ENTEROVIRAL INFECTIONS

Dr.B.Boyle
ENTEROVIRAL INFECTIONS
Contents of Lecture
 ENTEROVIRUSES
 Also Discuss , Viruses that cause
Gastroenteritis
 ROTAVIRUS
 SMALL ROUND STRUCTURED
VIRUSES e.g Norwalk virus or
Novovirus etc.
ROTAVIRUS
 ROTAVIRUS
 Description
 Epidemiology
 Pathogenesis
 Clinical Features
 Diagnosis
 Treatment
 The Future
 ROTAVIRUS
 First described in 1973 by electron
microscopy from duodenal biopsy
specimens
 Causes 40-60% of cases of diarrhoea in
cooler months in infants and children < 2
years
 Morphology-Rotaviruses
 Reoviridae Family
 Non-enveloped icosahedral
structure, 70nm
 EM: Wheel shape
 Capsid: Outer(VP7 and 4)
and Inner(VP6) proteins
 Core encloses 11 segments
of DS RNA
Genome encoded Structural
proteins VP1-7 and NSP 1-
5, NSP4 has enterotoxinlike
activity
 Epidemiology of Rotavirus
 Incubation period : 2-4 days
 Those affected :4-24 month old infants,
infection before and reinfection after this
usually asymptomatic (Breastfeeding
results in milder disease)
 Spread within families and institutions
 Human to human, faecal-oral route
 Found on fomites in childcare
 Epidemiology of Rotavirus
 Main cause of severe diarrhoea in children < 5
years
 130 million episodes per year in the world
 Between 600,000-870,000 deaths, mostly in the
developing world
 Rate of hospitalisation in developed world 2.5%
 Seasonal pattern
 Most persons infected by 3 years of age
 Group A predominates
Classfication-Rotavirus
 Groups,Subgroups
and serotypes
depending on the
antigenic properties
of the capsid proteins
 Group-VP6, seven
exist A-G, 2
subgroups 1-2
 Groups A,B,C cause
human infection
Rotavirus-Pathogensis
Infects

Mature Enterocytes(on tips of Small

Intestine villi)

Villous Atrophy

Compensatory Repopulation by immature

Secretor cells and secondary hyperplasia
 Mechanism of diarrhoea?

Enteric nervous system

stimulates Induction
Villous epithelium in relation Of intestinal Water
To secretory capacity of And electrolyte secretion
Crypt cells

Loss of permeability to
Macromolecules e.g Lactose,
Due to loss of disaccharideases
Rotavirus Damage to Small
Intestine
 Immune Response to
Rotavirus
 Localised Immune
response protects
against severe
subsequent infections
 NSP4 protein results
in cell mediated
immunity
 Outcome of Infection with
Viruses
 Lysis of cells e.g Influenza or polio
 Persistent infection e.g. cell remains alive and
continues to release virus particles e.g. Hepatitis B
, CHRONIC CARRIER STATE
 Latent Infection , no replication – Varicella
Zoster or retrovirues , if triggered leads to lysis
 Transformation of host cells e.g. warts or
papovaviruses, HTLV 1 and 2
 Clinical Presentation-
Rotavirus
 Abrupt onset of
vomiting followed
within hours by
watery, brown
copious diarrhoea,
often lasts 3-8 days
 If Severe 
Dehydration and
death or
hospitalisation
 DIAGNOSIS
 Clinically
 Latex agglutination
Kit testing for Group A
Rv antigen in stool
Enzyme Immunoassay
Group A
Rv antigen in stool Pos and neg
Less common EM and
molecular methods
 TREATMENT
 REHYRATE, oral and if severe
parenteral
 Some studies in immunocompromised
persons showing the use of Human
Immunoglobulin results in a reduction in
the duration of symptoms and decreases
viral sheeding
 ISOLATION of patient in hospital with
contact prescautions
 MANAGEMENT
 In Home: Washing of surfaces with soap
and water which may be contaminated
with Rotavirus
 70% ethanol solution will kill the virus on
environmental surfaces
 FAMILY: PICORNAVIRIDAE
Cardiovirus
RHINOVIRUS Aphthousvirus
ENTEROVIRUSES Type 1-100+ etc
Over 72+

