This document discusses enteroviruses, which are small RNA viruses that infect the gastrointestinal or respiratory tract. It covers the classification, properties, pathogenesis, clinical features, diagnosis and prevention of several enteroviruses including poliovirus, coxsackievirus, echovirus, and rhinovirus. Key points include that poliovirus can cause paralysis, there are live and inactivated polio vaccines, and global efforts aim to eradicate poliovirus transmission. Coxsackievirus A can cause herpangina while B is associated with myocarditis. Echoviruses commonly cause asymptomatic infections or rash. Rhinoviruses are a common cause of the common cold.

1. Dr V S Vatkar
Asso Prof
Microbiology Department
D Y Patil Medical College, Kolhapur

2. INTRODUCTION
 Under picornavirus group
 Small RNA viruses
 Non-enveloped, 20 to 30 nm
 Classification
 Enterovius: infects GIT
 Rhinivirus: infects nasopharynx
 Hepatovirus
 parechovirus

3. ENTEROVIRUSES

4. HISTORY
 Paralytic Ds of children
 Landsteiner & Popper: demonstrated experimental
transmission of ds in monkeys
 Ender, Weller & Robbins (1948) Nobel Prize:
demonstrated growth in non neural cell culture like:
human embryo cells , shows cytopathic changes

5. ENTEROVIRUSES
Viruses of the enteric tract
Most stable viruses
1) Poliovirus type 1 – 3
2) Coxsackievirus A (1 – 24)
3) Coxsackievirus B (1 – 6)
4) Echovirus (1 – 34)
5) Enteroviruses types 68 - 72

6. POLIOVIRUS
 Affinity for nervous tissues
 Morphology :
 Size 27-30 nm
 SS RNA
 60 capsomeres (subunits)
 Viral Proteins(VP1-VP4)
 Icosahedral symmetry
• VP1: major antigenic site for combination with type specific neutralizing Ab

7. RESISTANCE
 Resistant to ether ,chloroform , bile &
proteolytic enzymes of the intestinal tract,
detergents
 In feces : can survive up to month at 4 0 C
 Stable at pH 3
 years at -20°C
 55°C 30 mins
 MgCL2 protects the virus from heat inactivation.
 Does not survive lyophilisation
 Formaldehyde & oxidising disinfectants: destroy
virus

8. ANTIGENIC PROPERTIES
 Poliovirus strains classified into 3 types by
neutralization test – 1,2, and 3
 Type 1: the commonest & causes most epidemics
 Type 2: causes endemic infections
 Type 3: causes epidemics, type specific
 2 Antigens are recognized by CFT , ELIZA or PPTn
test -

9.  Antigen C : heated or H Ag, associated with empty
or non - infectious virus, anti C Ab : not protective,
not neutralizes viral infectivity
 Antigen D: native or N Ag, associated with whole
virion, type specific
 Antigen D is converted to Antigen C by heating the
virus at 56°C, anti D Ab protective
 Potency of injectable polio vaccine : measured in
terms of D Ag units.

10. PATHOGENESIS
 Transmission: Virus enters by oral route through
ingestion food & water contaminated with human
feces.
 Colonizes the nasopharynx & multiply initially
 Found in throat & feces in initial phases
 Then passes down to Peyer’s patches & epithelial cells
of alimentary canal & lymphatic system
 Inhalation of droplets can also be a mode of entry

11.  Goes to regional gr of LN
 Enters into blood stream (Primary Viremia)
 Further multiplication in reticuloendothelial system
 Virus again re-enters into blood stream (secondary
Viremia)
 Virus goes to spinal cord & brain (pass along axons of
peripheral nerves to CNS)

12.  In CNS: virus multiplies selectively in neurons &
destroys them.
 Degeneration of Nissl body (earliest change)
 Degeneration : irreversible, necrotic cell lyses or
phagocytosis by leucocytes or macrophages
 Anterior horn cells of spinal cord : mostly involved,
causes flaccid paralysis, post horn cells may also
involved

13.  Direct neural transmission to the CNS may occur
in special cases as in poliomyelitis, following
tonsillectomy
 Some cases encephalitis may occur , involves
brainstem extending up to motor & premotor areas
of cerebral cortex

14. CLINICAL FEATURES
 Inapparent infection: exposed to polio virus, 90-95%
susceptible individuals develop inapparent infection,
causes seroconversion only.
 Only 5-10% cases show clinical illness
 I P : 10 days (range 4 days – 4 weeks)
 Abortive poliomyelitis: (minor illness)- earliest
manifestations like fever, headache, sore throat,
malaise , last for 1-5 days

