A Case Report with Review of Survival Cases

Abstract

Balamuthia mandrillaris is one of the 4 amebas in fresh water and soil that cause diseases in humans. Granulomatous amebic encephalitis (GAE), caused by B. mandrillaris, is a rare but life-threatening condition. A 4-year-old, previously healthy, Thai girl presented with progressive headache and ataxia for over a month. Neuroimaging studies showed an infiltrative mass at the right cerebellar hemisphere mimicking a malignant cerebellar tumor. The pathological finding after total mass removal revealed severe necrotizing inflammation, with presence of scattered amebic trophozoites. Cerebrospinal fluid (CSF) obtained from lumbar puncture showed evidence of non-specific inflammation without identifiable organisms. A combination of pentamidine, sulfasalazine, fluconazole, and clarithromycin had been initiated promptly before PCR confirmed the diagnosis of Balamuthia amebic encephalitis (BAE). The patient showed initial improvement after the surgery and combined medical treatment, but gradually deteriorated and died of multiple organ failure within 46 days upon admission despite early diagnosis and treatment. In addition to the case, 10 survivors of BAE reported in the PubMed database were briefly reviewed in an attempt to identify the possible factors leading to survival of the patients diagnosed with this rare disease.

Repurposing the quinoline antibiotic nitroxoline to treat infections caused by the brain-eating amoebaBalamuthia mandrillaris

“…Because encystment appears to occur as a response to certain drug treatments, we also assessed the ability of each drug to inhibit the viability of pre-formed B. mandrillaris cysts. We Because there is no established treatment for GAE, patients commonly receive experimental combinations of antimicrobial agents in aggressive and prolonged treatment regimens with mixed outcomes (7,19,23,27,29,30,34,(53)(54)(55)(56)(57)(58)(59)(60)(61). In the present study, we aimed to address the critical need for new treatments of GAE by identifying novel amoebicidal compounds amongst known drugs using a high-throughput screening approach.…”

“…Laurie and White et al, Inhibition of Balamuthia mandrillaris by nitroxoline 6 sulfadiazine and flucytosine while azithromycin, pentamidine isethionate, miltefosine, and voriconazole (fluconazole derivative) exhibit amoebicidal or amoebistatic activity (11,41,50). Current treatments for B. mandrillaris CNS infections employing experimental combinations of these drugs have produced inconsistent outcomes including survival in some cases and fatality in others (7,19,23,27,29,30,34,(53)(54)(55)(56)(57)(58)(59)(60)(61). As the efficacy and specificity of current treatments remains uncertain, there is a clear need to identify additional drugs that can improve patient outcomes.…”

Denouement

“…The CSF findings of B. mandrillaris infection in the CNS resemble those of Acanthamoeba infections and include pleocytosis with lymphocytic predominance, elevated protein count and moderate hypoglycorrachia; although a normal CSF profile has also been reported. [6][7][8] Cysts and trophozoites may be visible in CSF and can confirm the diagnosis. In a microscopic examination of fresh, non-centrifuged CSF, actively moving trophozoites may be present.…”

“…3,4 Skin lesions, typically a painless plaque or ulcer in the center of the face or on an extremity, may be present and often precede the CNS manifestations. 7 Up to 50% of survivors have skin lesions as part of their presentation compared with only 25% of all patients with Balamuthia amebic encephalitis, suggesting that this feature may be associated with a favorable outcome, possibly because of earlier diagnosis and treatment.…”

“…13 In a review of 10 survivors of this disease, most were treated with antimicrobial combinations that included 1 or 2 antifungal agents plus a macrolide and pentamidine. 7 In conclusion, B. mandrillaris infection of the CNS is difficult to diagnose because the clinical symptoms mimic those of several other types of encephalitis, few laboratories perform appropriate diagnostic testing, and many physicians are unaware of the disease. The lack of recognition and subsequent delay in diagnosis might be a factor in its high mortality.…”