Granulomatous Amebic Encephalitis by Balamuthia mandrillaris in Pediatrics: Description of Seven Cases in an Institution

Granulomatous Amebic Encephalitis by Balamuthia mandrillaris in Pediatrics: Description of Seven Cases in an Institution | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Granulomatous Amebic Encephalitis by Balamuthia mandrillaris in Pediatrics: Description of Seven Cases in an Institution Maria eugenia Badaloni, Rodrigo A Blanco, Bartuluchi Marcelo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4790606/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Granulomatous amebic encephalitis (GAE) caused by Balamuthia mandrillaris is a rare and frequently fatal infection of the central nervous system (CNS), especially in pediatric patients. Objective To describe a series of seven pediatric cases of GAE caused by Balamuthia mandrillaris and analyze the current literature on this pathology. Materials and Methods A retrospective review of pediatric cases diagnosed with GAE by Balamuthia mandrillaris at the Hospital de Pediatría J.P. Garrahan between 2000 and 2023 was conducted. Clinical, radiological, histopathological data, and therapeutic management of these patients were analyzed. A literature search was conducted in the virtual library Pub-Med in high-impact factor journals. Results Of the seven cases analyzed, six underwent biopsy and died despite receiving required treatment. The only survivor to date was the patient who had the amebic granuloma completely removed, including the capsule, and completed specific antiparasitic treatment. Conclusion GAE by Balamuthia mandrillaris has an extremely high mortality rate in pediatric patients, occurring very shortly after the onset of the disease. In this case series, we have demonstrated that the complete surgical resection of the granulomatous lesion allowed the patient to remain disease-free with a seven-month follow-up. Balamuthia mandrillaris granulomatous amebic encephalitis pediatrics central nervous system infection antiparasitic treatment Figures Figure 1 Figure 2 Figure 3 Introduction Granulomatous amebic encephalitis (GAE) is an infection of the central nervous system (CNS) caused by free-living amebas, with Balamuthia mandrillaris being one of the most lethal. The infection is rare but highly fatal, primarily affecting immunocompromised individuals and, rarely, immunocompetent patients. Balamuthia mandrillaris was first isolated from the brain of a mandrill that died in San Diego, USA, and was classified as a new protozoan in 1993. There are two forms: cyst and trophozoite, which can infect humans through the respiratory tract or skin lesions with an uncertain incubation period ranging from weeks to years. After hematogenous dissemination, the ameba lodges in any organ, most frequently the brain and skin, causing clinical manifestations of GAE and cutaneous balamuthiasis. GAE is a chronic CNS infection that produces tissue lysis, causing a local inflammatory response with necrosis and granuloma formation. Clinically, it can present non-specifically with headaches, vomiting, fever, neurological focalization depending on the lesion location, and seizures. This pathology is particularly challenging in the pediatric population due to the difficulty of early diagnosis and the limited efficacy of available treatments, with a mortality rate of 95%. Materials and Methods A retrospective review of seven pediatric cases of GAE by Balamuthia mandrillaris diagnosed at the Hospital de Pediatría J.P. Garrahan between 2000 and 2023 was conducted. Collected data included clinical history, clinical manifestations, diagnostic imaging results, histopathological findings, administered treatments, and clinical evolution. Diagnostic confirmation was obtained through brain biopsy and histopathological analysis. A literature search was conducted in the virtual library Pub-Med in high-impact factor journals. Results Due to the low frequency of this disease and belonging to the same center, four of the cases included in this work are those reported by Galarza et al. in 2002. Here we analyze the following three contemporary cases. Case I A 10-year-old female patient with no relevant history presented with paresthesia and hemiparesis of the left side, vomiting, and generalized tonic-clonic seizures. An initial CT scan revealed a right parietal space-occupying mass, suspected to be a neoplasm. Ophthalmologic evaluation was normal. Serologies were negative. Lumbar puncture with normal cytochemical and negative cultures was performed. MRI showed a heterogeneous