ENTEROVIRAL INFECTIONS Dr.B.Boyle Copyright©breida

ENTEROVIRAL INFECTIONSENTEROVIRAL INFECTIONS

Dr.B.Boyle

CopyrightCopyright©breida©breida

ENTEROVIRAL INFECTIONSENTEROVIRAL INFECTIONSContents of LectureContents of Lecture

ENTEROVIRUSESAlso Discuss , Viruses that cause

GastroenteritisROTAVIRUSSMALL ROUND STRUCTURED

VIRUSES e.g Norwalk virus, Novovirus etc.


ROTAVIRUSROTAVIRUS


ROTAVIRUSROTAVIRUS

Description Epidemiology Pathogenesis Clinical Features Diagnosis Treatment The Future


ROTAVIRUSROTAVIRUS

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-RotavirusesMorphology-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 RNAGenome encoded Structural

proteins VP1-7 and NSP 1-5, NSP4 has enterotoxinlike activity


Epidemiology of RotavirusEpidemiology 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 Most common cause of noscomial diarrhoea Human to human, faecal-oral route Found on fomites in childcare


Epidemiology of RotavirusEpidemiology 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-RotavirusClassfication-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-PathogensisRotavirus-Pathogensis

Mature Enterocytes(on tips of Small Intestine villi)

Infects

Villous Atrophy

Compensatory Repopulation by immature Secretor cells and secondary hyperplasia

Cell death because of villous ischaemia CopyrightCopyright©breida©breida

Mechanism of diarrhoea?Mechanism of diarrhoea?

Villous epithelium in relation To secretory capacity of

Crypt cells

Loss of permeability to Macromolecules e.g Lactose,

Due to loss of disaccharideases

Enteric nervous system stimulates InductionOf intestinal Water

And electrolyte secretion


Immune Response to Immune Response to RotavirusRotavirus

Localised Immune response protects against severe subsequent infections

NSP4 protein results in cell mediated immunity


Outcome of Infection with Outcome of Infection with VirusesViruses

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-Clinical Presentation-RotavirusRotavirus

Abrupt onset of vomiting followed within hours by watery, brown copious diarrhoea, often lasts 3-8 days

If Severe Dehydration and death or hospitalisation


DIAGNOSISDIAGNOSIS

Clinically Latex agglutination

Kit testing for Group A

Rv antigen in stool

Enzyme Immunoassay

Group A

Rv antigen in stool

Less common EM and molecular methods

Pos and neg Pos and neg


TREATMENTTREATMENT

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


MANAGEMENTMANAGEMENT

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: PICORNAVIRIDAEFAMILY: PICORNAVIRIDAE

ENTEROVIRUSESOver 72+

RHINOVIRUSType 1-100+

POLIO virus type 1,2,3COXSACKIE A virus type 1-22,24

COXSACKIE B virus type 1-6E.C.H.O virus type 1-7,11-27,29-34

Numbered ENTEROVIRUSES type 68-71,73

Since 1967-all new ones are numbered

CardiovirusAphthousvirusetc

E.C.H.O = enteric cytopathic human orphanCopyrightCopyright©breida©breida

CharacteristicsCharacteristics

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


CharacteristicsCharacteristics

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 Clinical Manifestations of EV Infections(Mostly Children)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 VIRUSESCOXSACKIE VIRUSES

29+ immunogenic typesDivided into A and B on the basis of

different pathogenic potential for miceResult in a number of different clinical

presentations


COXSACKIE VIRUSESCOXSACKIE VIRUSES

Herangina Summer minor

illness Aseptic meningitis Neonatal Disease Colds

Hand , Foot and mouth illness

Myocarditis ? Diabetes mellitus Epidemic myalgia

(Bornholm Disease)


ECHO VirusesECHO Viruses

General properties similar to other enteroviruses

30+ antigenic typesResults in: - 1. Aseptic meningitis 2. Rash 3.Conjunctivits 4. Upper Respiratory Tract

InfectionCopyrightCopyright©breida©breida

ManagementManagement 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 VIRUSPOLIO VIRUS


