Case Report: Granulomatous Amebic Encephalitis due to Acanthamoeba spp. in an Immunocompetent Pediatric Patient

Granulomatous amebic encephalitis (GAE) caused by Acanthamoeba is a rare infection with central nervous system (CNS) involvement usually with fatal consequences. Currently, information regarding GAE in children is scarce and is limited only to case reports and case series. A 13-year-old immunocompetent male patient with a 6-month history of progressive and intermittent headaches presented to our institution. One week before hospital admission, the patient showed signs of CNS involvement. Magnetic resonance imaging revealed multiple lesions with supra- and infratentorial cerebral abscesses. An empiric treatment with combined antibiotics was given, but the patient died after 20 days of hospital stay. A postmortem diagnosis confirmed GAE. Although it is a rare disease in pediatric patients, GAE should be considered in children with a chronic history of fever, headache, and vomiting with CNS involvement.

Immunopathogenicity of Acanthamoeba spp. in the Brain and Lungs

Free-living amoebas, including Acanthamoeba spp., are widely distributed in soil, water, and air. They are capable of causing granulomatous amebic encephalitis, Acanthamoeba pneumonia, Acanthamoeba keratitis, and disseminated acanthamoebiasis. Despite low occurrence worldwide, the mortality rate of Acanthamoeba spp. infections is very high, especially in immunosuppressed hosts. Acanthamoeba infections are a medical problem, owing to limited improvement in diagnostics and treatment, which is associated with incomplete knowledge of pathophysiology, pathogenesis, and the host immune response against Acanthamoeba spp. infection. The aim of this review is to present the biochemical and molecular mechanisms of Acanthamoeba spp.–host interactions, including the expression of Toll-like receptors, mechanisms of an immune response, the activity of metalloproteinases, the secretion of antioxidant enzymes, and the expression and activity of cyclooxygenases. We show the relationship between Acanthamoeba spp. and the host at the cellular level and host defense reactions that lead to changes in the selected host’s organs.

Ac-HSP20 Is Associated With the Infectivity and Encystation of Acanthamoeba castellanii

Acanthamoeba castellanii is a pathogenic and opportunistic free-living amoeba that causes Acanthamoeba keratitis (AK) and granulomatous amebic encephalitis (GAE) in immunocompromised individuals. The biological and pathogenic characterizations behind this opportunistic protozoan is not fully understood. This study aimed to determine the biological functions of heat shock protein (HSP)-20 of A. castellanii (Ac-HSP20) involved in the maintenance of life cycle and the infectivity of A. castellanii. Immunoscreening A. castellanii cDNA library with A. castellanii infected rabbit sera identified three positive clones, one of them was a putative heat shock protein (Ac-HSP20). The recombinant 23 kDa Ac-HSP20 protein (rAc-HSP20) was successfully expressed in Escherichia coli BL21 (DE3) and purified using metal affinity chromatography. The rabbits immunized with rAc-HSP20 produced high titer antibody (1:25,600). Immunolocalization with the antibody identified the expression of native Ac-HSP20 on the surface of both A. castellanii trophozoites and cysts. Further, Western blot with antibody identified that the expression of native Ac-HSP20 was 7.5 times higher in cysts than in trophozoites. Blocking Ac-HSP20 on the membrane of trophozoites with specific antibody or silencing Ac-hsp20 gene transcription by siRNA inhibited their transformation into cysts at the early stage but returned to normal at the late stage by stimulating the transcription of Ac-hsp20. Incubation of trophozoites with anti-Ac-HSP20 IgG increased macrophage-involved phagocytosis to the protozoa and inhibited trophozoite infectivity on the cornea of rabbits compared with that without antibody. Our study provides that Ac-HSP20 is a surface antigen involved in the encystation and infectivity of A. castellanii and thus an important target for vaccine and drug development.