15. CLINICAL FEATURES
 Paralytic poliomyelitis: (Major illness)-
If the infection progresses ,the minor illness is followed by
major illness in 3-4 days
 Fever again (biphasic fever) with headache ,stiff neck and
other signs of meningitis- stage of viral invasion of the CNS
 Flaccid paralysis : depending on distribution of paralysis,
classified as SPINAL, BULBAR or SPINOBULBAR
 Mortality is 5-10 % mainly due to respiratory failure
 Recovery of paralised ms : next 4-8 wks, complete after 6
mnths, leaving behind varying degrees of residual paralysis
 Non paralytic poliomyelitis: ds dose not progress beyond
aseptic meningitis.

19. LAB. DIAGNOSIS
 Specimen: throat swab, feces (rectal swab), blood &
CSF
 Viral Isolation:
 Isolated from blood: primary viremia, little imp, can
be isolated from throat swab at this stage
 Feces: possible 80% cases in 1st wk, 50% till 3rd wk,
25% till 6th wk.
 CSF:

20.  Primary monkey kidney cell or tissue culture
(human or simian cell culture)
 Growth: detected by CYTOPATHIC effects in 2-3 days
 Identification by neutralization test with pooled or
specific antisera
 SEROLOGY: antibody rise: paired sera or CFT
 MOLECULAR diagnosis: Reverse Transcriptase PCR:
demo of viral RNA in CSF
 Sequencing: 3 types of strains : wild virus, Oral Polio
Vaccine Virus (OPV), Vaccine derived poliovirus
(VDPV)

21. PROPHYLAXIS
2 types of vaccines :
Active
immunization
a) Killed polio
vaccine (Salk)
b) Live attenuated
OPV (Sabin)
www.polioeradication.org
Polio
Paralysis for life Primarily affects children
Preventable with OPV

22. SALKS KILLED POLIO VACCINE/INACTIVATED
POLIO VACCINE
 Dev.by Salk in 1953
 Formalin inactivated prep. of 3 t/o polio viruses, grown on
monkey kidney tissue culture, inactivated with formaline
(1:4000) at 37 0 C for 12-15 days
 Deep subcut.or IM injection
 Produces long lasting immunity
 Induces serum antibodies IgM & IgG
 Does not induce IgA in the intestine and hence not able to
prevent alimentary tract infections

23. Vaccination schedule
 Three doses, given 4-6 weeks apart
 Booster dose six months later
 1st dose: after 6 mnths: maternal Ab does not interfere
 2nd dose: 4 -6 wks after 1st dose, induses better
seroconversion
 3rd dose: 6-12 mnths later,
 immunity lasts for 3-5 yrs, after booster dose

24. LIVE ATTENUATED OPV/SABIN VACCINE
 Dev.by Koprowsky, Cox & Sabin in 1962
 Contains live attenuated strains of polio viruses 1,2 and 3
 Shelf life 4 M at 4 - 8°C and 2 yrs.at -20°C
 Improper storage conditions and cold chain failure –
problem in dev.countries
 Administered orally
 Stimulates both IgA and humoral antibodies IgG and IgM

25.  OPV used in INDIA: contains
 Type 1 virus : 10 lakhs
 Type 2 virus : 2 lakhs
 Type 3 virus : 3 lakhs
 TC ID50 per dose ( 0.5 ml)
 Stabilized by MgCl2
 pH: 7.0

26. Safety
 OPV : tends to acquire neurovirulence on serial
enteric passages, may seen following vaccination.
Incidence ; very low.
 Vaccine associated paralytic polio or Vaccine
Derived Polio Virus (VDPV): rare strain of polio virus,
very rarely OPV strain converts into VDPV strain, polio
myelitis following vaccination
 Contraindication:
immunodeficient/immunocompromised person

27. Vaccination schedule
 Live attenuated OPV
 3 doses orally
 Zero dose (0 dose): at birth
 First dose along with DPT at
4-6 weeks (1 & 1/2mnth)
 2nd and 3rd – at an interval
of 4-6 weeks
 Booster dose at the age of
16 – 24 months

28. Issues related to vaccine failure
 Interference by other entero V, may be
Coxsackie B
 Frequent diarrhoea : prevents colonization
of virus in gut
 Breast feeding before & after vaccination
(maternal Ab present in breast milk)
 Inhibitors of polio V : present in saliva
 Proper maintenance of cold chain

