Topic Enterovirus by Thun
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Transcript of Topic Enterovirus by Thun
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ENTEROVIRUS
.
7/11/2554
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Abbreviation h/o history of
b/o because of
usu usually
occ occasionally
p/w present with
w/ with
w/o with out
CVA coxsakievirus A
CVB coxsakievirus B
EV Enterovirus
HFM Hand-foot-mouth
P plasma cell
M macrophage
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Virology Non-enveloped, icosahedral capsid
ssRNA
family Picornaviridae
Unlike other picornaviruses, Enterovirus
are stable over the wide range of pH
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http://pathmicro.med.sc.edu/virol/picorna.htm
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Original 5 subgenera1. Poliovirusesserotypes 1-3
2. Group A coxsackievirusesserotypes 1-22, 24
3. Group B coxsackievirusesserotypes 1-6
4. Echovirusesserotypes 1-9, 11-21, 24-27, 29-33
5. Enterovirusesserotypes 68-71
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Virology named b/o ability to multiply in GI
not a prominent cause of gastroenteritis
Susceptible to chlorine but resistant to
alcohol, detergents
Persist for days at room temperature
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How Important second most common viral infection after
Rhinovirus
Infants, children, and adolescents are
more likely to be susceptible
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PATHOGENESIS
Derived from studies of poliovirus Epithelium in GI submucosal lymphoid
regional LN (minor viremia)replication inRE (MAJOR viremia)
Spread directly from muscle to CNS
Limited to primates, bz their cells expressviral receptor
BCx 3-5 d after infection Shed from oropharynx up to 3 weeks, from
GI tract up to 12 weeks
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IMMUNITY
Serotype specific
Neutralizing Ab target on Capsid protein VP1
Humoral & Secretory immunity
IgM in 1-3 days disappear w/n 2-6 mo
IgG in 7-10 days (mostly IgG1, IgG3) persist for life
IgA (nasal/alimentary) in 2-4 wks/ persists for 15
yrs
CMI
Pt w/ CMIR defect severe enterovirus infection
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Epidemiology
Worldwide > 50% nonpoliovirus/ >90% poliovirus are
subclinical
Low socioeconomic (crowded, tropical,poor hygiene)
Infants, young children
Temperate climate; more in summer andfall
Tropics; no seasonal pattern
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TRANSMISSION
Shed in feces and respiratory tract secretions Direct and Indirect transmission
Swimming in seawater
EV 70, which causes acute hemorrhagicconjunctivitis, is spread by fomites, fingers, andophthalmologic instruments
via Placenta severe disease in Newborn
Infants in diapers who shed virus in the feces arethe most efficient disseminators of infection
No infected via blood transfusions or insect bites
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POLIOVIRUS
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Introduction
Polios gray
Myelos marrow or spinal cord
3 serotypes1. Wild type
2. Live attenuated OPV3. Vaccined derived poliovirus (cVDPVs)
Involve neurons in the grey matter, esp in anteriorhorns of spinal cord
Incubation 9-12 d Poliovirus can be isolated from spinal cord for first
few days after onset of paralysis
Permanent weakness 2/3 of pt
Poor prognosis; severe, require ventilator
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Clinical manifestations
unapparent illness severe paralysis death
Asymptomatic
Abortive poliomyelitis
manifested by fever, malaise, sore throat,anorexia, myalgias, headache, resolve in 3 d
Nonparalytic poliomyelitis Present of meningeal irritation
More systemic symptoms
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Manifestations
Spinal paralytic Biphasic phase but adult usu experience single
phase w/ prolonged prodrome symptoms
Severity varies from weakness of one muscle to
complete quadriplegia Asymmetrical distribution
Proximal > distal
Large muscle > small muscle
Most common pattern is one leg > one arm > alllimbs
Progression of weakness stops when afebrile
Sensory loss is rare
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Manifestations
Bulbar paralytic Dysphagia,pooling of secretions, nasal speech,
sometimes dyspnea
9thand 10thCN are most common
Most serious = involve circulatory andrespiratory centers
Polioencephalitis
Uncommon form
Principally in infants
Seizure are common, indistinguishable from otherviral encephalitis
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Complications
Paralysis of respiratory muscle
Airway obstruction due to CN
involvement
Myocarditis
GI hemorrhage
Paralytic ileus
Gastric dilatation
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Diagnosis
CSF indistinguishable from other viral
Isolated from throat in 1stweek, from
feces for several weeks
Unlike other enterovirus, poliovirusesrarely isolated from CSF
Isolation from CSF in evaluating cVDPVs
Serologic tests can not distinguishbetween wild type and vaccine type
infection
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Postpoliomyelitis Syndrome
New onset of weakness, fatigue,fasciculations, pain w/ atrophy, many years
after illness
Typically, involved muscles are the same Peak 25-35 y after acute poliomyelitis
Prognosis is good
Plateau in 1-10 y
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Poliovirus Immunization
Live attenuated vaccine immunity probably lifelong
2, 4, 6, 18 4-6
Inactivated vaccine DPT, HiB,
HeB 4, 5 6
http://en.wikipedia.org/wiki/Polio_vaccine " ...
