Topic Enterovirus by Thun

8/13/2019 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


18/65http://www.discoverymedicine.com/Didier-Hober/2010/08/27/enteroviral-pathogenesis-of-type-1-diabetes/


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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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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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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

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Topic Enterovirus by Thun