The ehrlichiae that cause disease in humans have been classified in a limited number of species based in large part on sequence analysis of rRNA genes. The pathogens are as follows: Ehrlichia chaffeensis, which causes human monocyte ehrlichiosis (HME); Ehrlichia ewingii, which causes E. ewingii ehrlichiosis; and Anaplasma phagocytophilum, which causes human granulocyte anaplasmosis (HGE). The same genera contain additional species that infect animals but apparently not humans. The human pathogens in the group have animal reservoirs and can cause disease in animals as well.

The Ehrlichia group organisms are obligate intracellular bacteria that are taxonomically grouped with the rickettsiae. They have tick vectors.

Properties of Ehrlichiae

Ehrlichiae and Anaplasma are small (0.5 µm), obligate intra cellular, Gram-negative bacteria. They infect circulating leukocytes, erythrocytes, and platelets, where they multiply within phagocytic vacuoles, forming clusters with inclusion-like appearance. These clusters of ehrlichiae are called morulae, which is derived from the Latin word for mulberry. The ehrlichiae and chlamydiae resemble each other in that both are found in intracellular vacuoles. The ehrlichiae, however, are similar to the rickettsiae in that they are able to synthesize adenosine triphosphate (ATP); the chlamydiae are not able to synthesize ATP.

Clinical Findings

 The incubation periods after a tick bite for both HME and HGE can range from 5 to 21 days. The clinical manifestations of ehrlichiosis in humans are nonspecific and include fever, chills, headache, myalgia, nausea or vomiting, anorexia, and weight loss. These manifestations are very similar to those of RMSF without the rash. E. chaffeensis frequently and A. phagocytophilum less often cause severe or fatal illness. Complications with HME include meningoencephalitis; renal failure; myocarditis; and respiratory failure, among other life threatening syndromes, including shock. Seroprevalence studies suggest that subclinical ehrlichiosis occurs frequently.

Laboratory Findings

 Laboratory abnormalities with HME and HGE include leukopenia, lymphopenia, thrombocytopenia, and elevated hepatic enzymes. The diagnosis is confirmed by observing typical morulae in white blood cells (granulocytes in HGA or E. ewingii and mononuclear cells in the case of HME). The sensitivity of microscopic examination for morulae is greatest during the first week of infection and ranges from 25% to 75%.

The indirect fluorescent antibody test can also be used to confirm the diagnosis. Antibodies are measured against E. chaffeensis and A. phagocytophilum. E. chaffeensis is also used as the substrate for E. ewingii because the two species share anti gens. Seroconversion from less than 1:64–1:128 or greater or a fourfold or greater rise in titer makes a confirmed serologic diagnosis of HME in a patient with a clinically compatible illness.

Multiple methods have been described for PCR detection of ehrlichiae in EDTA (ethylenediaminetetraacetic acid)-anticoagulated blood. Culture using a variety of tissue culture cell lines also can be used. PCR and culture are per formed in experienced reference laboratories and in a small number of commercial laboratories.

Treatment

Tetracycline, commonly in the form of doxycycline, is cidal for ehrlichiae and is the treatment of choice. Therapy is administered for 5–14 days. Rifamycins also are ehrlichiacidal. Limited data suggest that fluoroquinolones and chloramphenicol are not useful.

Epidemiology and Prevention

The incidence of human ehrlichioses is not well defined. E. chaffeensis has been found in ticks in at least 14 states in the southeastern, south central, and mid-Atlantic regions of the United States, but cases of HME have been reported in more than 30 states. This area corresponds to the area of distribution of the Lone Star tick, Amblyomma americanum. Cases of human monocytotropic ehrlichiosis in the western United States and in Europe and Africa suggest other tick vectors such as D. variabilis. In Oklahoma, which has the highest incidence of RMSF, human monocytotropic ehrlichiosis is at least as common. More than 90% of cases occur between mid April and October, and more than 80% of cases are in men. Most patients give histories of tick exposure in the month before onset of illness.

Cases of human granulocytotropic ehrlichiosis occur in the upper Midwest and East Coast states and in West Coast states. These areas correspond to the distribution of the tick vectors Ixodes scapularis and Ixodes pacificus, respectively.

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