Balamuthia mandrillaris
Encyclopedia
Balamuthia mandrillaris is a free-living leptomyxid amoeba
Leptomyxida
Leptomyxida is an order of Amoebozoa.It includes species such as Flabellula citata, Paraflabellula hoguae, Paraflabellula reniformis, Rhizamoeba saxonica and Leptomyxa reticulata....

 which is known to cause amoebiasis
Amoebiasis
Entamebiasis is a term for the infection more commonly known as amoebiasis.It became the preferred term in MeSH in 1991, but the term amoebiasis is used by the World Health Organization and by those working in the field of amoebiasis research....

 in humans, especially the deadly neurological condition known as granulomatous amoebic encephalitis
Granulomatous amoebic encephalitis
Granulomatous amoebic encephalitis is a central nervous system disease caused by certain species, especially species of Acanthamoeba and Balamuthia mandrillaris.The term is most commonly used with Acanthamoeba...

 (GAE). 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 for his contributions to the studies of parasitic and free-living amoebas.

Morphology

Balamuthia mandrillaris is a free-living, heterotroph
Heterotroph
A heterotroph is an organism that cannot fix carbon and uses organic carbon for growth. This contrasts with autotrophs, such as plants and algae, which can use energy from sunlight or inorganic compounds to produce organic compounds such as carbohydrates, fats, and proteins from inorganic carbon...

ic amoeba, consisting of a standard complement of organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....

s surrounded by a three-layered cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...

, and with an abnormally large, vesicular
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

. 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

Balamuthias life cycle 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
Brain biopsy
Brain biopsy is the removal of a small piece of brain tissue for the diagnosis of abnormalities of the brain. It is used to diagnose Alzheimer's disease, tumors, infection, inflammation, and other brain disorders....

 performed on infected individuals.

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
Granulomatous amoebic encephalitis
Granulomatous amoebic encephalitis is a central nervous system disease caused by certain species, especially species of Acanthamoeba and Balamuthia mandrillaris.The term is most commonly used with Acanthamoeba...

, 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
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

 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
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...

. Balamuthia lesions on the face may also lead to amoebic keratitis
Keratitis
Keratitis is a condition in which the eye's cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves impaired eyesight.-Types:...

, and usually results in facial swelling.

Balamuthia encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...

 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 failed to 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
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...

 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
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

.

Treatment

Balamuthia infection has only been successfully treated in two cases. Both were treated with a cocktail of antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s 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.

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 years old young woman and a 27 years old young 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-56 years male and 24 years male, both succumbed to encephalitis within a span of 40 days from transplantation. Other two were placed on preemptive therapy after the first two were reported and remain unaffected.

Other pathogenic amoebas

  • Acanthamoeba
    Acanthamoeba
    Acanthamoeba is a genus of amoebae, one of the most common protozoa in soil, and also frequently found in fresh water and other habitats. The cells are small, usually 15 to 35 μm in length and oval to triangular in shape when moving. The pseudopods form a clear hemispherical lobe at the anterior,...

     spp.
  • Naegleria fowleri
    Naegleria fowleri
    Naegleria fowleri is a free-living excavate form of protist typically found in warm bodies of fresh water, such as ponds, lakes, rivers, and hot springs. It is also found in soil, near warm-water discharges of industrial plants, and unchlorinated swimming pools in an amoeboid or temporary...


External links

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