enhancing lesion, positive restriction, and significant perilesional edema. Due to clinical worsening, a stereotactic biopsy of the lesion was performed, revealing free-living amebas, specifically Balamuthia mandrillaris. Treatment with albendazole, metronidazole, fluconazole, and rifampicin was initiated. The patient continued to deteriorate neurologically, dying 34 days after symptom onset. Case II An 11-year-old male with no significant pathological history presented with a 30-day history of vomiting, headache, and right-sided facial paralysis (VII nerve). Initial CT showed a left frontal space-occupying lesion. MRI demonstrated heterogeneous enhancement, positive restriction, and perilesional vasogenic edema. Malignant neoplasm was initially suspected. Serologies were negative. Lumbar puncture with negative cultures. Ophthalmologic examination was normal. Stereotactic biopsy and subsequent histopathological study confirmed Balamuthia mandrillaris infection. Treatment with amphotericin, fluconazole, albendazole, metronidazole, and miltefosine was administered. Despite treatment, the patient’s condition worsened, with disease progression both clinically and radiologically, leading to death 20 days after hospital admission. (Fig. 1 ) Case III A previously healthy 10-year-old female presented with febrile illness, having a history of acute otitis media and sinusitis in the 15 days prior to consultation. MRI revealed a left parietal lesion with perilesional edema, initially diagnosed as a bacterial brain abscess. Due to lack of response to antimicrobial treatment, clinical worsening (seizures and comprehension aphasia), and lesion progression in subsequent MRIs, surgical treatment was decided. An open biopsy without capsule resection was performed, aiming for a pathological diagnosis. Immunohistochemistry confirmed structures compatible with tachyzoites, confirming a necrotizing chronic granulomatous inflammatory process suggestive of toxoplasmosis. Treatment with pyrimethamine, sulfadiazine, and folinic acid was initiated. Due to lack of clinical improvement and lesion relapse in the surgical site, a new surgery for complete resection, including the granuloma capsule, was performed. The new sample revealed free-living amebas, specifically Balamuthia mandrillaris. Treatment with flucytosine, fluconazole, and azithromycin was started based on recommendations from the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics for Balamuthia mandrillaris. The patient remained asymptomatic with MRI showing no recurrence in the surgical site. Eight months later, antiparasitic treatment was discontinued, and she was discharged from the hospital, currently without neurological deficits. (Figs. 2 and 3 ) Discussion Granulomatous amebic encephalitis (GAE) caused by Balamuthia mandrillaris is a rare but highly lethal disease, especially in the pediatric population. In this case series, six of the seven patients died despite receiving specific antiparasitic treatment, highlighting the aggressive nature of this infection and the limitations of current therapies. However, one patient who underwent complete granuloma resection, including the capsule, survived and remains disease-free, underscoring the crucial importance of timely surgical intervention, including complete lesion removal. No case series of this disease were found in our literature search, only isolated cases reported as case reports [ 4 ] [ 5 ] [ 6 ]. Balamuthia mandrillaris is a free-living ameba that can invade the CNS via hematogenous routes or direct invasion from a skin or nasal lesion. Once in the CNS, the ameba induces a strong inflammatory response, forming granulomas that are difficult to treat due to their location and drug resistance. Most reported cases of GAE by Balamuthia mandrillaris occur in immunocompromised individuals, but cases in immunocompetent patients have been documented, suggesting other susceptibility factors may influence the infection. Initial symptoms of GAE are nonspecific and include headache, fever, nausea, and vomiting. As the disease progresses, focal neurological signs, seizures, and mental status deterioration appear. These nonspecific symptoms hinder early and accurate diagnosis. The diagnosis of GAE by Balamuthia mandrillaris is challenging due to the rarity of the disease and the nonspecificity of initial symptoms. MRI typically shows brain lesions that can be mistaken for tumors or abscesses. Definitive confirmation is obtained through brain biopsy and histopathological examination. In this series, the diagnosis