Unit 3 - Polio Virus & Other Enteroviruses Flashcards

1
Q

Describe a breif overview of Enteroviruses

A
  • Small RNA viruses
  • Naked
  • Picornaviridae family
  • Ubiquitous in nature
  • Entero” means intestine: transmitedd by an oral-fecal route
  • Over 70 distinct types of human enteroviruese: 20 recongizable clinical syndromes
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2
Q

What is the history of Polio?

A
  • Descriptions of poliomyelitis date to 1500 bc
  • Egyptian stele showing “foot drop”
  • Existed quietly for thousands of years as an endemic pathogen
  • Significant problem in northern Europe in the 1880s
  • Major epidemics largely unknown before the late 19th century
  • The 1916 New York City epidemic was one of the worst.
  • Poliomyelitis is rare today because of vaccination efforts.
  • Last cases of poliomyelitis in the US were in 1979 and 2005
  • unvaccinated persons from Amish communities
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3
Q

Why is polio a public health concern?

A
  • Disease of mysterious, seasonal appearance by 1910
  • It could paralyze respiratory muscles
  • 1 in 1,000 infected children
  • 1 in 75 infected adults
  • Infection had disfiguring, crippling, and sometimes fatal outcomes
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4
Q

What are the clinical features of Poliomyelitis?

A
  • Portal of entry: mouth
  • Person to person spread: oral–fecal route
  • Infants appear to be the most efficient transmitters of infection.
  • e.g., direct contact with feces when changing diapers or poor sanitary conditions
  • Average incubation period: 6–20 days
  • Poliovirus may be present in stool for 3–6 weeks and 2 weeks in saliva.
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5
Q

What are the course of Mild infections?

A
  • Variable
  • 95% of all poliovirus infections are asymptomatic
  • Asymptomatic persons shed virus in stool and are able to transmit the virus to others.
  • About 4%–8% of poliovirus infections cause mild symptoms:
  • Malaise
  • Gastrointestinal distress
  • Fever
  • Influenza-like illness
  • Sore throat
  • Complete recovery occurs within a week.
  • 1-2% of polio infections are associated with:
  • Minor illness followed by stiff neck/back, and/or legs
  • These symptoms last 2–10 days followed by a complete recovery
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6
Q

What are the course of Major Illness?

A

Occurs in less than 1% of all poliovirus infections

  • Flaccid paralysis = weakness
  • Inflammation and occasional destruction of neurons
  • Recovery can take up to two years and may be incomplete.
  • Weakened muscles (see Figure 11-3)
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7
Q

What are the Three forms of Major illness?

A
  1. Spinal Paralysis
  2. Bulbar
  3. Bulbospinal
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8
Q

What is Spinal Paralysis?

A
  • Most common
  • Viral invasion of the motor neurons of the anterior horn
  • Without nerve stimulation, muscles atrophy and become weak, floppy and poorly controlled, finally becoming completely paralyzed
  • Asymmetric paralysis (occurs on one side)
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9
Q

What is Bulbar?

A
  • Less common (2% of cases of paralytic polio)
  • Invasion & destruction of nerves within the bulbar region of the brain stem
  • Weakening of muscles involved in breathing, speaking, and swallowing
  • Patient may require an iron lung or respirator
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10
Q

What is Bulbospinal?

A
  • 19% of all cases of paralytic polio
  • Combination of spinal and bulbar paralysis
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11
Q

What is Post-Polio Syndrome? (PPS)

A
  • Occurs in 25-50% of individuals who recovered from childhood paralytic polio
  • Insidious; occurs 8–71 years post-polio infection
  • Average onset is 36 years post-recovery
  • More common in women than men
  • Not an infectious process (no viral shedding)
  • Most common symptoms:
  • New weakness in muscles or limbs involved at the time of acute poliomyelitis
  • Extreme fatigue
  • Pain in the muscles and joints
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12
Q

What causes PPS?

A
  • Muscle fibers of surviving motor neurons slowly deteriorate over time.
  • Nerve endings are eventually destroyed and permanent weakness occurs.
  • Effective management requires an interdisciplinary approach
  • manage pain, fatigue, anti-inflammatory therapy, etc.
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13
Q

What is the classicfication and Structure of Poliovirus?

A
  • Member of the Picornaviridae family
  • Small, 30 nm in diameter
  • Icosahedral-shaped
  • Non-enveloped
  • Acid-stable
  • (+) ssRNA genome ~7441 nucleotides in length
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14
Q

What is the stability of enteroviruses in the Environment?

