Background

Ehrlichiosis and Anaplasmosis are tick-borne bacterial diseases that infect animals and humans. These diseases are caused by organisms in the order Rickettsiales, family Anaplasmataceae, genera Ehrlichia and Anaplasma, and are classified as α-proteobacteria [1-4]. Clinical presentation for the two genera are similar and may include: fever, headache, myalgia, shaking chills, gastrointestinal symptoms, and rash. Laboratory findings may include: thrombocytopenia, leucopenia, and increase in serum transaminase. Evolutionary relationships indicate that Ehrlichia and Anaplasma species share a common ancestor with other intracellular parasites such as Neorickettsia, Wolbachia, Rickettsia, and Orientia [3-7]. Transmitted by the bite of an infected tick, these obligate intracellular gram-negative bacteria (0.4-1.5 μm in size) infect and replicate within membrane-bound compartments of host leukocytes [8-9]. Ehrlichia and Anaplasma species have genomes consisting of about 0.8-1.5 Mb which have lost redundant genes and developed host cell dependence for necessary functions through reductive evolutionary processes [10]. Both Ehrlichia and Anaplasma exploit and rely on host cell cholesterol for survival and entry into mammalian cells. Ehrlichia was named for Dr. Paul Ehrlich (1854-1915), a German physician, bacteriologist and Nobel Prize winner.

Role in Disease

Ehrlichia was first recognized in 1935 as a disease in dogs; however the first reported human case in the United States was not until 1986. Multiple species in this family of bacteria are known to cause human infection and different species have been documented in different areas of the world using molecular biology techniques. In the United States, species of concern include: Ehrlichia chaffeensis, Ehrlichia ewingii, Ehrlichia canis and Anaplasma phagocytophilum. The different species of Ehrlichia and Anaplasma are named for the type of leukocytes they infect, either monocytes or granulocytes (specifically neutrophils). Ehrlichia chaffeensis causes Human Monocytic Ehrlichiosis (HME) and is most common in the southern, eastern and south- central states, corresponding with its primary vector the Lone Star Tick (Amblyomma americanum). Ehrlichia ewingii is also transmitted by and found in the same geographical distribution as the Lone Star Tick, but differs from Ehrlichia chaffeensis in that it infects granulocytes instead of monocytes. Ehrlichia ewingii primarily infects deer and dogs and was thought of as a canine pathogen until four human cases were described in 1999 [5,16,17]. Ehrlichia canis, primarily a canine pathogen, has also recently been shown to infect humans, specifically monocytes [6-9]. Ehrlichia canis is transmitted by the Rhipicephalus genus of ticks found in the south-east, south central and Midwest states. Although the average annual reported incidence of Ehrlichia is 0.7 cases per 100,000,000 population, active surveillance in endemic areas has shown infection to be closer to 100-200 cases per 100,000 population [11-12]. Anaplasma phagocytophilum causes Human Granulocytic Anaplasmosis (HGA), previously known as Human Granulocytic Ehrlichiosis (HGE); both refer to the same disease now known as Anaplasmosis. Anaplasma phagocytophilum is endemic to the eastern, northeastern, north central and pacific states. The primary vector of Anaplasmosis in the eastern regions of the United States is the Blacklegged Tick (Ixodes scapularis), while the vector in the pacific region is the Western Blacklegged Tick (Ixodes pacificus). Roughly 600-800 cases of Anaplasmosis are reported to the CDC every year; however active surveillance in endemic areas has shown infection rates of greater than 50 cases per 100,000 population [13-15]. At present, little remains to be known about immunity resulting from Ehrlichia or Anaplasma exposure as there have been rare reports of reinfection. Many other tick-borne infections (known as co-infections) have been associated with these primary vectors, such as Lyme disease, Babesiosis, and Tularemia.

Ehrlichia Detection

There are three main detection strategies for the presence of Ehrlichia and Anaplasma: serologic, microscopic, and molecular. Blood-borne microscopic visualization of the bacteria is possible if the host has a current infection in the blood stream and if the parasitemia concentration is high enough. Serological testing relies on the presence of specific antibodies produced by the host in response to the infection (IgG or IgM). Molecular techniques such as Polymerase Chain Reaction (PCR) may also be used to detect the DNA signature of the organism in the blood stream if the concentration is within the detectible levels of the assay. Fry Laboratories confirms the signature of any suspicious band through DNA sequencing so that results are unambiguous. PCR testing for Ehrlichia and Anaplasma is currently in development at Fry Laboratories. By utilizing all three testing methods, individual assay weaknesses may be addressed.

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