Anaplasma phagocytophilum

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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 Red Pencil Icon.png
Missing taxonomy template ( fix ): Anaplasma
Species:
Template:Taxonomy/Anaplasma A. phagocytophilum
Binomial name
Template:Taxonomy/Anaplasma Anaplasma phagocytophilum
(Foggie 1949) Dumler et al. 2001 [1]
Synonyms

Rickettsia phagocytophila ovis
Rickettsia phagocytophila
Cytoecetes phagocytophila
Cytoecetes phagocytophila

Contents

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]

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]

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. [4]

Hosts

Hosts include goat, cattle, horse and dog. Cattle infections had been suspected but were only first confirmed by Nieder et al. 2012. [5]

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]

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]

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]

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. [6]

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. [7]
Doxycycline Doxycycline 100mg capsules.jpg
Doxycycline

Antibiotic therapy

Patients with 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. [7]

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

Related Research Articles

Ehrlichiosis is a tick-borne disease of dogs usually caused by the rickettsial agent 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. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide.

<i>Dermacentor variabilis</i> Species of tick

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. It may take several days for the host to experience 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.

<span class="mw-page-title-main">Anaplasmosis</span> Medical condition

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 processes. Anaplasmosis can also be referred to as "yellow bag" or "yellow fever" because the infected animal can develop a jaundiced look. Other signs of infection include weight loss, diarrhea, paleness of the skin, aggressive behavior, and high fever.

<span class="mw-page-title-main">Ehrlichiosis</span> Medical condition

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.

<i>Anaplasma</i> Genus of bacteria

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

<i>Ehrlichia</i> Genus of bacteria

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> Species of tick

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 was also named Ixodes dammini until it was shown to be the same species in 1993. It is a hard-bodied tick found in the eastern and northern Midwest of the United States as well as in 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.

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.

<i>Ehrlichia ewingii</i> Species of bacterium

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.

<span class="mw-page-title-main">Human granulocytic anaplasmosis</span> Medical condition

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.

<span class="mw-page-title-main">Human monocytotropic ehrlichiosis</span> Medical condition

Human monocytotropic ehrlichiosis 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).

<span class="mw-page-title-main">African tick bite fever</span> Medical condition

African tick bite fever (ATBF) is a bacterial infection spread by the bite of a tick. Symptoms may include fever, headache, muscle pain, and a rash. At the site of the bite there is typically a red skin sore with a dark center. The onset of symptoms usually occurs 4–10 days after the bite. Complications are rare but 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, Africa and recently in the Kimberley region of Australia. 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.

Borrelia miyamotoi is a bacterium of the spirochete phylum in the genus Borrelia. A zoonotic organism, B. miyamotoi can infect humans through the bite of several species of hard-shell Ixodes ticks, the same kind of ticks that spread B. burgdorferi, the causative bacterium of Lyme disease. Ixodes ticks are also the primary vector in the spread of babesiosis and anaplasmosis.

Anaplasma bovis is gram negative, obligate intracellular organism, which can be found in wild and domestic ruminants, and potentially a wide variety of other species. It is one of the last species of the Family Anaplasmaceae to be formally described. It preferentially infects host monocytes, and is often diagnosed via blood smears, PCR, and ELISA. A. bovis is not currently considered zoonotic, and does not frequently cause serious clinical disease in its host. This organism is transmitted by tick vectors, so tick bite prevention is the mainstay of A. bovis control, although clinical infections can be treated with tetracyclines. This organism has a global distribution, with infections noted in many areas, including Korea, Japan, Europe, Brazil, Africa, and North America.

Neoehrlichia mikurensis (NM), previously known as Candidatus Neoehrlichia mikurensis, is an intracellular, gram-negative bacteria belonging to the family Anaplasmataceae. Using ticks as vectors, it spreads between animals - mainly rodents, but other mammals as well as humans can get infected. After Borrelia and Rickettsia, it is believed to be the third most common tick-borne pathogen able to infect humans. Between 2009 and 2019, 45 human cases of NM-infections were found in Sweden.

References

  1. ↑ Page Anaplasma on lpsn.dsmz.de
  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. ↑ Brown, Wendy C.; Barbet, Anthony F. (2016-02-15). "Persistent Infections and Immunity in Ruminants to Arthropod-Borne Bacteria in the Family Anaplasmataceae". Annual Review of Animal Biosciences . Annual Reviews. 4 (1): 177–197. doi:10.1146/annurev-animal-022513-114206. ISSN   2165-8102. PMID   26734888.
  6. ↑ 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. S2CID   20043230.
  7. 1 2 "Human Anaplasmosis Information for Health Professionals: Diagnostic tests". Diseases. Minnesota Department of Health. Archived from the original on 2019-02-13. Retrieved 2011-04-27.
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