was confirmed in six patients through biopsies, but biopsy alone was insufficient to improve survival despite antiamebic treatment. GAE treatment is complex and no standardized protocol exists due to the rarity of the disease. Combinations of antiparasitic drugs such as pentamidine, flucytosine, sulfadiazine, clarithromycin, and azithromycin have been used with limited results. In our series, all patients who only received biopsy and pharmacological treatment died, highlighting the limited efficacy of current antiparasitic treatments when not accompanied by appropriate surgical intervention. The survival of the only patient who underwent complete granuloma resection suggests that total surgical removal of the lesion, including the capsule, is crucial for improving prognosis in cases of GAE by Balamuthia mandrillaris. Complete resection appears to be a determining factor for survival, possibly due to reduced amebic load and local immune response modulation [ 7 ]. Further studies and case reports are needed to establish standardized treatment protocols and improve outcomes for patients affected by this devastating disease. This finding is consistent with reports in the literature indicating that aggressive surgical intervention, combined with antiparasitic treatment, can offer a better chance of survival. Exposure to Balamuthia mandrillaris can occur through contact with contaminated soil or freshwater. Many cases of amebic keratitis have been reported in patients with daily contact lens use [ 8 ]. Although the infection is extremely rare, understanding specific risk factors and transmission mechanisms is crucial for preventing future cases [ 9 ]. Conclusion GAE by Balamuthia mandrillaris represents a significant challenge in the pediatric population due to its high mortality and difficulty in establishing an early diagnosis. Complete lesion excision, along with an appropriate antiparasitic treatment regimen, appears to be essential for improving prognosis. Ongoing research, education, and national case reporting on this disease are crucial for improving future clinical outcomes. Declarations Competing Interests The authors did not receive support from any organization for the submitted work. No funding was received to assist with the preparation of this manuscript. No funds, grants, or other support was received. The authors have no relevant financial or non-financial interests to disclose. The authors have no competing interests to declare that are relevant to the content of this article. All authors certify that they have no affiliations with, or involvement in any organization or entity with any financial interests or non-financial interests in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article. Consent It has been agreed upon with the relatives of the patients described in the case, who have notified the institution and our service that they have no objection to publishing this case; they are even grateful to be able to contribute to the medical community. Consent has been obtained and accepted. Author Contribution All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by M. Eugenia Badaloni. The first draft of the manuscript was written by M. Eugenia Badaloni. Writing, review, and editing were performed by M. Eugenia Badaloni and Rodrigo Alberto Blanco. Gisela Pascuetin added information for the manuscript. Marcelo Bartuluchi participated in the surgery. Supervision was performed by Romina Argañaraz. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Galarza M, Cuccia V, Sosa FP, Monges JA. Pediatric granulomatous cerebral amebiasis: a delayed diagnosis. Pediatr Neurol. 2002 Feb;26(2):153-6. doi: 10.1016/s0887-8994(01)00360-5. PMID: 11897483. https://www.cdc.gov/balamuthia/hcp/clinical-care/index.html Cary LC, Maul E, Potter C, Wong P, Nelson PT, Given C 2nd, Robertson W Jr. Balamuthia mandrillaris meningoencephalitis: survival of a pediatric patient. Pediatrics. 2010 Mar;125(3):e699-703. doi: 10.1542/peds.2009-1797. Epub 2010 Feb 1. PMID: 20123772. Fan X, Chen T, Yang H, Gao Y, Chen Y. Encephalomyelomeningitis Caused by Balamuthia mandrillaris: A Case Report and Literature Review. Infect Drug Resist. 2023 Feb 2;16:727-733. doi: 10.2147/IDR.S400692. PMID: 36756612; PMCID: PMC9901442. Yi Z, Zhong J, Wu H, Li X, Chen Y, Chen H, Yang Y, Yu X. Balamuthia mandrillaris encephalitis in a child: case report and literature review. Diagn Microbiol Infect Dis. 2021 Aug;100(4):115180. doi: 10.1016/j.diagmicrobio.2020.115180. Epub 2020 Aug 21. PMID: 33887622. Hu J, Zhang Y, Yu Y, Yu H, Guo S, Shi D, He J, Hu C, Yang J, Fang X, Xiao Y. Encephalomyelitis Caused by Balamuthia mandrillaris in a Woman With Breast Cancer: A Case Report and Review of the Literature. Front Immunol. 