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Anaplasma phagocytophilum

Anaplasma phagocytophilum is a bacterium that causes human anaplasmosis (HA). This disease is also known as human granulocytic anaplasmosis and previously was called human granulocytic ehrlichiosis. A. phagocytophilum is an obligate, intracellular bacterium that lives and multiplies within cytoplasmic vacuoles of granulocytes. Infection with A. phagocytophilum induces a systemic inflammatory response, which is thought to cause tissue damage.

In the United States, HA incidence is highest in the northeastern and upper Midwestern states (Wisconsin and Minnesota), but the geographic range appears to be expanding. The black legged tick, Ixodes scapularis, is the principal vector for A. phagocytophilum in the northeastern and Midwestern United States, while Ixodes pacificus is the vector along the West Coast. Seasonality of anaplasmosis is bimodal, with the first peak occurring in June and July and a second peak during October. Blacklegged ticks also transmit Borrelia burgdorferi and Babesia microti, which cause Lyme disease and babesiosis, respectively. Simultaneous infections with A. phagocytophilum and B. burgdorferi or B. microti are possible.

Incubation period between the bite of an infected tick bite and disease is 5 to 10 days. Symptoms include fever, headache, malaise, myalgia, and shaking chills. Rash is present in less than 10% of patients. Gastrointestinal symptoms and central nervous system involvement occur much less frequently than in Rocky Mountain spotted fever and ehrlichiosis. In most cases, the illness is self-limiting and the fever resolves within 48 to 72 hours after treatment is initiated. Predictors of more severe illness include advanced age, immunosuppression, diabetes and delay in treatment. Overall mortality rate is 0.5-1%.

Characteristic laboratory findings in anaplasmosis include thrombocytopenia, leukopenia, elevated hepatic transaminase levels, increased numbers of immature neutrophils, and mild anemia. Blood smear examination might reveal morulae within granulocytes. CSF evaluation is usually normal.

Blood smear examination for intracytoplasmic morulae in granulocytes requires examination of 800 to 1000 granulocytes at high magnification by an experienced medical laboratory scientist or pathologist. This test often leads to false positive results because morulae are mistaken for other intracytoplasmic inclusions.

Definitive diagnosis is usually accomplished with serology and PCR. IgG and IgM antibodies can be detected by an immunofluorescence assay (IFA). The presence of IgM antibody is consistent with acute infection. Positive IgG antibody suggests current or previous infection. In general, the higher the titer, the more likely it is that the patient has an active infection. Serologic crossreactivity between A. phagocytophilum and E. chaffeensis is minimal. Reference range for A. phagocytophilum IgG is <1:64 and IgM is <1:20. Specimen requirement for antibody testing is a red top tube of blood.

Polymerase chain reaction allows direct detection of circulating pathogen-specific DNA in patients' whole blood during the acute phase of disease. Melting curve analysis of real time polymerase chain reaction can detect and distinguish between Anaplasma phagocytophilum, Ehrlichiosis chaffeensis, Ehrlichia muris-like organism, and Ehrlichia ewingii. Specimen requirement is one lavender top tube of blood.

 

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