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Histopathologic spectrum and immunohistochemical diagnosis of amebic meningoencephalitis
Jeannette Guarner1, Jeanine Bartlett, Wun-Ju Shieh
1Infectious Disease Pathology Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1405 Clifton Road NE, Atlanta, GA 30322, USA. Jeanette.Guarner@choa.org
Abstract:
Traditionally, Naegleria fowleri infections are labeled primary amebic meningoencephalitis because of prominent meningeal neutrophilic inflammation. Acanthamoeba spp. and Balamuthia mandrillaris are labeled granulomatous amebic encephalitis because of parenchymal granulomatous inflammation. We compared histopathologic and immunohistochemical features of 18 cases with central nervous system free-living ameba infections. Immunohistochemical assays using polyclonal antibodies that reacted specifically against each genus identified 11 patients with Balamuthia infection, four with N. fowleri, and three with Acanthamoeba. Immunohistochemical assays highlighted the presence of trophozoites that were difficult to identify with hematoxylin and eosin stains in areas of necrosis or where macrophages were abundant. Immunohistochemical assays also demonstrated the presence of granular antigens inside macrophages and blood vessel walls. Amebic cysts were observed in three patients with Acanthamoeba infection and in three with Balamuthia. Patients with Acanthamoeba infection showed granulomatous inflammation. Patients with Naegleria infection had neutrophilic inflammation. Balamuthia infections showed a spectrum of inflammation that ranged from primarily neutrophils to granulomas. Meningitis was present in 88% of cases. Immunohistochemical assays were useful to demonstrate the presence of granular antigens and confirmed the genus of the ameba. The spectrum of inflammation in cases of Balamuthia meningoencephalitis is broader than previously described. The term amebic meningoencephalitis describes better the histopathologic findings than the currently used classification of primary amebic meningoencephalitis and granulomatous amebic encephalitis.
Insights
Free-living ameba infections of the central nervous system, including Balamuthia mandrillaris, Naegleria fowleri, and Acanthamoeba, exhibit diverse inflammatory patterns. Immunohistochemistry aids in genus identification and reveals antigens within tissues.
Area of Science:
- Neuropathology
- Infectious Diseases
- Microbiology
Background:
- Central nervous system (CNS) infections by free-living amebas are classified based on observed inflammation: primary amebic meningoencephalitis (PAM) for Naegleria fowleri and granulomatous amebic encephalitis (GAE) for Acanthamoeba and Balamuthia.
- Distinct histopathological features, specifically the type of inflammatory response (neutrophilic vs. granulomatous), traditionally define these classifications.
- Accurate genus identification is crucial for understanding disease pathogenesis and patient outcomes.
Purpose of the Study:
- To compare the histopathologic and immunohistochemical features of CNS infections caused by different genera of free-living amebas.
- To evaluate the utility of immunohistochemical assays in identifying amebic trophozoites and confirming genus.
- To reassess the current classification of amebic meningoencephalitis based on observed histopathological findings.
Main Methods:
- Histopathologic and immunohistochemical analysis of 18 CNS free-living ameba infection cases.
- Use of genus-specific polyclonal antibodies for immunohistochemical detection of Balamuthia, Naegleria, and Acanthamoeba.
- Comparison of inflammation patterns (neutrophilic, granulomatous) and presence of trophozoites and cysts.
Main Results:
- Immunohistochemistry identified 11 Balamuthia, 4 Naegleria, and 3 Acanthamoeba infections, highlighting trophozoites often missed by H&E staining.
- Balamuthia infections showed a spectrum of inflammation, from neutrophilic to granulomatous, challenging the traditional GAE classification.
- Meningitis was prevalent (88%), and immunohistochemistry confirmed amebic genus and detected antigens in macrophages and blood vessels.
Conclusions:
- Immunohistochemistry is a valuable tool for diagnosing amebic CNS infections, identifying trophozoites, and confirming the causative genus.
- Balamuthia infections present a broader inflammatory spectrum than previously recognized, encompassing features of both PAM and GAE.
- The term 'amebic meningoencephalitis' is proposed as a more encompassing descriptor for the histopathologic findings in these infections.
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