Anaplasma phagocytophilum

Last updated

Anaplasma phagocytophilum
Anaplasma phagocytophilum cultured in human promyelocytic cell line HL-60.jpg
Human HL60 cells containing Anaplasma phagocytophilum (indicated by arrows) which are basophilic intracytoplasmic inclusions when stained with Wright-Giemsa stain
Scientific classification
A. phagocytophilum
Binomial name
Anaplasma phagocytophilum
(Foggie 1949) Dumler et al. 2001 [1]

Rickettsia phagocytophila ovis
Rickettsia phagocytophila
Cytoecetes phagocytophila
Cytoecetes phagocytophila


Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum) [2] is a Gram-negative bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis. [3]

Anaplasmosis disease, mostly animal, caused by bacteria of the genus Anaplasma

Anaplasmosis is a disease caused by a rickettsial parasite of ruminants, Anaplasma spp and is therefore related to rickettsial disease. The microorganisms are Gram-negative, and infect red blood cells. They are transmitted by natural means through a number of haematophagous species of ticks. The Ixodes tick that commonly transmits Lyme disease also spreads anaplasmosis.

Human granulocytic anaplasmosis human disease

Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium that is typically transmitted to humans by ticks of the Ixodes ricinus species complex, including Ixodes scapularis and Ixodes pacificus in North America. These ticks also transmit Lyme disease and other tick-borne diseases.

A. phagocytophilum is a Gram-negative, obligate 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. [4]


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. [4]


An endosome is a membrane-bound compartment inside a eukaryotic cell. It is an organelle of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane, in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature.

Role in human disease

A. phagocytophilum causes human granulocytic anaplasmosis (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. [4]

Thrombocytopenia A blood platelet disease characterized by a low platelet count in the blood.

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood.

Clinical signs in animals

The disease is multisystemic, but the most severe changes are anaemia and leukopenia. This organism causes lameness, which can be confused with symptoms of Lyme disease, another tick-borne illness. It is a vector-borne zoonotic disease whose morula can be visualized within neutrophils (a type of white blood cell) from the peripheral blood and synovial fluid. It can cause lethargy, ataxia, loss of appetite, and weak or painful limbs. [3]

Leukopenia is a decrease in the number of leukocytes. Found in the blood, they are the white blood cells, and are the body's primary defense against infection. Thus leukopenia places individuals at increased risk of infection.

Lyme disease Infectious disease caused by Borrelia bacteria, spread by ticks

Lyme disease, also known as Lyme borreliosis, is an infectious disease caused by a bacterium named Borrelia spread by ticks. The most common sign of infection is an expanding area of redness on the skin, known as erythema migrans, that appears at the site of the tick bite about a week after it occurred. The rash is typically neither itchy nor painful. Approximately 70–80% of infected people develop a rash. Other early symptoms may include fever, headache and tiredness. If untreated, symptoms may include loss of the ability to move one or both sides of the face, joint pains, severe headaches with neck stiffness, or heart palpitations, among others. Months to years later, repeated episodes of joint pain and swelling may occur. Occasionally, people develop shooting pains or tingling in their arms and legs. Despite appropriate treatment, about 10 to 20% of people develop joint pains, memory problems, and tiredness for at least six months.


Neutrophils are the most abundant type of granulocytes and the most abundant type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.

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 lysosomes. A. phagocytophilum then divides until cell lysis or when the bacteria leave to infect other cells. [4]

P-selectin glycoprotein ligand-1 protein-coding gene in the species Homo sapiens

Selectin P ligand, also known as SELPLG or CD162, is a human gene.

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 produced by neutrophil phagocyte oxidase assembly. It also disrupts normal neutrophil function, such as endothelial cell adhesion, transmigration, motility, degranulation, respiratory burst, and phagocytosis. [4] 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. [5]

Laboratory diagnosis

These tests can be performed to determine an A. phagocytophilum infection:

  1. 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.
  2. Intracellular Inclusions (morulae) are visualized in granulocytes on Wright- or Giemsa- stained blood smears.
  3. Polymerase chain reaction assays are used to detect A. phagocytophilum DNA. [6]
Doxycycline Doxycycline 100mg capsules.jpg

Antibiotic therapy

Patients suffering from HGA undergo doxycycline 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 and/or thrombocytopenia. [6]

In animals, antibiotics such as oxytetracycline, sulphamethazine, sulphadimidine, doxycycline, and trimethoprim-sulphonamides have been used. [3]

Related Research Articles

Ehrlichiosis (; also known as canine rickettsiosis, canine hemorrhagic fever, canine typhus, tracker dog disease, and tropical canine pancytopenia is a tick-borne disease of dogs usually caused by the organism Ehrlichia canis. Ehrlichia canis is the pathogen of animals. Humans can become infected by E. canis and other species after tick exposure. German Shepherd Dogs are thought to be susceptible to a particularly severe form of the disease, other breeds generally have milder clinical signs. Cats can also be infected.

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. Tick-borne illnesses are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. Because individual ticks can harbor more than one disease-causing agent, patients can be infected with more than one pathogen at the same time, compounding the difficulty in diagnosis and treatment. As of 2016, 16 tick-borne diseases of humans are known.

Meningoencephalitis central nervous system disease that involves encephalitis which occurs along with meningitis

Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.

<i>Dermacentor variabilis</i> species of arachnid

Dermacentor variabilis, also known as the American dog tick or wood tick, is a species of tick that is known to carry bacteria responsible for several diseases in humans, including Rocky Mountain spotted fever and tularemia. It is one of the best-known hard ticks. Diseases are spread when it sucks blood from the host, which could take several days for the host to experience some symptoms.