http://en.wikipedia.org/wiki/Polio_vaccinehttp://en.wikipedia.org/wiki/Polio_vaccinehttp://en.wikipedia.org/wiki/Polio_vaccine -
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Vaccine associated Poliomyelitis
OPV 1 in 2.5 million doses
2000x in immunodeficient, esp
hypo/agammablobulinemia
No case report since 1999
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Treatment
Supportive
Hot moist packs
Physical therapy
Mechanical ventilation
Postural drainage, suction
Catheterization
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ENTEROVIRUSES
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SUMMER GRIPPE(Nonspecific febrile illness)
Grippe (old term) = Influenza Freq occurs in summerand early fall
other respiratory virus often late fall and earlyspring
Most common manifestationof Enterovirus
Manifestations Incubation 3-6 d
Last for 3-4 d
Indistinguishable from rhinovirus, mycoplasma pneumonia,
unless accompanied by aseptic meningitis, exanthem or otherclinical features of enterovirus
Coryza
Laryngotracheobronchitis (Croup)
Bronchiolitis
Pneumonia; interstitial/ patchy
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GENERALIZED DISEASE OF THENEWBORN
Most serious in 1stweek of life but up to 3 mo
Resembling bacterial sepsis
Vertical transmission
Fever, irritability, lethargy Leukocytosis w/ left shift, thrombocytopenia,
elevated in liver function, CSF pleocytosis
Complication; myocarditis, hypotension, fulminanthepatitis, DIC, meningitis, meningoencephalitis,
pneumonia Management;
Supportive
IVIG justified given in extremely poor prognosis b/o
lack of evidence
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Acute viral meningitis 90% of children/young adult
class B enteroviruses (CVB, Echovirus)
Manifestation in infants < 3 mo highest rates of aseptic meningitis, bz LP are routinely
performed minority have symptoms
Manifestations in Children/young Adult more severe, onset is gradual or abrupt
Fever, chills headache, meningismus in 1/3, photophobia,pain on EOM
Pharyngitis and URI often present
sometimes biphasic, as in poliomyelitis
May take weeks to return to normal activity
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Acute viral meningitis
CSF WBC usu 10-500 and occ 500-1,000 or
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Acute viral meningitis
DDx incompletely rx bacterial meningitis
Arboviruses
Lymphocytic choriomeningitis virus
Leptospirosis
Lyme borreliosis
HIV
Mumps
TB meningitis
Management/ Prognosis conscious, weakness, petechial/purpura more serious
illness
Paracetamol
Pleconaril, progress in clinical trials reduce duration
Children, fever and meningismus subside in few days1 wk
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Encephalitis
Less common (Aseptic meningitis >> Encephalitis) CVA 9, CVB 2,5, Echovirus 6,9, EV 71
Perinatal; only one of generalized viral symptoms
Manifestions in children/Adult mild encephalopathy to severe generalized encephalitis w/
seizure, paresis, coma Partial motor seizure
Hemichorea
Acute cerebellar ataxia
EV 71 brainstem encephalitis noncardiogenic
pulmonary edema Hypogammaglobulinemia, agammaglobulinemia, severe
combined immunodeficiency chronic meningitis,encephalitis
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Paralytic diseases by non-polioEnterovirus
CVA, CVB, EV
Outbreaks of poliomyelitis-like in Russia, Eastern Europe,Thailand, Taiwan, India
Manifestations Less severe than poliovirus
Weakness > Flaccid
CN involvement unilateral oculomotor palsy
GBS; CVA 2, 5, 9, Echovirus 6, 22 Transverse myelitis; CVB 4, Echovirus 5
Chronic fatigue syndrome
Dancing eye syndrome; opsoclonus-myoclonus , CVB 3