POLIO virus type 1,2,3

COXSACKIE A virus type 1-22,24
COXSACKIE B virus type 1-6
E.C.H.O virus type 1-7,11-27,29-34
Numbered ENTEROVIRUSES type 68-71,73
Since 1967-all new ones are numbered
E.C.H.O = enteric cytopathic human orphan
 Characteristics
 VIRON= naked , small
(25-30 nm) icosahedral
capsid enclosing postive
sense single stranded
RNA
 Enteroviruses are
resistant to p H 3-9,
Heat, Mild sewage
treatment and
detergents, conditions in
GIT = FACILATES
faecal oral spread
Characteristics
 Rhinovirus labile to
acidic p H
 Genome of
Enteroviruses is m RNA
 Naked genome is
sufficient for infection
 Replication in cytoplasm
 Cytolytic viruses
 Clinical Manifestations of EV
Infections(Mostly Children)
 Neurological: e.g
Poliomyelitis, Aseptic
meningitis and
encephalitis
 Neonate: neonatal sepsis
EV 11
 Non-specific febrile illness
 Hepatitis gi etc
 Haemorrhagic
conjunctivitis, COX A24
and EV 71
 Respiratory Symptoms e.g
colds, herangina
 Skin Exanthem with
meningitis
 Myocarditis
 Those associated with
Coxsackie viruses
 Spread: Faecal oral route ,
respiratory route and
peripartum mother to infant
or fomite transmission
 IP: 3-6 DAYS
 COXSACKIE VIRUSES
 29+ immunogenic types
 Divided into A and B on the basis of
different pathogenic potential for mice
 Result in a number of different clinical
presentations
 COXSACKIE VIRUSES
 Herangina  Hand , Foot and
 Summer minor mouth illness
illness  Myocarditis
 Aseptic meningitis  ? Diabetes mellitus
 Neonatal Disease  Epidemic myalgia
 Colds (Bornholm Disease)
 HAND/FOOT/MOUTH

Coxsackie
A16
H/F/M
 ECHO Viruses
 General properties similar to other
enteroviruses
 30+ antigenic types
 Results in: - 1. Aseptic meningitis
2. Rash
3.Conjunctivits
4. Upper Respiratory Tract
Infection
ENTEROVIRUS 71
 Management
 Supportive
 Capsid function inhibitors: Pleconaril, broad
spectrum, potent to Rhino and enteroviruses, good oral
bioavailibility
 This compound binds to the floor of a VP1 and VP3
canyon floor , prevents binding to receptor on cells
 Used in cases of meningoencephalitis shown to be
effective
 As humoral immunity is the body`s defence for
enteroviruses, those who have deficiencies (congenital –
or acquired)are given Intravenous Immunoglobulin
POLIO VIRUS
 Polioviruses
 are RNA ,
ENTEROVIRUSES
 3 Serotypes 1, 2 ,3
 Major cause of paralytic
poliomyelitis and now
seeing post polio
syndrome
 Global Eradication
Programme of WHO
 EPIDEMIOLOGY
 Human host
 Spread: Faecal oral or Respiratory routes
 More common in infants and young children, but
risk of paralytic disease increases with age
 No indigeous wild type polio in U.S since 1979,
imported in 1993, last wild type case in Ireland 1984
 Vaccine Associated Paralytic Polio(VAPP) WHEN
ORAL POLIO VACCINE (OPV) was in
use( Reversion to wild type) now inactivated polio
vaccine used(IPV) used in Ireland since 2001
 EPIDEMIOLOGY
 Risk of VAPP is one case per 2.5 million
doses, greatest risk with first dose
 If using OPV strict hygiene after nappy
changing or toileting should be observed
for 6 weeks
 PRESENT VACCINE
SCHEDULE
At birth- 1 month BCG Usually in maternity
hospitals

*At 2 months Diphtheria

Whooping Cough
Tetanus 5-in-1(G.P)
Hib
Inactivated Polio
+
Meningococcal C
*At 4 months Diphtheria
Whooping Cough
Tetanus
Hib 5-in-1(G.P)
Inactivated Polio
+
Meningococcal C
 PRESENT SCHEDULE
*At 6 months Diphtheria
Whooping Cough
Tetanus 5-in-1(G.P)
Hib
Inactivated Polio
+
Meningococcal C

*At 12- 15 months Measles

Mumps MMR
Rubella,
Hib1 Hib1
 PRESENT SCHEDULE
**4-5 YEARS Diphtheria
Whooping Cough
4-in-1
Tetanus
Inactivated Polio
+
Measles
MMR
Mumps
Rubella

**11-12 YEARS Measles

Mumps
MMR
Rubella
Omit if 2 previous doses
have been given
 PRESENT SCHEDULE
**11-14 years Tetanus
Diphtheria (low dose)
Td

**10-14 years if not BCG2

protected(immune) (AN INTERVAL OF 4
WEEKS AFTER MMR)

Under 23 years(Colleges Meningococcal C

etc)

•From Family Doctor

1: A single dose of Hib vaccine if child presents after 13 months and has no previous Hib vaccine
2: Only those known to be tuberculin negative and have no previous BCG
**These immunizations are generally administered in schools by Health Boards
 Clinical Presentations of
Poliovirus Infection
 Approx. 95% of infections are ASYMPTOMATIC
 Minor illness in 4-8% of lowgrade fever, sore throat
 Aseptic Meninigits in 1-5%
 Asymmetrical acute flaccid paralysis with areflexia of
limbs involved in 0.1%-2% of infections (Respiratory
Muscles may be involved)
 Residual Paralytic Diease in 2/3 of these
 Some develop Post-Polio syndrome 30-40 years post
infection with return of muscle pain and weakness
Poliomyelitis
Poliomyelitis
 Pathogenesis of Enteroviral
Infection
Evades
Virus Replicates in Binds Enterocytes
Nasopharnyx Acidic PH Receptor coded by Ch 19

