??? (Enterovirus)

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??????????

• ????????
• ??? ???

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??? (Enterovirus)

• ?? Picornaviridae (pico? rnaRNA)
• ???????????? 30 nm??????? RNA ()
• ???????
• ????? (50oC 1 hr)
• ??? (0.3)???? (0.1N)?? (0.3-0.5 ppm)

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??? (Enterovirus) 67 ?

• ?????? ???????
• ??? (coxsackievirus)
• A ? 1-24 (A23 ??) ? 23 ?
• B ? 1-6 ? 6 ?
• ?? (echovirus)
• 1-34 (8,10,28 ??) ?31 ?
• enteric cytopathogenic human orphan virus
• ???? (newer enteroviruses)
• 68, 69, 70, 71

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???????

• ???? ????
• ???????? ????
• ????????
• ????
• ???????????
• ??????????
• ???????

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NTUH Experience Year 1998

• 1871 outpatients hand-foot-mouth disease or
  herpangina
• Male/female1.8
• 8.8 lt12 M/O
• 71.8 1-4 Y/O
• 18.6 5-14 Y/O
• 0.8 gt15 Y/O

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Number of cases and outcome of severe HFMD and
herpangina in Taiwan, 1998
Ho, M. et al., N Engl J Med 1999341929-35. Liu
CC, et al., J Clin Virol 20001723-30.
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?????

• ????????????
• ?????????
• ?????????????
• ??????
• 40-90

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?????

• ???
• ???
• ??
• ????
• ??????
• ??? 70 ? ? ????????
• ????
• ??????????????

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?????

• ?? ???
• ???? ??
• ???? (minor viremia)
• ?????
• ??
• ????
• ??
• ???

?????? (major viremia)
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?????

• ??? 2-3 ? (1-35 ?)
• ??? -3 -- 35 ?
• ????
• ?? ??????
• ???
• ????

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???????

• ?????
• ????
• ????????,??????
• ??????
• ????????
• ???????

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??????

• ????????
• ???? ??
• ???? (???????????)
• ????? (meningeal sign)
• ????? ???
• ??????

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?????

• ??????????????????
• ???? ??
• ???? (???????????)
• ?????? (meningeal sign)
• ????????
• ????? ????
• ??????,??????????

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??????

• ????
• ??????? 1-2 ?
• ?
• ??????????? ????
• ?????????
• X ? ????????
• ????????

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???????? ?????
????? ?? ?? ?????? ??? 1/5
-- 2/3 ??? B ??? (B1-B4) ??
11 ?
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Enterovirus Neonatal infection

• Most vulnerable age for severe infection
• 666 neonates
• culture at 24 hr, 1 wk, 2 wk, 3 wk, 1 mo
• nonpolio infection 12.8
• risk factors
• lower socioeconomic status
• lack of breast-feeding
• 50/100,000 coxsackie B
• vs 12/100,000 herpes simplex infection

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?????

• ??
• ????
• ?? ???? 4-5 ?
• ??
• ????
• ????????

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?????

• ?????
• ??
• ????
• ???
• ?????
• ????? (IVIG)
• ????,?????????????
• Immune modulation (??????)

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?????

• ????????
• ??
• ??
• ??????
• ???????
• ?? ?
• ??????, ? Salk ???? (IPV)

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??? 71 (Enterovirus 71)

• 1969 ???????????
• ???????????????????
• ???????

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??? 71 (Enterovirus 71)

• ???????
• ?????
• ????
• ?????? (polio-like syndrome)
• 10-30 ???????
• 1/2 ??????
• ?????????????

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1998 ??? 71 in Taiwan I

• ???? 1980 ??, 1986 ??, 1995(?) ?? AFP ?? ? 5-6
  ????? ?
• ????????????
• ???????????
• ????? ? ??????????????????????? ? ????
• ???? ? ????? ? ????

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1998 ??? 71 in Taiwan II

• ???
• ?????
• ???????
• 50-75 ?????????
• ??? ? 1-10/100,000
• ????
• ????
• ???? (?????)
• ????

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???????
Polio Cox A Cox B ECHO
????
??????
???
????? - -
??? - - -
????? -
???? - (EV71)
?? -
?????
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The clinical course of EV71 Infections

• Stage 1 Onset
• HFMD, herpangina, fever
• Stage 2 Encephalomyelitis
• Limb weakness, lethargy, headache, vomiting,
  upward gaze, seizure
• Stage 3 ANS dysfunction (Present Stage 3A)
  Neurogenic bladder, paralytic ileus, insomnia,
  profuse sweating, hyperglycemia, leukocytosis,
  tachycardia
• Stage 4 Pulmonary edema (Present Stage 3B)
• Tachypnea, hypoxia, shock
• Chang LY, et al.
  Lancet 1999

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Staging of EV71 Infection Patient

• Neurologic syndrome
• Aseptic meningitis
• Rhombencephalitis
• Grade I (myoclonus with tremor, ataxia, or both)
• Grade II (myoclonus with cranial-nerve
  involvement)
• Grade III (rapid cardiopulmonary failure)
• Acute flaccid paralysis

• Stage I hand, foot, and mouth disease
• Stage II meningoencephalitis
• Stage IIIa ANS dysregulation
• Stage IIIb cardiovascular collapse, pulm edema
• Stage IV recovery

Lin, et al. Clin Infect Dis 200234(suppl
2)S52-57
Huang, et al. N Engl J Med 1999 341936-42
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???????

• ?????????????????????????????
• ??
• 1. ??????,???????????????
• 2.??????????(??????????????????????????????)?
• 3. ???????????????,??????,??????????????????39???
  ??3??????? (myoclonic jerk) ??????????????????????
  ?(gt150mg/dl)??????(gt17500/mm3)?

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???????

• ??????
• ?????????
• ??

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???????

• Fluid restriction and administration of osmotic
  diuretics for those with signs of increased
  intracranial pressure
• Furosemide for those suspected having fluid
  overload
• IVIG was administered
• Blood pressure, oximeter, coma scale and blood
  sugar were closely monitored
• Patients were managed in ICU if they had
  tachypnea/apnea, hypertension/hypotension, signs
  of increased intracranial pressure or
  hyperglycemia

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?????????

• ???????,?????????????

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?? (encephalitis)

• ????????,?????????????,???????,????????,?????????

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?????????

• Patients in Stage 3 when they required ventilator
  support and inotropic agents
• Stage 3A (hypertension and pulmonary edema)
• ICU management continuous fluid restriction,
  administration of milrinone to control severe
  hypertension and to increase cardiac output
• early intubation with positive pressure
  mechanical ventilation with increased positive
  end expiratory pressure for pulmonary edema
• High frequency oscillatory ventilator was
  considered if pulmonary edema or hemorrhage
  persisted or if patients developed severe
  hypoxemia
• Stage 3B (hypotension). When a patient