Oral infection of immunocompetent and immunodeficient mice with Balamuthia mandrillaris amebae

Abstract

Balamuthia mandrillaris is an opportunistic agent of lethal granulomatous amebic encephalitis (GAE). In mice, we have shown that intranasally instilled B. mandrillaris amebae infect the brain via the olfactory nerve pathway. In this study, we raised the question whether this ameba might also reach the brain after an oral/gastrointestinal infection. Immunocompetent (WT) and immunodeficient (RAG) mice received B. mandrillaris amebae by gavage into the esophagus. Mice of both groups became ill and some died (WT 20%, RAG 40%) within 42 days. All orally infected mice revealed B. mandrillaris amebae in the central nervous system. Outwardly intact amebae and/or specific antigen were found widely distributed in various organs and the stool. The data indicate that oral infection with B. mandrillaris leading to GAE is possible. Exit from the gastrointestinal tract and dissemination remains unresolved. Though stool cultures were negative, transmission of this highly pathogenic ameba via stool cannot be ruled out.

Assessment of Balamuthia mandrillaris-specific serum antibody concentrations by flow cytometry

“…castellanii (group 2) serum and A. lenticulata (group 3) amoebae. However, when diluted 1:400 as in our immunohistology studies (Kiderlen et al 2007), not cross-reactivity was observed between the different rabbit antisera and heterologous amoebae in whatever combination. These data also accentuate the antigenic differences between the morphological groups of Acanthamoeba and the need to test with the appropriate antiserum or serum combinations.…”

“…mandrillaris serum has recently been described (Kiderlen et al 2007). Sera against A. comandoni Pb30/40, A. castellanii 1BU and A. lenticulata 72/2 were produced following the same procedure but without UV-attenuating the amoebae.…”

“…Later, the pathogen was adapted to axenic culture first in modified Chang's special medium (Kiderlen et al 2006), then in BM-3 medium (Schuster and Visvesvara 1996) in plastic culture flasks (Falcon, BD Labware, Franklin Lakes, USA) at 37°C in humidified normal atmosphere with 6% CO 2 . Every 3-6 months, the amoeba was passaged in BALB/c scid/scid mice by intranasal inoculation as described (Kiderlen et al 2007) and reisolated from infected brain tissue 17-21 days later. Acanthamoeba comandoni Pb30/40, A. castellanii 1BU (ATCC PRA-113) and Acanthamoeba lenticulata 72/2 (ATCC 50705) amoebae, all kindly provided by Julia Walochnik, were grown in axenic culture in proteose peptone-yeast extract-glucose medium (Walochnik et al 2000) at 30°C in humidified normal atmosphere with 6% CO 2 .…”

Another case of canine amoebic meningoencephalitis—the challenges of reaching a rapid diagnosis

“…This observation has not been reported for canine cases. Experimentally, it has been shown that B. mandrillaris can also invade the body via the gut, following ingestion (Kiderlen et al 2007) and/or by aspiration via the nose (Kiderlen and Laube 2004). Subsequent haematogenous spread and localisation within the body is thought to take place (Schuster and Visvesvara 2004a;Siddiqui and Khan 2008).…”

Delivery of amphotericin B nanosuspensions to the brain and determination of activity against Balamuthia mandrillaris amebas

“…AmB has attracted further interest for the treatment of newly emerging diseases such Balamuthia mandrillaris amebic encephalitis. 5 This pathogen is responsible for central nervous system infections associated with major neuron disruption and loss of vital cerebral functions leading to death. In vitro assays have shown that AmB has a strong amebicidal activity, but in vivo the low bioavailability of AmB limits its activity, especially when applied against B. mandrillaris amebas persisting in the brain.…”