2022 Jan 5;12:768065. doi: 10.3389/fimmu.2021.768065. PMID: 35069540; PMCID: PMC8766823. Baig AM. Pathogenesis of amoebic encephalitis: Are the amoebae being credited to an 'inside job' done by the host immune response? Acta Trop. 2015 Aug;148:72-6. doi: 10.1016/j.actatropica.2015.04.022. Epub 2015 Apr 27. PMID: 25930186. Visvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis. 2010 Dec;23(6):590-4. doi: 10.1097/QCO.0b013e32833ed78b. PMID: 20802332. Bhosale NK, Parija SC. Balamuthia mandrillaris: An opportunistic, free-living ameba - An updated review. Trop Parasitol. 2021 Jul-Dec;11(2):78-88. doi: 10.4103/tp.tp_36_21. Epub 2021 Oct 20. PMID: 34765527; PMCID: PMC8579774. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4790606","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":337584657,"identity":"20aeb7b2-e3e2-44ae-8b08-770b4f73668e","order_by":0,"name":"Maria eugenia Badaloni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYLACxgYgYgcyEiqABDNzA5FamEFazoC0MJKihbENysUH+CXSLz5g3GEn29/MfOzBw3m10fztQC0/Krbh1CI5I6fYgPFMsvGMw2zpBonbjufOOMzYwNhz5jZOLQY3ctIkGNuYExsO85hJJG47ltsA1MLM2IZbi/2NnPQfjG31ifPBWuYcy51PSIuBRPoxoK8PJ24Aa2moyd1ASIvEmTfMEolnjhtvPMyWJpFw7EDuRqCWg/j8wt+e/vDDxx3VsvOONx+T/FFTlzvv/OGDD35U4NbCwMBjwJCA4B0GkwfwqAcC9gfIvDr8ikfBKBgFo2BEAgDUil7Xh2oMtwAAAABJRU5ErkJggg==","orcid":"","institution":"Hospital de Pediatría “Juan P. 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Intraoperative image of the amebic granuloma in Case III. \u003cstrong\u003eB\u003c/strong\u003e. Intraoperative image of the site after complete resection with hemostatic material in Case III.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4790606/v1/70345d6c3eb015863308df3b.jpg"},{"id":65608151,"identity":"8dc96d8a-38bc-4bdf-9ada-31433288c3ea","added_by":"auto","created_at":"2024-09-30 13:02:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":569142,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4790606/v1/1f9974e3-1ed7-4d8a-91f5-77b80a38dea2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Granulomatous Amebic Encephalitis by Balamuthia mandrillaris in Pediatrics: Description of Seven Cases in an Institution","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGranulomatous amebic encephalitis (GAE) is an infection of the central nervous system (CNS) caused by free-living amebas, with Balamuthia mandrillaris being one of the most lethal. The infection is rare but highly fatal, primarily affecting immunocompromised individuals and, rarely, immunocompetent patients. Balamuthia mandrillaris was first isolated from the brain of a mandrill that died in San Diego, USA, and was classified as a new protozoan in 1993. There are two forms: cyst and trophozoite, which can infect humans through the respiratory tract or skin lesions with an uncertain incubation period ranging from weeks to years. After hematogenous dissemination, the ameba lodges in any organ, most frequently the brain and skin, causing clinical manifestations of GAE and cutaneous balamuthiasis. GAE is a chronic CNS infection that produces tissue lysis, causing a local inflammatory response with necrosis and granuloma formation. Clinically, it can present non-specifically with headaches, vomiting, fever, neurological focalization depending on the lesion location, and seizures. This pathology is particularly challenging in the pediatric population due to the difficulty of early diagnosis and the limited efficacy of available treatments, with a mortality rate of 95%.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eA retrospective review of seven pediatric cases of GAE by Balamuthia mandrillaris diagnosed at the Hospital de Pediatr\u0026iacute;a J.P. Garrahan between 2000 and 2023 was conducted. Collected data included clinical history, clinical manifestations, diagnostic imaging results, histopathological findings, administered treatments, and clinical evolution. Diagnostic confirmation was obtained through brain biopsy and histopathological analysis. A literature search was conducted in the virtual library Pub-Med in high-impact factor journals.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDue to the low frequency of this disease and belonging to the same center, four of the cases included in this work are those reported by Galarza et al. in 2002. Here we analyze the following three contemporary cases.