AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

In the past 10 years in the United States, 3 emerging tick-borne diseases caused by the obligate intracellular bacteria of the genus Ehrlichia have been recognized. Human monocytic ehrlichiosis (HME) was first described in 1986 and is caused by Ehrlichia chaffeensis. Human granulocytotropic anaplasmosis (HGA), formerly known as human granulocytic ehrlichiosis (HGE), was described in 1993 and is caused by Anaplasma phagocytophilia. Both types have been referred to as spotless Rocky Mountain spotted fever. Ehrlichia ewingii was described in 1999 as an agent of human ehrlichiosis.

Pathophysiology

The hematopoietic system is the main organ system affected. However, the GI, immune, and nervous systems also are involved.

Frequency

United States

Ehrlichiosis is a seasonal disease observed mainly from April to September. In 1999, ehrlichiosis became reportable to the CDC. In 2002, 511 cases of HGA were reported. The 3 states that reported the most cases were New York (159 cases), Minnesota (149 cases), and Rhode Island (65 cases). In 2003, 362 cases of HGA were reported. The 3 states that reported the most cases were Minnesota (77 cases), Rhode Island (63 cases), and New York (62 cases).

In 2002, 216 cases of HME were reported. The 3 states that reported the most cases were Missouri (50 cases), Tennessee (26 cases), and New York (19 cases). In 2003, 321 cases of HME were reported. The 3 states that reported the most cases were Maryland (51 cases), Tennessee (33 cases), and Oklahoma (33 cases).

International

Human granulocytotropic anaplasmosis has been reported throughout Europe. As of March 2003, 65 cases of confirmed HGA were reported.

Ehrlichia sennetsu causes a mononucleosislike illness in Japan and Malaysia.

Mortality/Morbidity

The total duration of illness for HME and HGA is unknown. No chronic cases have been reported at this time.

• The HME mortality rate is reported to be 2-5%, while that for HGA is 7-10%.
• HME has a reported hospitalization rate as high as 60%, while that for HGA is 28-54%.

Sex

Males are affected more than females in HME and HGA. In 2002, the CDC reported that of the 511 cases of HGA, 282 were males and 226 were females (3 cases did not specify sex). HME had a similar distribution, with 129 males and 86 females among the 216 cases in 2001 (1 case did not specify sex).

• The incidence rates per 100,000 for males were 0.21 for HGA and 0.1 for HME. For females, the rates were 0.16 for HGA and 0.06 for HME.

Age

• Cases are reported more frequently in adults than in children. The highest age range is between 40 and 64 years.
• Elderly patients (>60 y) are more likely than others to develop severe infections and account for most of deaths due to this disease.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The histories for HME, HGA, and E ewingii infection are similar and may include the following:

• Tick bites or exposure (>90% in 1 series) (Patients usually present within 1 week of tick bite.)
• Fevers (>90%)
• Headaches (>85%)
• Malaise (>70%)
• Myalgias (>70%)
• Rigors (60%)
• Nausea (40%)
• Vomiting (40%)
• Anorexia (40%)
• Confusion (20%)
• Rash (10%) (These can occur anywhere on the body, not necessarily at the site of the tick bite.)

Physical

No specific findings that assist in making the diagnosis are evident on clinical examination.

Causes

Target cells for the pathogens are macrophages or granulocytes.

• In HME, the following ticks may affect the macrophages:
• • Lone-star tick (Amblyomma americanum)
  • American dog tick (Dermacentor variabilis)
• In HGA, the following ticks may affect the granulocytes:
• • Blacklegged tick (Ixodes scapularis)
  • American dog tick (D variabilis)
• In E ewingii infection, the Lone-star tick (A americanum) may affect the granulocytes.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The CBC count may indicate the following:
• • Leukopenia
  • Thrombocytopenia
  • Morulae in peripheral granulocytes (25-80%) but not in monocytes (Morulae are cytoplasmic vacuoles in which Ehrlichia species grow.)
• Wright staining of blood smears may be performed. Blood smears may only be positive in up to 60% of cases.
• Mild-to-moderate elevations of aminotransferase levels may be present.

Other Tests

• Indirect fluorescent antibody test
• • HME is present with a 4-fold increase in the antibody titer (minimum titer, 1:64) or a single high antibody titer (>1:128).
  • HGA is present with a 4-fold increase in the antibody titer (minimum titer, 1:80).
• Polymerase chain reaction
• • PCR is a research tool available in selected hospitals.
  • The Centers for Disease Control and Prevention perform this test, but submission of samples requires prior approval.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

Do not delay treatment to wait for confirmatory laboratory results. With a strong suspicion of ehrlichiosis, start antibiotic treatment as soon as possible.

Consultations

Consult an infectious disease specialist, particularly if the patient is a child or is pregnant.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antibiotic treatment should begin as soon as the diagnosis is ascertained. Antipyretics may be necessary.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In/Out Patient Meds

• Continue doxycycline for 3 days after defervescence, for a minimum of 5-7 days.

Deterrence/Prevention

• Wear light-colored clothes.

• Tuck pants into socks.

• Use insect repellent.

• Regularly examine the body for ticks.

• Promptly remove ticks by using forceps. (A feeding period of 3-48 h is required before disease is transmitted.)

Complications

• Compared with other patients, elderly patients have a higher risk of death.

• Laboratory test results are necessary to make the diagnosis.

• An alternative antibiotic for children aged 8 years or younger and for pregnant patients is not available.

Prognosis

• A favorable outcome is associated with the early use of antibiotics.

• Many cases of HGA and HME may be subclinical and self limited.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to determine a history of tick bite
• Failure to consider the diagnosis in patients with flulike symptoms during the summer season

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Aguero-Rosenfeld ME, Horowitz HW, Wormser GP, et al. Human granulocytic ehrlichiosis: a case series from a medical center in New York State. Ann Intern Med. Dec 1 1996;125(11):904-8. [Medline].
• Bakken JS, Dumler JS, Chen SM, et al. Human granulocytic ehrlichiosis in the upper Midwest United States. A new species emerging?. JAMA. Jul 20 1994;272(3):212-8. [Medline].
• 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].
• 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].
• 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].
• Dumler JS, Bakken JS. Ehrlichial diseases of humans: emerging tick-borne infections. Clin Infect Dis. May 1995;20(5):1102-10. [Medline].
• Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann Intern Med. May 1 1994;120(9):736-43. [Medline].
• Heilpern KL. Update: human ehrlichiosis--Maryland and Wisconsin, 1994. Ann Emerg Med. Jul 1998;32(1):108-10. [Medline].
• Maeda K, Markowitz N, Hawley RC, et al. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med. Apr 2 1987;316(14):853-6. [Medline].
• McQuiston JH, McCall CL, Nicholson WL. Ehrlichiosis and related infections. J Am Vet Med Assoc. Dec 15 2003;223(12):1750-6. [Medline].
• Schaffner W, Standaert SM. Ehrlichiosis--in pursuit of an emerging infection. N Engl J Med. Jan 25 1996;334(4):262-3. [Medline].
• Strle F. Human granulocytic ehrlichiosis in Europe. Int J Med Microbiol. Apr 2004;293 Suppl 37:27-35. [Medline].
• Walker DH, Dumler JS. Emergence of the ehrlichioses as human health problems. Emerg Infect Dis. Jan-Mar 1996;2(1):18-29. [Medline].

Article Last Updated: Feb 9, 2007