Balamuthia mandrillaris is a free-living amoeba that, like some related amoebae in the genus Acanthamoeba (which it resembles in tissue sections examined by light microscopy), can cause granulomatous amebic encephalitis (GAE), also known as balamuthia amoebic encephalitis (BAE), in individuals with compromised immune systems. Balamuthia mandrillaris has only recently been isolated from the environment and has also been isolated from autopsy specimens of infected humans and animals. It was first discovered in 1986 from the brain necropsy of a mandrill baboon (Papio sphinx) that died of a neurological disease at the San Diego Zoo Wild Animal Park, CA, U.S.A . (Siddiqui and Khan 2008).
The B. mandrillaris life cycle has only two stages, a dormant cyst stage and an actively feeding and dividing trophozoite stage (B. mandrillaris has no flagellated stage). The trophozoites replicate by mitosis (the nuclear membrane does not remain intact). Although the trophozoites are the infective stage, both cysts and trophozoites gain entry into the body through various means. Entry can occur through the nasal passages to the lower respiratory tract or via ulcerated or broken skin. When B. mandrillaris enters the respiratory system or through the skin, it can invade the central nervous system by hematogenous dissemination, causing granulomatous amebic encephalitis (GAE) or disseminated disease, or skin lesions, in individuals who are immune competent as well as those with compromised immune systems. Balamuthia mandrillaris cysts and trophozoites are found in tissue. (Centers for Disease Control Parasites and Health website)
Among the many genera of free-living amoebae that exist in nature, members of only four genera have a known association with human disease: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. Balamuthia mandrillaris are soil amoebae. In vitro, B. mandrillaris can feed on small amoebae (Acanthamoeba and Naegleria) and they may do so in nature. To date, B.mandrillaris is the only known species in the genus Balamuthia and it causes GAE in both humans and other animals. Balamuthiasis is similar to GAE caused by Acanthamoeba, and occurs in immunocompromised hosts, including HIV/AIDS patients and intravenous drug users; it has also been reported from immunocompetent individuals, especially young children and older individuals. The disease has a chronic, subacutephase that develops over a period of time spanning from 2 weeks to 2 years. Balamuthia mandrillaris is also known to cause a skin infection similar to that caused by Acanthamoeba. (Visvesvara et al. 2007).
Balamuthia mandrillaris infection of the skin and central nervous system has been reported with increasing frequency in recent years and this has been described as an emerging disease especially affecting people of Hispanic origin, although it remains unclear whether this is due to genetic susceptibility or occupational exposure (Matin et al. 2008; Siddiqui and Khan 2008; Bravo et al. 2011). Bravo et al. (2011) note that recognition of the skin lesion and early diagnosis can lead to successful intervention to combat this otherwise fatal infection. Although this amoeba has a worldwide distribution, its prevalence is higher in South America. Bravo et al. review diagnostic methods (including those based on molecular biology) and the different therapeutic strategies that have resulted in survival of patients. They note that a recent report dealing with organ transplant transmission of this infection has made it a subject of interest in transplant medicine.
BAE is a serious human disease with fatal consequences and a mortality rate of more than 95% even with available treatments. Unlike Acanthamoeba, Balamuthia can produce encephalitis in relatively immunocompetent individuals, almost always resulting in death. Since its identification in1986 and the first human cases, more than 100 cases of BAE have been reported and the actual number of BAE infections is likely far higher. BAE cases have been reported worldwide. The majority of BAE patients exhibit characteristic skin lesions. Siddiqui and Khan compare the epidemiology and clinical features of infection with B. mandrillaris versus Naegleria fowleri. (Siddiqui and Khan 2008)
Like other free-living amoebae, such as Acanthamoeba, Naegleria, and Hartmannella, B. mandrillaris can act as a host for intracellular survival of bacteria, including the causative agent of Legionnaires’ disease, Legionella pneumophila. The ability of amoebae to host bacteria enhances bacterial infectivity for mammalian cells, increases their transmission to susceptible hosts, and may enhance the pathogenicity of the host amoeba. (Matin et al. 2008)
Balamuthia mandrillaris is a free-living amoeba that is known to cause a type of amoebiasis in humans, especially the deadly neurological condition known as granulomatous amoebic encephalitis (GAE). B. mandrillaris is found in the environment 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 not been definitively isolated in nature, but 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 Balamuthia genus is named in honor of the late Professor William Balamuth (1914-1981) for his contributions to the studies of parasitic and free-living amoebas.
Balamuthia 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, vesicular nucleus. On average, a Balamuthia trophozoite is approximately 30–120 µm in diameter. The cysts fall approximately in this range as well.
Balamuthia's life cycle, like 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 binucleate 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.[dead link]
Balamuthia mandrillaris may enter the body through the lower respiratory tract or through open wounds. Upon introduction, the amoebas may form a skin lesion, or migrate to the brain. Once in the brain, Balamuthia causes a condition known as granulomatous amoebic encephalitis, which is usually fatal. The symptoms of infection by Balamuthia are unclear, as only a few definitive cases of Balamuthia infection have been described thus far. Balamuthia-induced GAE can cause focal paralysis, seizures, and brainstem symptoms such as facial paralysis, difficulty swallowing, and double vision.
Balamuthia is also known to cause a variety of non-neurological symptoms, and often causes skin lesions, through which the amoeba may enter the bloodstream and migrate to the brain. Many patients experiencing this particular syndrome report a skin lesion (sometimes similar to those caused by Staphylococcus aureus or other bacteria), which does not respond well to dermatologic treatment. The lesion is usually localised and very slow to heal, or fails to heal altogether. In some presentations, the lesion may be mistaken for certain forms of skin cancer. Balamuthia lesions on the face may also lead to amoebic keratitis, and usually results in facial swelling.
Culturing and identification
Balamuthia is most easily identifiable in a brain biopsy performed on an individual suffering from Balamuthia meningoencephalitis. The amoeba cannot be cultured on an agar plate coated with gram-negative bacteria because unlike most amoeba, Balamuthia mandrillaris does not feed on bacteria. Instead the amoeba must be cultured on primate hepatic cells or human brain microvascular endothelial cells, or HBMECs, 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 antiparasitics, although it is unclear if any or all of these medications played a part in treatment. 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 five-year-old girl and a 64 year old man, developed encephalitis caused by the free living B. mandrilaris. After diagnosed, they were given effective antimicrobial therapy. Both patients recovered.
According to a MMWR report published in September 2010, 2 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 preemptive therapy and remain unaffected. A second cluster of transplant transmitted balamuthia in Arizona was reported in the same weekly report. There were four recipients 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 preemptive therapy after the first two were reported and remain unaffected.
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