granulomatous amoebic encephalitis

GAE starts slowly, with symptoms like headache, nausea, dizziness, irritability and a low-grade fever. The CNS symptoms depend on the part of the brain that is infected. Changes in behavior are an important sign. Other CNS signs may include seizures, focal neurologic signs, diplopia (double vision), cranial nerve palsies, ataxia, confusion, and personality changes.{{Cite journal| vauthors = Duggal SD, Rongpharpi SR, Duggal AK, Kumar A, Biswal I |date=2018-01-22|title=Role of Acanthamoeba in Granulomatous Encephalitis: A Review|url=https://www.researchgate.net/publication/322909551|journal=Journal of Infectious Diseases & Immune Therapies|language=en|volume=2017}}

Some of the symptoms may mimic glioma (especially brainstem glioma), or other brain diseases, which may hamper timely diagnosis. The symptoms are caused by inflammatory necrosis of brain tissue brought on by compounds released from the organisms.{{cite journal|vauthors=Lowichik A, Rollins N, Delgado R, Visvesvara GS, Burns DK|title=Leptomyxid amebic meningoencephalitis mimicking brain stem glioma|journal=AJNR Am J Neuroradiol|date=April 1995|volume=16|issue=4 Suppl|pages=926–929|pmid=7611076|pmc=8332274}}

The condition can be difficult for doctors to diagnose, because it is a rare disease.{{cite journal | vauthors = Matsui T, Maeda T, Kusakabe S, Arita H, Yagita K, Morii E, Kanakura Y | title = A case report of granulomatous amoebic encephalitis by Group 1 Acanthamoeba genotype T18 diagnosed by the combination of morphological examination and genetic analysis | journal = Diagnostic Pathology | volume = 13 | issue = 1 | pages = 27 | date = May 2018 | pmid = 29747695 | pmc = 5943995 | doi = 10.1186/s13000-018-0706-z | doi-access = free }} A brain biopsy will reveal the presence of infection by pathogenic amoebas. In GAE, these present as general inflammation and sparse granules. On microscopic examination, infiltrates of amoebic cysts and/or trophozoites will be visible.{{cite journal | vauthors = Kofman A, Guarner J | title = Infections Caused by Free-Living Amoebae | journal = Journal of Clinical Microbiology | volume = 60 | issue = 1 | pages = e0022821 | date = January 2022 | pmid = 34133896 | pmc = 8769735 | doi = 10.1128/JCM.00228-21 }}

The causative organism for SAE was originally identified as Sappinia diploidea,{{Cite journal| pmid = 11368696| year = 2001| last1 = Gelman | first1 = B. B.| last2 = Rauf| last3 = Nader| last4 = Popov| last5 = Borkowski| last6 = Chaljub| last7 = Nauta| last8 = Visvesvara| title = Amoebic encephalitis due to Sappinia diploidea| volume = 285| issue = 19| pages = 2450–2451| journal = JAMA: The Journal of the American Medical Association| doi = 10.1001/jama.285.19.2450 | first2 = S. J. | first3 = R. | first4 = V. | first5 = J. | first6 = G. | first7 = H. W. | first8 = G. S.}}{{Cite journal| pmid = 14575235| year = 2003| last1 = Gelman | first1 = B. B.| last2 = Popov| last3 = Chaljub| last4 = Nader| last5 = Rauf| last6 = Nauta| last7 = Visvesvara| title = Neuropathological and ultrastructural features of amebic encephalitis caused by Sappinia diploidea| volume = 62| issue = 10| pages = 990–998| journal = Journal of Neuropathology and Experimental Neurology | first2 = V. | first3 = G. | first4 = R. | first5 = S. J. | first6 = H. W. | first7 = G. S. | doi=10.1093/jnen/62.10.990| doi-access = free}} but is now considered to be Sappinia pedata.{{Cite journal| last1 = Qvarnstrom | first1 = Y.| last2 = Da Silva | first2 = A.| last3 = Schuster | first3 = F.| last4 = Gelman | first4 = B.| last5 = Visvesvara | first5 = G.| title = Molecular confirmation of Sappinia pedata as a causative agent of amoebic encephalitis| journal = The Journal of Infectious Diseases| volume = 199| issue = 8| pages = 1139–1142| year = 2009| pmid = 19302010 | doi = 10.1086/597473| doi-access = free}}

Antifungal drugs including ketoconazole, miconazole, 5-flucytosine and pentamidine have been shown to be effective against Acanthamoeba in vitro.{{cite web | vauthors = Wang J, Nichols L, Martinez AJ | title = Final Diagnosis -- Granulomatous Amoebic Encephalitis Due to Acanthamoeba castellanii | url = http://path.upmc.edu/cases/case156/dx.html | work = Department of Pathology | publisher = University of Pittsburgh }}

{{See also|Balamuthia mandrillaris#Treatment}}

Like with Acanthamoeba, infection of the brain with this organism rapidly turns fatal in most cases.{{cite journal | vauthors = Akpek G, Uslu A, Huebner T, Taner A, Rapoport AP, Gojo I, Akpolat YT, Ioffe O, Kleinberg M, Baer MR | display-authors = 6 | title = Granulomatous amebic encephalitis: an under-recognized cause of infectious mortality after hematopoietic stem cell transplantation | journal = Transplant Infectious Disease | volume = 13 | issue = 4 | pages = 366–373 | date = August 2011 | pmid = 21338461 | doi = 10.1111/j.1399-3062.2011.00612.x | s2cid = 31162954 }} However some survivors have been reported:

