Human Granulocytic Anaplasmosis, Human Monocytic Ehrlichiosis, and Ehrlichia ewingii Ehrlichiosis

Human Granulocytic Anaplasmosis, Human Monocytic Ehrlichiosis, and Ehrlichia ewingii Ehrlichiosis
James W. Myers
Dima Youssef
INTRODUCTION
  • Anaplasma phagocytophilum (A. phagocytohilum), Ehrlichia chaffeensis (E. chaffeensis), and Ehrlichia ewingii (E. ewingii) are tick-borne pathogens.
  • They cause human granulocytic anaplasmosis (HGA), human monocytic ehrlichiosis, and E. ewingii ehrlichiosis, respectively.
  • They cause illness in patients ranging from an asymptomatic seroconversion to mild, severe, or, rarely, fatal disease.
  • Obligate intracellular bacterial pathogens of the family Anaplasmataceae
  • Transmitted by Ixodes spp. or Amblyomma americanum ticks
  • Ehrlichia and Anaplasma have the characteristic gram-negative cell wall structure but lack important cell membrane components including lipopolysaccharide and peptidoglycan.
  • The ehrlichial cell wall is rich in cholesterol, which is derived from the host cell.
  • Cholesterol-rich cell walls may function as ligands for stimulation of innate and acquired immune responses.
CLINICAL SYNDROMES
1. Human monocytotropic ehrlichiosis: HME
Epidemiology
  • Tick-borne infectious disease transmitted by several tick species, especially Amblyomma species.
    • E. chaffeensis belongs to the family Anaplasmataceae.
    • The lone-star tick Amblyomma americanum is the main vector, but Dermacentor variabilis and Ixodes pacificus may play a smaller role as well.
      • Amblyomma ticks have three feeding stages (larval, nymph, and adult); each developmental stage feeds only once.
      • Transstadial (i.e., larva-nymph-adults) transmission of Ehrlichia occurs during nymph and adult feeding stages because larvae are uninfected.
      • Ehrlichia are not maintained by transovarial transmission.
    • White-tailed deer, Odocoileus virginianus, are the principal reservoir, but other species play a smaller role as well.
      • Dogs
      • Coyotes
      • Red foxes
      • Raccoons
      • Opossums
      • Birds
    • Missouri, Oklahoma, Tennessee, Arkansas, and Maryland are higher incidence states.
    • Some cases are reported from Asia, Europe, and Brazil, too.
    • Rates of HME of 100 to 200 cases per a population of 100,000 in endemic areas
    • Usually occur from April to September.
    • The median age for HME is 50 years.
    • Most of the patients are male.
Pathogenesis
  • The most frequently infected blood cells are monocytes, but lymphocytes, atypical lymphocytes, promyelocytes, metamyelocytes, and band and segmented neutrophils have also been infected.
  • Infected cells typically contain only one or two morulae.
  • Following entry into mononuclear phagocytes, E. chaffeensis inhibits phagolysosome fusion involving genes controlled by a two-component regulatory system.
  • E. chaffeensis also suppresses and induces host genes to facilitate their intracellular survival.
  • Downregulation of Th1 cytokines such as IL-12 and IL-18, which are important inducers of adaptive Th1-mediated immune responses.
  • Ehrlichial infection is curtailed by NKT, CD4, and CD8 T lymphocytes, antibodies, IFN-γ, IL-10, and TNF-α.
  • The toxic shock manifestations of HME are related to proinflammatory cytokines, including interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α).
Frequent Pathologic Findings of HME
  • Myeloid hyperplasia
  • Megakaryocytosis in the bone marrow.
  • Erythrophagocytosis
  • Plasmacytosis
  • Focal hepatocellular necrosis
  • Hepatic granulomas
  • Cholestasis
  • Splenic and lymph node necrosis
  • Diffuse mononuclear phagocyte hyperplasia of the spleen, liver, lymph node, and bone marrow
  • Perivascular lymphohistiocytic infiltrates of various organs including kidney, heart, liver, meninges, and brain
  • Interstitial mononuclear cell pneumonitis
  • Lymphohistiocytic foci, centrilobular and/or coagulation necrosis, Kupffer cell hyperplasia, and marked monocytic infiltration.
General Clinical Features
  • Incubation period ranges from 5 to 21 days with a mean of 7 days.
  • HME is a more severe disease than HGA or human ewingii ehrlichiosis (HEE), with 42% of cases requiring hospitalization, and a case-fatality rate of 3%.
  • Seventeen percent of patients develop life-threatening complications, especially if the patient is immunocompromised.
  • Prodrome is characterized by malaise, low-back pain, or gastrointestinal symptoms, or the patient may develop sudden onset of fever (often >39°C).
  • Fever (>95%)
  • Headache (60% to 75%)
  • Myalgias (40% to 60%)
  • Nausea (40% to 50%)
  • Arthralgias (30% to 35%)
  • Malaise (30% to 80%)
  • Cough, pharyngitis, lymphadenopathy, diarrhea, vomiting, abdominal pain, and changes in mental status (10% to 40%)
  • A skin eruption is relatively common among children with HME, occurring in 66% of pediatric cases compared to 21% of adults.
  • Rash is seen in 10% of cases of HME
    • Most often maculopapular.
    • Petechial
    • Erythroderma
    • Usually spares the face, palms, and soles of the feet.
  • Less frequently reported: conjunctivitis, dysuria, and peripheral edema.
  • Altered mental status and abdominal pain (in children and pregnant women).
  • Complications with HME
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Jun 22, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on Human Granulocytic Anaplasmosis, Human Monocytic Ehrlichiosis, and Ehrlichia ewingii Ehrlichiosis

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