関: A. phagocytophilum、Ehrlichia equi、Ehrlichia phagocytophila、HGE agent

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/15 17:08:01」(JST)

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Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum)^[1] 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.^[2]

Anaplasma 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.^[3]

Biology

Anaplasma 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.^[3]

Role in human disease

Anaplasma phagocytophilum causes human granulocytic anaplasmosis. This disease was first identified in 1990, although this pathogen was known to cause veterinary disease since 1932. Since 1990, incidence of this disease 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 were seen within the neutrophils in the blood. Other symptoms include fever, headache, absence of skin rash, leucopenia, thromboctytopenia and mild injury to the liver.^[3]

Clinical signs in animals

The disease is multisystemic, but the most severe changes are anaemia and leukopenia. This organiam causes lameness which in often confused with 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. Can cause lethargy, ataxia, inappentance, and weak or painful limbs.^[2]

Bacterial mechanism

Anaplasma 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 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.^[3]

This bacterium has the ability to affect neutrophils by altering the function of the host cell. 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.^[3] 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.^[4]

Laboratory diagnosis

Three 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.^[5]

Doxycycline

Antibiotic therapy

Patients suffering from human granulocytic anaplasmosis (HGA) undergo doxycycline therapy, 100 mg twice daily until the patient’s fever subsides for at least three days. This drug has been the most beneficial to these 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.^[5]

In animals, antibiotics such as oxytetracycline, sulphamethazine, sulphadimidine, doxycycline and trimethoprim-sulphonamides have been used.^[2]

References

^ 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.
^ ^a ^b ^c Tick-Borne Fever reviewed and published by WikiVet, accessed 12 October 2011.
^ ^a ^b ^c ^d ^e 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.
^ 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.
^ ^a ^b "Human Anaplasmosis Information for Health Professionals: Diagnostic tests". Diseases. Minnesota Department of Health.

External links

Anaplasma phagocytophilum HZ Genome Page
Anaplasma phagocytophilum at the US National Library of Medicine Medical Subject Headings (MeSH)
Walid MS, Ajjan M, Patel N (2007). "Borreliosis And Human Granulocytic Anaplasmosis Coinfection With Positive Rheumatoid Factor And Monospot Test: Case-Report". The Internet Journal of Infectious Diseases 6 (1). doi:10.5580/1efc.
Zhang L, Liu Y, Ni D, et al. (November 2008). "Nosocomial transmission of human granulocytic anaplasmosis in China". JAMA 300 (19): 2263–70. doi:10.1001/jama.2008.626. PMID 19017912.

UpToDate Contents

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1. ヒトエーリキア症およびアナプラズマ症 human ehrlichiosis and anaplasmosis
2. エーリキアの生物学 biology of ehrlichiae
3. ライム病の治療 treatment of lyme disease
4. 成人におけるライム病の臨床症状 clinical manifestations of lyme disease in adults
5. 好中球減少症における感染の原因 infectious causes of neutropenia

English Journal

Synanthropic Birds Associated with High Prevalence of Tick-Borne Rickettsiae and with the First Detection of Rickettsia aeschlimannii in Hungary.

Hornok S, Csörgő T, de la Fuente J, Gyuranecz M, Privigyei C, Meli ML, Kreizinger Z, Gönczi E, Fernández de Mera IG, Hofmann-Lehmann R.Source1 Department of Parasitology and Zoology, Faculty of Veterinary Science, Szent István University , Budapest, Hungary .
Vector borne and zoonotic diseases (Larchmont, N.Y.).Vector Borne Zoonotic Dis.2013 Jan 5. [Epub ahead of print]
Abstract The aim of this study was to analyze synanthropic birds as risk factors for introducing ticks and tick-borne pathogens into human settlements, with an emphasis on rickettsiae. Altogether 184 subadult ticks were found on 5846 birds. Tick infestation was most prevalent during the spring. In
PMID 23289394

Lyme disease and human granulocytic anaplasmosis coinfection: impact of case definition on coinfection rates and illness severity.

