Measles Virus Study Notes

Virus Viability: Can persist in aerosols in the air for over 30 minutes
Basic Reproduction Number (R0): Ranges from 12 to 18, indicating high transmissibility
Historical Note: Was considered eliminated in the US as of the year 2000
Definitions:
- Elimination: Reduction of disease incidence to zero in a specific area
- Eradication: Permanent reduction to zero of the global incidence of infection
**Current Issues:
- Anti-vaccination and vaccine hesitancy leading to an *immediate risk* of losing elimination status.

Transmission: Spread through respiratory droplets
Initial Replication Sites: Mucosal epithelium in the respiratory tract
Pathway of Infection:
- From respiratory tract to lymph nodes, then bloodstream (viremia)
- Spreads to all organs using primary, secondary, and tertiary lymphatic tissues
Clinical Symptoms Onset (9-19 days post-infection):
  - Fever
  - Cough
  - Koplik Spots: Tiny white lesions appearing in the mouth
  - Maculopapular rash
  - Transient immunosuppression lasting 1-2 years
  - Severe symptoms: Delirium, high fever, conjunctivitis
  - Potential for neurological complications

Acute Disseminated Encephalomyelitis (ADEM):
  - Occurs in 1 in 1000 infections
  - A demyelinating disorder that arises within days or weeks post-infection.
  - Resulting from an autoimmune response with antibodies targeting myelin proteins. Typically affects individuals >4 years old.
Measles Inclusion Body Encephalitis (MIBE):
  - Seen primarily in immunocompromised individuals
  - Often leads to lethal outcomes, occurring days to months after infection or vaccination with live attenuated virus
  - Caused by hyperfusogenic virions
Subacute Sclerosing Panencephalitis (SSPE):
  - Results from mutant virions lacking envelope proteins
  - Characterized as a chronic infection in the central nervous system
  - Also known as Dawson’s Disease
  - Incidence rate: 2 in 10,000 infections in children, teens, and young adults; 1 in 609 in infants
  - Symptoms occur between 1 month and 27 years post-infection and recovery, including:
    - Stage 1: Nonspecific neurological symptoms
    - Stage 2: Seizures, vision loss, jerky movements, dementia
    - Stage 3: Movement issues evolve into twisting movements and rigidity; may lead to blindness or death
    - Stage 4: Progressive loss of consciousness leading to a vegetative state, paralysis; death may result from fever, heart failure, or inability to regulate autonomic functions
    - Most susceptible individuals are those <2 years old.

Cell Attachment:
  - The virus attaches to cells using Signaling Lymphocyte Activation Molecule Family Member 1 (SLAMF1, or CD150) or nectin-4
  - These molecules are expressed by dendritic cells, thymocytes, hematopoietic stem cells (HSCs), as well as T and B cells
  - Membrane fusion triggers conformational change releasing RNP complexes into the cytoplasm.
Viral Replication Process:
  - Viral RNA along with L, N, and P proteins forms an RNP complex to initiate transcription
  - Viral mRNA is produced for translation
  - Subsequently, the switch is made to genomic RNA production
  - Accumulation of viral proteins and RNP complexes at the plasma membrane occurs culminating in virus assembly.

Focus Group Exercise: Examine and discuss the functions and roles of the following proteins in MV virulence:
  - C protein
  - V protein
  - H and F proteins

Definition: Also referred to as transient immunosuppression
  - Caused by depletion of memory lymphocytes leading to lymphopenia
  - New measles virus-specific lymphocytes are produced, strong immunity against measles is developed, but immunity to other infections diminishes
  - This condition can last more than 2 years, with an average duration of 27 months
  - Unique characteristic of measles infection that can complicate public health efforts.

Group Activity: Break into pairs to analyze specific figures. Description requirements:
- What is depicted in the figure
- The role of that process in MV virulence.

Group Activity: Similar to previous exercise, break into pairs for this figure analysis:
  - Describe methods used
  - Discuss results
  - Summarize the take home message from each figure.

Historical Context: Andrew Wakefield's publication claimed that the measles vaccine causes autism (1998)
- Publication retracted in 2010 but misinformation still fuels vaccination opposition
Impact of Anti-Vaccination Sentiments:
  - RFK Jr. and incidents in Samoa, including a child's death due to improper vaccine preparation (July 8, 2018), igniting further anti-vaccination sentiments.
  - Post-event, vaccination rates dropped by 31%.
  - June 2019: RFK Jr. collaborates with anti-vaccination activists, promoting anti-vaccine campaigns.
  - Outbreak Events:
    - 10/19 outbreak initiated by a traveler lasts 4 months, with 5520 total cases (2.75% of the population), resulting in 79 deaths (1.43% fatality rate).
    - At least 20% of infants aged 6-11 months contracted the disease.
    - 61 out of 79 deaths were among children aged 4 and under; 75 out of 79 deaths occurred in individuals aged 15 and under.
- Ongoing Measles Outbreaks:
  - Texas (August 12, 2025): 2144 cases reported.
  - South Carolina (October 2, 2025): 997 cases reported, outbreak ongoing.

Discussion Points:
  - Should vaccination exemptions be permitted? Discuss the merits and demerits of religious and medical exemptions.
  - For those in favor of exemptions: outline necessary procedures for obtaining them, including proof of religious belief or medical conditions. Discuss the accessibility of obtaining exemptions and how to regulate them.
  - For those against providing exemptions: discuss enforcement strategies, considering issues of religious/personal freedoms and medical status.