William Kwan UNC Medicine-Pediatrics The Ehrlichioses William Kwan UNC Medicine-Pediatrics

Objectives Overview of 3 human Ehrlichioses Microbiology Epidemiology Diagnosis Treatment

Microbiology of Ehrlichiae Gram-negative obligate intracellular bacteria that grow in vacuoles (morulae) Two Ehrlichiae species and Anaplasma cause three forms of human Ehrlichioses Ehrlichia chaffeensis Ehrlichia ewingii Anaplasma phagocytophila

Human Monocytic Ehrlichiosis (HME) Agent: Ehrlichia chaffeensis Vector: Lone Star tick (and sometimes Dog tick) Higher prevalence during late spring and early summer Southeast, south central, and mid-Atlantic Fever (97%), malaise (84%), headache (81%), myalgia (68%) Diarrhea (25-68%), rash (36%, but only 6% at presentation), confusion (20%) Complications: ARDS, meningoencephalitis, fulminant infection, hemorrhage Mortality in 2-5% Leukopenia (60-74%), thrombocytopenia (72%), elevated LFT’s (90%)

Human Monocytic Ehrlichiosis (HME) Diagnosis based on clinical suspicion Most common diagnostic test: Serology using indirect fluorescence antibody to E. chaffeensis Fourfold rise in titers between acute sera (on presentation) and convalescent sera (drawn 2-4 weeks later) Single titer of 1:128 may be diagnostic but no established threshold

Human Monocytic Ehrlichiosis (HME) Peripheral blood smear or examination of buffy coat may show rare morulae (1-20%)

Human Monocytic Ehrlichiosis (HME) Peripheral blood smear or examination of buff coat may show rare morulae (1-20%) PCR techniques being developed Immunochemical staining of tissue (e.g. lymph nodes, liver, spleen, lung)

Human Monocytic Ehrlichiosis (HME) Treatment of choice: Doxycycline 100mg bid x 10 days or up to 3-5 days following defervescence Alternative choice: Rifampin 300mg x 7-10 days Pregnancy: If disease not life-threatening: Rifampin If disease life-threatening: Doxycycline

Human Granulocytic Anaplasmosis (HGA) Formerly called Human Granylocytic Ehrlichiosis Agent: Anaplasma phagocytophila Vector: Deer tick Higher prevalence during late spring and early summer Northeast Symptoms are very similar to those in HME Exception: Rash is very rare Leukopenia, thrombocytopenia, elevated LFT’s May have concurrent infection with Lyme Disease and much less commonly Babesiosis

Human Granulocytic Anaplasmosis (HGA) Initial diagnosis based on clinical suspicion Serology using IFA to A. phagocytophila Four-fold rise in titers between acute and convalescent sera Peripheral blood smear or buffy coat examination may show morulae (20-80%, higher than for HME) PCR Immunochemical tissue staining Treatment is same as for HME: Doxycycline (or Rifampin)

Ehrlichiosis Ewingii Agent: E. ewingii Vector: Lone Star tick Higher prevalence during summer Symptoms similar to HME but less severe Usually diagnosed in immunocompromised IFA utilizes E. chaffeensis antigen No criteria for diagnostic serologies Treat with Doxycycline

Take-Home Points HME and HGA are very similar diseases HME more common in southeast, south central, mid-Atlantic HGA more common in northeast HGA may be accompanied by Lyme Disease Treatment is Doxycycline 100mg bid x 7-10 days or up to 3-5 days after defervescence Rifampin may be used in pregnant patients with non-life threatening disease Bacteria cartoons are corny

References Dumler et al., “Ehrlichioses in Humans: Epidemiology, Clinical Presentation, Diagnosis, and Treatment.” The Journal of Clinical Infectious Diseases. July 2007; 45: S45-51. Kasper et al., Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw Hill, 2005. Sexton et al., “The Human Ehrlichioses.” UpToDate Online. Stone et al., “Human Monocytic Ehrlichiosis.” Journal of the American Medical Association. November 10, 2004; 292: 2263 - 227.