Balamuthia mandrillaris: Morphology, biology, and virulence

Abstract

Balamuthia mandrillaris is a protist pathogen that can cause encephalitis with a fatality rate of >95%. This is due to our incomplete understanding of the pathogenesis and pathophysiology of B. mandrillaris encephalitis. B. mandrillaris has two stages in its life cycle, an active trophozoite stage during which it divides mitotically. However, under unfavorable conditions, the trophozoite transforms into a dormant cyst stage. A major concern during the course of therapy is that B. mandrillaris can transform into cysts. Cysts are highly resistant to physical and chemical conditions and present a problem in successful antimicrobial chemotherapy. Several lines of evidence suggest that B. mandrillaris encephalitis develops as a result of hematogenous spread, but it is unclear how circulating amoebae enter the central nervous system and cause inflammation, blood-brain barrier disruption, and neuronal injury. Recent studies have identified several parasite-host determinants for B. mandrillaris translocation of the blood-brain barrier, and host inflammatory markers that may be associated with neuronal injury. These determinants may provide important targets for the prevention and treatment of this devastating infection. Here, we present a brief overview of the current understanding of the morphology, biology, pathogenesis, and pathophysiology of B. mandrillaris encephalitis.

Keywords: Balamuthia mandrillaris; biology; encephalitis; morphology; pathogenesis; virulence.

Figure 1

The life cycle of Balamuthia mandrillaris. Under favorable conditions, B. mandrillaris remains in the active trophozoites form, as observed under phase-contrast microscope (×250) exhibiting distinct filamentous characteristics. Under harsh conditions, trophozoites differentiate into round cysts (×250)

Figure 2

Transmission electron micrograph of a Balamuthia mandrillaris cyst. The wall is made up of a thin, wavy ectocyst, a fibrous mesocyst, and a thick round endocyst. The cytoplasm is filled with numerous pinocytotic vacuoles and/or vesicles as well as mitochondria

Figure 3

The model of Balamuthia amoebic encephalitis. Amoebae enter the body via the nose and either enter into lungs or travel along the olfactory neuroepithelial route, finally leading to amoebae invasion of the central nervous system

Figure 4

The direct and indirect virulence factors that most likely contribute to the pathogenesis of Balamuthia amoebic encephalitis