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Ehrlichiosis
Updated: Jun 2, 2009
Introduction
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Background
Ehrlichiosis is more properly considered as 2 distinct, but related, diseases caused by different tick-borne bacteria. The Rickettsiae family was reorganized in 2001 to rename some of the Ehrlichia as Anaplasma to reflect this fact. Ehrlichiosis and anaplasmosis differ in the pathophysiology of the disease, laboratory findings, and the geographic distribution of the vector species.
Ehrlichia and Anaplasma species are obligate intracellular coccobacilli that historically have been recognized as veterinary pathogens, usually with ticks as vectors. The genus Ehrlichia was established in honor of the German microbiologist Paul Ehrlich, who discovered it in the United States in 1945. The first incident of human ehrlichiosis was reported in Japan in 1954. The first incident of human ehrlichiosis in the United States was documented in 1986.1 In 1991, Ehrlichia chaffeensis was isolated from a military recruit stationed at Fort Chaffee, Arkansas. In 1994, Anaplasma phagocytophilum was isolated from 12 patients in Minnesota and Wisconsin.
The disease and organism names have changed in the last few years, making the situation confusing to some degree. The 2 diseases are best thought of as affecting either macrophages (human monocytic ehrlichiosis [HME], caused by E chaffeensis) or granulocytes (human granulocytic anaplasmosis [HGA], caused by A phagocytophilum).2
HGA was formally known as human granulocytic ehrlichiosis (HGE), and A phagocytophilum was formally known as Ehrlichia phagocytophilum and Ehrlichia equi; the species were combined in the reorganization. Because the tick vector and geographic range for HGA is the same as that of Lyme disease, the 2 may coexist in the same patient, and care should be taken because amoxicillin can treat early Lyme disease but is not effective against HGA; doxycycline is an effective therapy for both.
In 1999, Buller et al reported 4 incidents of ehrlichiosis in Missouri due to Ehrlichia ewingii.3 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.
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.4
Characteristics of Ehrlichiosis Versus Anaplasmosis
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Table
| Ehrlichiosis | Anaplasmosis | |
| Cell type Affected | Macrophage | Granulocyte |
| Organism | E chaffeensis | A phagocytophilum |
| Vector | Amblyomma americanum (Lone Star tick) | Ixodes scapularis (black-legged tick), Ixodes pacificus (the 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 |
| Ehrlichiosis | Anaplasmosis | |
| Cell type Affected | Macrophage | Granulocyte |
| Organism | E chaffeensis | A phagocytophilum |
| Vector | Amblyomma americanum (Lone Star tick) | Ixodes scapularis (black-legged tick), Ixodes pacificus (the 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 |
Both ehrlichiosis and anaplasmosis are reportable diseases in the United States.
Pathophysiology
The primary target cell for HME is the macrophage, and the primary target for 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.
Ehrlichia species proceed through elementary bodies, initial bodies, and morulae (distinctive membrane-bound, intracytoplasmic bacterial aggregates).
Potential pathology findings believed to be associated with HME include the following:
- Focal necrosis of the liver, spleen, and lymph nodes
- Multiorgan perivascular lymphohistiocytic infiltrates
- Hemophagocytosis of the liver, spleen, lymph nodes, and bone marrow
- Intersitial pneumonitis and pulmonary hemorrhage
- Frequent granulomas observed in bone marrow biopsy
- Suppression or dysregulation of the immune system
Frequency
United States
Both HME and HGA are underreported but are now subject to national reporting requirements. State health departments reported 742 cases of HME and 449 cases of HGA during 1986-1997, but 1,176 for the year 2001-2002.5,6 Annual incidence overall was 0.6 HGA cases per million population for and 1.4 HME cases per million population. This rising incidence is likely due to a mixture of improved recognition and reporting, as well as increased encroachment of humans into areas where the vectors are located.
HME was reported most commonly from the southeastern and south-central states, whereas HGA was reported most often in Wisconsin and Minnesota. Approximately 66% of HME cases have occurred in rural areas, and 68% of cases have been reported from May-July.
International
Evidence of human ehrlichiosis has been reported in residents of Western Europe, Scandinavia, and Africa.
Mortality/Morbidity
Ehrlichiosis is a severe disease, with more than 60% of patients requiring hospitalization; however, some hospitalizations are to rule out other potentially life-threatening conditions.
- Of all patients with HME, 25% required intensive care therapy.
- Case fatality rates are 2-3% for HME and 1% for HGA.
Race
No racial predilection has been reported.
Sex
Ehrlichiosis is predominantly reported in males (75%), most likely due to a high rate of high-risk outdoor activities.
Age
A median age of 44 years is reported. Older patients are more likely to have a more severe course of illness.
Anaplasmosis incidence by age. Courtesy of the Centers for Disease Control and Prevention.
Ehrlichiosis incidence by age. Courtesy of the Centers for Disease Control and Prevention.
