Visvesvara et al., 1993
Visvesvara et al., 1993
Balamuthia mandrillaris is a free-living amoeba that is known to cause the deadly neurological condition known as granulomatous amoebic encephalitis (GAE). B. mandrillaris is found in the soil and water and was first discovered in 1986 in the brain of a baboon that died in the San Diego Wild Animal Park. B. mandrillaris can infect the body through skin wounds or by inhaling the dust containing Balamuthia. Balamuthia has been isolated in nature. It is believed to be distributed throughout the temperate regions of the world. This is supported somewhat by the presence of antibodies to Balamuthia present in healthy individuals. The genus name Balamuthia was given by Govinda Visvesvara (b. September 28, 1931), in honor of his late mentor, the renowned parasitologist William Balamuth (1914–1981) for his contributions to the studies of parasitic and free-living amoebae. It was in 1993 when Visvesvara isolated and studied the pathogen for the first time.
B. mandrillaris is a free-living, heterotrophic amoeba, consisting of a standard complement of organelles surrounded by a three-layered cell wall, and with an abnormally large cell nucleus. On average, a Balamuthia trophozoite is about 30 to 120 μm in diameter. The cysts fall around this range, as well.
Balamuthia's lifecycle, like the Acanthamoeba, consists of a cystic stage and a trophozoite stage, both of which are infectious, and both of which can be identified as inclusions in the brain tissue on microscopic examination of brain biopsies performed on infected individuals. The trophozoite is pleomorphic and uninucleated, but binucleated forms are occasionally seen. Cysts are also uninucleated, possessing three walls: an outer thin irregular ectocyst, an inner thick endocyst, and a middle amorphous fibrillar mesocyst.
B. mandrillaris is larger than human leukocytes, thus making phagocytosis impossible. Instead, the immune system attempts to contain them at the portal of entry by mounting a type IV hypersensitivity reaction. They may enter the body through the lower respiratory tract or through open wounds. Upon introduction, the amoeba may form a skin lesion, or may migrate to the brain, causing a condition known as granulomatous amoebic encephalitis, (GAE), which is usually fatal. This granulomatous feature is mostly seen in immunocompetent patients; immunocompromised individuals exhibit a "perivascular cuffing". Balamuthia-induced GAE can cause focal paralysis, seizures, and brainstem symptoms such as facial paralysis, difficulty swallowing, and double vision.
Balamuthia may also cause a variety of non-neurological symptoms, including skin lesions, which can progress to GAE. Patients experiencing this particular syndrome may report a skin lesion (often similar to those caused by methicillin-resistant Staphylococcus aureus), which does not respond well to topical antibiotics. The lesion is usually localised and very slow to heal, or fails to heal altogether. In some presentations, the infection may be mistaken for certain forms of skin cancer or leishmaniasis. Balamuthia lesions on the face often cause swelling.
Culturing and identification
Balamuthia is most easily identifiable in a brain biopsy performed on an individual suffering from GAE. The amoeba cannot be cultured on an agar plate coated with E. coli because unlike Naegleria or Acanthamoeba - Balamuthia mandrillaris does not feed on bacteria (at least in laboratory conditions). Instead, Balamuthia must be cultured on primate liver or human brain microvascular endothelial cells (the cells that constitute the blood–brain barrier).
Balamuthia infection has had successful treatments. In two cases, both were treated with a cocktail of antibiotics and antifungal drugs, although if any or all of these medications played a part in treatment is unclear. Both victims suffered permanent neurological deficits as a result of their infection. Another two cases were presented and both of these individuals received successful treatments due to discovering the infection early. Two individuals, a 5-year-old girl and a 64-year-old man, developed GAE. After diagnosis, they were treated with flucytosine, pentamidine, fluconazole, sulfadiazine, a macrolide antibiotic and Phenothiazines. Both patients recovered.
According to a MMWR report published in September 2010, two confirmed cases of Balamuthia transmission occurred through organ transplantation in December 2009 in Mississippi. Two kidney recipients, a 31-year-old woman and a 27-year-old man, suffered from post-transplant encephalitis due to Balamuthia. The woman died in February 2010 and the man survived with partial paralysis of right arm. The CDC was notified by a physician on December 14, 2009, about possible transplant transmission in these two patients. Histopathologic testing of donor and recipient tissues confirmed the transmission. Two other patients who received heart and liver transplants from the same donor, but in different hospitals, were placed on pre-emptive therapy and remain unaffected. A second cluster of transplant-transmitted Balamuthia in Arizona was reported in the same weekly report. Four recipients were identified, two from Arizona (liver and kidney-pancreas), one from California (kidney), and another from Utah (heart). Recipients from Arizona—a 56-year-old male and a 24-year-old male—both succumbed to encephalitis within a span of 40 days from transplantation. The other two were placed on pre-emptive therapy after the first two were reported and remain unaffected.
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- https://www.cdc.gov/balamuthia/index.html for images: Cyst of B. mandrillaris and Trophozoite of B. mandrillaris in culture. Credit: DPDx