Augusto Julio Martinez

Free‐living, Amphizoic and Opportunistic Amebas

Amebas belonging to the genera Naegleria, Acanthamoeba and Balamuthia are free‐living, amphizoic and opportunistic protozoa that are ubiquitous in nature. These amebas are found in soil, water and air samples from all over the world. Human infection due to these amebas involving brain, skin, lung and eyes has increased significantly during the last 10 years. The epidemiology, immunology, protozoology, pathology, and clinical features of the infections produced by these protozoa differ strikingly.

Balamuthia mandrillaris, n. g., n. sp., agent of amebic meningoencephalitis in humans and other animals.

ABSTRACT. We recently reported the isolation of a leptomyxid ameba from the brain of a mandrill baboon that died of meningo‐encephalitis. Based on light and electron microscopic studies, animal pathogenicity tests, and immunofluorescence patterns, we conclude that our isolate differs fundamentally from the other two amebas (Leptomyxa and Gephyramoeba) included in the Order Leptomyxida. We therefore created a new genus, Balamuthia, to accommodate our isolate and described it as Balamuthia mandrillaris to reflect the origin of the type species. Briefly, B. mandrillaris is a pathogenic ameba that causes amebic encephalitis in humans and animals. It has trophic and cyst stages in its life cycle, and is uninucleate with a large vesicular nucleus and a central nucleolus. Mature cysts have a tripartite wall consisting of an outer loose ectocyst, an inner endocyst and a middle mesocyst. Unlike Acanthamoeba and Naegleria, the other two amebas that cause amebic encephalitis in humans, Balamuthia will not grow on agar plates seeded with enteric bacteria. However, Balamuthia grows on a variety of mammalian cell cultures and kills mice following intranasal or intraperitoneal inoculation. Based on immunofluorescence testing, 35 cases of amebic encephalitis in humans and three in other animals have been identified worldwide as being caused by Balamuthia.

Granulomatous amebic encephalitis: a review and report of a spontaneous case from Venezuela

Granulomatous amebic encephalitis (GAE), or meningoencephalitis due to Acanthamoeba spp. and leptomyxid ameba are uncommon CNS infections that generally occur in immunocompromised hosts. We describe a case of GAE caused by Balamuthia mandrillaris previously designated as a leptomyxid ameba, in an apparently healthy 14-year-old Venezuelan boy. This case was characterized by sudden onset of seizures, focal neurologic signs and by a prolonged clinical course (from November 1992 to March 1993). Neuroimaging studies showed cerebral hypodense lesions in cerebral hemispheres, brain stem and cerebellum. Microscopically, we found a chronic granulomatous inflammatory reaction with necrotizing angiitis, large numbers of amebic trophozoites and few cysts in perivascular spaces and within necrotic CNS tissue. The amebas were identified as B. mandrillaris based on their immunofluorescence reactivity with the anti-B. mandrillaris serum. So far, 30 cases of GAE due to B. mandrillaris have been recognized in humans, two in AIDS patients. No visceral involvement by free-living amebas or any other significant abnormality was observed. This patient developed “spontaneous” GAE, but it remains possible that an undiagnosed abnormality in cell-mediated immunity or a deficient humoral immune response may explain the susceptibility of this patient to this opportunistic infection.

The neuropathology of intestinal failure and small bowel transplantation

Abstract The aim of this study was to elucidate the neuropathological substrate of intestinal failure before and after small bowel transplantation (SBT). Retrospective analysis of complete autopsy or brain biopsy specimens of 17 patients with intestinal failure (12 children and 5 adults) were studied. Patients were divided into two groups. Group I (transplanted group; n = 13) included those patients who underwent intestinal transplantation under tacrolimus and steroids immunosuppressive therapy. Group II (control group) included 4 children with intestinal failure who were candidates for SBT and died while awaiting an intestinal allograft. Central nervous system (CNS) abnormalities were seen in 92% of the SBT recipients and in 100% of SBT candidates. The neuropathological lesions of SBT recipients included: (a) vascular lesions: global brain ischemia, infarcts, intracranial hemorrhage and edema (7 children/2 adults; 69%); (b) cerebral atrophy (6 children; 46%); (c) Alzheimer type II gliosis (5 children/4 adults; 69%); (d) infection (3 patients; 23%) due to cytomegalovirus (1 child), Aspergillus fumigatus (1 adult) and progressive multifocal leukoencephalopathy (PML)-like (1 adult); (e) Epstein-Barr virus-related cerebral post-transplant lymphoproliferative disorder (2 children; 15%); and (f) central pontine and extrapontine myelinolysis (1 child; 7.5%). The neuropathological lesions of SBT candidates were Alzheimer type II astrocytosis (4 patients), vascular changes (4 patients), brain atrophy (4 patients) and cerebral candidiasis (1 patient). CNS vascular, metabolic and infectious pathology are significant causes of morbidity and mortality in patients suffering intestinal failure, both before and after SBT. Brain atrophy was a frequent finding and may be related to nutritional and developmental inadequacy of long-term total parenteral nutrition.

Balamuthia mandrillaris: its pathogenic potential.

In 1958, Clyde G. Culbertson predicted the occurrence in humans of infection by free-living amebas (6). A few years later, Rodney F. Carter and Malcolm Fowler, in Adelaide, Australia, reported the first human cases of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri [2, 91. Since then, hundreds of cases of infection caused by Acanthamoeba spp. and Naegleria fowleri have been published all over the world [20]. During the last 10 years, another opportunistic ameba, B. mandrillaris has been added to the list of pathogenic, opportunistic free-living amebas [ I , 3-5, 7, 8, 10-12, 15-27,

Naegleria australiensis ssp. italica: Experimental study in mice

A subspecies of Naegleria australiensis, N. australiensis italica, pathogenic for mice, was recently isolated and identified from an Italian thermal spa. We describe the histopathological changes of the central nervous system with experimental infection of albino mice. The histopathological patterns are intermediate to those seen with infection caused by N. fowleri and N. australiensis or Acanthamoeba spp. An acute inflammatory reaction was present within the choroid plexus, ependyma, midbrain, cerebellum, and basal ganglia. Occasional single amebic trophozoites were found within some microabscesses. Cysts were not identified. Involvement of the olfactory neuroepithelium and of the nasal mucosa was not detected.