Ehrlichia/Anaplasma are tiny (0.2-2 µm) obligate, intracytoplasmic, gram-negative organisms that resemble Rickettsia; divide by binary fission; and multiply within the cytoplasm of infected white blood cells. Clusters of Ehrlichia multiply in host monocyte vacuoles (phagosomes) to form large, mulberry-shaped aggregates called morulae. (See Etiology.)
Ehrlichia inclusion bodies, such as morulae, are visible in the cytoplasm of infected mononuclear phagocytic cells after 5-7 days. The type of ehrlichiosis that develops varies and depends on the infecting species and the type of leukocyte infected. Human granulocytic anaplasmosis (HGA), formerly known as human granulocytic ehrlichiosis (HGE), is caused by Anaplasma phagocytophilum, which infect granulocytes. In contrast, human monocytic ehrlichiosis (HME) is caused by Ehrlichia chaffeensis, which infects monocytes. (See Table, below.) (See Etiology.)
HGA and HME cause the same clinical manifestations. Therefore, the term ehrlichiosis is used for both types of infections. The total duration of illness for HME and HGA is unknown. No chronic cases have been reported at this time. (See History and Physical Examination.)
Table. Characteristics of HME Versus HGA (Open Table in a new window)
|Human monocytic ehrlichiosis (HME)||Human granulocytic anaplasmosis (HGA)|
|Cell type Affected||Monocytes||Granulocytes|
|Organism||E chaffeensis||A phagocytophilum|
|Vector||Amblyomma americanum (Lone Star tick)||Ixodes scapularis (black-legged tick), Ixodes pacificus (Western black-legged tick) in California, Ixodes ricinus in Europe, and probably Ixodes persulcatus in parts of Asia|
|Location||Southeastern and south-central United States||Wisconsin and Minnesota, less active in New York and Connecticut, also California|
|Rash||30% of adults, 60% of children||Rare|
|Prognosis||~3% mortality||< 1% mortality|
Complications of ehrlichiosis include the following:
Because the tick vector and geographic range for HGA is the same as that for Lyme disease, rarely the 2 may coexist in the same patient; doxycycline is effective therapy for both. (See Treatment and Medication.)
In October 2008, a report was made of an apparent nosocomial infection with A phagocytophilum that was transmitted from blood donated by an infected woman who had spent time in Minnesota just prior to donating.
The major antigenic determinants of Ehrlichia are surface membrane proteins. These antigenic proteins are complex and consist of thermolabile and thermostable components. In terms of kilodalton (kd) molecular weight, the key protein bands associated with HME are the 27-, 29-, and 44-kd bands. The major antigenic determinants associated with HGA include the 40-, 44-, and 65-kd bands.
In 1999, Buller et al reported 4 incidents of ehrlichiosis in Missouri due to Ehrlichia ewingii.  The associated disease may be clinically indistinguishable from infection caused by E chaffeensis or A phagocytophilum; however, laboratory testing can distinguish these incidents from HGA and HME. (See Workup.)
See 7 Bug Bites You Need to Know This Summer, a Critical Images slideshow, for helpful images and information on various bug bites.
Educate patients in endemic ehrlichiosis areas to take proper precautions when traveling through wooded and/or tick-infested areas. (See Deterrence and Prevention.)
For patient education information, see Ticks.
Ehrlichia and Anaplasma species, members of the family Rickettsiae, are gram-negative, obligate, intracellular coccobacilli that resemble Rickettsia species. All 3 are forms of Alphaproteobacteria.
Like Rickettsia, Ehrlichia organisms gain access to the blood via a bite from an infected tick. A americanum (Lone Star tick, seen in the image below) is the principle tick vector of E chaffeensis and is the primary vector of human monocytic ehrlichiosis (HME). A phagocytophilum may be transmitted from Ixodes persulcatus ticks and possibly Dermacentor variabilis (dog tick/wood tick).
The primary target cell for HME is the macrophage, and the primary target for human granulocytic anaplasmosis (HGA) is the granulocyte. Intracellular infection is established within phagosomes, most often found in macrophages in the liver, spleen, lymph nodes, bone marrow, lung, kidney, and CNS.