Minor Viraemia, Endocytosed , replication in

Replication in organs Peyer`s patches

Major Viraemia Skeletal Muscle Anterior Motor

+ Trophism Neuromuscular Ascends along Neuron horn
+ Virulence Endplate Motor Nerves cells
To CNS*
 Communciability
 This is greatest shortly before and after onset of
clinical illness when virus in the throat and it is
excreted in high concentrations in faeces
 For OPV RECIPIENTS, VIRUS IN THE
THROAT 1-2 WEEKS AND FAECES FOR
SEVERAL WEEKS USUALLY MAX 6-8
WEEKS IN NORMAL
IMMUNOCOMPOTENT INDIVIDUAL.
 Surveillance
 For Acute flaccid paralysis
 Since September 1998
 Two faecal specimens 24-48 hours apart
for viral culture as soon as possible after
onset of acute flaccid paralysis
 Faeces most likely to yield virus
 Diagnosis
 Clinical Presentation
 Laboratory
Diagnosis
 Faecal, Throat (2 or
more samples),
CSF(Culture and
RT-PCR)
 TREATMENT/PREVENTION
 Supportive
 Prevention is by Vaccination.
 Global Eradiation Programme
 Part of Routine immunisation schedule
and travellers to endemic areas should be
vaccinated
Global Eradication programme
 SLV-NLV-Novovirus-
Calciviruses
 Family: Calciviridae
 Single Stranded RNA, ps
 Consists of Single
Structural Capsid
protein with icosahedric
symmetry but has 32
cup-shaped depressions
on the axes of the
Icosahedron hence the
name calyx
 Multiple antigenic types
 Epidemiology
 Genotype 1,11 and 4 are associated with outbreaks
 Often affecting institutions
 Commonest cause of gastroenteritis outbreaks in
2nd quarter 2005, with 32 outbreaks and 675
persons ill, 72% of cases
 Present circulating genotype in Ireland since 2004
is Genotype 11.4 JAM strain
 Review: Lopman et al Lancet Feb 2004
 Pathogenesis of Disease
 Not fully understood although some evidence
suggesting it may be simliar to Rotavirus
 Causes delayed gastric emptying
 Immunity: infection induces specific IG G/A/M
even if there is previous exposure
 2 weeks post infection there is ⇧ in jejunal Ig A ,
resistance to reinfection lasts 4-6 months,
 NO LONG TERM PROTECTION
 Accounts for >85% of non-bacterial outbreaks of
gastroenteritis
 EPIDEMIOLOGY
 Sporadic cases however
causes epidemic outbreaks
 Examples: on cruise ships,
hotels, Institutions and
hospitals
 Spread: Person to person via
faecal oral route or through
contaminated food or water
or fomites
 Incubation Period: 12-72
hours
 Vomitus /Faeces infectious
CLINICAL FEATURES
 DIARRHOEA
 VOMITING
 Commonly accompanied
by fever, malaise, myalgia
and abdominal cramps
 Symptoms last 1 day to 70
hours usually
 Virus excreted 5 to 7 days
after the onset of symptoms
in half of people although
may last 13 days
 Diagnosis(sample: stool)
 Electron Microscopy  Reverse Transcriptase
 Labour intense Polymerase chain
 Relatively insensitive reaction (RT-PCR)
 Used in Sporadacic cases
 Used in outbreaks as large
numbers can be processed
 EIA efficiently
Stool tested, can have a
result in a few hours
Not labour intensive
Evaluation of kits must be
carried out for
sensitivity/specificity
 Treatment
 Supportive therapy: rehydration,
electrolyte replacement
 Isolation of Hospitalised patient
 Control Measures: Standard and
Contact precautions
 No Vaccine
 Suspect an outbreak in hospital
if
 Projectile vomiting in >50% of cases
 Duration of illness 12-60 hours
 Incubation period 15-48 hours
 Staff and patients ill
 Stools negative for bacterial pathogens and
C.difficile and other viruses
 Control Measures in
Hospital Outbreaks
 Isolation or Cohort
 Contact Precautions- disposable
plastic apron/ gloves, Hand
Hygiene
 Close Ward to Admissions
 Non-essential personnel
excluded
 Avoid Transfers
 If Staff unwell not return to
work until free from symptoms
48 hours
 Increase frequency of ward
cleaning
 Vomit/Faeces to be cleaned
and disinfected promptly
 Hypochlorite(0.1%) used to
disinfect surfaces
 Cohort Staff
 Limit Movement
 Ward not reopened until 72
hours after last new case or
after last
vomiting/diarrhoea
 Terminal cleaning
 The Future
 Plasmidic DNA and Antigen Vaccines
 Interrrupt Transmission
 Supportive Therapy