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Chronic meningoencephalitis inImmunocompromised
Agammaglobulinemic host
Echoviruses
Manifestations
Varies from absent, nuchal rigidity, headache,papilledema, seizure, weakness, tremors, ataxia
Fluctuation, disappear, steadily progress
Dermatomyositis like syndrome > 50% Some w/ Chronic hepatitis
CSF; lym, protein
Enterovirus recovered from CSF over mo-yr
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Chronic meningoencephalitis inImmunocompromised
Prophylaxis/Management IVIG but relaspe even after long term use
Pleconaril?
Other Immunocompromised host CVA 1
Hematopoietic cell allograft
Difficult to distinguish from GVH enteritis
Receiving Anti-CD 20 (rituximab)
CNS infection
Paralysis
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1. Rubelliform and Morbiliform
2. Roseoliform
3. Herpetiform
4. Petechial and Purpuric
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Exanthems1. Rubelliform or morbiliform
Echovirus 9
Common < 9year-old
Rash w/ fever simultaneously
Face Neck Chest Extremities
Season LN Pruritus CoryzaConjunctivitis Enanthem
Echovirus
Summer
-
-
-
Koplik like
Rubella + +Measle + Koplik spot
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Exanthems2. Roseoliform
As in roseola, rash does not appear untill
defervescence
Fever last 24-36 h then; Discrete, nonpruritic, salmon-pink MP ~ 1 cm
on face, upper part of chest (persist 1-5 d)
Boston exanthem; Echovirus 16
CVB 1, 5, Echovirus 11, 25
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Exanthems3. Herpetiform exanthems
HFM
Herpangina
4. Petechial Echovirus 9, CVA 9
Confused w/ meningococcus if aseptic
meningitis occur simultaneously Gianotti-Crosti syndrome; a/w CVA 16
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Hand-Foot-Mouth Disease
EV 71 outbreaks in SEA a/w severe CNS
CVA 16, EV 71
Incubation 4-6 d
< 10 y
Manifestations
Fever, anorexia, malaise
sore throat
tendervesicular on buccal mucosa, tongue, dorsum of
hands, palms
Vesicle may form bullae and quickly ulcerate
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Hand-Foot-Mouth Disease
Eczema coxsakium; disseminated in infant w/preexisting atopic eczema
Highly infectious; attack rate 100% among youngchildren
Resolve in 1 wk DDx
Herpes simplex
Chicken pox; oral lesion is less
Herpetic gingivostomatitis; more ill, CLN +ve
Herpangina; posterior pharynx
Complications; CNS disease, myocarditis,pulmonary hemorrhage
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Herpangina Herpes = vesicular eruption Angina = quinsy or inflammation of throat
Vesicular enanthem of fauces, soft palate + fever
sorethroat, odynophagia CVA> CVB, Echovirus, EV
Sorethroat precede enanthem several hr to day
Fever subside w/n 2-4 d
papulovesicular lesion on erythematous base
persist for week
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Herpangina Variant: Acute lymphonodular pharyngitis
Constrast to herpes stomatitis, EV is not a/w
gingivitis
DDx
Bacterial tonsillitis
Viral pharyngitis
HFM disease
Aphthous
stomatitis
Herpetic
gingivostomatitis
B h l di
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Bornholm disease(Pleurodynia)
CVB, rare echovirus, CVA
Acute enteroviral infection of skeletal muscle
Chest pain more common in adults
Abdominal pain more common in children
1stdescribed in 1872 by Daae and Homann as
acute muscular rheumatism spread by contagion
Involved muscle are tender to palpation Pathogenesis
Believe that direct viral invasion of muscles but lack
evidence support
B h l di
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Bornholm disease(Pleurodynia)
Manifestations