HME and HGA are more severe in those with impaired splenic function.
Occurrence in the United States
The distribution of ehrlichiosis in the United States mirrors the tick distribution and appropriate mammalian vectors (eg, white-footed mouse, white-tailed deer). Ehrlichiosis occurs where mammalian hosts are in contact with the appropriate tick vector (ie, A americanum,D variabilis,Ixodes ticks). (See the maps below.)
Most cases of ehrlichiosis in the United States occur in California and Texas and in the southeast and northeast regions of the country, with some cases occurring in the north-central states west of the Great Lakes.
Ehrlichiosis is a seasonal disease observed mainly from April to September. In 1999, ehrlichiosis became reportable to the US Centers for Disease Control and Prevention (CDC). In 2005, 786 cases of human granulocytic anaplasmosis (HGA) were reported. The 3 states that reported the most cases were New York (221 cases), Minnesota (186 cases), and Wisconsin (155 cases). [4, 5] In 2006, 646 cases of HGA were reported. The 3 states that reported the most cases were New York (235 cases), Minnesota (177 cases), and Wisconsin (49 cases). 
A 2011 study confirmed that B burgdorferi and A phagocytophilum share the same enzootic life cycle suggesting that it is important to monitor areas endemic for Lyme disease for HGA. In this study, La Crosse, WI is centrally located in a well-documented Lyme disease focus. HGA was identified by PCR in the blood of 53 patients with clinical findings consistent with HGA confirming that this region endemic for Lyme should now also be considered part of the upper Midwestern focus of endemnicity for HGA. 
In 2005, 506 cases of human monocytic ehrlichiosis (HME) were reported. The 3 states that reported the most cases were New York (85 cases), Oklahoma (79 cases), and New Jersey (64 cases). In 2006, 578 cases of HME were reported. The 3 states that reported the most cases were New York (141 cases), Missouri (73 cases), and New Jersey (67 cases).
A 2011 report identified a new ehrlichia species in 4 patients in the Minnesota and Wisconsin areas. All patients had the traditional clinical syndrome and responded to treatment. On testing, 17 of 697 Ixodes scapularis ticks collected in Minnesota or Wisconsin were positive for the same ehrlichia species by polymerase chain-reaction testing and genetic analyses revealed that this new ehrlichia species was closely related to E muris. 
Ehrlichiosis occurs essentially worldwide, and the frequency parallels the distribution of the appropriate tick vectors for the transmission of Ehrlichia bacteria and the mammalian hosts. 
Ehrlichia sennetsu causes a mononucleosis-like illness in Japan and Malaysia.
The rates of HME and HGA are higher in males than in females, most likely due to a higher rate of participation in high-risk outdoor activities among males.
In 2006, the CDC reported that of the 646 cases of HGA, 357 were males and 273 were females (16 cases did not specify sex). HME had a similar distribution, with 337 males and 234 females among the 578 cases in 2006 (7 cases did not specify sex).
The incidence rates per 100,000 for males were 0.26 for HGA and 0.24 for HME. For females, the rates were 0.19 for HGA and 0.16 for HME.
Ehrlichiosis is reported more frequently in adults than in children. The highest age range is between 40 and 64 years. (See the graphs below.)
Ehrlichiosis carries an excellent prognosis in healthy hosts. A favorable outcome is associated with the early use of antibiotics. 
The mortality rate for human monocytic ehrlichiosis (HME) is reported to be 2-5%, while that for HGA is 7-10%.
Elderly patients (>60 y) are more likely than others to develop severe infections and account for most deaths due to ehrlichiosis. In addition, ehrlichiosis may be severe in immunocompromised hosts, manifesting as a Rocky Mountain spotted fever (RMSF)–like illness that may be fatal. The great majority of cases of ehrlichiosis are asymptomatic. Most cases present as mild-to-moderate acute febrile illnesses, but some cases are severe/life threatening.
HME has a reported hospitalization rate as high as 60%, while that for HGA is 28-54%.
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