Balamuthia amoebic encephalitis
Balamuthia mandrillaris is a free-living amoebae found in soil and water, which can cause a rare and potentially fatal infection in humans called Balamuthia amoebic encephalitis (BAE). The infection typically occurs when the amoeba enters the body through the nose, eyes, or broken skin, and travels to the brain, where it causes inflammation and damage to brain tissue.
Balamuthia amoebic encephalitis is a very rare disease.
About 39% of the infected patients were found to be immunocompromised which is extremely rare clinically. The presence of trophozoites in diseased tissue is an important basis for the pathological diagnosis.
Symptoms of BAE typically develop over several weeks to months and can include headache, fever, nausea, vomiting, seizures, and neurological symptoms such as confusion, difficulty speaking, and weakness.
Treatment of BAE typically involves a combination of antimicrobial drugs and supportive care to manage symptoms and prevent complications. However, the effectiveness of treatment can be limited, and many patients do not survive the infection.
Prevention of BAE involves avoiding exposure to potentially contaminated water and soil, and taking precautions to protect the nose and eyes from exposure, such as wearing a mask when working in dusty environments or swimming in freshwater lakes or rivers.
Nanotechnology was used to conjugate Zinc oxide with Ampicillin, Ceftrixon, Naringin, Amphotericin B, and Quericitin, and the amoebicidal activity and host cell cytotoxicity of these resulting compounds were investigated. The compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT were found to reduce N. fowleri viability to 35.5%, 39.6%, 52.0%, 50.8%, 35.9%, and 69.9%, respectively, and B. mandrillaris viability to 40.9%, 48.2%, 51.6%, 43.8%, and 62.4%, respectively, when compared with their corresponding controls. Furthermore, the compounds reduced N. fowleri-mediated and B. mandrillaris-mediated host cell death significantly. Additionally, the compounds showed limited cytotoxicity against human cells; cell toxicity was 35.5%, 36.4%, 30.9%, 36.6%, and 35.6%, respectively, for the compounds ZnO-CD-AMPi, ZnO-CD-CFT, ZnO-CD-Nar, ZnO-CD-AMB, and ZnO-CD-QT. Furthermore, the minimum inhibitory concentrations to inhibit amoeba growth by 50% were determined for N. fowleri and B. mandrillaris. The MIC50 for N. fowleri were determined to be 69.52 µg/mL, 82.05 µg/mL, 88.16 µg/mL, 95.61 µg/mL, and 85.69 µg/mL, respectively; the MIC50 of the compounds for B. mandrillaris were determined to be 113.9 µg/mL, 102.3 µg/mL, 106.9 µg/mL, 146.4 µg/mL, and 129.6 µg/mL, respectively. Translational research to further develop therapies based on these compounds is urgently warranted, given the lack of effective therapies currently available against these devastating infections 1)
It is a serious condition with a high mortality rate and can be difficult to diagnose and treat. The infection can progress rapidly and can cause severe brain damage and death if left untreated.
Liu et al. report clinical data from a patient with Balamuthia GAE to improve physician understanding of the disease and diagnostic accuracy of imaging and reduce misdiagnosis. A 61-year-old male poultry farmer presented with moderate swelling pain in the right frontoparietal region without obvious inducement three weeks ago. Head computed tomography(CT) and magnetic resonance imaging(MRI) revealed a space-occupying lesion in the right frontal lobe. Initially, clinical imaging diagnosed it as a high-grade astrocytoma. The pathological diagnosis of the lesion was inflammatory granulomatous lesions with extensive necrosis, suggesting amoeba infection. The pathogen detected by metagenomic next-generation sequencing (mNGS) is Balamuthia mandrillaris, and the final pathological diagnosis was Balamuthia granulomatous amoebic encephalitis.
When a head MRI shows irregular or annular enhancement, clinicians should not blindly diagnose common diseases such as brain tumors. Although Balamuthia GAE accounts for only a tiny proportion of intracranial infections, it should be considered in the differential diagnosis of intracranial lesions 2).
A 61-year-old woman with a history of an orthotopic heart transplant was hospitalized with a new-onset headache. Magnetic resonance imaging (MRI) of the brain revealed T2 hyperintense signal involving the left occipital lobe with leptomeningeal enhancement and mild vasogenic edema. Initial neurologic examination was normal; however, after 7 days she developed imbalance, visual disturbances, night sweats, bradyphrenia, alexia without agraphia, and right hemianopsia. Brain MRI showed enlargement of the left occipital mass and worsening edema. Stereotactic needle biopsy showed nondiagnostic necrosis. The patient continued to deteriorate despite dexamethasone. Cerebrospinal fluid (CSF) suggested infection, and cytomegalovirus CSF polymerase chain reaction (PCR) was positive. The patient received vancomycin, imipenem, and ganciclovir. After obtaining a positive serum beta-D-glucan (Fungitell), amphotericin was added. Despite the best medical efforts, the patient died. Postmortem broad-range PCR sequencing of the brain tissue was positive for rare amoeba Balamuthia mandrillaris 3).
A patient in California, USA, with rare and usually fatal Balamuthia mandrillaris granulomatous amebic encephalitis survived after receiving treatment with a regimen that included the repurposed drug nitroxoline. Nitroxoline, which is a quinolone typically used to treat urinary tract infections, was identified in a screen for drugs with amebicidal activity against Balamuthia 4).
An 80-year-old man presented with subacute mental status change, dizziness, and left-sided vision loss. Magnetic resonance imaging demonstrated a ring-enhancing right parietooccipital lesion.
Observations: Biopsy and laboratory testing demonstrated an amoebic Balamuthia mandrillaris infection. Fewer than 200 cases of this infection have been recognized in the United States, and no standardized treatment regimen currently exists.
Lessons: Rapid antimicrobial therapy with miltefosine, azithromycin, fluconazole, flucytosine, sulfadiazine, and albendazole was initiated. The pathophysiology, diagnosis, and management of this infection and the patient’s course were reviewed. The importance of biopsy for pathologic and laboratory diagnosis and rapid treatment initiation with a multidisciplinary team was reinforced 5).