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Table of Contents    
Year : 2016  |  Volume : 64  |  Issue : 1  |  Page : 14-15

Amoebic meningoencephalitis: A high index of suspicion is needed for an early diagnosis

Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication11-Jan-2016

Correspondence Address:
Ravindra Kumar Garg
Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.173618

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How to cite this article:
Garg RK, Malhotra HS. Amoebic meningoencephalitis: A high index of suspicion is needed for an early diagnosis. Neurol India 2016;64:14-5

How to cite this URL:
Garg RK, Malhotra HS. Amoebic meningoencephalitis: A high index of suspicion is needed for an early diagnosis. Neurol India [serial online] 2016 [cited 2021 Apr 23];64:14-5. Available from:

Thamtam et al., have described a fatal case of amoebic meningoencephalitis in a newly diagnosed patient with systemic lupus erythematosus in whom the etiological diagnosis (Acanthamoeba) was established on postmortem analysis.[1]

Acanthamoeba species, Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea are a group of free-living amoebae known to affect human beings and cause fulminant meningoencephalitis.[2] Among these four genera, the first three are better known and characterized, whereas the last one is extremely rare. The infections caused by Acanthamoeba and Balamuthia are opportunistic in nature and lead to the development of granulomatous amoebic meningoencephalitis; on the other hand, Naegleria involves the central nervous system directly leading to primary amoebic meningoencephalitis.

Maintaining a strong index of suspicion cannot be overemphasized in such cases because of the rarity of the disease, the fulminant course (>90% mortality), and the paucity of effective management options. Probably as a consequence, we have not moved much from the very first description of “acute pyogenic meningitis” probably due to Acanthamoeba by Fowler almost 5 decades back.[3] In his excellent précis of four cases, he described a fulminant, fatal infection involving the meninges and the brain, which evolved over 4 to 5 days from symptoms suggestive of the respiratory system involvement. An analogy to animal inoculation models was drawn, and an exhaustive staining and culture protocol was adopted to make the diagnosis. All patients were subjected to a postmortem analysis, where the basal forebrain was found to be preferentially involved pointing toward nasal mucosa as the portal of entry. Infection due to “some species” of Acanthamoeba was thus postulated.

The pathophysiology of amoebic meningoencephalitis is still an enigma, and of late, the mechanisms appear to be shifting from agent-based pathogenic potential to host-based immunogenic response.[4] A short summary of the features based on the published reports and models of amoebic meningoencephalitis and primary amoebic meningoencephalitis is provided in [Table 1]. The various hypotheses describing the infection by Acanthamoeba can broadly be divided into contact-dependent and contact-independent mechanisms.[5] Central to contact-dependent mechanisms is the phenomenon of cytoadhesion, which is mediated by the mannose-binding protein. Once binding occurs, an alteration in the cell cycle of brain microvascular endothelial cells is initiated, leading to the death of cells; a breach in the blood–brain barrier is thus achieved by Acanthamoeba. Among the contact-independent mechanisms, apparently the most important one is the paracellular transmigration pathway effectuated by the serine proteases and metalloproteases secreted by Acanthamoeba. These extracellular proteases facilitate the entry of Acanthamoeba into the deeper strata of tissue from the systemic circulation. Besides the de novo pathogenic potential of Acanthamoeba, it is important to understand that these amoebae may actually host a number of bacteria (defined as amoeba-resistant bacteria), which may complicate the actual picture of meningoencephalitis, painting it bacterial-pyogenic.[6]Legionella, Chlamydiae, Coxiella, Vibrio cholera, and Helicobacter pylori are few such bacteria resistant to the phagocytic effect of the metabolically active stage of amoebae. Given the fact that amoebic meningoencephalitis commonly affects patients with immunodeficiency, one should be ready to embrace surprises.
Table 1: Comparison of amoebic meningoencephalitis disease states

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Diagnosing amoebic meningoencephalitis reliably caused by Acanthamoeba depends on either the direct demonstration of trophozoites/cysts (supplemented with immunohistochemistry) on the culture and performance of polymerase chain reaction study.[7] Genotyping may then be done for further classification. Given a very high case fatality rate, most patients tend to be diagnosed postmortem. Histopathological examination of the brain and the exudate/infiltrate available is the most important diagnostic investigation available. The recovery of the organism from the cerebrospinal fluid is relatively better with Acanthamoeba when compared with Balamuthia; thus, in suspected patients, cerebrospinal fluid culture and polymerase chain reaction should be preferred for an antemortem diagnosis. Similarly, stereotactic biopsy of the brain lesions may be performed.

The treatment options for amoebic meningoencephalitis secondary to Acanthamoeba are limited and not very effective. Again, the lack of numbers does not allow for the planning of a trial to study the various treatment options. The available data suggest the use of pentamidine, trimethoprim–sulfamethoxazole, miltefosine, sulfadiazine, flucytosine, hyperbaric oxygen, and fluconazole, itraconazole, or voriconazole in different combinations.[1],[8],[9] Miltefosine, especially, appears promising, and the Centers for Disease Control and Prevention has made it available in view of the devastating nature of the illness.[10]

  References Top

Thamtam VK, Uppin MS, Pyal A, Kaul S, Rani YJ, Sundaram C. Fatal granulomatous amoebic encephalitis caused by Acanthamoeba in a newly diagnosed patient of systemic lupus erythematosus. Neurol India 2016;64:101-4.  Back to cited text no. 1
  Medknow Journal  
Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 2007;50:1-26.  Back to cited text no. 2
Fowler M, Carter RF. Acute pyogenic meningitis probably due to Acanthamoeba sp.: A preliminary report. Br Med J 1965;2:740-2.  Back to cited text no. 3
Baig AM. Pathogenesis of amoebic encephalitis: Are the amoebas being credited to an 'inside job'done by the host immune response? Acta Trop 2015;148:72-6.  Back to cited text no. 4
Elsheikha HM, Khan NA. Protozoa traversal of the blood-brain barrier to invade the central nervous system. FEMS Microbiol Rev 2010;34:532-53.  Back to cited text no. 5
Greub G, Didier R. Microorganisms resistant to free-living amoebae. Clin Microbiol Rev 2004;17:413-33.  Back to cited text no. 6
Walochnik J, Scheikl U, Haller-Schober EM. Twenty years of Acanthamoeba diagnostics in Austria. J Eukaryot Microbiol 2015;62:3-11.  Back to cited text no. 7
Maritschnegg P, Sovinz P, Lackner H, Benesch M, Nebl A, Schwinger W, et al. Granulomatous amebic encephalitis in a child with acute lymphoblastic leukemia successfully treated with multimodal antimicrobial therapy and hyperbaric oxygen. J Clin Microbiol 2011;49:446-8.  Back to cited text no. 8
Webster D, Umar I, Kolyvas G, Bilbao J, Guiot MC, Duplisea K, et al. Treatment of granulomatous amoebic encephalitis with voriconazole and miltefosine in an immunocompetent soldier. Am J Trop Med Hyg 2012;87:715-8.  Back to cited text no. 9
Centers for Disease Control and Prevention (CDC). Investigational drug available directly from CDC for the treatment of infections with free-living amebae. MMWR Morb Mortal Wkly Rep 2013;62:666.  Back to cited text no. 10


  [Table 1]


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