A

Resistant to:

  • pH levels less than 3 (stomach acid)
  • Digestion by most proteases
  • Detergents
  • 70% alcohol
  • Solvents (e.g., ether and chloroform)
  • Disinfectants (e.g., 5% Lysol, 1% QUATS)
  • May be stable several days to several weeks at 4oC (39.2oF)
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15
Q

What are the inactivation/Disinfection Protocols?

A
  • Chlorine bleach
  • Hydrochloric acid
  • Aldehydes
  • Heat 50oC (122oF) for one hour (in the absence of calcium and magnesium)
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16
Q

What are the Laboratory Diagnosis of Poliovirus Infections?

A
  • Most common method: isolate virus from stool samples or swab of the pharynx
  • Grows well in characterized in any human or monkey kidney cell lines (causes good CPEs)
  • Identify serotype with neutralization assays
  • Nucleic acid methods: PCR and sequencing used to determine if the infection is caused by “wild-type” virus (encountered in nature) or “vaccine” virus
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17
Q

What is the cellular Pathogenesis?

A
  • Humans and non-human primates are the only known natural hosts of polioviruses.
  • Does not infect other experimental animals (e.g., mice)
  • Likely due to the lack of poliovirus receptor
  • Once ingested, polioviruses invade two lymphoid tissues:
  • Peyer’s patches (aggregations of lymphoid tissue on small intestine)
  • Tonsils
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18
Q

How does Poliovirus Spread through the bloodstream?

A
  • Major viremia: flu-like symptoms; sore throat; headache; fever
  • Penetration of the CNS appears to be incidental & provides no known benefit to the virus
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19
Q

What is the small percent of patients who have poliovirus?

A
  • Polioviruses carried via the bloodstream to the anterior horn cells of the spinal cord

Results in lesions in the spinal cord and brain

  • Motor neuron destruction
  • Paralysis
  • Respiratory arrest
  • Death
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20
Q

What is the Viral Replication of Polioviruses?

A
  • Polioviruses attach to host cells via the poliovirus receptor (PVR; also called CD155).
  • Binding causes a conformational change in the internal capsid protein VP4.
  • Capsid swells and a pore is formed, through which the viral + ssRNA genome is “injected” into the cytoplasm
  • Uncoating event is not precisely known
  • Receptor-mediated endocytosis may also occur
  • Virion RNA serves as an mRNA that is translated into a single, highly autocatalytic polyprotein.
21
Q

Polio Entry

A
22
Q

Describe the Poliovirus Genome

A
  • 5′ end contains a small basic viral protein (VPg)
  • primer for RNA synthesis; new (-) ssRNA serves as template for new (+) ssRNA
  • 5′ end also contains a cloverleaf or tRNA-like structure that serves as an internal ribosomal entry site (IRES).
  • The 3′ end of the genome is polyadenylated.
23
Q

What is involved in the treatment of Poliomyelistis?

A
  • During the Polio era in the United States:

Drinker respirators (“iron lungs”) introduced in the 1930s

  • Sister Kenny:

Physical therapy rather than immobilization of the affected muscles
Hot packs and hot baths
Success was controversial
Foundation for modern physical therapy

  • There is no cure.

Treatment is supportive care, including physical therapy.
No antivirals are available.

24
Q

What is the Iron Lung/Drinker Respirator?

A
  • Negative pressure ventailator
  • Pumps controlling airflow periodically decrease and increase the air pressure within the chamber and on the chest it cause lungs to fill and expel.
25
Q

What famous president had Polio?

A

Franklin Delano Roosevelt

  • 32nd president of the United States; contracted “polio” at age 39 (Guillain-Barre Syndrome?)
  • Roosevelt went to Warm Springs Georgia in the 1920s in hopes that the warm water would improve his polio-induced paraplegia
  • constant visitor for 2 decades; died there in 1945
  • Roosevelt Warm Springs Institute for Rehabilitation
26
Q

What was the March of Dimes?

A
  • The March of Dimes was established by FDR to fight polio.
  • The mission focus was shifted to premature birth and birth defects.
  • Sabin and Salk received grant funds for their research.
27
Q

What do you prevent Poliomyelistis?