A canine vector-borne disease (CVBD) is one of "a group of globally distributed and rapidly spreading illnesses that are caused by a range of pathogens transmitted by arthropods including ticks, fleas, mosquitoes and phlebotomine sandflies." CVBDs are important in the fields of veterinary medicine, animal welfare, and public health. Some CVBDs are of zoonotic concern.

Ehrlichiosis is a tick-borne bacterial infection, caused by bacteria of the family Anaplasmataceae, genera Ehrlichia and Anaplasma. These obligate intracellular bacteria infect and kill white blood cells.

Anaplasma is a genus of bacteria of the alphaproteobacterial order Rickettsiales, family Anaplasmataceae.

Ehrlichia is a genus of Rickettsiales bacteria that are transmitted to vertebrates by ticks. These bacteria cause the disease ehrlichiosis, which is considered zoonotic, because the main reservoirs for the disease are animals.

<i>Ixodes scapularis</i> parasit ixodes scapularis

Ixodes scapularis is commonly known as the deer tick or black-legged tick, and in some parts of the US as the bear tick. It is a hard-bodied tick of the eastern and northern Midwestern United States and southeastern Canada. It is a vector for several diseases of animals, including humans and is known as the deer tick owing to its habit of parasitizing the white-tailed deer. It is also known to parasitize mice, lizards, migratory birds, etc. especially while the tick is in the larval or nymphal stage.

Heartwater is a tick-borne rickettsial disease of domestic and wild ruminants. It is caused by Ehrlichia ruminantium - an intracellular Gram-negative coccal bacterium. The disease is spread by bont ticks, which are members of the genus Amblyomma. Affected mammals include cattle, sheep, goats, antelope, and buffalo, but the disease has the biggest economic impact on cattle production in affected areas. The disease's name is derived from the fact that fluid can collect around the heart or in the lungs of infected animals.

Ehrlichia chaffeensis is an obligate intracellular, Gram-negative species of Rickettsiales bacteria. It is a zoonotic pathogen transmitted to humans by the lone star tick. It is the causative agent of human monocytic ehrlichiosis.

Ehrlichia ewingii is a species of rickettsiales bacteria. It has recently been associated with human infection, and can be detected via PCR serological testing. The name Ehrlichia ewingii was proposed in 1992.

Human monocytotropic ehrlichiosis

Human monocytotropic ehrlichiosis (HME) is a form of ehrlichiosis associated with Ehrlichia chaffeensis. This bacterium is an obligate intracellular pathogen affecting monocytes and macrophages.

Ehrlichiosis ewingii infection is an infectious disease caused by an intracellular bacteria, Ehrlichia ewingii. The infection is transmitted to humans by the tick, Amblyomma americanum. This tick can also transmit Ehrlichia chaffeensis, the bacteria that causes human monocytic ehrlichiosis (HME).

African tick bite fever

African tick bite fever (ATBF) is a bacterial infection spread by the bite of a tick. Symptoms may include fever, headache, muscles pains, and a rash. At the site of the bite there is typically a red skin sore with a dark center. Onset usually occur 4–10 days after the bite. Complications are rare, however may include joint inflammation. Some people do not develop symptoms.

Ehrlichia canis is an obligate intracellular bacterium that acts as the causative agent of ehrlichiosis, a disease most commonly affecting canine species. This pathogen is present throughout the United States, South America, Asia, and Africa. First defined in 1935, E. canis emerged in the United States in 1963 and its presence has since been found in all 48 contiguous United States. Reported primarily in dogs, E. canis has also been documented in felines and humans, where it is transferred most commonly via Rhipicephalus sanguineus, the brown dog tick.

Ehrlichia Wisconsin HM543746 is an unnamed tick bacterium that spread through Minnesota and Wisconsin in 2009 and is similar to Ehrlichia muris.

The Heartland virus (HRTV) is a tick-borne phlebovirus of the Bhanja virus serocomplex discovered in 2009. The Lone Star Tick transmits the virus to people when feeding on blood. As of 2017, only five Midwestern United States have reported 20 human infections, namely Arkansas, Indiana, Missouri, Oklahoma, and Tennessee; symptoms resemble those of two other tick-borne infections ehrlichiosis and anaplasmosis. The reservoir host is unknown, but deer, raccoon, coyotes, and moose in 13 different states have antibody titers against the virus.


  1. Page Anaplasma on
  2. Dumler JS, Barbet AF, Bekker CP, et al. (2001). "Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila". Int. J. Syst. Evol. Microbiol. 51 (Pt 6): 2145–65. doi:10.1099/00207713-51-6-2145. PMID   11760958.
  3. 1 2 3 Tick-Borne Fever reviewed and published by WikiVet, accessed 12 October 2011.
  4. 1 2 3 4 5 Dumler JS, Choi KS, Garcia-Garcia JC, et al. (December 2005). "Human granulocytic anaplasmosis and Anaplasma phagocytophilum". Emerging Infect. Dis. 11 (12): 1828–34. doi:10.3201/eid1112.050898. PMC   3367650 . PMID   16485466.
  5. Thomas V, Fikrig E (July 2007). "Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection". Cell. Microbiol. 9 (7): 1730–7. doi:10.1111/j.1462-5822.2007.00908.x. PMID   17346310.
  6. 1 2 "Human Anaplasmosis Information for Health Professionals: Diagnostic tests". Diseases. Minnesota Department of Health.