Measles Lecture Notes

Measles Overview

  • Definition: Measles is caused by an enveloped RNA-containing virus.

  • Genetic Relation: It is genetically related to the canine distemper virus.

Virus Classification

  • Families: Measles virus falls under the Paramyxoviridae family.

Clinical Disease Naming

  • Rubeola: The clinical disease caused by the measles virus is known as rubeola.

  • Difference from Rubella: Rubeola should not be confused with rubella, which is also known as German measles.

Pathogenesis of Clinical Disease

  • Transmission:

    • Measles virus is transmitted via the respiratory route through respiratory droplets.

    • These droplets can remain infectious in the air for several hours.

  • Initial Infection Site:

    • The initial site of infection occurs within the epithelial cells of the respiratory tract.

  • Incubation Period:

    • The incubation period for measles is typically between 9 to 11 days.

  • Clinical Presentation:

    • Initial symptoms include:

    • Sudden onset of sneezing and congestion.

    • Cough.

    • Rapidly increasing fever.

    • Redness of the eyes and photophobia.

  • Viremia: The virus spreads to local lymph nodes and subsequently enters the bloodstream, where a viremia is established in monocytes/macrophages.

Subsequent Symptoms

  • Koplik’s Spots:

    • These are tiny bluish-white spots on a red base that appear within the mouth 2 to 4 days after infection.

  • Further Spread:

    • The virus disseminates through the blood (viremia) to the liver, spleen, and skin.

  • Infection of Endothelial Cells:

    • The virus infects endothelial cells of small blood vessels in the skin.

    • The onset of the rash coincides with the appearance of cellular immunity.

    • The rash is characterized by the action of CD4+ DTH T cells that recognize virus-infected endothelial cells.

    • The destruction of these cells results in tiny hemorrhages under the skin, presenting as a rash specific to measles (not vesicles as seen in smallpox).

Rash Characteristics

  • Rash Appearance:

    • The rash appears first on the forehead and behind the ears.

    • Within 24 to 48 hours, the rash spreads to the face, neck, trunk, and limbs.

    • The rash persists for around 10 days.

  • Immunity:

    • Following recovery from measles, individuals gain life-long immunity to re-infection.

Mortality and Complications

  • Mortality Rates:

    • Deaths due to measles virus infection vary:

    • 0.1% in industrialized countries.

    • Up to 15% in developing countries.

  • Neurological Complications:

    • The measles virus can invade the brain, causing various neurologic complications, including life-threatening acute encephalitis.

Neurologic Diseases Associated with Measles

  • Complications Overview:

    • Acute disseminated encephalomyelitis (ADEM).

    • Measles inclusion body encephalitis (MIBE).

    • Subacute sclerosing panencephalitis (SSPE).

Summary of Neurologic Complications

Disease

Host

Onset

Incidence

Pathology

Time Course

Acute disseminated encephalomyelitis (ADEM)

Normal > 2 yr

1:1,000

Inflammation, demyelination

Monophasic, weeks

Measles inclusion body encephalitis (MIBE)

Immunocompromised

Any

1:10

Inclusion bodies

Progressive, months

Subacute sclerosing panencephalitis (SSPE)

Normal < 2 yr

1:10,000

Inclusion bodies, inflammation

Progressive, years

Subacute Sclerosing Panencephalitis (SSPE) Pathogenesis

  • M Protein: Expression of the M protein is low, with mutations throughout the mRNA encoding the M protein.

  • Functional Implications: These alterations interfere with the assembly and budding of the virus, contributing to persistent measles virus infection and SSPE.

Clinical Course of SSPE

  • Age of Onset: The age of onset for neurologic disease is typically around 8 to 10 years, but occurrences have been reported as late as age 35.

  • Stages of SSPE:

    • First Stage: Behavioral problems and decline in school performance appear quickly after onset.

    • Second Stage: Occurrence of intellectual decline, motor function disturbances (myoclonic jerks and seizures), retinitis, optic nerve atrophy, and cerebellar ataxia.

    • Third Stage: The child may lapse into a stuporous state.

    • Fourth Stage: Characterized by loss of cortical function, potential mutism, coma, and death.

Immunological Implications of Measles Infection

  • Impact on Immune Memory: Measles virus infection significantly impairs the immune system’s memory B cells, erasing between 11% to 73% of a person’s protective antibodies to other infections (e.g., influenza, hepatitis, tuberculosis).

  • Resulting Susceptibility: This immunosuppression following the resolution of acute measles virus viremia increases susceptibility to these other infectious agents.

Immunization and Vaccine Efficacy

  • Lifelong Immunity: Once a person has had a clinical case of measles, they are immunized for life.

  • Impact of MMR Vaccine:

    • The incidence of measles significantly decreased in the United States post-immunization introduction.

    • Rates of measles-associated encephalitis are significantly lower in vaccinated individuals.

    • SSPE incidence reduced by a factor of 10 in vaccinated persons.

    • The measles vaccine helps protect the immune system’s memory from being erased.

Global Eradication Efforts

  • Vaccination Potential: Measles could potentially be eradicated globally through an aggressive vaccination program.

  • Public Concerns: Fears that measles vaccination (MMR vaccine) may contribute to autism have led to increased measles incidence, notably in the United Kingdom and more recently in the United States.