Granulomatous amoebic encephalitis explained

Granulomatous amoebic encephalitis
Symptoms:Fever, headaches, personality changes
Complications:seizures, coma, risk of death
Causes:Acanthamoeba spp., Balamuthia mandrillaris, and Sappinia pedata
Treatment:Nitroxoline, miltefosine

Granulomatous amoebic encephalitis (GAE)[1] is a rare, often fatal, subacute-to-chronic central nervous system disease caused by certain species of free-living amoebae[2] of the genera Acanthamoeba, Balamuthia and Sappinia.[3] [4] The term is most commonly used with Acanthamoeba. In more modern references, the term "balamuthia amoebic encephalitis" (BAE) is commonly used when Balamuthia mandrillaris is the cause.[5] [6] [7] [8] Similarly, Sappinia amoebic encephalitis (SAE) is the name for amoebic encephalitis caused by species of Sappinia.[9]

Symptoms and signs

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.[10]

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.

Diagnosis

The condition can be difficult for doctors to diagnose, because it is a rare disease.[11] 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.[12]

Pathophysiology

The causative organism for SAE was originally identified as Sappinia diploidea,[13] [14] but is now considered to be Sappinia pedata.[15]

Treatment

Acanthamoeba

Antifungal drugs including ketoconazole, miconazole, 5-flucytosine and pentamidine have been shown to be effective against Acanthamoeba in vitro.[16]

Balamuthia

Like with Acanthamoeba, infection of the brain with this organism rapidly turns fatal in most cases.[17] 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."[18]

In one case, cloxacillin, ceftriaxone, and amphotericin B were tried, but this treatment protocol did not prove effective.[19]

In 2018 a metagenomic sequencing analysis identified Nitroxoline as amoebicidal agent against the Balamuthia mandrillaris.[20]

In 2021 a patient recovered after treatment with nitroxoline.[21] [22] 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.

Sappinia

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

Prognosis

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.[23]