Two patients survived after being successfully treated with a therapy consisting of flucytosine, pentamidine, fluconazole, sulfadiazine, and azithromycin. Thioridazine or trifluoperazine was also given. Successful treatment in these cases was credited to "awareness of Balamuthia as the causative agent of encephalitis and early initiation of antimicrobial therapy."{{cite journal | vauthors = Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS | title = Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases | journal = Clinical Infectious Diseases | volume = 37 | issue = 10 | pages = 1304–1312 | date = November 2003 | pmid = 14583863 | doi = 10.1086/379020 | doi-access = free }}

In one case, cloxacillin, ceftriaxone, and amphotericin B were tried, but this treatment protocol did not prove effective.{{cite journal | vauthors = Intalapaporn P, Suankratay C, Shuangshoti S, Phantumchinda K, Keelawat S, Wilde H | title = Balamuthia mandrillaris meningoencephalitis: the first case in southeast Asia | journal = The American Journal of Tropical Medicine and Hygiene | volume = 70 | issue = 6 | pages = 666–669 | date = June 2004 | pmid = 15211011 | doi = 10.4269/ajtmh.2004.70.666 | doi-access = free }}

In 2018 a metagenomic sequencing analysis identified Nitroxoline as amoebicidal agent against the Balamuthia mandrillaris.{{cite journal |last1=Laurie |first1=Matthew T. |last2=White |first2=Corin V. |last3=Retallack |first3=Hanna |last4=Wu |first4=Wesley |last5=Moser |first5=Matthew S. |last6=Sakanari |first6=Judy A. |last7=Ang |first7=Kenny |last8=Wilson |first8=Christopher |last9=Arkin |first9=Michelle R. |last10=DeRisi |first10=Joseph L. |last11=Bassler |first11=Bonnie |year=2018 |title=Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen Balamuthia mandrillaris |journal=mBio |volume=9 |issue=5 |doi=10.1128/mBio.02051-18 |issn=2150-7511 |pmc=6212833 |pmid=30377287}}

In 2021 a patient recovered after treatment with nitroxoline.{{cite news |last1=Kornei |first1=Katherine |title=Repurposed drug battles 'brain-eating' amoeba |date=2023 |publisher=Science |doi=10.1126/science.adh0048 |url=https://doi.org/10.1126/science.adh0048 |access-date=10 February 2023}}{{cite journal |last1=Spottiswoode |first1=Natasha |last2=Pet |first2=Douglas |last3=Kim |first3=Annie |last4=Gruenberg |first4=Katherine |last5=Shah |first5=Maulik |last6=Ramachandran |first6=Amrutha |last7=Laurie |first7=Matthew T |last8=Zia |first8=Maham |last9=Fouassier |first9=Camille |last10=Boutros |first10=Christine L |last11=Lu |first11=Rufei |last12=Zhang |first12=Yueyuan |last13=Servellita |first13=Venice |last14=Bollen |first14=Andrew |last15=Chiu |first15=Charles Y |date=2023 |title=Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline |journal=Emerging Infectious Diseases |volume=29 |issue=1 |pages=197–201 |doi=10.3201/eid2901.221531 |last16=Wilson |first16=Michael R |last17=Valdivia |first17=Liza |last18=DeRisi |first18=Joseph L|pmid=36573629 |pmc=9796214 }} The man had been given a recommended drug therapy (pentamidine, sulfadiazine, azithromycin/clarithromycin, fluconazole, flucytosine, and miltefosine) but progressed negatively. Therefore, with the permission of the FDA the regime was complemented with the unapproved drug. Nitroxoline had previously been identified via a clinical metagenomic next-generation sequencing analysis to be a compound that could be repurposed as an amoebicidal agent against Balamuthia mandrillaris. The brain abscess shrank only one week later and the man later recovered.

It has been treated with azithromycin, pentamidine, itraconazole, and flucytosine.

Even with treatment, CNS infection with Acanthamoeba is often fatal, and there are very few recorded survivors, almost all of whom had permanent neurocognitive deficits. The prognosis is largely influenced by the time of diagnosis, how virulent and sensitive the Acanthamoeba strain is, and, most crucially, the immune status of the affected person. Due to it commonly being an opportunistic infection, the prognosis is generally poor, with a mortality rate approaching 90%.

Sappinia pedata can cause GAE, however only one case of GAE due to S. pedata infection has ever been reported, and the patient survived without any long-term consequences.{{cite web |url=https://www.cdc.gov/parasites/sappinia/faqs.html |url-status=dead |archive-url=https://web.archive.org/web/20111018194802/http://cdc.gov/parasites/sappinia/faqs.html |archive-date=2011-10-18 | work = U.S. Centers for Disease Control and Prevention | title = Sappinia - Frequently Asked Questions (FAQs) }}

• Naegleriasis, an almost invariably fatal infection of the brain by the percolozoan Naegleria fowleri

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{{Amoebozoa diseases}}

{{CNS diseases of the nervous system}}

{{DEFAULTSORT:Granulomatous Amoebic Encephalitis}}

Category:Waterborne diseases

Category:Encephalitis

Category:Rare infectious diseases