Human granulocytic anaplasmosis: causes, symptoms, diagnosis, treatment, prognosis, and prevention

Human granulocytic anaplasmosis (HGA), also known as anaplasmosis, is an acute, febrile, systemic disease caused by invasion of human peripheral blood neutrophils by anaplasma phagocytophilum, mainly manifested by headache, myalgia, pancytopenia, and elevated serum transaminase, and is a natural focal disease transmitted by ticks.


Anaplasma phagocytophilum, formerly known as human granulocytic ehrlichiosis, is spherical, oval, or fusiform, 0.2 - 1.0μm long, Gram-negative, obligate intracellular parasite. After infecting neutrophils, the pathogens survive and replicate in the form of membrane-bound inclusion bodies. In Giemsa stain, the inclusion bodies are purple in the cytoplasm and are mulberry shaped in optical microscopy. An inclusion body composed of several to dozens of pathogens, more common in blood smears at the early stage of infection.


Source of infection

The reservoir hosts of anaplasma phagocytophilum are mainly white-footed mice and wild rats. In Europe, red deer, cattle, goats, and sheep can be continuously infected. Continuous infections of animal hosts are a basic condition for the pathogens to maintain natural circulation.

Modes of transmission

Anaplasmosis is transmitted mainly by tick bites. After bites of host animals carrying pathogens, mainly wild and domestic animals such as rats, deer, cows, goats, and sheep, ticks bite humans, and the pathogens can enter the human body. In addition, direct contact with body fluids or blood of critically ill patients or animal carriers can also cause transmission.


Humans are generally susceptible to anaplasmosis.


Anaplasma phagocytophilum enters the human body after tick bites, and enters organs through microvascular or lymphatic vessels. The pathogen has no fimbriae and capsules and lacks lipopolysaccharide and peptidoglycan, so it is presumed that its entry is mainly through the receptor-mediated endocytic pathway.

Infected granulocytes can have significant changes in cell functions, such as significantly reduced endothelial cell adhesion, circulation, degranulation, and phagocytosis, which can affect host cell gene transcription and apoptosis, causing cytokine disorders and phagocytosis dysfunction, eventually leading to immunopathology.

In addition, after infection, anti-anaplasma phagocytophilum antibodies produced by the immune response binding to anaplasma phagocytophilum antigen on the surface of the host cells mediates the attack of host cells by immunologically competent cells. The pathogen is an intracellular parasite, so that cellular immunity, especially CD4+ T lymphocyte, plays an important role in tissue damage while eliminating the pathogen.

The main pathological changes of human granulocytic anaplasmosis are systemic lymphocyte infiltration in multiple organs and monocytosis in the liver, spleen, and lymph nodes. The main target cell of the pathogen is mature granulocytes. Annaplasma phagocytophilum can be seen in neutrophils in blood, spleen, lung, liver, and other organs in immunohistochemistry.

Signs and Symptoms

The incubation period is usually 7 - 14 days, averagely 9 days.

Acute onset is present. The main symptoms are fever, mostly continuous high fever up to 40 °C or above, general malaise, fatigue, headache, muscle soreness, nausea, vomiting, anorexia, and diarrhea. Some patients have cough and sore throat. Apathy and relatively slow pulse can be found in physical examinations. Superficial lymphadenopathy and rash may occur in few patients. Multiple organ dysfunction syndrome may occur.

Severe patients may have interstitial pneumonia, pulmonary edema, acute respiratory distress syndrome, and secondary bacterial, viral, and fungal infections. Hemorrhage in the skin, lung, and digestive tract may occur due to severe thrombocytopenia and coagulopathy in few patients. If without prompt treatment, patients may die from multiple organ dysfunction syndrome, such as respiratory failure and acute renal failure, and disseminated intravascular coagulation.

Old patients, patients with immunodeficiency, and patients with hormone therapy are mostly severe after infection.


On the basis of epidemiology such as a history of exposure to ticks or blood and body fluids of infected patients or animals, clinical findings, and mulberry-shaped inclusions in neutrophils on the peripheral blood smear, the disease can be diagnosed.


Macrolides, such as erythromycin, roxithromycin, azithromycin, clarithromycin, have a good effect against typhus.

Tetracyclines, such as tetracycline, doxycycline, and minocycline, are effective to treat typhus, but are contraindicated in children aged under 8 years, pregnant women, and lactating women.

Quinolones, such as ofloxacin, ciprofloxacin, pefloxacin, fleroxacin, lomefloxacin, and enoxacin, can be administered, but contraindicated in children aged under 8 years, pregnant women, and lactating women.

Rifampicin can be administered in children, patients allergic to doxycycline, and patients who cannot use tetracyclines.

Sulfonamides can promote the replication of the pathogen and are contraindicated.


The mortality is below 1%. If treated promptly, most patients have a good prognosis. Death may occur in patients with severe complications, such as sepsis, toxic shock, toxic myocarditis, acute renal failure, respiratory distress syndrome, disseminated intravascular coagulation, and multiple organ dysfunction.


Exposure to ticks, body fluids and blood of infected patients or animals should be avoided. Ticks, mice, and rats should be eliminated.