GENERAL CHARACTERISTICS
Balamuthia mandrillaris is uncommon and was thought to be a harmless soil organism, with no relevance for infecting mammals. However, since the appearance of B. mandrillaris was first seen at the San Diego Wild Animal Park in a gibbon that died of meningoencephalitis, a number of primates, as well as dogs, sheep, and horses, have died of CNS infection caused by this organism. Approximately 100 cases of human amebic encephalitis worldwide have been identified with about half of the cases diagnosed within the United States. Death can occur from a week to several months after the onset of symptoms. Patients eventually die with a massive CNS infection. Genotyping studies indicate that lethal infections caused by B. mandrillaris are due to a single species with a global distribution.
The life cycle is similar to that of Acanthamoeba spp.; like Acanthamoeba spp., Balamuthia does not have a flagellated stage in the life cycle. Both trophozoites and cysts are found in CNS tissue, and their sizes are similar to those of Acanthamoeba trophozoites and cysts. It is difficult to differentiate Balamuthia from Acanthamoeba spp. in tissue sections under a light microscope. Using electron microscopy, the cysts are characterized by having three layers in the cyst wall: an outer wrinkled ectocyst, a middle structure–less mesocyst, and an inner thin endocyst. Under light microscopy, they appear to have two walls: an outer irregular wall and an inner round wall. In some cases, Balamuthia trophozoites in tissue sections appear to have more than one nucleolus in the nucleus. In such cases, it may be possible to distinguish Balamuthia amebae from Acanthamoeba organisms on the basis of nuclear morphology, because Acanthamoeba trophozoites have only one nucleolus.
PATHOGENESIS AND SPECTRUM OF DISEASE
The disease is very similar to GAE caused by Acanthamoeba spp. The clinical presentation is subacute or chronic and is usually not associated with swimming in fresh water. No characteristic clinical symptoms, laboratory findings, or radiologic indicators have been found to be diagnostic for GAE. Whether single or multiple, the lesions in the brain involve mainly the cerebral cortex and subcortical white matter. Symptoms include head ache, nausea, vomiting, fever, visual disturbances, dysphagia, seizures, and hemiparesis. The clinical course ranges from a few days to several months. In immunocompetent hosts, an inflammatory response occurs; however, with rare exceptions, these patients also tend to die with severe CNS disease.
LABORATORY DIAGNOSIS
B. mandrillaris does not grow well on E. coli–seeded non nutrient agar plates. However, these organisms can be cultured in mammalian cell cultures using monkey kidney cells and MRC, HEp-2, and diploid macrophage cell lines. Using human brain microvascular endothelial cells, B. mandrillaris has been cultured postmortem from brain and CSF from a case of granulomatous amebic meningoencephalitis. A cell-free growth medium is also commercially available. Although serum antibodies have been identified in infections, laboratory testing is not routinely available.
THERAPY
In vitro studies indicate that B. mandrillaris is susceptible to pentamidine isethiocyanate and that patients may benefit from this treatment. Other studies indicate that ketoconazole, propamidine isethionate, clotrimazole, and certain biguanides have amebicidal activity.
