Balamuthia mandrillaris

Balamuthia mandrillaris
Scientific classification
Domain:	Eukaryota
Kingdom:	Amoebozoa
Class:	Lobosea
Order:	Acanthopodida
Family:	Balamuthiidae
Genus:	Balamuthia
Species:	B. mandrillaris
Binomial name
Balamuthia mandrillaris

Balamuthia mandrillaris is a free-living leptomyxid amoeba that is known to cause 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.

Morphology

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. GoTo: http://www.cdc.gov/balamuthia/index.html for images: Cyst of B. mandrillaris and Trophozoite of B. mandrillaris in culture. Credit: DPDx

Life cycle

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.

Pathology

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.

Balamuthia encephalitis is an extremely deadly disease, and as of 2008, only seven recoveries had been reported, all with lasting brain damage.

Prevalence

Infection with Balamuthia is extremely rare, and the amoeba is not considered a cause for public health concern, despite its wide geographic range, since only immunocompromised individuals are at a significant risk of contracting Balamuthia meningoencephalitis.

The first case of infection transmitted from an allogeneic transplant was reported in December 2009, when two kidney transplant recipients became infected after each received a kidney from the same infected donor. Two recipients of other organs from the donor did not become infected.

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.

Treatment

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.^{[citation needed]} 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.

In a recently published article (published ahead of print at - Antimicrobial Agent and Chemotherapy-ASM Journals) Mannan et al at Aga Khan university, department of Biological and Biomedical sciences have found already clinically used drugs to have substantial killing effects on both trophozoite and cystic form of this pathogen in an in-vitro study, with more than 95% cidal effects on Acanthamoeba Castellanii T4 keratitis variant. The same group of drugs have shown encouraging effects on Balamuthia mandrillaris and Naegleria Fowleri

Deaths related to Balamuthia mandrillaris

Matt Moore, a firefighter from Murrieta, California, fell ill in November 2007. When a biopsy was done in January 2008, they found his brain had been invaded by Balamuthia mandrillaris. He died on March 10, 2008. According to the California Encephalitis Project report published in the July 18, 2008 Morbidity and Mortality Weekly Report, a total of 10 encephalitis cases were known to have been caused by the amoeba between 1997 and 2007.

Organ transplantation

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.

Other pathogenic amoebas

• Acanthamoeba spp.
• Naegleria fowleri

Related amoebas

• Gephyramoeba spp.

See also

• Balamuthia infection

External links

• Balamuthia — Centers for Disease Control and Prevention
• A summary of Balamuthia,
• Intalapaporn P, Suankratay C, Shuangshoti S, Phantumchinda K, Keelawat S, Wilde H (June 2004). "Balamuthia mandrillaris meningoencephalitis: the first case in southeast Asia". Am. J. Trop. Med. Hyg. 70 (6): 666–9. PMID 15211011. 
• Schuster FL, Dunnebacke TH, Booton GC, et al. (July 2003). "Environmental isolation of Balamuthia mandrillaris associated with a case of amebic encephalitis". J. Clin. Microbiol. 41 (7): 3175–80. doi:10.1128/JCM.41.7.3175-3180.2003. PMC 165348. PMID 12843060. 
• Photomicrographs of Balamuthia and Other Pathogenic Amoebas
• MR and CT Imaging of Balamuthia Mandrillaris from MedPix
• Centers for Disease Control and Prevention (CDC) (July 2008). "Balamuthia amebic encephalitis—California, 1999–2007". MMWR Morb. Mortal. Wkly. Rep. 57 (28): 768–71. PMID 18636064.