29. PULSE POLIO IMMUNIZATION
 To eradicate polio myelitis globally .
 Mass immunization of OPV on a single day to all
children aged 0-5 years in the community
irrespective of their OPV vaccination status
 whether they are vaccinated or not, through
Universal Immunization Program (UPI)
 Two doses at the interval of 4-6 wks during low
polio transmission period (Nov to Feb) during
Winter season
 Development of Herd Immunity

30. EPIDEMIOLOGY
 Exclusively a Human
disease
 Feces- imp. source of
spread of virus in the
community
 Warm weather –
conducive to virus spread
 Type 1 – causes epidemics
 Type 2 – paralytic
poliomyelitis
 WHO- 13th May 1988-
Global eradication by
2000

31. Polio situation in the world
 Status of polio transmission:
 Endemic countries: currently wild polio V is endemic
in only Pakistan, Afghanistan & Nigeria. Nigeria
reported last case in August 2016
 Wild polio virus cases: in 2017, 22 wild polio v cases
were reported globally (17-Afghanistan & 8-Pakistan),
99 vaccine derived polio cases (CVDOV-2) reported
from Democratic Republic of Congo (21) & Syria
Republic (74)
 Currently all natural cases : due to wPV caused by
type 1, no natural cases due to type 2 & type 3 (since
1999 & 2013)

32.  India: declared polio free since March 2014 (last
natural case was detected in January 2011)
 Global eradication of polio & Endgame
strategic plan:
- interruption of wild polio virus transmission
- strengthening of immunization system: step
wise withdrawal of OPV along with switching over to
IPV
- polio free world by 2018
- infrastructure, man power, funds, knowledge &
experience

33. COXSACKIEVIRUS
 1949 in Coxsackie village in USA
 Resemble polio viruses in properties & epi.
 Infects suckling mice but not the adult mice
 Classified in 2 groups, based on the patho.changes they
produce
 Group A and Group B
 By neutralization test –
 Group A – divided into 24 types
 Group B - divided into 6 types

34. GROUP A COXSACKIE VIRUSES
1. Aseptic meningitis:
caused by all types of Gr B v
& A7, A9 Gr A v
2. Herpangina (Vesicular
pharyngitis) – caused by
types 2,4,5,6,8 and 10
Abrupt onset of
fever, pharyngitis ,pain
in abdomen,
headache

35. 3. Hand-foot and
Mouth disease –
caused by types 5
and 16:Presents as a
vesicular lesion
involving hands,
mouth and feet

36. GROUP B COXSACKIE VIRUSES
1. Epidemic myalgia – Bornholm disease
Fever, stitch like pain in chest & abdo.
2. Myocarditis and Pericarditis (type 1-5) –
3. Aseptic meningitis with paralysis
4. Juvenile diabetes – pancreatitis Gr B-4
5. Neonatal infections – Hepatitis,
meningoencephalitis
6. Respiratory infection: Gr A & Gr B (common
cold), pneumonia: GrB type B4 & B5

37.  Acute haemorrhagic conjunctivitis: caused by Gr A-
24 & Enterovirus 70
 Self limiting conjunctival ds
 IP: 1 day
 Complete recovery: within 8 days

38. Lab. diagnosis
Virus isolation from feces or the lesions
a. Inoculation into suckling mice
b. Tissue culture – kidney cells of monkeys

39. ECHOVIRUSES
 Enteric Cytopathogenic Human Orphan (ECHO) viruses
 34 types – 1 to 34 except 10 and 28 (Rhinoviruses)
 Alimentary tract
 Faeco-oral route
 Some echoviruses agglutinate human RBC’s
 Resistant to 20% ether

40. CLINICAL FEATURES
 Most infections are asymptomatic
 Rash with fever
 Resp.diseases
 Paralysis
 Infantile diarrhoea
 Pericarditis and
 Aseptic meningitis

42. Lab. diagnosis
Specimens are :
1. Throat secretions
2. Stool
3. CSF
Isolation of the virus – inoculation into
kidney cells of monkey

43. ENTEROVIRUSES 68 - 72
68 : Isolated from pharyngeal secretions of children with
pneumonia and bronchitis
69 : Not asso. with any human disease
70 : Acute hemorrhagic conjunctivitis
71 : Isolated from cases of meningitis & encephalitis
72 : Hepatitis virus type A

44. RHINOVIRUS GR
 Common cold
 Three spp of rhino v (A, B & C) : inf in humans
 C/F: IP: 2-4 days, symptoms : similar to other viruses
causing common cold (corona v, adeno v, entero v,
parainfluenza v & influenza v)
 Sneezing, nasal obstruction, nasal discharge, sore
throat but no fever
 Average 1-2 attacks per year