Lymphoreticular and Hematopoetic Infections 
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After the bacterium Ehrlichia or Anaplasma phagocytophilum is injected into the bloodstream by a tick, it enters either a monocyte or granulocyte, depending on the species of the bacterium. It replicates in the phagosome of the cell and destroys it. Currently, two species of Ehrlichia, E. chaffeensis and E. ewingii, and one species of Anaplasma (A phagocytophilum) have been discovered in the US that cause disease in humans.

Three basic types of ehrlichiosis have been observed in the US: Ehrlichia chaffeensis, the agent of human monocytic ehrlichiosis; E ewingii, the agent of canine granulocytic ehrlichiosis; and A phagocytophilum, the agent of human anaplasmosis (formerly called human granulocytic ehrlichiosis). The symptoms of these diseases are similar to those of Rocky Mountain spotted fever, with the exception that a rash is less common in ehrlichiosis or anaplasmosis.


E chaffeensis infects primarily mononuclear cells (monocytes and macrophages) and causes human monocytic ehrlichiosis. E ewingii causes canine granulocytic ehrlichiosis and primarily infects neutrophils and occasionally eosinophils. It causes a disease very similar to human monocytic ehrlichiosis and human anaplasmosis. Humans who acquire canine granulocytic ehrlichiosis are accidental hosts.  A phagocytophilum the agent of human anaplasmosis primarily infects neutrophils.


Many infections are so mild that individuals are asymptomatic and do not consult a physician; if patients have symptoms, they begin 5–10 days after a tick bite.

Symptoms of human monocytic ehrlichiosis include fever, headache, malaise, and muscle aches. In children, particularly, a maculopapular or petechial rash can be seen later in the disease process; about 40–50% of adults will develop the rash. Other manifestations may include nausea, vomiting, diarrhea, cough, joint pain, and mental confusion. Important laboratory findings include leukopenia, thrombocytopenia, and elevated liver enzymes. If untreated, the disease can be severe; as many as 50% of all patients require hospitalization. Severe manifestations of the disease may include prolonged fever, renal failure, disseminated intravascular coagulopathy, meningoencephalitis, adult respiratory distress syndrome, seizures, or coma. Approximately 2–3% of untreated patients die from the infection.

Symptoms of canine granulocytic ehrlichiosis are similar to those of human monocytic ehrlichiosis. Disease usually is not seen in immunocompetent individuals. Most symptomatic infections are seen in people who have other medical conditions that cause immunosuppression (e.g., HIV infection, splenectomy, transplantation patients, and patients receiving immunosuppressive drugs).

Symptoms of human anaplasmosis are similar to those of human monocytic ehrlichiosis and canine granulocytic ehrlichiosis; the rash is less common than in human monocytic ehrlichiosis and occurs in only 10% of patients. Severe illness, as seen with human monocytic ehrlichiosis and canine granulocytic ehrlichiosis, can also occur, especially if the disease is untreated. As many as 50% of all patients with human anaplasmosis require hospitalization. Without treatment, the fatality rate can be as high at 1%.

Patients with compromised immunity caused by immunosuppressive therapies (e.g., corticosteroids or cancer chemotherapy), HIV infection, or splenectomy are more likely to develop severe disease following infection with any of these three pathogens.



The hematopoietic system is the main organ system infected in patients with ehrlichiosis and human anaplasmosis. The bacteria are obligate intracellular parasites that multiply in the phagosome of the host cell. The organisms produce mulberry-shaped vacuole-bound intracytoplasmic inclusions in the leukocyte called morulae, which aids in diagnosing these diseases. The immune response to the organisms is beneficial in eliminating the bacteria, but is harmful in that most of the damage to the host results from the immune response to the infection.


Ehrlichiosis and human anaplasmosis are difficult diseases to diagnose because they are similar to many other diseases. The clinical (e.g., laboratory test results and signs and symptoms) and epidemiologic clues (e.g., history of tick bite) can aid in the initial diagnosis. Microscopy of Wright or Giemsa stained peripheral blood samples is of limited value in detecting the morulae in human monocytic ehrlichiosis but can be of value in diagnosing patients with human anaplasmosis. Morulae-containing cells can be detected in only 10% of patients with human monocytic ehrlichiosis; however, 20–80% of patients with human anaplasmosis show visible morulae in stained peripheral blood smears.

The most common means of confirming a clinical diagnosis of ehrlichiosis and human anaplasmosis is by PCR and serology. Serologic evaluations are conducted using the indirect immunofluorescence assay. Antibodies in the serum bind to the organisms on a slide and are detected by a fluorescein-labeled conjugate. Amplification of the bacterial DNA by PCR is the next most frequently used method for detecting infection. This test is available through the Centers for Disease Control and Prevention and some state health laboratories, as well as a number of research and commercial laboratories. 

Direct isolation of the organism remains the gold standard for confirmatory diagnosis, but it is the most difficult and time-consuming approach. Both E chaffeensis and A phagocytophilum have been recovered from the blood of acutely ill patients using canine DH82 and human HL-60 cells, respectively. E chaffeensis has been observed within 7–36 days in culture. A phagocytophilum may be seen within 7–12 days after inoculation of cells with patient blood.

Therapy and Prevention

The drug of choice in treating all ehrlichiosis and human anaplasmosis is doxycycline. Due to the serious consequences of untreated infections, treatment should not be postponed until the diagnosis is confirmed.

Infections can be prevented by limiting exposure to ticks. In persons exposed to tick-infested habitats, prompt, careful inspection and removal of crawling or attached ticks is an important method of preventing disease. Bacteria are transmitted from the tick to humans after several hours of attachment.

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Revised 11/20/14
©2014, Neal R. Chamberlain, Ph.D., All rights reserved

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