A
  • In 1909 Landsteiner and Popper reproduced poliomyelitis in rhesus monkeys.
  • Injected a filtrate of ground-up CNS tissue from a boy who had died of polio into the peritoneum of the monkeys.
  • For the next 40 years, research was limited because animals (monkeys) were needed to do the research.
28
Q

Ways of Prevention Continued:

A
  • 1949: Advent of cell cultures by Enders, Robbins, and Weller

=Cultivation of polioviruses in non-nervous tissues
=Soon began to propagate monkey kidney cells

  • 1950s: Monkeys were treated in the nose with picric acid, sodium alum, zinc sulfate

=Same treatment tried in humans without promising results
=Quickly abandoned this treatment

  • 1950: Hammon showed experimentally that passive immunization could halt infection and reduce disease severity
  • 1953: Gamma globulin failed to prevent poliovirus infection in humans
29
Q

What is involved in the Inactivated Vaccines?

A
  • Jonas Salk

=Grew polioviruses in monkey kidney cells
=Inactivated the viruses with formalinlb

=Albert Milzer took a similar approach but used UV to inactivate polioviruses.

  • By 1953, preliminary tests of Salk’s inactivated vaccine on children and adolescent volunteers were favorable.
  • Mass vaccination trials using Salk’s inactivated vaccine began.
30
Q

What is Salk’s Inactivated Vaccine (IPV)?

A
  • Licensed in 1955 by the FDA
  • 70% effective in preventing poliovirus infection
31
Q

What is the Cutter Vaccine Episode? (1955)

A
  • Cutter, manufacturer of the Salk vaccine, produced vaccine that was inadequately inactivated.
  • 260 cases of vaccine-related poliomyelitis
  • 126 cases through family contacts
  • 94 cases from vaccination
  • 40 cases by community contacts
  • Did not change the public confidence in the vaccine.
  • Led to new requirements for safety testing of the vaccine
  • Pharmaceutical GMPs (good manufacturing practices)
  • Surveillance unit set up at the CDC to maintain and scrutinize vaccination programs
32
Q

What are the live, attenuated poliovirus Vaccines?

A
  • Developed by Albert Sabin
  • More appealing because it was believed that an active infection came closest to producing the natural situation
  • Attenuated strains should produce longer-lasting immunity (no need for booster immunizations).
  • Major concern: Would attenuated strains revert to wild-type?
33
Q

What was involved in the attenuation of Poliovirus strains for vaccine development?

A
  • Monkey testicular cells or intracerebral passages in rhesus monkeys
  • Passaged by feeding chimpanzees and collecting excreted strains
  • Cynomolgus monkey kidney tissue culture cells (MKTC cells)
  • SV40 virus contamination
34
Q

What was the Sabin Strain Attenuation/Passaging Process?

A
  • Attenuation process “weakened” virus by introducing mutation in IRES region

Three Strains:

  1. Sabin Type 1 - Strain Mahoney 1
  2. Sabin Type 2- Strain P712
  3. Sabin Type 3 - Strain Leon III
35
Q

What are the field trials of the Sabin Vaccine?

A
  • Difficult to gain support for trials of another poliovirus vaccine
  • Already had the Salk vaccine that was 70% effective
  • 1958: First large scale field trial
  • 200,000 children in Singapore vaccinated with an attenuated Sabin serotype 2 poliovirus vaccine
  • Same year (1958) Professor Mikhail Petrovich Chumakov, Director of the Poliomyelitis Research Institute in Moscow, manufactured more virus using seed strains from Sabin
  • 15 million Russians vaccinated in just over a year with no untoward effects
  • By 1960, 100 million Russians vaccinated with no untoward effects
36
Q

What else is involved in the Live, Attenuated Sabin Vaccine?

A
  • Large field trials in Russia provided confidence that Sabin’s attenuated strains were safe.
  • Within 10 years, two vaccines were available against poliovirus.
  • IPV (Salk) and OPV (Sabin)
  • Sabin’s vaccine included three serotypes.
  • It was administered orally (few drops of liquid).
  • Oral polio vaccine (OPV)
37
Q

What is the U.S. CDS’s Vaccination Recommendation today?

A
  • No longer use of OPV to avoid vaccine-associated paralytic polio (VAPP)
  • Children get:

4 doses of IPV @ 2 months
4 doses of IPV @ 4 months
1 dose of IPV @ 6–18 months
1 booster IPV dose @ 4–6 years

38
Q

What were the eradicatino efforts?

A
  • 1988 WHO goal: global eradication of poliovirus by the year 2000
  • Poliovirus eradication considered possible because:

Two vaccines are available.
No animal reservoir
Three attenuated serotypes are stable.
OPV is inexpensive and easy to administer in mass vaccination campaigns.

