Evaluating patients suspected of HGE or HME

Ehrlichiosis is a group of emerging zoonotic infections

caused by Anaplasma and Ehrlichia species, which are

obligate intracellular, gram-negative rickettsial organisms

that infect human leukocytes.

Human granulocytic ehrlichiosis (HGE) is caused by the

tick-borne rickettsia, Anaplasma phagocytophilum, which is

transmitted by contact with ixodes ticks. The deer mouse

is the animal reservoir, and the epidemiology of this

infection is very much like that of Lyme disease (caused

by Borrelia burgdorferi) and babesiosis (caused by

Babesia microti), which have the same tick vector as

human ehrlichiosis (HE). HGE is most prevalent in the upper

Midwest and in other areas of the United States (US) that are

endemic for Lyme disease.

Febrile illnesses accompanied by granulocytic cytoplasmic

inclusions (morulae) in patients are suggestive of ehrlichial

infection. Selective infection of granulocytes results in an acute

febrile illness following tick exposure and may include laboratory

findings of leukopenia or thrombocytopenia. However, these

latter findings also may be present in patients with Lyme disease

or babesiosis. Ticks coinfected with both borrelia and ehrlichia

may transmit both pathogens.

Human monocytic ehrlichiosis (HME) is caused by Ehrlichia

chaffeensis, which is transmitted by the Lone Star tick, Amblyomma

americanum. The deer is believed to be the animal reservoir,

and most cases of HME have been reported from the southeastern

and south-central regions of the US.

Ehrlichia ewingii, the known cause of canine granulocytic ehrlichiosis,

can occasionally cause an HME-like illness in humans. Clinical

features and laboratory abnormalities are similar to those of

Ehrlichia chaffeensis infection, and antibodies to Ehrlichia ewingii

cross-react with current serologic assays for detection of antibodies

to Ehrlichia chaffeensis.

Infective forms of the rickettsial organisms are injected during tick

bites and the organisms enter the vascular system where they infect

leukocytes. They are sequestered in host-cell membrane-limited

parasitophorous vacuoles known as morulae. These morulae can

be readily observed on Giemsa or Wright's stained smears of

peripheral blood from infected persons. Macrophages in organs of

the reticuloendothelial system also are infected. Asexual reproduction

occurs in white blood cells (WBCs) where daughter cells are

formed and liberated upon rupture of the WBCs.

Most cases of ehrlichiosis are probably subclinical or mild, but the

infection can be severe and life-threatening with a 2-3% mortality

rate. Fever, fatigue, malaise, headache, and other "flu-like" symptoms,

including myalgias, arthralgias, and nausea, occur most commonly.

Central nervous system involvement can result in seizures and coma.

Diagnosis of HE has been difficult because the patient's clinical course

is often mild and nonspecific. This symptom complex is easily confused

with other illnesses such as influenza, or other tick-borne zoonoses

such as Lyme disease, babesiosis, and Rocky Mountain spotted fever.

Clues to the diagnosis of ehrlichiosis in an acutely febrile patient after

tick exposure include laboratory findings of leukopenia or thrombocyto-

penia and elevated serum aminotransferase levels. However, while

these abnormal laboratory findings are frequently seen, they are not

specific. PCR techniques allow direct detection of pathogen-specific

DNA from patients' whole blood during the acute phase of disease.

Serologic testing is usually done only for confirmatory purposes, by

demonstrating a 4-fold rise or fall in specific antibody titers to ehrlichia

or anaplasma antigens.

Negative

Positive results indicate presence of specific DNA from Ehrlichia

chaffeensis, Ehrlichia ewingii, or Anaplasma phagocytophilum and

supports the diagnosis of HE.

Negative results indicate absence of detectable DNA from any

of these 3 pathogens in specimens, but it does not negate the

presence of the organism or active/recent disease.

Since DNA of Ehrlichia ewingii is indistinguishable from that of

Ehrlichia canis by this rapid PCR assay, a positive result for

-Ehrlichia ewingii/Ehrlichia canis-  indicates the presence of

DNA from either of these 2 organisms.

A negative result does not indicate absence of disease.

Inhibitory substances may be present in the patient's whole

blood specimen.

Inadequate specimen draw or improper conditions for

storage and/or transport may invalidate test results.

This test may detect DNA of Ehrlichia canis (reported to cause

asymptomatic infection in Venezuela only) and Ehrlichia

muris (which has not been reported to cause human infections).

This PCR test does not detect DNA of Ehrlichia sennetsu, which

has been reported to cause a rare mononucleosis-like illness

in humans (in Japan and Malaysia).

1.   Bakken JS, Dunler JS:  Human granulocytic ehrlichiosis.

      Clin Infect Dis 2000 Aug;31(2):554-560

2.   Dunler JS, Bakken JS:  Human ehrlichioses: newly recognized

      infections transmitted by ticks. Ann Rev Med 1998;49:201-213

3.   Krause PJ, McKay K, Thompson CA, et al:  Disease-specific

      diagnosis of coinfecting tickborne zoonoses: babesiosis,

      human granulocytic ehrlichiosis, and Lyme disease. Clin

      Infect Dis 1999 May 1;34(9):1184-1191

4.   McQuiston JH, Paddock CD, Holman RC, Childs JE:  The

      human ehrlichioses in the United States. Emerging Infect

      Dis 1999 Sept-Oct;5(5):635-642