Human Ehrlichiosis

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Human Ehrlichiosis

• Bio488L
• 3/14/2006
• Akiko Osaki

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Introduction of Ehrlichiosis

• Ehrlichiosis-several tick-borne disease that is
  spread by a type of bacteria (Rickettsiae)
  especially ticks.
• Ehrlichiosis is caused by several bacterial
  species among the genus Ehrlichia (have been
  recognized since 1935)
• 3 species of Ehrlichia in the United States 1
  species of Ehrlichia in Japan are known to cause
  human diseases.
• Others could be recognized in the future

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Ehrlichiae

• Small, Gram (-)bacteria that invade leukocyte
  (white blood cells)
• Typically appear as minutes
• round-bacteria(cocci)
• range 1-3µm in diameter
• Ehrlichiae-in the leukocytes-divide to form
  vacuole-bound colonies-known as morulae

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Ehrlichia

• Classified as a member of the tribe Ehrlichieae
• Classified as a member of the family
  Rickettsiaceae
• In this genus-7 species
• Eg) E.canis, E.chaffeensis, E.equi, E.
  phagocytophila, E. risticii, E.ewingii, and E.
  sennetsu

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Natural History

• Many cases of human diseases-are caused by
  zoonotic pathogens-are maintained by animal host
  in their natural cycles
• Many zoonoses-require a vector
• Eg) mosquito, tick , mite
• Zoonose-are transmitted from animal host to human
  host

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Natural History 2

• Ixodidae (hard ticks)-associated with ehrlichiae
• Have 4 stages in their life cycle
• egg?larva ?nymph ?adult
• After the eggs hatch-each stage must feed once to
  develop into the next stage.
• Larvae-are uninfected with ehrlichiae when they
  begin to look for a bloodmeal
• Tick become infected with ehrlichiae-while
  feeding on blood from the host in either the
  larval or nymphal stage
• Adult stage-ehrlichiae may be transmitted to the
  following host during the feeding process.

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Natural History 3

• Both male and female ticks-may bite humans
• Most transmission-the females
• In US-nymphal and adult stage-responsible for
  transmission of ehrlichiae depends on species

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History

• In 1953-The 1st Ehrlichial pathogen of human was
  identified in Japan
• Ehrlichia sennetsu-causes Sennetsu fever and
  swollen lymph nodes.
• This disease-very rare outside the Far East and
  Southeast Asia
• Most cases-Western Japan

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History

• In mid-1980s-Human diseases caused by Ehrlichia
  species have been recognized in the United
  States.
• The ehrlichioses-a group of clinically similar,
  but epidemiologically and etiologically
  different
• Disease caused by Ehrlichia chaffeensis, E.
  ewingii, and a bacterium extremely similar or
  identical to E.phagocytophila

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In the United States(1st organism)

• Ehrilichia chaffeensis-human ehrlichiosis and 1st
  discovered in 1987
• Occurred primarily in southeastern and south
  central regions of US
• Primarily transmitter-the lone star tick,
  Amblyomma americanum

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Ehrlichia chaffeensis

• Ehrlichia chaffeensis-is transmitted by the lone
  star tick (Amblyomma americanum)
• White-tail deer-a major host of lone star ticks
  and one natural reservoir for E.chaffeensis
• The distribution of the lone star tick

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Ehrlichia chaffeensis

• Primarily infects-mononuclear leukocytes
• Predominant-monocytes and macrophages
• Occasionally-granulocytes

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In the United States (2nd organism)

• Human granulocytic ehrlichiosis (HGE)-2nd
  recognized ehrlichial infection of humans in US
• Discovered in 1994
• HGE-is transmitted by the blacklegged tick
  (Ixodes scapularis) western blacklegged tick
  (Ixodes pacificcus)
• Extremely similar or identical to the veterinary
  pathogens Ehrlichia equi and Ehrlichia
  phagocytophilia

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Ixodes scapularis

• the blacklegged tick (Ixodes scapularis)
• The distribution of Ixodes scapularis-in the
  northeastern and upper midwestern US

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Western blacklegged tick (Ixodes pacificcus)

• western blacklegged tick (Ixodes pacificcus)
• The distribution of Ixodes pacificcus-in northern
  California

