Blood smear analysis in babesiosis, ehrlichiosis, relapsing fever, malaria, and Chagas disease

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Ehrlichiosis, nicknamed Rocky Mountain “spotless” fever, is a seasonal, tick-borne disease caused by obligate intracellular bacteria. Bacteria of the genus Ehrlichia grow within the cytoplasmic vacuoles of leukocytes and cause mainly zoonotic infections. Several species, especially Ehrlichia chaffeensis and Anaplasma phagocytophilum, are recognized as human pathogens.17,18E chaffeensis infects mononuclear cells, causing a condition known as human monocytic ehrlichiosis (HME). A phagocytophilum infects neutrophils, producing a condition called human granulocytic anaplasmosis (HGA).

Deer are the principal reservoir for E chaffeensis19; white-footed mice, other rodents, and deer are the principal reservoirs for A phagocytophilum. HME is transmitted by Dermacentor and Ixodes ticks, and HGA by Ixodes ticks. Human infection usually occurs in the spring and summer, when tick exposure is greatest. Co-infection of ticks with the organisms causing Lyme disease or babesiosis may result in simultaneous transmission of these diseases.

More than 1,000 cases of HME have been reported in the southeastern, south-central, and mid-Atlantic regions of the United States.20 The prevalence of HME in the United States appears to follow that of Rocky Mountain spotted fever. Some cases have been described in New England and in the Pacific Northwest. The more than 600 reported cases of HGA have come from Wisconsin, Minnesota, Connecticut, New York, Massachusetts, California, Florida, and Western Europe.21,22 The distribution of HGA follows that of Lyme disease, because the two diseases share the same tick vector.

Acute onset of fever and myalgias

HME and HGA have an incubation period of 1 to 2 weeks. The symptoms are similar and are usually acute, ranging from mild to severe. Most patients have fever, chills, malaise, headache, and myalgias. Many also have nausea, vomiting, cough, and arthralgias. Symptoms are similar to those in Rocky Mountain spotted fever (caused by Rickettsia rickettsii), except that rash is uncommon in HME (seen in approximately a third of patients) and rare in HGA.23–25 Neurologic findings, such as altered sensorium and neck stiffness, may be accompanied by lymphocytic pleocytosis and elevated protein levels in the cerebrospinal fluid.26 Subclinical and subacute presentations (eg, a fever lasting up to 2 months) are uncommon. No chronic cases have been reported.

The estimated death rate is 1% to 10%, and hospitalization rates are as high as 60%. Most deaths occur in the elderly, often following such complications as congestive heart failure,27 cardiac tamponade, respiratory or renal failure, seizures, and coma. Patients with human immunodeficiency virus infection also have a poor prognosis. Convalescence may be prolonged.

Laboratory abnormalities include leukopenia, thrombocytopenia, and elevated hepatic transaminase levels. Leukopenia may be associated with lymphopenia or neutropenia. Lymphopenia occurs early in the course of illness and is usually followed by an atypical lymphocytosis. Prolonged symptoms are associated with a decreased total neutrophil count and an increased band neutrophil count.28

Suspect ehrlichiosis in endemic areas in patients with fever, leukopenia, or thrombocytopenia

Ehrlichiosis should be suspected when a febrile patient with leukopenia or thrombocytopenia has been exposed to ticks in an endemic area. Even patients whose cell counts and liver enzyme levels are normal should be evaluated if the clinical and epidemiologic situations suggest this disease.

Figure 2. Morula of Anaplasma phagocytophilum in the cytoplasm of a neutrophil (arrow) (Wright stain, original magnification ×100).

The peripheral blood smear should be examined for intracytoplasmic inclusions (morulae) within mononuclear cells (for HME) and within neutrophils (for HGA) (Figure 2). Blood smear examination is more likely to be positive in patients with HGA than in those with HME. Because the number of infected leukocytes may be low, examination of more than 500 white blood cells on a Wright-stained smear is recommended.29 Buffy coat examination, which allows for concentrated white blood cell analysis, improves the diagnostic yield.

Other diagnostic tests include polymerase chain reaction and serologic assays, which are highly sensitive and specific.30,31 Because the organisms are difficult to culture in vitro, blood cultures are not useful diagnostically.


Doxycycline 100 mg twice daily for 7 to 10 days is the treatment of choice for both HME and HGA. No role has been defined for fluoroquinolones for treating these diseases. Avoiding ticks and removing ticks promptly are the best preventive strategies.

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