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Anaplasma phagocytophilum

Microbiology > Bacteriology > Intracellular bacteria > Anaplasmataceae
Anaplasma  phagocytophilum

Structure:
• Order Rickettsiales, family Anaplasmataceae
• Obligate, intracellular Gram negative bacteria that grow within membrane bound vacuoles in granulocytes.  Genetically related to Ehrlichia species but with sufficient differences to warrant a separate genus.

Epidemiology:
• Identified in 1994 and originally called HGE (human granulocytic ehrlichiosis). Most cases of human granulocytic anaplasmosis (HGA) occur from April to October.
• The blacklegged tick, Ixodes scapularis, is the vector of A. phagocytophilum in Eastern and North Central United States; the western blacklegged tick, Ixodes pacificus, is the principal vector in the north central and pacific coastal states.
• The white-footed mouse and deer are the primary reservoirs, in addition, elk, sheep and wild rodents (mice, squirrels, chipmunks, voles) may also serve as reservoirs.
• Ixodes scapularis may also transmit Lyme’s disease and Babesiosis.  In Connecticut, co-infection with Lyme’s disease may occur in 3-15% of patients.
• Transmission through transfusions with blood and platelets has also been reported.

Pathobiology:
• This bacteria is able to multiply in the granulocytic phagosome (morulae) and is able to prevent fusion with lysosomes, escaping exposure and destruction by hydrolytic enzymes.
• Protected from antibody during intracellular growth.
• Initiates an inflammatory response (macrophage activation) that contributes to the disease pathology.

Disease manifestations:
• Clinical presentation may range from asymptomatic to severe.  Onset of illness occurs 1-2 weeks after exposure to an infected tick. Common signs and symptoms include fever, chills, headache, and myalgias; 25-50% with nausea, vomiting and arthralgias; <5% have a rash.
• Leukopenia: WBC < 4,500/mm3 , increased number of bands.
• Thrombocytopenia: platelets < 150,000/mm3  (more common than leukopenia).
• Increased liver function tests, specifically aminotransferase levels.

Laboratory diagnosis:
• Microscopy:  Intracellular inclusions (morulae) visualized in the cytoplasm of granulocytes on Wright- or Giemsa-stained blood smears. However, this is an insensitive method for the detection of anaplasma as only a small percent of cells may be infected.
• Polymerase chain reaction (PCR) assays to detect A. phagocytophilum DNA. This test is most sensitive in the first week of illness.
• Serology: Increased antibody titers are usually observed 3-6 weeks after illness onset. Therefore, a negative test during the first week of illness does not rule out anaplasmosis.
• A small percent of patients will retain detectable antibody for several years, however,                re-infection may occur when antibodies wane.

Differential Diagnosis:  
• Resembles other tick-borne diseases, such as Rocky Mountain Spotted Fever (RMSF). RMSF, unlike HGA, is usually characterized by a rash and less likely to have leukopenia. R. rickettsi, which causes RMSF, infects endothelial cells and is not evident in blood smears.
• Febrile disease in an endemic area when ticks are active.
• Mononucleosis, West Nile virus

Treatment:
• First line treatment is doxycycline therapy: 100 mg twice daily for 5-10 days with defervescence occurring within 48 hrs.
• Rifampin has been used successfully in pregnant women and children.
• Ineffective antibiotics include penicillins, cephalosporins, fluoroquinolones, macrolides, and aminoglycosides.

Prevention and control:
• Avoid tick-infested areas, use tick repellants and protective clothing, prompt removal of embedded ticks.  

Related concepts
A. phagocytophilum, anaplasmosis, tick-borne disease, Ixodes scapularis, Ixodes pacificus,  granulocyte, morulae
Morulae of Anaplasma  phagocytophilum in PMN, blood smear (Public Health Image Library)

 
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