Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum) is a gram-negative bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis

Anaplasmosis

Anaplasmosis is a disease caused by a rickettsial parasite of ruminants, Anaplasma spp. The organism occurs in the white blood cells and is transmitted by natural means through a number of haematophagous species of ticks...

 in sheep and cattle, also known as Tick-Borne Fever and Pasture Fever, and also causes the zoonotic disease Human granulocytic anaplasmosis

Human granulocytic anaplasmosis

Human granulocytic anaplasmosis is an infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium that is typically transmitted to humans by at least three kinds of ticks, including Ixodes scapularis, Ixodes pacificus, and Dermacentor variabilis...

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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 can be determined that it has a unique adaptation and pathogenetic mechanism.

Biology

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

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, there has been an increase in this disease and it is now recognized in Europe. This disease was first identified due to a Wisconsin patient who died with a severe febrile illness 2 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.

Clinical signs in animals

The disease is multisystemic but the most severe changes are an anaemia and a leucopaenia. Animals will show lethargy, weight loss and appear to waste away.

Bacterial Mechanism

Anaplasma phagocytophilum binds to 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 bacteria 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. Anaplasma phagocytophilum then divides until cell lysis or when the bacteria leaves to infect other cells.

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. 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 bacterium dissemination into the neutrophil.

Laboratory Diagnosis

There are three tests that can be performed to determine an Anaplasma phagocytophilum infection. They are :

1. Indirect Immunofluorescence Assay (IFA) which is the principal test used to detect HA 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 (PCR) assays is used to detect A. phagocytophilum DNA.

Antibiotic Therapy

Patients suffering from Human Granulocytic Anaplasmosis (HA) 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 these patients infected with the bacteria. Some other tetracycline drugs are also effective. In general patients with symptoms of HA 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.

In animals, antibiotics such as oxytetracycline

Oxytetracycline

Oxytetracycline was the second of the broad-spectrum tetracycline group of antibiotics to be discovered.Oxytetracycline works by interfering with the ability of bacteria to produce proteins that are essential to them. Without these proteins the bacteria cannot grow, multiply and increase in numbers...

, sulphamethazine, sulphadimidine, doxycycline

Doxycycline

Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

and trimethoprim-sulphonamides have been used.

External links

• Anaplasma phagocytophilum HZ Genome Page
• Walid MS, Ajjan M, Patel N: "Borreliosis And Human Granulocytic Anaplasmosis Coinfection With Positive Rheumatoid Factor And Monospot Test: Case-Report". The Internet Journal of Infectious Diseases. 2007; Volume 6, Number 1.
• "Nosocomial Transmission of Human Granulocytic Anaplasmosis in China". JAMA. 2008;300(19):2263–2270.