Anaplasma Phagocytophilum
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''Anaplasma phagocytophilum'' (formerly ''Ehrlichia phagocytophilum'') is a
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
bacterium that is unusual in its tropism to neutrophils. It causes
anaplasmosis Anaplasmosis is a tick-borne disease affecting ruminants, dogs, and horses, and is caused by ''Anaplasma'' bacteria. Anaplasmosis is an infectious but not contagious disease. Anaplasmosis can be transmitted through mechanical and biological vector ...
in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis.Tick-Borne Fever
reviewed and published by WikiVet, accessed 12 October 2011.
''A. phagocytophilum'' is a Gram-negative,
obligate {{wiktionary, obligate As an adjective, obligate means "by necessity" (antonym '' facultative'') and is used mainly in biology in phrases such as: * Obligate aerobe, an organism that cannot survive without oxygen * Obligate anaerobe, an organism ...
bacterium of neutrophils. It causes human granulocytic anaplasmosis, which is a tick-borne rickettsial disease. Because this bacterium invades neutrophils, it has a unique adaptation and pathogenetic mechanism.


Biology

''A. phagocytophilum'' is a small, obligate, intracellular bacterium with a Gram-negative cell wall. It is 0.2–1.0 μm and lacks a lipopolysaccharide biosynthetic machinery. The bacterium first resides in an early endosome, where it acquires nutrients for binary fission and grows into small groups called morulae. This bacterium prefers to grow within myeloid or granulocytic cells.


Hosts

Hosts include
goats The goat or domestic goat (''Capra hircus'') is a species of goat-antelope that is mostly kept as livestock. It was domesticated from the wild goat (''C. aegagrus'') of Southwest Asia and Eastern Europe. The goat is a member of the famil ...
,
cattle Cattle (''Bos taurus'') are large, domesticated, bovid ungulates widely kept as livestock. They are prominent modern members of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Mature female cattle are calle ...
,
horses The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 milli ...
and dogs. Cattle infections had been suspected but were only first confirmed by Nieder et al. 2012.


Role in human disease

''A. phagocytophilum'' causes human granulocytic
anaplasmosis Anaplasmosis is a tick-borne disease affecting ruminants, dogs, and horses, and is caused by ''Anaplasma'' bacteria. Anaplasmosis is an infectious but not contagious disease. Anaplasmosis can be transmitted through mechanical and biological vector ...
(HGA). This disease was first identified in 1990, although this pathogen was known to cause veterinary disease since 1932. Since 1990, incidence of HGA has increased, and it is now recognized in Europe. This disease was first identified due to a Wisconsin patient who died with a severe febrile illness two weeks after a tick bite. During the last stage of the infection, a group of small bacteria was seen within the neutrophils in the blood. Other symptoms include fever, headache, absence of skin rash, leucopenia, thrombocytopenia, and mild injury to the liver.


Clinical signs in animals

The disease is multisystemic, but the most severe changes are anaemia and
leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...
. This organism causes lameness, which can be confused with symptoms of
Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...
, another tick-borne illness. It is a vector-borne zoonotic disease whose morula can be visualized within
neutrophil Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in differe ...
s (a type of white blood cell) from the peripheral blood and synovial fluid. It can cause
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness, or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overw ...
,
ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
, loss of appetite, and weak or painful limbs.


Bacterial mechanism

''A. phagocytophilum'' binds to fucosylated and sialylated scaffold proteins on neutrophil and granulocyte surfaces. A type IV secretion apparatus is known to help in the transfer of molecules between the bacterium and the host. The most studied ligand is PSGL-1 ( CD162). The bacterium adheres to PSGL-1 (CD162) through the 44-kDa major surface protein-2 (Msp2). After the bacterium enters the cell, the endosome stops maturation and does not accumulate markers of late endosomes or phagolysosomes. Because of this, the vacuole does not become acidified or fused to
lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...
s. ''A. phagocytophilum'' then divides until cell lysis or when the bacteria leave to infect other cells. This bacterium has the ability to affect neutrophils by altering their function. It can survive the first encounter with the host cell by detoxifying
superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
produced by neutrophil phagocyte oxidase assembly. It also disrupts normal neutrophil function, such as endothelial cell adhesion, transmigration, motility, degranulation, respiratory burst, and phagocytosis. It causes an increase in the secretion of IL-8, a chemoattractant that increases the phagocytosis of neutrophils. The purpose of this is to increase bacterial dissemination into the neutrophil.


Laboratory diagnosis

These tests can be performed to determine an ''A. phagocytophilum'' infection: #Indirect immunofluorescence assay is the principal test used to detect infection. The acute and convalescent phase serum samples can be evaluated to look for a four-fold change in antibody titer to ''A. phagocytophilum''. #Intracellular Inclusions (morulae) are visualized in granulocytes on Wright- or Giemsa- stained blood smears. #Polymerase chain reaction assays are used to detect ''A. phagocytophilum'' DNA.


Antibiotic therapy

Patients with HGA undergo
doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
therapy, 100 mg twice daily until the patient's fever subsides for at least 3 days. This drug has been the most beneficial to those patients infected with the bacteria. Some other tetracycline drugs are also effective. In general, patients with symptoms of HGA and unexplained fever after a tick exposure should receive empiric doxycycline therapy while their diagnostic tests are pending, especially if they experience
leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...
and/or thrombocytopenia. In animals, antibiotics such as oxytetracycline, sulphamethazine, sulphadimidine,
doxycycline Doxycycline is a Broad-spectrum antibiotic, broad-spectrum antibiotic of the Tetracycline antibiotics, tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat pneumonia, bacterial p ...
, and trimethoprim- sulphonamides have been used.


References


External links


''Anaplasma'' phagocytophilum HZ Genome Page
* * {{Taxonbar, from=Q292189 Rickettsiales Bacteria described in 1949 Pathogenic bacteria