Paralytic Poliomyelitis: The Plague of the 1950s

Paralytic Poliomyelitis: The Plague of the 1950s

Overview of Poliomyelitis

  • Definition: Poliomyelitis (from the Greek polios, meaning gray, and myelos, meaning spinal cord) is characterized by destruction of the anterior horn cells of the spinal cord.

Transmission and Pathogenesis

  • Vacuums of Infectious Diseases: New and sometimes more deadly infectious diseases often fill vacuums left by previous diseases.

  • Pathogenesis:

    • Step 1: Ingested poliovirus infects the oropharynx (tonsils) and intestines.

    • Mechanism: The virus penetrates the mucosa via specialized cells (M cells) overlying the submucosal lymphoid tissue (Peyer's patches).

    • Results: Intestinal submucosal tissues are the most efficient site of replication (~10810^{8} virus particles/gm tissue).

    • Step 2: Virus spreads to regional lymph nodes leading to "minor viremia" in the blood (asymptomatic).

    • Site of spread includes bone marrow, liver, and spleen.

    • Most infections are subclinical (>90% of cases).

    • Step 3: In <10% of cases, virus replication in reticuloendothelial tissue leads to "major viremia"

    • Timeline: Occurs 3 to 7 days after initial infection; coincides with onset of clinical symptoms.

    • Symptoms: Fever, headache, sore throat. 4-8% of infected individuals experience minor illness with resolution in 1 to 2 days.

    • Step 4: Poliovirus spreads from blood to the central nervous system (CNS).

    • Mechanism: The precise mechanism for crossing the blood-brain barrier remains unresolved.

    • Timeline: Coincides with clinical symptoms of "major illness" 9 to 12 days after initial infection.

    • Symptoms: Abrupt onset headache, vomiting, intense myalgias, motor weakness. 0.1-1.0% of infected persons experience major illness.

    • Note: Approximately one-third of CNS diseases are limited to a nonparalytic form (meningitis) resolving within 10 days.

    • Step 5: Virus produces necrotic lesions and inflammatory infiltrates in the anterior horn of the spinal cord and brainstem motor nuclei.

    • Virus recovery from the spinal cord occurs only in the initial days of paralysis.

    • Lesions may persist for months; severity of paralysis correlates with lesion intensity, not distribution.

Subclasses of Paralytic Poliomyelitis

  • Spinal Paralytic Poliomyelitis: Weakness of muscles supplied by motor nerves; includes most skeletal muscles.

  • Bulbar Paralytic Poliomyelitis: Weakness of muscles supplied by cranial nerves; affects facial muscles, tongue, swallowing, and respiration.

  • Coexistence: Spinal and bulbar forms often occur simultaneously.

Prognosis and Mortality

  • Paralysis typically progresses for 1 to 3 days post-onset.

  • Recovery: Most limb paralysis patients experience some recovery within weeks to months.

    • Very little additional strength regain after 9 months; permanent residual deficits can occur.

  • Overall Mortality:

    • Spinal paralytic poliomyelitis: 4-6% mortality.

    • Bulbar paralytic poliomyelitis: 20-40% mortality.

    • Cause of death: Respiratory failure due to paralysis affecting diaphragm and intercostal muscles.

Historical Context

  • Early References: Hippocrates described poliomyelitis-like illnesses that occurred seasonally (late summer-early autumn).

  • Biblical Mentions: References to individuals with paralyzed, atrophied limbs.

Changes in Sanitation and Immunity

  • Epidemiology: Poliovirus spread via fecal-oral route.

  • Sanitation Improvements: Transition from open sewage to closed systems disrupts natural exposure to the virus in children, resulting in a loss of herd immunity.

Immune Response to Poliovirus

  • Types of Antibodies Induced:

    • Serum Immunity: Serum antibodies (IgG) present in the bloodstream.

    • Gut Immunity: Secretory IgA prevents the virus from entering the bloodstream from the intestinal tract (critical adaptation unknown at the onset of the epidemic).

Misconceptions about Transmission

  • Initial beliefs suggested respiratory spread or insect vectors (e.g., flies, cockroaches) contributed to poliovirus transmission.

Early Vaccines and Research

  • Brodie Vaccine (1934): Killed vaccine derived from monkey spinal cord homogenate, treated with formalin.

  • Kolmer Vaccine: Live attenuated vaccine through passage in monkey brains.

  • Both vaccines tested with over 10,000 children but doubts arose during polio seasons (autumn 1935).

Schultz Procedure (1935)

  • Proposed route of virus entry via the CNS through olfactory bulb:

    • Administered alum (zinc sulfate) nasally in monkeys, suggesting protection against poliomyelitis.

    • Led to demands for large clinical trials on children during the 1936 Southern U.S. epidemic.

Public Acceptance of Vaccines and Procedures

  • Motivations for Acceptance:

    • Fear of paralytic poliomyelitis.

    • Desperate parents seeking protection for children.

    • Influence of media reports encouraging vaccine trust.

Important Findings in Poliovirus Research

  • 1949: Discovery of poliovirus growth in nonneural tissue cultures and identification of three distinct antigenic types, each capable of causing disease.

  • 1952: Evidence of poliovirus presence in monkeys' blood during studies.

Vaccine Development

  • Early Salk Vaccine Development:

    • 1952: Infected children administered type 1 vaccine monitored for antibody response.

    • 1953: Uninfected children tested under similar conditions.

  • Process deemed slow and methodical; public respected Salk's cautious approach.

National Clinical Trial of Salk Vaccine (1954)

  • Trial Overview:

    • Participants: 1,829,916 children enrolled.

    • Groups: Observed (vaccinated vs. unvaccinated) and placebo (vaccinated vs. placebo).

  • Results (April 12, 1955):

    • Vaccine efficacy: 62% (observed) and 70% (placebo).

    • Efficacy varied by virus type and vaccine batch; considered safe with no vaccine-induced disease.

Sabin Vaccine Clinical Trial (1957/1958)

  • Conducted in the USSR with 4.5 million recipients of live oral vaccine.

  • Results (June 1959):

    • Good serum antibody and gut antibody (IgA) responses.

    • Important: No reversion to wild-type virus and no need for boosters.

Acute Flaccid Myelitis (AFM)

  • Description: A rare disease resembling paralytic poliomyelitis.

  • Incidence: Approximately 25 cases noted in California (August 2014).

  • Symptoms: Sudden limb weakness, muscle tone loss, facial drooping, swallowing difficulties, slurred speech, breathing issues.

  • Pathology: Affects gray matter of the spinal cord; suspected cause is enterovirus D68.

  • Trends: AFM incidence peaks biennially following enterovirus D68 outbreaks.