Updated: Jun 2, 2009
| Clinical Image Atlas Click to view clinical images on the features, causes, epidemiology, diagnosis, and treatment of Lyme disease. |
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
| 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 |
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:
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.
Evidence of human ehrlichiosis has been reported in residents of Western Europe, Scandinavia, and Africa.
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.
No racial predilection has been reported.
Ehrlichiosis is predominantly reported in males (75%), most likely due to a high rate of high-risk outdoor activities.
A median age of 44 years is reported. Older patients are more likely to have a more severe course of illness.
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.
Physical findings vary. The patient may be confused. Physical examination may reveal the following:
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.
| Endocarditis, Bacterial | Meningitis, Bacterial |
| Henoch-Schoenlein Purpura | Meningococcal Infections |
| Malaria | Rheumatic Fever |
| Meningitis, Aseptic | Syphilis |
Tick-borne Diseases, Colorado
Relapsing Fever
Acute or chronic gonococcemia
Typhoid fever
Collagen vascular disease
Idiopathic thrombocytopenic purpura
Malaria
Miliary tuberculosis
Erythema multiforme/nodosum
Neoplastic diseases
Haverhill and rat-bite fever (Streptobacillus moniliformis)
Early treatment is critical. Consider the possibility of ehrlichiosis when patients have a febrile illness and history of recent tick exposure.
The American Academy of Pediatrics recommends doxycycline as first-line therapy for suspected or proven human granulocytic anaplasmosis (HGA) and human monocytic ehrlichiosis (HME). Ordinarily, tetracyclines are not administered to children younger than 8 years; however, chloramphenicol is the alternative treatment option and is associated with aplastic anemia. Additionally, oral chloramphenicol is no longer available in the United States. Chloramphenicol has also been associated with treatment failures and is inactive against A phagocytophilum in vitro .
Several case reports have detailed successful treatment of mild, nonlife-threatening anaplasmosis (not ehrlichiosis) with rifampin in patients in whom doxycycline was contraindicated (eg, allergy, pregnancy).
Doxycycline is considered the DOC for ehrlichiosis. Use rifampin only as an alternative treatment for mild anaplasmosis if doxycycline is contraindicated. For these indications, age younger than 8 years is not considered a contraindication for doxycycline.
Usually bacteriostatic. Inhibits protein synthesis by binding to 30S and 50S ribosomal subunits.
100 mg PO/IV bid
4.4 mg/kg/d PO/IV divided bid; not to exceed 200 mg/d
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can increase hypoprothrombinemic effects of anticoagulants; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction; doxycycline is the only tetracycline that does not require a dose reduction in renal failure
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; consider drug serum level determinations in prolonged therapy; use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.
300 mg PO/IV bid; not to exceed 600 mg/d
10 mg/kg PO/IV bid; not to exceed 600 mg/d
Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid or pyrazinamide may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFT findings occur)
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
Schneider JG. Human ehrlichiosis: a case study. Clin Lab Sci. Winter 2009;22(1):3-8. [Medline].
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].
Demma LJ, Holman RC, McQuiston JH, Krebs JW, Swerdlow DL. Human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States, 2001-2002. Ann N Y Acad Sci. Oct 2006;1078:118-9. [Medline].
[Guideline] Chapman AS, Bakken JS, Folk SM, et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. Mar 31 2006;55(RR-4):1-27. [Medline]. [Full Text].
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].
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
Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Nicholas John Bennett, MB, BCh, PhD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics
Disclosure: Nothing to disclose.
Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.
Walid Abuhammour, MD, FAAP, Associate Professor of Pediatrics, Michigan State University; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center
Walid Abuhammour, MD, FAAP is a member of the following medical societies: American Medical Association and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.
Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital
Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Pediatric Infectious Diseases Society, Royal Australasian College of Physicians, and Royal College of Pathologists of Australasia
Disclosure: Nothing to disclose.
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner
Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.
Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching
Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None
© 1994-
by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)