See also

Notes and References

  1. Sarica FB, Tufan K, Cekinmez M, Erdoğan B, Altinörs MN . A rare but fatal case of granulomatous amebic encephalitis with brain abscess: the first case reported from Turkey . Turkish Neurosurgery . 19 . 3 . 256–259 . July 2009 . 19621290 .
  2. Nguyen L, Perloff S . Steele RW . Amebic Meningoencephalitis: Overview . EMedicine . 2018-07-24 .
  3. Guarner J, Bartlett J, Shieh WJ, Paddock CD, Visvesvara GS, Zaki SR . Histopathologic spectrum and immunohistochemical diagnosis of amebic meningoencephalitis . Modern Pathology . 20 . 12 . 1230–1237 . December 2007 . 17932496 . 10.1038/modpathol.3800973 . free .
  4. Jayasekera S, Sissons J, Tucker J, Rogers C, Nolder D, Warhurst D, Alsam S, White JM, Higgins EM, Khan NA . 6 . Post-mortem culture of Balamuthia mandrillaris from the brain and cerebrospinal fluid of a case of granulomatous amoebic meningoencephalitis, using human brain microvascular endothelial cells . Journal of Medical Microbiology . 53 . Pt 10 . 1007–1012 . October 2004 . 15358823 . 10.1099/jmm.0.45721-0 . free .
  5. da Rocha-Azevedo B, Tanowitz HB, Marciano-Cabral F . Diagnosis of infections caused by pathogenic free-living amoebae . Interdisciplinary Perspectives on Infectious Diseases . 2009 . 251406 . 2009 . 19657454 . 2719787 . 10.1155/2009/251406 . free .
  6. Matin A, Siddiqui R, Jung SY, Kim KS, Stins M, Khan NA . Balamuthia mandrillaris interactions with human brain microvascular endothelial cells in vitro . Journal of Medical Microbiology . 56 . Pt 8 . 1110–1115 . August 2007 . 17644721 . 10.1099/jmm.0.47134-0 . free .
  7. Siddiqui R, Khan NA . Balamuthia amoebic encephalitis: an emerging disease with fatal consequences . Microbial Pathogenesis . 44 . 2 . 89–97 . February 2008 . 17913450 . 10.1016/j.micpath.2007.06.008 .
  8. Schuster FL, Yagi S, Gavali S, Michelson D, Raghavan R, Blomquist I, Glastonbury C, Bollen AW, Scharnhorst D, Reed SL, Kuriyama S, Visvesvara GS, Glaser CA . 6 . Under the radar: balamuthia amebic encephalitis . Clinical Infectious Diseases . 48 . 7 . 879–887 . April 2009 . 19236272 . 10.1086/597260 . free .
  9. Da Rocha-Azevedo . B.. Tanowitz . H.. Marciano-Cabral . F.. Diagnosis of infections caused by pathogenic free-living amoebae. Interdisciplinary Perspectives on Infectious Diseases. 2009. 1–14. 2009. 19657454. 10.1155/2009/251406. 2719787. free.
  10. Duggal SD, Rongpharpi SR, Duggal AK, Kumar A, Biswal I . 2018-01-22. Role of Acanthamoeba in Granulomatous Encephalitis: A Review. Journal of Infectious Diseases & Immune Therapies. en. 2017.
  11. Matsui T, Maeda T, Kusakabe S, Arita H, Yagita K, Morii E, Kanakura Y . A case report of granulomatous amoebic encephalitis by Group 1 Acanthamoeba genotype T18 diagnosed by the combination of morphological examination and genetic analysis . Diagnostic Pathology . 13 . 1 . 27 . May 2018 . 29747695 . 5943995 . 10.1186/s13000-018-0706-z . free .
  12. Kofman A, Guarner J . Infections Caused by Free-Living Amoebae . Journal of Clinical Microbiology . 60 . 1 . e0022821 . January 2022 . 34133896 . 8769735 . 10.1128/JCM.00228-21 .
  13. 11368696. 2001. Gelman . B. B.. Rauf. Nader. Popov. Borkowski. Chaljub. Nauta. Visvesvara. Amoebic encephalitis due to Sappinia diploidea. 285. 19. 2450–2451. JAMA: The Journal of the American Medical Association. 10.1001/jama.285.19.2450 . S. J. . R. . V. . J. . G. . H. W. . G. S..
  14. 14575235. 2003. Gelman . B. B.. Popov. Chaljub. Nader. Rauf. Nauta. Visvesvara. Neuropathological and ultrastructural features of amebic encephalitis caused by Sappinia diploidea. 62. 10. 990–998. Journal of Neuropathology and Experimental Neurology . V. . G. . R. . S. J. . H. W. . G. S. . 10.1093/jnen/62.10.990. free.
  15. Qvarnstrom . Y.. Da Silva . A.. Schuster . F.. Gelman . B.. Visvesvara . G.. Molecular confirmation of Sappinia pedata as a causative agent of amoebic encephalitis. The Journal of Infectious Diseases. 199. 8. 1139–1142. 2009. 19302010 . 10.1086/597473. free.
  16. Web site: Wang J, Nichols L, Martinez AJ . Final Diagnosis -- Granulomatous Amoebic Encephalitis Due to Acanthamoeba castellanii . Department of Pathology . University of Pittsburgh .
  17. Akpek G, Uslu A, Huebner T, Taner A, Rapoport AP, Gojo I, Akpolat YT, Ioffe O, Kleinberg M, Baer MR . 6 . Granulomatous amebic encephalitis: an under-recognized cause of infectious mortality after hematopoietic stem cell transplantation . Transplant Infectious Disease . 13 . 4 . 366–373 . August 2011 . 21338461 . 10.1111/j.1399-3062.2011.00612.x . 31162954 .
  18. Deetz TR, Sawyer MH, Billman G, Schuster FL, Visvesvara GS . Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases . Clinical Infectious Diseases . 37 . 10 . 1304–1312 . November 2003 . 14583863 . 10.1086/379020 . free .
  19. Intalapaporn P, Suankratay C, Shuangshoti S, Phantumchinda K, Keelawat S, Wilde H . Balamuthia mandrillaris meningoencephalitis: the first case in southeast Asia . The American Journal of Tropical Medicine and Hygiene . 70 . 6 . 666–669 . June 2004 . 15211011 . 10.4269/ajtmh.2004.70.666 . free .
  20. Laurie . Matthew T. . White . Corin V. . Retallack . Hanna . Wu . Wesley . Moser . Matthew S. . Sakanari . Judy A. . Ang . Kenny . Wilson . Christopher . Arkin . Michelle R. . DeRisi . Joseph L. . Bassler . Bonnie . 2018 . Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen Balamuthia mandrillaris . mBio . 9 . 5 . 10.1128/mBio.02051-18 . 2150-7511 . 6212833 . 30377287.
  21. News: Kornei . Katherine . Repurposed drug battles 'brain-eating' amoeba . 2023 . Science . 10.1126/science.adh0048 . 10 February 2023.
  22. Spottiswoode . Natasha . Pet . Douglas . Kim . Annie . Gruenberg . Katherine . Shah . Maulik . Ramachandran . Amrutha . Laurie . Matthew T . Zia . Maham . Fouassier . Camille . Boutros . Christine L . Lu . Rufei . Zhang . Yueyuan . Servellita . Venice . Bollen . Andrew . Chiu . Charles Y . 2023 . Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline . Emerging Infectious Diseases . 29 . 1 . 197–201 . 10.3201/eid2901.221531 . Wilson . Michael R . Valdivia . Liza . DeRisi . Joseph L. 36573629 . 9796214 .
  23. Web site: Sappinia - Frequently Asked Questions (FAQs) . dead . https://web.archive.org/web/20111018194802/http://cdc.gov/parasites/sappinia/faqs.html . 2011-10-18 . U.S. Centers for Disease Control and Prevention .

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