Clinical
History
Approximately 68% of patients with human monocytic ehrlichiosis (HME) reported a tick bite, and 83% of patients have a history of tick exposure in the 4-week period before onset of symptoms. Onset is abrupt or subacute. Symptoms are nonspecific and resemble those of Rocky Mountain spotted fever.
- Fever: All patients have a fever of more than 38°C.
- Headache
- Myalgia and arthralgia
- Anorexia and nausea
- Malaise and photophobia
- Skin rash
- Rash is less common in ehrlichiosis than in Rocky Mountain spotted fever. Rash is rare in patients with anaplasmosis.
- Skin rash is more common in children than adults (approximately 60% in children vs 30% in adults).
- Rash usually occurs on the trunk, legs, arms, or face and may be macular, maculopapular, and/or petechial.
- Rash on the palms or the soles is found in fewer than 10% of patients.
- Immunosuppression: Pre-existing immunosuppression is a risk factor in 12% of patients with HME and 6% of patients with human granulocytic anaplasmosis (HGA).
Physical
Physical findings vary. The patient may be confused. Physical examination may reveal the following:
- Rash
- Hepatosplenomegaly
- Systolic murmur
- Nuchal rigidity (if meningitis is present)
- Cervical or inguinal adenopathy
- Conjunctivitis
- Strawberry tongue
- Pharyngitis or tonsillar exudate
- Genital or oral ulcers
- Abnormal gait
Causes
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.
- Different species are identified by sequencing and analysis of 16S ribosomal RNA (rRNA).
- A americanum (Lone Star tick) is the putative vector of HME.
- I scapularis (black-legged tick) is the principal vector of HGA. I pacificus (the western black-legged tick) is the main vector in California.
Map of the United States showing the distribution of the Lone Star Tick, which is the principle vector for ehrlichiosis.
Established and reported distribution of anaplasmosis vectors Ixodes scapularis and Ixodes pacificus, by county, in the United States from 1907-1996. Courtesy of the Division of Vector-Borne Infectious Diseases at the Centers for Disease Control and Prevention.
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| References |
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References
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Ganguly S, Mukhopadhayay SK. Tick-borne ehrlichiosis infection in human beings. J Vector Borne Dis. Dec 2008;45(4):273-80. [Medline].
Buller RS, Arens M, Hmiel SP, et al. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N Engl J Med. Jul 15 1999;341(3):148-55. [Medline].
Anaplasma phagocytophilum transmitted through blood transfusion--Minnesota, 2007. MMWR Morb Mortal Wkly Rep. Oct 24 2008;57(42):1145-8. [Medline].
McQuiston JH, Paddock CD, Holman RC, Childs JE. The human ehrlichioses in the United States. Emerg Infect Dis. Sep-Oct 1999;5(5):635-42. [Medline].
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Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA. Jan 17 1996;275(3):199-205. [Medline].
Committee on Infectious Diseases. Ehrlichiosis. In: Red Book. 2006:281-4.
Dumler JS, Barbet AF, Bekker CP, et al. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila. Int J Syst Evol Microbiol. Nov 2001;51(Pt 6):2145-65. [Medline].
Dumler JS, Choi KS, Garcia-Garcia JC, et al. Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerg Infect Dis. Dec 2005;11(12):1828-34. [Medline].
Glushko GM. Human ehrlichiosis. Postgrad Med. Jun 1997;101(6):225-30. [Medline].
Jacobs RF, Schutze GE. Ehrlichiosis in children. J Pediatr. Aug 1997;131(2):184-92. [Medline].
Laudicina RJ, Hilger AE. Human ehrlichiosis: a case review. Clin Lab Sci. 1997;10(3):149-66.
Ogden NH, Woldehiwet Z, Hart CA. Granulocytic ehrlichiosis: an emerging or rediscovered tick-borne disease?. J Med Microbiol. Jun 1998;47(6):475-82. [Medline].
Schaffner W, Standaert SM. Ehrlichiosis--in pursuit of an emerging infection. N Engl J Med. Jan 25 1996;334(4):262-3. [Medline].
Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. Nov 1 2006;43(9):1089-134. [Medline]. [Full Text].
Further Reading
Keywords
ehrlichiosis, human monocytic ehrlichiosis, HME, human granulocytic ehrlichiosis, HGE, human granulocytic anaplasmosis, HGA, tick-borne disease, Rickettsiae, Ehrlicia, Anaplasma, anaplasmosis, coccobacilli, Ehrlichia chaffeensis, Anaplasma phagocytophilum, human monocytic ehrlichiosis, HME, human granulocytic anaplasmosis, HGA, human granulocytic ehrlichiosis, HGE, Lyme disease, Ehrlichia phagocytophilum, Ehrlichia equi, Ehrlichia ewingii, Amblyomma americanum, Ixodes scapularis, Ixodes pacificus, Ixodes ricinus, Ixodes persulcatus, Rocky Mountain spotted fever, myalgia, arthralgia, malaise, photophobia
