Polioviruses and Poliomyelitis

• Polioviruses and Poliomyelitis are the subject of study in Virology (BMEdSc-MVI3MV1).

Outline of Topics:

• Introduction and History
• Epidemiology
• Polioviruses – Basic virology
• Pathogenesis
• Clinical features
• Laboratory diagnosis
• Immunization
• AFP surveillance
• Polio Eradication Initiative

Introduction and History

• Polio found as early as 3000BC Egyptian hieroglyphics
• First described in England in 1789 by Michael Underwood with worldwide epidemics afterwards
• In 1952 in the US, polio peaked with >20,000 paralytic cases
• First polio vaccine was created in 1955 (inactivated) known as SALK
• Second polio vaccine came in 1961 (live attenuated) known as SABIN

Epidemiology

• Global eradication programs have dramatically reduced wild poliovirus transmission
• Only three countries currently have wild-type virus transmission: Nigeria, Afghanistan, and Pakistan
• India has been polio-free for over 2 years
• South Africa has been wild-type polio-free for over 20 years
• Humans are the only known reservoirs
• Spread occurs person to person, via the faeco-oral route
• Infection typically peaks in summer months
• Poliovirus is highly infectious among susceptible individuals
• Infected individuals are infectious seven days before and after the onset of symptoms
• Virus can be shed in stool for up to 6 weeks

Basic Virology

• Family: Picornaviridae
• Genus: Enterovirus
• Species: Human enterovirus C; Virus: poliovirus 1, 2 and 3
• Small, non-enveloped viruses with a ssRNA genome
• Capsid proteins allow the virus to attach to a cellular receptor, CD155 of the immunoglobulin superfamily.

Types of Polioviruses

• Three types of wild poliovirus (WPV) exist with 3 serotypes
• Type 1 is the only WPV serotype still in circulation today.
• Type 2 was eradicated in September 2015.
• Type 3 was eradicated in October 2019.

Pathogenesis

• Poliovirus enters the digestive tract via the mouth
• Primary infection site locations are epithelial and lymphoid tissue associated with the oropharynx and gut
• Virus production at the primary site leads to a transient viremia
• Afterwards the virus may infect the CNS

Clinical Spectrum

• Abortive poliomyelitis is a mild febrile illness with an incubation of 1-3 days.
• Aseptic meningitis is a self-limiting condition without parenchymal involvement, lasting around 2 weeks (+/-).
• Paralytic poliomyelitis has an incubation of 4-10 days
• Paralysis is usually preceded by a prodrome of headaches and shooting muscular aches
• Paralysis can be bulbar (brainstem involvement, respiratory impairment)
• Paralysis can be spinal (acute flaccid paralysis, usually in one limb)
• Paralysis can also be bulbo-spinal (both)

Post-Polio Syndrome

• Characterized by onset of new weakness, fatigue, and myalgia decades after paralytic poliomyelitis
• Progressive muscular atrophy due to ongoing motor nerve damage

OPV vs IPV

• Oral Polio Vaccine (OPV-SABIN)
  • Live, attenuated (weakened) virus
  • Administered by drops
  • Effective at reducing transmission in developing countries
  • Part of eradication strategy
  • Inexpensive
  • Easy to administer
  • Provides mucosal/gut immunity
  • Protects close contacts who are unvaccinated
• Inactivated Polio Vaccine (IPV-SALK)
  • Killed virus
  • Administered by injection
  • Highly effective
  • Commonly used in developed countries
  • More expensive than OPV
  • Requires trained health workers
  • Provides immunity through blood
  • Carries no risk of VAPP or VDPV
  • Both vaccines are needed to fully eradicate polio!

Types of Oral Polio Vaccines

• Trivalent OPV (tOPV)
  • Types 1, 2, and 3
  • Mixture of live attenuated poliovirus of all 3 serotypes
• Bivalent OPV (bOPV)
  • Types 1 and 3
  • Replaced the trivalent vaccine in routine immunization
• Monovalent OPV (mOPV)
  • Type 1, 2, or 3
  • Primarily used for immunization in areas where only type 1 or type 3 is circulating
• OPV is still the primary vaccine for eradication.

Paralysis Associated with OPV

• OPV offers effective protection against polio, but in very rare cases, can lead to paralysis:
• Vaccine Associated Paralytic Polio (VAPP)
  • Vaccine virus spontaneously changes and becomes capable of causing disease to the nervous system
  • Occurs in 1 case per 2.4 million vaccine doses administered
  • 250-500 cases/year
  • 40% of VAPP cases are from type 2 OPV
• Circulating Vaccine Derived Poliovirus (cVDPV)
  • Rare outbreaks as person-to-person spread of vaccine strain mutates/changes to a highly transmissible form capable of causing disease to the nervous system
  • Occurs in areas/countries with low immunity against polio
  • 97% of cVDPVs are from type 2 OPV
  • Low coverage is a main factor for the occurrence of cVDPVs

AFP (Acute Flaccid Paralysis)

• AFP is a clinical syndrome characterized by rapid onset of weakness, including (less frequently) weakness of the muscles of respiration and swallowing, progressing to maximum severity within several days to weeks

Role of AFP surveillance

• Identify high-risk groups and communities
• Monitor progress on immunization efforts
• Certify a country as polio-free if AFP indicators are met
• Plan for supplementary immunization

Laboratory Diagnosis

• Routine diagnosis is not offered
• Stool samples are submitted to a reference lab (e.g. NICD) for Acute Flaccid Paralysis surveillance programme
• Acute flaccid paralysis is a notifiable condition
• All cases with AFP & <15 years old must be notified and investigated by submitting 2 stool samples within 2 weeks of onset of symptoms
• Laboratory methods of diagnosis include:
  • Viral isolation- using cell culture
  • Serum neutralization – for subtype identification
  • Molecular methods to differentiate between wild-type virus and vaccine-associated viruses