\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCase I\u003c/h2\u003e \u003cp\u003eA 10-year-old female patient with no relevant history presented with paresthesia and hemiparesis of the left side, vomiting, and generalized tonic-clonic seizures. An initial CT scan revealed a right parietal space-occupying mass, suspected to be a neoplasm. Ophthalmologic evaluation was normal. Serologies were negative. Lumbar puncture with normal cytochemical and negative cultures was performed. MRI showed a heterogeneous enhancing lesion, positive restriction, and significant perilesional edema. Due to clinical worsening, a stereotactic biopsy of the lesion was performed, revealing free-living amebas, specifically Balamuthia mandrillaris. Treatment with albendazole, metronidazole, fluconazole, and rifampicin was initiated. The patient continued to deteriorate neurologically, dying 34 days after symptom onset.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCase II\u003c/h2\u003e \u003cp\u003eAn 11-year-old male with no significant pathological history presented with a 30-day history of vomiting, headache, and right-sided facial paralysis (VII nerve). Initial CT showed a left frontal space-occupying lesion. MRI demonstrated heterogeneous enhancement, positive restriction, and perilesional vasogenic edema. Malignant neoplasm was initially suspected. Serologies were negative. Lumbar puncture with negative cultures. Ophthalmologic examination was normal. Stereotactic biopsy and subsequent histopathological study confirmed Balamuthia mandrillaris infection. Treatment with amphotericin, fluconazole, albendazole, metronidazole, and miltefosine was administered. Despite treatment, the patient\u0026rsquo;s condition worsened, with disease progression both clinically and radiologically, leading to death 20 days after hospital admission. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCase III\u003c/h2\u003e \u003cp\u003eA previously healthy 10-year-old female presented with febrile illness, having a history of acute otitis media and sinusitis in the 15 days prior to consultation. MRI revealed a left parietal lesion with perilesional edema, initially diagnosed as a bacterial brain abscess. Due to lack of response to antimicrobial treatment, clinical worsening (seizures and comprehension aphasia), and lesion progression in subsequent MRIs, surgical treatment was decided. An open biopsy without capsule resection was performed, aiming for a pathological diagnosis. Immunohistochemistry confirmed structures compatible with tachyzoites, confirming a necrotizing chronic granulomatous inflammatory process suggestive of toxoplasmosis. Treatment with pyrimethamine, sulfadiazine, and folinic acid was initiated. Due to lack of clinical improvement and lesion relapse in the surgical site, a new surgery for complete resection, including the granuloma capsule, was performed. The new sample revealed free-living amebas, specifically Balamuthia mandrillaris. Treatment with flucytosine, fluconazole, and azithromycin was started based on recommendations from the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics for Balamuthia mandrillaris. The patient remained asymptomatic with MRI showing no recurrence in the surgical site. Eight months later, antiparasitic treatment was discontinued, and she was discharged from the hospital, currently without neurological deficits. (Figs.\u0026nbsp;2 and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eGranulomatous amebic encephalitis (GAE) caused by Balamuthia mandrillaris is a rare but highly lethal disease, especially in the pediatric population. In this case series, six of the seven patients died despite receiving specific antiparasitic treatment, highlighting the aggressive nature of this infection and the limitations of current therapies. However, one patient who underwent complete granuloma resection, including the capsule, survived and remains disease-free, underscoring the crucial importance of timely surgical intervention, including complete lesion removal. No case series of this disease were found in our literature search, only isolated cases reported as case reports [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Balamuthia mandrillaris is a free-living ameba that can invade the CNS via hematogenous routes or direct invasion from a skin or nasal lesion. Once in the CNS, the ameba induces a strong inflammatory response, forming granulomas that are difficult to treat due to their location and drug resistance. Most reported cases of GAE by Balamuthia mandrillaris occur in immunocompromised individuals, but cases in immunocompetent