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Human granulocytic ehrlichiosis(HGE)

• Primarily infects-granulocytes
• Eg) neutrophils and rarely eosinophils
• This species very similar or identical to
  E.phagocytophila and E. equi

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In the United States (3rd organism)

• Ehrlichia ewingii-the most recently recognized
  human pathogens
• Occurred in Missouri, Oklahoma, and Tennessee
• Most-underlying immunosuppression

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Ehrlichia ewingii

• Not known completely
• dogs-reservoir host
• Vector-the lone star tick (Amblyomma americanum)
• Cause Canine granulocytic ehrlichiosis
• Discovered in south central and southeastern
  states-Arkansas, Georgia, Mississippi, Missouri,
  North Carolina, Oklahoma, Tennessee, and Virginia
• Human cases-in Missouri, Oklahoma, and Tennessee

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Ehrlichia ewingii

• Primarily infects-neutrophils
• Occasionally infects-eosinophils
• Produces-a disease clinically similar to HME and
  HGE.

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Signs and Symptoms (acute phase)

• The acute stage of the disease-occurs most-in
  spring and summer
• lasts 2-4 weeks
• Clinical sign fever, muscle aches, bleeding
  disorders, and vasculitis, vomiting, nausea,
  diarrhea, cough, join pain, confusion, and
  occasionally rash

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Signs and Symptoms (Chronic phase)

• Clinical sign pale gums due to anemia, bleeding
  due to thrombocytopenia, vasculitis, coughing,
  polyuria, polydipsia, lameness, ophthalmic
  diseases-such as retinal hemorrhage and anterior
  uveitis and neurological disease
• Ehrlichiosis can be a severe disease especially
  if untreated

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Signs and Symptoms (severe cases)

• Patients-require hospitalization
• Severe manifestations of the disease prolonged
  fever, renal failure, intravascular coagulopathy,
  meningoencephalitis, disseminated, adult
  respiratory distress syndrome, seizures
• The severity of ehrlichiosis may be related in
  part to the immuno status of the patient
• ? Persons who are immunocompromised-caused by
  immunosuppressive therapies
• Eg) cortiocosteroids or cancer chemotherapy
• ?HIV infection, or splenectomy

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Diagnosis and Laboratory Detection

• 3 type methods
• Serologic-indirect immunofluorescence assay (IFA)
• Molecular-amplification of the ehrlichial DNA by
  PCR
• Culture-based

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Diagnosis and Laboratory Detection(serologically)

• Serologic testing of blood-to detect the presence
  of antibodies against the ehrlichia organism by
  indirect immunofluorescence (IFA)
• Abs in the serum bind to the organisms on a slide
  and detected by a fluorescein-labeled conjugate
• Problems there is not standardized Ag, conjugate
  or agreement on what constitutes a positive
  result

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Serologic detection

• Problems-during the acute phase of infection-test
  can be falsely negative because the body will no
  have had time to make antibodies to the
  infection.
• Solve-test should be repeated
• Blood tests-if the disease is present-abnormalitie
  s in the members of red blood cells, white blood
  cells and platelets.

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Molecular Detection

• Amplification of the ehrlichial DNA by PCR
• Among the individual-analytical and diagnostic
  sensitivity -change
• In HGE, the organism detected by PCR from the
  blood of clinically ill patients 3-5 weeks

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Culture-based

• Direct isolation of the organism
• Problems most difficult and time-consuming
  approach E. chaffeensis-typically has been
  observed within 7-36 days in culture
• HGE agent-has been seen within 7-12 days after
  inoculation of cells with patients blood

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Treatments

• Treatment for ehrlichiosis-use the antibiotics
  such as tetracycline or doxycycline for at least
  6-8 weeks
• Fever-subside within 24-72 hours after treatment
  with doxycycline or tetracycline (response to the
  drugs)-keep dosing drugs at least 5 days
• Rifampin for pregnancy

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Prevention and Control

• Most effective prevention-to control tick by
  limiting exposure to ticks
• Removal of attachment ticks
• Tetracycline at a lower dose-daily for 200 days
  during the tick season in endemic regions.