Lecture 17 Paralytic Poliomyelitis

What does Poliomyelitis cause?

destruction of the anterior horn cells of spinal cord

How many serotypes of poliomyelitis that cause destruction of the anterior horn cells are there in humans?

3, Type 1-3

Picornavirus

Spanish pico for “point” (10^-12), referring to small size of virion and RNA

Virion:  Nucleocapsid with icosahedral symmetry
Nonenveloped virion
30 nm diameter

Genome:  Linear single-stranded RNA
Encodes for 6-8 proteins (4 structural proteins)

Poliovirus is what type of virus?

Enterovirus, replicates in the gut

How are the serotypes of poliovirus are distinguished?

In vitro neutralization with type-specific antisera

Pathogenesis

(know the %s)
1.  Ingested poliovirus infects oropharynx (tonsils) + intestines
>Penetrates mucosa via specialized cells (M cells) overlying submucosal lymphoid tissue (Peyers patches)
>Intestinal submucosal tissues are most efficient replication site(~10⁸ virus particles/gm tissue)

2.  Poliovirus spreads to regional lymph nodes to give rise to “minor viremia” in the blood
>Transient and clinically silent (asymptomatic)
>Virus spreads systemically to other lymph nodes, bone marrow, liver, and spleen
>Virus replication usually contained resulting in subclinical infection (>90% of cases) 

3.  In <10% of cases, further virus replication in reticuloendothelial tissue leads to “major viremia”
>Coincides with onset of clinical symptoms associated with “minor illness” (3-7 days after initial infection)  
>Fever, headache, sore throat
>4-8% of infected persons experience minor illness that resolves in 1-2 days without further symptoms

4.  Poliovirus spreads from the blood → central nervous system
>Precise mechanism by which the virus crosses BBB unknown
>Onset of clinical symptoms associated with “major illness” (9-12 days after initial infection)
>Abrupt onset of headache, vomiting, intense myalgias of   limb and skeletal muscles, motor weakness
>0.1-1.0% of infected persons experience major illness
>1/3 of cases of CNS disease is limited to a meningitis that resolves in 10 days (nonparalytic poliomyelitis)

5.  Virus travels within the CNS to produce necrotic lesions and inflammatory infiltrates distributed within gray matter of anterior horn of spinal cord as well as motor nuclei of pons / medulla
>Virus recoverable from spinal cord for only first several days of paralysis  
>Necrotic lesions and inflammatory infiltrates may persist for months
>Severity of clinical paralysis depends more on intensity of lesions rather than their distribution

Spinal Paralytic Poliomyelitis

>Weakness of muscles supplied by motor nerves
>Includes most skeletal muscles of the body
>4-6% mortality

•Bulbar Paralytic Poliomyelitis

>Weakness of muscles supplied by cranial nerves
>Affects facial muscles, tongue, swallowing, respiration
>20-40% mortality, respiratory failure due to paralysis of diaphragm + intercostal muscles

Prognosis

Paralysis most often progresses for 1-3 days after onset

•Most patients with limb paralysis experience some recovery of function within weeks to months after acute disease

•Very little additional recovery of strength after 9 months(after 9 months ur screwed)

•Residual motor deficits range from minor weakness to permanent flaccid paralysis

Paralytic poliomyelitis has been with us for thousands of years …

but in endemic form, occurring only sporadically

Hippocrates and polio

•described poliomyelitis-like illness that occurred in late summer - early autumn (“polio season”)

Infantile Paralysis

endemic → epidemic disease in late 19th century in north Europe + USA

called this because it caused rapid paralysis in children, typically due to diaphragm paralysis was death caused

Sanitation Changes

virus spreads via fecal-oral route

sewage in streets→ kids play in streets → exposed to polio naturally → immunity to polio

Closed sewer systems → kids don’t play in doodoo → don’t get exposed to polio → loss of herd immunity and buildup on nonimmune people 

Poliovirus Antibody induction

•Serum (blood) immunity
  >Serum antibodies
  >IgG

•Gut immunity
  >Antibodies produced within intestinal tract (Peyer’s patches)
  >Secretory IgA [Prevents virus from entering blood from the intestinal tract]

Transmission

initially thought to be respiratory or insects (flies + roaches)

Actually fecal-oral route

Brodie Vaccine (1934)

>Killed vaccine (New York City Health Department)
>Prepared from homogenized spinal cord taken from monkey infected with poliovirus
>Suspension treated with formalin to inactivate virus

Kolmer Vaccine (1934)

>Live attenuated vaccine (Institute of Cutaneous Research)
>Prepared by passage of poliovirus through monkey brains

Results of Brodie v Kolmer

Both vaccines suck ass at protecting the monkeys

Kolmer vaccine caused paralysis, and caused more cases to occur

Schultz Procedure (1935)

•Hypothesis of the time was that poliovirus entered the CNS through the olfactory bulb of the nose