patients have been documented, suggesting other susceptibility factors may influence the infection. Initial symptoms of GAE are nonspecific and include headache, fever, nausea, and vomiting. As the disease progresses, focal neurological signs, seizures, and mental status deterioration appear. These nonspecific symptoms hinder early and accurate diagnosis. The diagnosis of GAE by Balamuthia mandrillaris is challenging due to the rarity of the disease and the nonspecificity of initial symptoms. MRI typically shows brain lesions that can be mistaken for tumors or abscesses. Definitive confirmation is obtained through brain biopsy and histopathological examination. In this series, the diagnosis was confirmed in six patients through biopsies, but biopsy alone was insufficient to improve survival despite antiamebic treatment. GAE treatment is complex and no standardized protocol exists due to the rarity of the disease. Combinations of antiparasitic drugs such as pentamidine, flucytosine, sulfadiazine, clarithromycin, and azithromycin have been used with limited results. In our series, all patients who only received biopsy and pharmacological treatment died, highlighting the limited efficacy of current antiparasitic treatments when not accompanied by appropriate surgical intervention. The survival of the only patient who underwent complete granuloma resection suggests that total surgical removal of the lesion, including the capsule, is crucial for improving prognosis in cases of GAE by Balamuthia mandrillaris. Complete resection appears to be a determining factor for survival, possibly due to reduced amebic load and local immune response modulation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Further studies and case reports are needed to establish standardized treatment protocols and improve outcomes for patients affected by this devastating disease. This finding is consistent with reports in the literature indicating that aggressive surgical intervention, combined with antiparasitic treatment, can offer a better chance of survival. Exposure to Balamuthia mandrillaris can occur through contact with contaminated soil or freshwater. Many cases of amebic keratitis have been reported in patients with daily contact lens use [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Although the infection is extremely rare, understanding specific risk factors and transmission mechanisms is crucial for preventing future cases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eGAE by Balamuthia mandrillaris represents a significant challenge in the pediatric population due to its high mortality and difficulty in establishing an early diagnosis. Complete lesion excision, along with an appropriate antiparasitic treatment regimen, appears to be essential for improving prognosis. Ongoing research, education, and national case reporting on this disease are crucial for improving future clinical outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not receive support from any organization for the submitted work.\u003c/p\u003e\n\u003cp\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eNo funds, grants, or other support was received.\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eThe authors have no competing interests to declare that are relevant to the content of this article.\u003c/p\u003e\n\u003cp\u003eAll authors certify that they have no affiliations with, or involvement in any organization or entity with any\u003c/p\u003e\n\u003cp\u003efinancial interests or non-financial interests in the subject matter or materials discussed in this manuscript.\u003c/p\u003e\n\u003cp\u003eThe authors have no financial or proprietary interests in any material discussed in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIt has been agreed upon with the relatives of the patients described in the case, who have notified the institution and our service that they have no objection to publishing this case; they are even grateful to be able to contribute to the medical community. Consent has been obtained and accepted.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by M. Eugenia Badaloni. The first draft of the manuscript was written by M. Eugenia Badaloni. Writing, review, and editing were performed by M. Eugenia Badaloni and Rodrigo Alberto Blanco. Gisela Pascuetin added information for the manuscript. Marcelo Bartuluchi participated in the surgery. Supervision was performed by Romina Arga\u0026ntilde;araz. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGalarza M, Cuccia V, Sosa FP, Monges JA. Pediatric granulomatous cerebral amebiasis: a delayed diagnosis. Pediatr Neurol. 