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ENTEROVIRAL INFECTIONS mumps

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					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             Respiratory Symptoms
  Poliomyelitis, Aseptic         e.g colds, herangina
  meningitis and                Skin Exanthem with
  encephalitis                   meningitis
 Neonate: neonatal sepsis      Myocarditis
  EV 11                         Those associated with
 Non-specific febrile           Coxsackie viruses
  illness                       Spread: Faecal oral
 Hepatitis gi etc               route , respiratory route
 Haemorrhagic                   and peripartum mother
  conjunctivitis, COX A24        to infant or fomite
and EV 71                        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 outbreaks as large
  Used in Sporadacic cases
                                    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             Vomit/Faeces to be
   Contact Precautions-             cleaned and disinfected
    disposable plastic apron/        promptly
    gloves, Hand Hygiene            Hypochlorite(0.1%) used
   Close Ward to Admissions         to disinfect surfaces
   Non-essential personnel         Cohort Staff
    excluded                        Limit Movement
   Avoid Transfers                 Ward not reopened until
   If Staff unwell not return       72 hours after last new
    to work until free from          case or after last
    symptoms 48 hours                vomiting/diarrhoea
   Increase frequency of           Terminal cleaning
    ward cleaning
             The Future
 Plasmidic DNA and Antigen Vaccines
 Interrrupt Transmission
 Supportive Therapy

				
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