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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