•In 1935, Schultz (Stanford University) sprayed a solution of alum (zinc sulfate) into noses of monkeys
>Appeared to show that nasal administration of alum protected monkeys from developing poliomyelitis
>Suggested that alum would coagulate proteins of the mucous membranes of the nose and form a barrier to protect nerve endings of olfactory bulb from poliovirus infection

•Due to publicity, there was a public demand for large clinical trial to test procedure on children

•1936→  large poliomyelitis epidemic in the South USA

First clinical trial of Schultz Procedure (1936)

•Conducted in Alabama during epidemic in 1936
>4000+ children received the procedure, but no controls
>Results showed no protective effects

•Schultz refused to accept negative results of clinical trial
>He concluded that nasal spray was administered improperly + recipient must lose his/her sense of smell for the procedure to be effective

Second clinical trial of Schultz Procedure (1937)

•Conducted in Toronto during epidemic in 1937
>5000 children received the procedure, 5000 receive placebo (control)
>Tests performed to be sure that children lost all sense of smell
>Results showed no protective effects

Important findings of the Polio Vaccine

•1949 - Poliovirus found to grow in tissue culture in cells not from the nervous system (nonneural cells)

•1949 - Three distinct antigenic types of poliovirus identified; each capable of causing disease and inducing type-specific antibody

•1952 - Poliovirus found in the blood of monkeys in experimental studies

Live v Killed Vaccine

Live attenuated vaccine
Pros: Excellent immunity; no booster
Cons: Difficult to prepare; safety issues

Killed vaccine
Pros: Quick to prepare and safe
Cons: Transient immunity; boosters needed

Salk Vaccine Development Decisions

•Choose a suitable strain of virus to represent each of the three antigenic virus types

•Choose a treatment to inactivate virus yet preserve its ability to stimulate an immune response (antigenicity)

•Choose a safe course for clinical trials to evaluate vaccine’s immunogenicity and efficacy in humans

Early Salk Vaccine Development

[just know bro went slowly in development]

1952
Group of children already infected with poliovirus administered type 1 vaccine and followed for increase in type 1 serum antibodies

1953
Group of children not infected with poliovirus administered type 1 vaccine and followed for development of type 1 serum antibodies

Salk Vaccine National Clinical Trial

•Nationwide clinical trial conducted in April of 1954, 1.8 mill kids enrolled

•Clinical trial divided into two areas
>Observed areas: vaccinated kids compared with unvaccinated kids
>Placebo areas:  200,000 vaccinated kids compared with 200,000 placebo kids

Results (April 12,1955):
>Observed areas: 62% effective
>Placebo areas: 70% effective 

Efficacy varies from viral type and batch-to-batch, but was safe and effective

Some vaccine recipients experienced an outbreak in Cali, but was a manufacturing error (maybe due to monkey virus SV40 contamination?)

Sabin Vaccine Clinical Trial 1957-1958

•4.5 million people inoculated with live vaccine in USSR

•Oral vaccine used to induce gut immunity

•Results announced in June of 1959
>Vaccine stimulated good serum antibody
>Vaccine stimulated good gut antibody (IgA)
>No reversion to wildtype virus (no disease)
>No boosters needed

Replaced Salk vaccine in 1960 since polio outbreak in Florida [people refused to get booster aka noncompliance]

Clinical trial of Sabin [Trivalent Oral Polio Vaccine] in sugar/syrup, 1962 release with no publicity 

Poliomyelitis Eradication Initiative

Eradicated in the US, North + South America

Type 2+3 polio eradicated worldwide

Type 1 only in Pakistan + Afghanistan with few cases (Aug 2024, 14 cases)

Reemergence

July 2022, unvax adult in New York got polio by Type 2 [one case is considered an outbreak, since many ppl may be asymptomatic]

Type 2 found in sewer sample, and is everywhere actually

NY vaccination rate is only 60%, while US is only 37% → herd immunity going away

Acute Flaccid Myelitis

•A rare polio-like disease appeared in ~25 children in California in August 2014

•Disease resembles paralytic poliomyelitis

•Clinical presentation includes sudden limb weakness, loss of muscle tone and reflexes, facial and eyelid dropping, difficulty in moving the eyes, difficulty swallowing, slurred speech, and difficulty breathing

•Pathology affects the gray matter of the spinal cord

•Enterovirus D68 is the suspected cause

•The incidence of AFM peaks every two years following outbreak of enterovirus D68

•There have been 781 confirmed cases in the United States since the CDC began tracking the infectious disease in August 2014

•As of September 2025, there have been 8 confirmed cases out of 18 patients under investigation

•Mortality rate low with 2 patients dying from confirmed acute flaccid myelitis, one in 2017 and one in 2020

•However, morbidity remains high with victims showing upper limb and/or lower limb weakness or paralysis associated with cerebrospinal fluid pleocytosis