Basic features of Ehrlichia and Anaplasma
- Gram negative
- Obligate intracellular bacteria
- Grow in membrane-bound vacuoles in leukocytes, particularly:
- Light microscopy:
- Individual organisms are difficult to appreciate.
- Frequently visualized as morulae (microcolony of organisms within a vacuole)
Clinically relevant species
The most notable species are:
- Ehrlichia chaffeensis → human monocytic ehrlichiosis (HME)
- Anaplasma phagocytophilum → human granulocytic anaplasmosis (HGA)
Rare causes of ehrlichiosis in humans:
- E. ewingii
- E. muris eauclairensis
Epidemiology and Risk Factors
- Incidence in the United States:
- HME: 3.2 cases per million per year
- HGA: 6.3 cases per million per year
- Endemic areas in the United States:
- South Central
- Upper Midwest and Great Lakes
- Endemic areas outside the United States:
- Southeast Asia
- South America
- Incidence is higher in men than women.
- Commonly occurs between April and September
- Travel to or living in an endemic area
- Owning pets
- Participating in outdoor activities in wooded areas:
For severe disease:
- HIV infection
- Organ transplant
- The elderly and young children
- Tick vectors:
- E. chaffeensis is transmitted by Amblyomma americanum (Lone Star tick).
- A. phagocytophilum is transmitted by Ixodes ticks.
- Iatrogenic (rare):
- Blood transfusion
- Solid organ transplantation
A wide range of wild and domestic animals can serve as reservoirs. The most notable are:
- White-tailed deer (E. chaffeensis)
- White-footed mice (A. phagocytophilum)
- Surface proteins:
- Allow binding to host cells for entry
- Antigenic variation helps with evading a host’s immune system.
- Bacterial effector proteins:
- Translocate into a host cell
- Modify the cell’s cytoskeleton to allow bacterial entry
- Allow bacteria-containing vacuoles to avoid lysosome fusion
- Alter gene expression in the host cell nucleus
Human monocytic ehrlichiosis:
- E. chaffeensis is introduced into the skin during a tick bite.
- Infects monocytes and macrophages
- Spreads through the lymphatics or blood to:
- Bone marrow
- Lymph nodes
- The clinical presentation is due to the effects of the host’s inflammatory response.
Human granulocytic anaplasmosis:
- A. phagocytophilum is introduced into the skin during a tick bite → neutrophil recruitment
- A. phagocytophilum enters neutrophils:
- Alters intracellular killing
- Induces neutrophil activation and cytokine release → contributes to tissue injury and clinical manifestations
- Infection spreads hematogenously.
Signs and symptoms
The incubation period is typically 1–2 weeks, and the clinical presentation can vary greatly.
Features of both HME and HGA:
- Nonspecific symptoms:
- GI symptoms:
- Abdominal pain
- Respiratory symptoms:
- Shortness of breath
Findings more commonly seen in HME:
- Macular, maculopapular, or petechial
- More common in children
- Neurological symptoms:
- Change in mental status
- Neck stiffness
- Myocarditis and heart failure
- Pericardial effusion and tamponade
- Renal failure
- Septic shock
- Hemophagocytic lymphohistiocytosis (rare, severe complication of HGA)
Diagnosis and Management
- Indirect fluorescent antibody testing
- ELISA antibody testing
- PCR to detect organism DNA
- Buffy coat or peripheral blood smear examination: Intracytoplasmic morulae are seen in peripheral blood leukocytes.
Supporting laboratory studies:
- ↑ AST and ALT
- ↑ Alkaline phosphatase
- ↑ Lactate dehydrogenase
- ↑ Creatinine
Doxycycline is the antibiotic of choice.
- Treatment should be initiated in patients with suspected HME or HGA while laboratory testing is pending.
- If patients do not improve with therapy, they should be evaluated for a concurrent Babesia infection.
Avoiding tick bites is key to preventing these diseases.
- Wearing appropriate protective clothing
- Using tick repellents
- Inspecting for ticks after outdoor activity
- Removing any attached ticks to reduce the risk of infection
- Tick control on domestic animals
- Doxycycline prophylaxis after a tick bite is not recommended.
Comparison of Gram-negative Tick-borne Bacteria
|Organism||Ehrlichia chaffeensis||Anaplasma phagocytophilum||Rickettsia rickettsii||Borrelia burgdorferi|
|Disease||HME||HGA||Rocky Mountain spotted fever||Lyme disease|
|Vector||Lone Star tick||Ixodes tick||Dermacentor tick||Ixodes tick|
|Reservoir||White-tailed deer||White-footed mouse||Dermacentor tick|
|Geographical distribution in the United States||Southeast and South Central states||Northeast and upper Midwest states||Southeast and South Central states||Northeast and Midwest states|
IFA: immunofluorescent antibody
- Babesiosis: a tick-borne infection caused by Babesia. Patients can be asymptomatic or develop fever, fatigue, malaise, and arthralgias. Asplenic, immunocompromised, and elderly patients are at risk for severe disease, causing hemolytic anemia, thrombocytopenia, hepatosplenomegaly, renal failure, and death. Diagnosis is confirmed with a peripheral blood smear, serologic testing, and PCR. Management includes antimicrobials such as atovaquone plus azithromycin.
- Rocky Mountain spotted fever: a disease caused by Rickettsia rickettsii that presents with fever, fatigue, headache, and a rash following a tick bite. However, this disease is associated with the Dermacentor tick, and the rash presents more frequently than in HME or HGA. Diagnosis is made based on the clinical features, biopsy of the rash, and serologic testing. Management involves antibiotics, including doxycycline.
- Viral hepatitis: liver inflammation caused by an infection with the hepatitis virus. Patients may present with a viral prodrome of fever, anorexia, and nausea. Right upper quadrant abdominal pain, jaundice, and transaminitis also occur. The diagnosis is made with viral serologic testing and will differentiate hepatitis from HME or HGA. Management of acute hepatitis is supportive.
- Mononucleosis: a disease caused by the Epstein-Barr virus that is characterized by fever, fatigue, lymphadenopathy, and pharyngitis. These latter 2 features are less commonly seen in HME or HGA. Diagnosis is based on clinical features and testing, such as a heterophile antibody test or serology. Management is supportive.
- Lyme disease: an infection caused by B. burgdorferi, which is transmitted by the Ixodes tick. Presentation depends on the stage of the disease and may include a characteristic erythema migrans rash. Neurological, cardiac, ocular, and joint manifestations are also common in later stages. Diagnosis relies on clinical findings and tick exposure and is supported by serological testing. Antibiotics are used for treatment.
- Brucellosis: an infection caused by Brucella, which spreads predominantly after the ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly. Diagnosis is based on clinical manifestations, exposure history, serology, and culture studies. Management involves a combination of antibiotics, including doxycycline, rifampin, and aminoglycosides.
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