Ehrlichia

• Causes human monocytotropic ehrlichiosis, aka. "Rocky Mountain spotless fever"

Background

Microbiology

• Small, obligately intracellular Gram-negative bacteria
• Related to Anaplasma and Rickettsia genera
• E. chaffeensis is the most common cause of human infection
• E. ewingii, E. muris, R. muris-like agent, E. canis, and E. ruminantium can all cause human disease, with slightly different tick vectors and mammalian hosts
• Cells have two ultrastructural forms: larger reticulate cells (RC) and small, dense core cells (DC)
• Intracellularly, they form aggregates called morulae (mulberries)

Epidemiology

• E. chaffeensis is primarily found in south-central and eastern North America
• Vectors are a variety of ticks:
  • E. chaffeensis is transmitted by Amblyomma americanum ticks (the Lone Star tick)
  • E. ewingiiis transmitted by Amblyomma americanum and Dermacentor variabilis
  • E. muris is transmitted by Ixodes persulcatus and Haemaphysalis flava
  • E. muris-like agent is transmitted by Ixodes scapularis
  • Of note, it is not transmitted transovarially in the ticks
• Reservoirs
  • The main reservoir is White-tailed deer
  • For E. chaffeensis, others include humans, dogs, coyotes, and marsh deer
  • For E. ewingii, dogs, humans, and deer
• Rick factors
  • Incidence peaks in May to August
  • Exposure is rural or suburban, and usually involves recreational, peridomestic, occupational, and military activities
    • Therefore, 60% male

Pathophysiology

• After inoculation, spreads lymphangitically and hematogenously to reach and invade macrophages and granulocytes
  • Intracellular morulae also found in blood, bone marrow, liver, lymph nodes, spleen, and CSF macrophages
  • Affects almost any organ except for endothelium
• Surface porin proteins are responsible for antigenic variation and host cell adhesion
• The dense core cells also secrete TRP120, which is involved adhesion but also has effects on host cell DNA and DNA transcription
• DC cells predominate soon after infection, then give way to RC cells
• Most of the pathology is caused by host responses, including toxic shock
  • Increased TNF-alpha, IL 1-alpha and 1-beta, IL-6, IL-10, and defective Th1 cytokines (IFN-gamma and IL-2)

Clinical Presentation

E. chaffeensis (human monocytotropic ehrlichiosis)

• Usually causes a mild-to-severe multisystem illness in immunocompetent
  • Can cause overwhelming infection in immunosuppressed, especially HIV/AIDS
• Incubation period of 7 days
• Fever, headache, myalgias, and malaise are most common
• Nausea and vomiting in a half, and weight loss
• Can also have diarrhea, rash, cough, altered mental status
  • Rash is maculopapular or petechial, and more frequent in children
• Often accompanied by leukopenia, thrombocytopenia, and anemia
  • Likely from peripheral consumption rather than bone marrow suppression
  • Causes neutropenia and lymphopenia
  • Thrombocytopenia usually not severe
  • Bone marrow may show a compensatory hypercellularity
• Elevated liver enzymes is almost universal, and AKI in a third of patients
• Severe complications include ARDS, DIC, and death
  • Also, hemophagocytic lymphohistiocytosis with E. chaffeensis
• 50% of cases require hospitalization, and 10% have severe complications, and 2-3% die
• The illness usually lasts about 3 weeks (1 week in hospital), followed by prolonged convalescence

E. ewingii and E. muris

• Mostly affects immunocompromised patients
• Presents similarly to HME, but less severe

Differential Diagnosis

• Rocky Mountain spotted fever

Diagnosis

• Should be treated empirically without waiting for diagnosis
• Major method of diagnosis is IFA serology, looking for a fourfold rise in titres over the course of disease, with a minimum peak of 1:64
  • Usually peaks at 6 weeks
• Diagnosis can be suggested by morulae on blood film (in monocytes), but insensitive unless overwhelming infection
• Culture not used outside of research
• PCR is possible

Management

• Doxycycline 100 mg po bid
• Can use rifampin as second-line, for pregnant women and children