Microbiology, parasitology & COVID-19



Editorial Board Member: Patricia Tsang, M.D., M.B.A.
Rajeshwari Chellappan, M.B.B.S., M.P.H.
Sixto M. Leal, Jr., M.D., Ph.D.

Last author update: 19 December 2022
Last staff update: 19 December 2022

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PubMed Search: Balamuthia

Rajeshwari Chellappan, M.B.B.S., M.P.H.
Sixto M. Leal, Jr., M.D., Ph.D.
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Cite this page: Chellappan R, Leal SM. Balamuthia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/parasitologybalamuthia.html. Accessed June 1st, 2023.
Definition / general
  • Taxonomy: genera Balamuthia, family Balamuthiidae
  • Single celled, free living amoeba discovered from brain tissue fragments of a mandrill baboon (old world monkey) that died from a neurological condition at San Diego Zoo Wild Animal Park in California in 1986 (Clin Microbiol Rev 2008;21:435)
  • Rare cause of chronic granulomatous amebic encephalitis, disseminated disease or skin lesions in immunocompetent and immunocompromised individuals
  • Enters nasal passages or ulcerated broken skin
  • Hematogenous dissemination to the central nervous system (CNS)
  • Similar disease spectrum as Acanthamoeba
Essential features
  • 2 stage life cycle (Trop Parasitol 2015;5:15)
  • Trophozoite: 12 - 60 μm in diameter, infective, pleomorphic, uninucleated / binucleated, with 1 - 3 nucleoli (helps differentiate from Acanthamoeba) and long, slender pseudopodia
  • Cyst: 6 - 30 μm, dormant round cells that form under harsh conditions; double walled with wrinkled fibrous outer wall (exocyst); 1 or 2 nuclei
  • Skin, brain, spinal cord
  • Entry via nasal passages or broken skin; rarely organ donation with dissemination to the CNS (Trop Parasitol 2015;5:15)
  • It is transmitted on contact with skin wounds and cuts or when dust containing the parasite is breathed (e.g., during gardening)
  • Organisms are difficult to eradicate with tropism to blood vessels
  • Initial acute inflammatory response develops into chronic granulomatous inflammation with persistent perivascular ameba involving CD4 and CD8 T cells, epithelioid histiocytes and multinucleated giant cells
  • In immunocompromised patients, granulomas may or may not be present
Clinical features
  • Skin:
    • Involvement of face, palate, extremities and trunk (Clin Infect Dis 2019;68:1815)
    • Single or disseminated chronic plaque-like ulcerated skin lesion; may be mistaken for chronic fungal or mycobacterial infection and progress to CNS disease
  • CNS:
    • Granulomatous amebic encephalitis:
      • Indolent progression initially over weeks to months
      • Usually fatal with 90% mortality
    • Hematogenous spread from skin or nasal passages (Clin Infect Dis 2019;68:1815)
    • Meningoencephalitis: fever, headache, stiff neck, nausea, vomiting, lethargy with neurological deficits including ataxia, impaired speech, focal deficit and seizures
  • Identification of cysts or trophozoites in brain or skin biopsy
  • Skin:
    • Biopsy and microscopic evaluation of formalin fixed paraffin embedded (FFPE) tissue
    • Direct microscopic examination with Calcofluor white dye
    • RT-PCR on fresh tissue is required for definitive diagnosis
  • CNS:
    • Cerebrospinal fluid (BMC Microbiol 2008;8:210)
      • High lymphocytes, low glucose, high protein
      • Extremely rare to identify amebae on cerebrospinal fluid
    • Biopsy and microscopic evaluation of FFPE tissue
    • RT-PCR on fresh tissue or cerebrospinal fluid required for definitive diagnosis
      • In the U.S., the CDC offers RT-PCR for B. mandrillaris and morphologic mimics Naegleria fowleri and Acanthamoeba species
      • Negative cerebrospinal fluid RT-PCR result does not rule out intraparenchymal brain infection
  • CDC ID pathology branch offers immunohistochemical staining
  • Antibodies in serum
  • Culture requires special media and is not available in clinical labs
Case reports
  • Miltefosine in combination with drugs such as flucytosine, pentamidine, fluconazole, sulfadiazine and either azithromycin / clarithromycin (Clin Infect Dis 2010;51:e7)
Microscopic (histologic) description
  • Chronic granulomatous inflammation with cysts or trophozoites surrounding blood vessels
  • Cysts have 2 walls: wrinkled fibrous outer exocyst and inner endocyst and appear hexagonal, spherical or star shaped
    • Refractive granules may be present in the inner wall with no pores
    • May be uninucleate / binucleate
  • Trophozoites are pleomorphic with long pseudopodia
    • May be uninucleate / binucleate with multiple nucleoli in infected tissue
  • Reference: Trop Parasitol 2015;5:15
Microscopic (histologic) images

Contributed by Sixto M. Leal, Jr., M.D., Ph.D.
B. mandrillaris trophozoite and cysts

B. mandrillaris trophozoite and cysts

Differential diagnosis
  • Tuberculosis:
    • Acid fast bacilli within granulomatous inflammation
  • Acanthamoeba:
    • Inner wall (endocyst) with hexagonal, spherical, star shaped or polygonal morphology
    • Molecular identification often necessary for definitive distinction
  • Naegleria:
    • Acute illness and inflammation are predominant
    • Cysts do not form in human tissues
    • Granular cytoplasm with many vacuoles, single large nucleus and dense karyosome with no margination
  • Sappinia pedata:
  • Neurocysticercosis:
    • Cysticerci present
    • Pathognomonic calcaneous corpuscles within cestode tissue
  • Histoplasma:
    • Intracellular, uniformly sized, oval to round budding yeasts
  • Mold infection:
  • Reference: Emerg Microbes Infect 2020;9:1379
Board review style question #1

A 13 year old girl presented with a 1 year history of a cutaneous skin lesion and recent onset of dizziness, blurry vision, diplopia and worsening headaches. Brain CT showed hypodense regions in the left lateral ventricle and a brain biopsy revealed granulomatous inflammation and the perivascular organisms shown above. What microscopic features can be used to distinguish this organism from Acanthamoeba species?

  1. Endocyst structure
  2. Exocyst structure
  3. Multiple nucleoli
  4. Vacuolated cytoplasm
Board review style answer #1
A. Endocyst structure. Balamuthia mandrillaris resembles Acanthamoeba and may require molecular identification for definitive identification in granulomatous CNS lesions. However, the inner wall (endocyst) of Acanthamoeba may exhibit hexagonal, spherical, star shaped or polygonal morphology that distinguishes it from the more uniform endocyst of Balamuthia species.

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Reference: Balamuthia
Board review style question #2
A 58 year old man presented with 2 month history of sporadic headaches that have increased in frequency. Fundoscopy showed bilateral papilledema and retinal hemorrhages. Brain CT showed a hypodense lesion in right temporal lobe. It was suspected to be brain tumor and resected. Amebic trophozoites were identified. What test can confirm the diagnosis?

  1. Cerebrospinal fluid microscopy
  2. Culture on agar
  3. Real time (RT) PCR
  4. Serology
Board review style answer #2
C. Real time PCR can detect up to a single organism per reaction and distinguish between Acanthamoeba, Balamuthia and Naegleria. PCR on fresh tissue is optimal. PCR on cerebrospinal fluid can be helpful to render the diagnosis but does not rule out intraparenchymal infection if negative.

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Reference: Balamuthia
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