39
Q

What are the roadblocks to poliovirus Eradication?

A
  • Poliovirus is a contagious (oral–fecal route) and stable virus.
  • Use of IPV in tropical regions is problematic.
  • IPV is inefficient in preventing the spread of virus.
  • Some resistance to mass vaccination
  • How can we tell if the vaccine is successful?
  • only 1 out of 100 people suffer from the paralytic polio
40
Q

What is the progress towards poliovirus eradication?

A
  • Significant progress between 1988 and 2003
  • 2003 reduced from 125 to 6 polio-endemic countries
  • New pockets of cases in as many as 26 countries that had been polio-free
  • WHO intensifying efforts
  • Educational programs to reinforce the importance and safety of vaccination
41
Q

What was involved in the Endemic Polio?

A

Endemic polio viruses eliminated from all but 3 countries in the world (Nigeria, Pakistan, and Afghanistan); India removed in February 2012

42
Q

What was the Final Inch (2009)?

A
  • Documentary focusing on the ongoing efforts to eradicate polio in India, Pakistan, and Afghanistan
  • Funded in part by Google to promote public awareness about polio and the efforts of public health workers.
  • “National Immunization Day” in slum areas of India and Pakistan in April 2007
43
Q

What is the endemic Polio in Nigeria?

A
  • Polio infection rates have skyrocketed nearly 800% in Nigeria in 2009

121 cases in 2012 and 4 cases in 2013

  • Immunization program temporarily shut down in 2003 because safety questions about the polio vaccine arose
  • Nigeria, along with several other poor nations, uses an oral polio vaccine (OPV)

more affordable, more accessible, and can protect entire villages
Live-attenuated; causes polio at a rate of 2-4 cases per million

  • Both socio-political and cultural beliefs lent to a unfavorable perception of the vaccine

“Polio vaccine was contaminated with antifertility drugs so that young Muslim girls would be unable to reproduce”

  • 10 volunteer polio vaccinators killed in February 2013; 9 female polio workers killed in Pakistan in December 2012

setback to progress on the polio campaign in the region

44
Q

What are some other enteroviruses?

A
  • At least 70 enteroviruses are known to infect humans.
  • The majority of enterovirus infections are asymptomatic or cause mild or self-limiting infections in children.
  • Four groups of enteroviruses:
  1. Polioviruses

Non-polio

  1. Group A Coxsackie viruses
  2. Group B Coxsackie viruses
  3. Echoviruses
45
Q

What else is involved with Enteroviruses?

A
  • Some cause myocarditis and dilated cardiomyopathy (DCM)
  • Inflammation of the myocardium
  • Enlarged heart; congestive heart failure
  • 50% mortality rate with DCM
  • 70% of the general population has been exposed to cardiotropic viruses
  • ½ experience acute viral myocarditis
  • About 14%–21% of respiratory disease is associated with enterovirus infections
  • Mild, self-limiting disease
46
Q

What is Coxsackie Virueses?

A
  • Discovered in 1948-49 by NYS DOH scientist Gilbert Dalldorf

===Work done in monkeys suggested that fluid collected from a non-polio virus preparation could protect against the crippling effects of polio
===Attempted to isolate protective viruses from the feces of polio patients ( 1st in Coxsackie, NY)

  • Cause a variety of infections and were subdivided into groups A and B based on their pathology in newborn mice
47
Q

What are Group A and Group B involved in Coxsackie Viruses?

A

Group A

  • Infect skin and mucous membranes
  • Cause mouth sores, acute hemorrhagic conjunctivitis, and hand, foot and mouth (HFM) disease
  • Nonspecific febrile illnesses, rashes, upper respiratory tract disease, and aseptic meningitis
  • Causes paralysis and death in mice

Group B

  • Infect the heart, pleura, pancreas, and liver
  • Cause pleurodynia, myocarditis, pericarditis, and hepatitis
  • Pericardial effusion (“fluid around the heart”)
  • Development of insulin-dependent diabetes (IDDM)
48
Q

What is Hand, Foot and Mouth Disease?

A
  • Affects infants and children (nursery school epidemics)
  • Moderately contagious and is spread through direct contact with the mucus, saliva, or feces of an infected person
  • 3-7 day incubation period
  • Fever, painful sores may appear in the mouth and/or throat
  • Rash may become evident on the hands, feet, mouth, tongue
  • No specific treatment