2002 Feb;26(2):153-6. doi: 10.1016/s0887-8994(01)00360-5. PMID: 11897483.\u003c/li\u003e\n\u003cli\u003ehttps://www.cdc.gov/balamuthia/hcp/clinical-care/index.html\u003c/li\u003e\n\u003cli\u003eCary LC, Maul E, Potter C, Wong P, Nelson PT, Given C 2nd, Robertson W Jr. Balamuthia mandrillaris meningoencephalitis: survival of a pediatric patient. Pediatrics. 2010 Mar;125(3):e699-703. doi: 10.1542/peds.2009-1797. Epub 2010 Feb 1. PMID: 20123772.\u003c/li\u003e\n\u003cli\u003eFan X, Chen T, Yang H, Gao Y, Chen Y. Encephalomyelomeningitis Caused by Balamuthia mandrillaris: A Case Report and Literature Review. Infect Drug Resist. 2023 Feb 2;16:727-733. doi: 10.2147/IDR.S400692. PMID: 36756612; PMCID: PMC9901442.\u003c/li\u003e\n\u003cli\u003eYi Z, Zhong J, Wu H, Li X, Chen Y, Chen H, Yang Y, Yu X. Balamuthia mandrillaris encephalitis in a child: case report and literature review. Diagn Microbiol Infect Dis. 2021 Aug;100(4):115180. doi: 10.1016/j.diagmicrobio.2020.115180. Epub 2020 Aug 21. PMID: 33887622.\u003c/li\u003e\n\u003cli\u003eHu J, Zhang Y, Yu Y, Yu H, Guo S, Shi D, He J, Hu C, Yang J, Fang X, Xiao Y. Encephalomyelitis Caused by Balamuthia mandrillaris in a Woman With Breast Cancer: A Case Report and Review of the Literature. Front Immunol. 2022 Jan 5;12:768065. doi: 10.3389/fimmu.2021.768065. PMID: 35069540; PMCID: PMC8766823.\u003c/li\u003e\n\u003cli\u003eBaig AM. Pathogenesis of amoebic encephalitis: Are the amoebae being credited to an \u0026apos;inside job\u0026apos; done by the host immune response? Acta Trop. 2015 Aug;148:72-6. doi: 10.1016/j.actatropica.2015.04.022. Epub 2015 Apr 27. PMID: 25930186.\u003c/li\u003e\n\u003cli\u003eVisvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis. 2010 Dec;23(6):590-4. doi: 10.1097/QCO.0b013e32833ed78b. PMID: 20802332.\u003c/li\u003e\n\u003cli\u003eBhosale NK, Parija SC. Balamuthia mandrillaris: An opportunistic, free-living ameba - An updated review. Trop Parasitol. 2021 Jul-Dec;11(2):78-88. doi: 10.4103/tp.tp_36_21. Epub 2021 Oct 20. PMID: 34765527; PMCID: PMC8579774.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Balamuthia mandrillaris, granulomatous amebic encephalitis, pediatrics, central nervous system infection, antiparasitic treatment","lastPublishedDoi":"10.21203/rs.3.rs-4790606/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4790606/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGranulomatous amebic encephalitis (GAE) caused by Balamuthia mandrillaris is a rare and frequently fatal infection of the central nervous system (CNS), especially in pediatric patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo describe a series of seven pediatric cases of GAE caused by Balamuthia mandrillaris and analyze the current literature on this pathology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective review of pediatric cases diagnosed with GAE by Balamuthia mandrillaris at the Hospital de Pediatría J.P. Garrahan between 2000 and 2023 was conducted. Clinical, radiological, histopathological data, and therapeutic management of these patients were analyzed. A literature search was conducted in the virtual library Pub-Med in high-impact factor journals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the seven cases analyzed, six underwent biopsy and died despite receiving required treatment. The only survivor to date was the patient who had the amebic granuloma completely removed, including the capsule, and completed specific antiparasitic treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGAE by Balamuthia mandrillaris has an extremely high mortality rate in pediatric patients, occurring very shortly after the onset of the disease. In this case series, we have demonstrated that the complete surgical resection of the granulomatous lesion allowed the patient to remain disease-free with a seven-month follow-up.\u003c/p\u003e","manuscriptTitle":"Granulomatous Amebic Encephalitis by Balamuthia mandrillaris in Pediatrics: Description of Seven Cases in an Institution","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 13:38:45","doi":"10.21203/rs.3.rs-4790606/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"76124c2a-59d4-47ba-80ac-5043ee68109b","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T12:53:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 13:38:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4790606","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4790606","identity":"rs-4790606","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}