Ehrlichia species

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

Background

Small, obligately intracellular Gram-negative bacteria
Related to Anaplasma and Rickettsia genera
Includes the following species:
- E. chaffeensis is the most common cause of human infection
- Other species that can cause disease in humans includes E. ewingii, E. muris, E. muris-like agent, E. canis, and E. ruminantium, 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)

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

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)

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

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