No prodrome, begin w/ abrupt onset
Spasmodic and relapsing
Lower rib cage or upper abdominal region
Fever, sorethroat, headache may occur, but no
coryza
Aseptic meningitis, orchitis may occur in < 10% If severe, pt lies still in bed, appears acutely ill
Persist for 4-6 days
B h l di
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Bornholm disease(Pleurodynia)
DDx
Pneumonia
Pulmonary infarction
MI
Pre-eruptive phase of Zoster
Acute abdomen
Management Analgesics; Paracetamol, NSAIDs, Opioids
Application of heat
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Other skeletal myositis
Generalized polymyositis Focal myositis
Localized to thighs
Fever, chills, weakness, CK, edema ofinvolved muscle groups
Myoglobinemia, myoglobinuria
Recovered rapidly
Dermatomyositis-like; B-cell deficient w/persistent EV infection
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Myopericarditis CVB, CVA 4, 16, Echovirus 9,22
Other; adenovirus, Influenza A, parvovirus B19, mumps virus,vaccinia virus, M.pneumoniae, RSV, EBV, VZV, measles
2/3 are male
Pathogenesis Reach the heart during MAJOR viremia
Replication in myocytes myocyte necrosis focalinfiltration of PMN, Lym, P, M
Healing insterstitial fibrosis, myocyte loss
Manifestations 2/3 p/w URI 7-14 d chest pain, dyspnea, arrhytmias, HF
asymptomatic intractable HF and death
EKG; ST-T changes, Q waves, VT, heart block
Up to 10% DCM
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Myopericarditis
Diagnosis Recovery agent from oropharynx, feces, serologic of
recent infection
Pericardial fluid, Heart muscles biopsy but rarelyavailable
Management Bed rest, pain relief, rx HF, arrhythmias
Pleconaril, effective in small number of patients, but noRCT
IVIG, prednisolone
RCT failed to show benefit Course and Prognosis
Persistent abnormal EEG (10-20%), cardiomegaly (5-10%), chronic HF, chronic constrictive pericarditis
Prognosis; children better than adults
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Acute hemorrhagic conjunctivitis
EV 70, CVA 24 Transmission
Contagious and spread rapidly
Finger or fomites directly to the eye
Crowding and unsanitary living, poor Reuse of water for bathing, sharing towels
Manifestation Begin abruptly and peak w/n 24 h
Severe eye pain, blurred, photophobia, waterydischarge begin in one eye rapidly progress toother
Edema, chemosis, subconjunctival hemorrhage 70-90%
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Acute hemorrhagic conjunctivitis
Punctate keratitis, conjunctival follicles
Tender preauricular adenopathy
Recovery in 10 days
Diagnosis
Conjunctival swabs during first 3 d Complications
Secondary bacterial infection
Acute motor paralysis
DDx Epidemic keratoconjunctivitis by adenovirus
Treatment and Prevention Symtomatic
Good sanitation
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Gastrointestinal diseases
Acute hepatitis CVB, EV
Mild and self limited
Acute pancreatitis CVB 1, 5, EV 6, 11, 22, 30
Viral gastroenteritis ?
Epidemic diarrhea EV 11, 14, 18
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Other manifestations
Common cold Type 1 Diabetes?
Parotitis
Bronchitis
Bronchiolitis
Croup
Infectious
Lymphocytosis
Polymyositis Acute arthritis
Acute nephritis
HUS?
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http://pathmicro.med.sc.edu/virol/picorna.htm
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Treatment
Mild and resolve spontaneously Intensive supportive care may be needed
for cardiac, hepatic, CNS disease
IVIG, ITIG, IVTIG in enteroviralmeningoencephalitis and dermatomyositis
in pt w/ hypogammaglobulinemia,
agammaglobulinemia
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References