PoliovirusesPolioviruses

are RNA , ENTEROVIRUSES

3 Serotypes 1, 2 ,3 Major cause of paralytic

poliomyelitis and now seeing post polio syndrome

Global Eradication Programme of WHO


EPIDEMIOLOGYEPIDEMIOLOGY 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


EPIDEMIOLOGYEPIDEMIOLOGY

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 PRESENT VACCINE SCHEDULESCHEDULE

At birth- 1 month BCG Usually in maternity hospitals

*At 2 months Diphtheria

Whooping Cough

Tetanus

Hib

Inactivated Polio

+

Meningococcal C

5-in-1(G.P)


Whooping Cough

Tetanus

Hib

Inactivated Polio

+

Meningococcal C

5-in-1(G.P)


PRESENT SCHEDULEPRESENT SCHEDULE


Whooping Cough

Tetanus

Hib

Inactivated Polio

+

Meningococcal C

5-in-1(G.P)

*At 12- 15 months Measles

Mumps

Rubella,

Hib1

MMR

Hib1



**4-5 YEARS Diphtheria

Whooping Cough

Tetanus

Inactivated Polio

+

Measles

Mumps

Rubella

4-in-1

MMR

**11-12 YEARS Measles

Mumps

Rubella MMR

Omit if 2 previous doses have been given



**11-14 years Tetanus

Diphtheria (low dose)Td

**10-14 years if not protected(immune)

Under 23 years(Colleges etc)

BCG2

(AN INTERVAL OF 4 WEEKS AFTER MMR)

Meningococcal C

•From Family Doctor1: A single dose of Hib vaccine if child presents after 13 months and has no previous Hib vaccine2: 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 Clinical Presentations of Poliovirus Infection 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


Pathogenesis of Enteroviral Pathogenesis of Enteroviral InfectionInfection

Virus Replicates in Nasopharnyx

Binds Enterocytes Receptor coded by Ch 19

Evades

Acidic PH

Endocytosed , replication inPeyer`s patches

Minor Viraemia,Replication in organs

Major Viraemia+ Trophism+ Virulence

Skeletal MuscleNeuromuscular

Endplate

Ascends alongMotor Nerves

Anterior MotorNeuron horn

cellsTo CNS*

*Spinal, Bulbar, Medullary Red=specifc for polio


CommunciabilityCommunciability

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 Surveillance

For Acute flaccid paralysisSince September 1998Two 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


TREATMENT/PREVENTIONTREATMENT/PREVENTION

Supportive Prevention is by Vaccination.Global Eradiation ProgrammePart of Routine immunisation schedule

and travellers to endemic areas should be vaccinated


SLV-NLV-Novovirus-SLV-NLV-Novovirus-CalcivirusesCalciviruses

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


Pathogenesis of DiseasePathogenesis 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

gastroenteritisCopyrightCopyright©breida©breida

EPIDEMIOLOGYEPIDEMIOLOGY 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 FEATURESCLINICAL FEATURES

DIARRHOEA VOMITING Commonly accompanied

by fever, malaise, myalgia and abdominal cramps

Symptoms last 1 day to 2 weeks

Virus excreted 5 to 7 days after the onset of symptoms in half of people although may last 13 days


Diagnosis(sample: stool)Diagnosis(sample: stool)

Electron Microscopy Labour intense Relatively insensitive Used in Sporadacic

cases

Reverse Transcriptase Polymerase chain reaction (RT-PCR)

Used in outbreaks as large numbers can be processed efficiently


TreatmentTreatment

Supportive therapy: rehydration, electrolyte replacement

Isolation of Hospitalised patientControl Measures: Standard and

Contact precautionsNo Vaccine


Control Measures in Control Measures in Hospital OutbreaksHospital 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 72 hours

Increase frequency of ward cleaning

Vomit/Faeces to be cleaned and disinfected promptly

Hypochlorite(0.1%) used to disinfect surfaces

Cohort Staff Movement unaffected to

affected area Ward not reopened until 72

hours after last new case or after last vomiting/diarrhoea

Terminal cleaning


The FutureThe Future

Plasmidic DNA and Antigen VaccinesInterrrupt TransmissionSupportive Therapy


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ENTEROVIRAL INFECTIONS Dr.B.Boyle Copyright©breida