Horowitz HW, Aguero-Rosenfeld ME, Holmgren D, McKenna D, Schwartz I, Cox ME, Wormser GP.SourceDivision of Infectious Diseases, Department of Medicine.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.Clin Infect Dis.2013 Jan;56(1):93-9. doi: 10.1093/cid/cis852. Epub 2012 Oct 5.
Background. Lyme disease is transmitted by the bite of the Ixodes scapularis tick, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Conflicting data exist on the frequency of coinfection and on whether Lyme-HGA coinfected patients have more sym
PMID 23042964

Anaplasma phagocytophilum Asp14 Is an Invasin That Interacts with Mammalian Host Cells via Its C Terminus To Facilitate Infection.

Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ, Ottens AK, Mastronunzio JE, Truchan HK, Walker NJ, Borjesson DL, Fikrig E, Carlyon JA.SourceDepartments of Microbiology and Immunology.
Infection and immunity.Infect Immun.2013 Jan;81(1):65-79. doi: 10.1128/IAI.00932-12. Epub 2012 Oct 15.
Anaplasma phagocytophilum, a member of the family Anaplasmataceae, is the tick-transmitted obligate intracellular bacterium that causes human granulocytic anaplasmosis. The life cycle of A. phagocytophilum is biphasic, transitioning between the noninfectious reticulate cell (RC) and infectious dense
PMID 23071137

Japanese Journal

Prevalence of Tick Borne Pathogens in Horses from Italy

LAUS Fulvio,VERONESI Fabrizia,PASSAMONTI Fabrizio,PAGGI Emanuele,CERQUETELLA Matteo,HYATT Doreene,TESEI Beniamino,FIORETTI Daniela Piergili
Journal of Veterinary Medical Science, 2013
… In order to investigate the prevalence of tick-borne diseases, equine piroplasmosis, equine granulocytic anaplasmosis and Lyme borreliosis in Central Italy, blood samples from 300 horses were analyzed for the presence of antibodies against Babesia caballi, Theileria equi, Anaplasma phagocytophilum and Borrelia burgdorferi using the IFAT. … phagocytophilum and B. … phagocytophilum, reflecting an unprecedented degree of multiple exposures to TBPs in horses. …
NAID 130003362124

Survey on Tick-Borne Pathogens in Thoroughbred Horses in the Hidaka District, Hokkaido, Japan

YBAÑEZ Adrian Patalinghug,SATO Fumio,NAMBO Yasuo,FUKUI Takashi,MASUZAWA Toshiyuki,OHASHI Norio,MATSUMOTO Kotaro,KISHIMOTO Toshio,INOKUMA Hisashi
Journal of Veterinary Medical Science 75(1), 11-15, 2013
… Using the indirect fluorescent antibody (IFA) method, 3.4, 92.0 and 97.7% of the horses showed antibody titers of ≥80 against Anaplasma phagocytophilum, Rickettsia helvetica, and Borrelia garinii, respectively. … Using PCR, DNAs from the peripheral blood of all horses were found negative with any Anaplasma, Rickettsia and Borrelia spp., while those from Haemaphysalis megaspinosa ticks were found positive for Anaplasma sp. …
NAID 130001879687

Prevalence of Lyme Borrelia in Ixodes persulcatus Ticks from an Area with a Confirmed Case of Lyme Disease

MURASE Yusuke,KONNAI Satoru,GITHAKA Naftaly,HIDANO Arata,TAYLOR Kyle,ITO Takuya,TAKANO Ai,ANDO Shuji,KAWABATA Hiroki,TSUBOTA Toshio,MURATA Shiro,OHASHI Kazuhiko
Journal of Veterinary Medical Science 75(2), 215-218, 2013
… persulcatus ticks were coinfected with Anaplasma phagocytophilum and B. …
NAID 130001879630

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★リンクテーブル★

リンク元	「アナプラズマ・ファゴサイトフィルム」「HGE agent」「A. phagocytophilum」
関連記事	「Anaplasma」「anaplasma phagocytophilum」「phagocytophilum」

「アナプラズマ・ファゴサイトフィルム」

Ehrlichiaceae
Scientific classification
Kingdom:	Bacteria
Phylum:	Proteobacteria
Class:	Alpha Proteobacteria
Order:	Rickettsiales
Family:	Ehrlichiaceae
Genus:	Anaplasma
Species:	A. phagocytophilum
Binomial name
	Anaplasma phagocytophilum;