Measles, Mumps, Rubella, Varicella

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Measles, Mumps, Rubella, Varicella

• MedCh 401
• Lecture 6

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Measles, Mumps, Rubella

• Common childhood diseases
• May be associated with severe complications/death
• More often in adults
• Measles - pneumonia, encephalitis
• Mumps - aseptic meningitis, deafness, orchitis
• Rubella - congenital rubella syndrome
• Respiratory transmission

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Measles

• 14-day incubation period for respiratory-acquired
  infections
• 6-10 days if acquired parenterally
• remains the leading cause of vaccine-preventable
  death in children

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Measles virus attenuation

• Start with attenuated Endersattenuated Edmonston
  strain
• Propagate in chick embryo cell culture

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Measles vaccine efficacy

• 1941 - 894,134 U.S. cases
• 1995 - 288 U.S. cases

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Vaccine failure

• Infants vaccinated at lt12m who were born to
  naturally-infected mothers may not develop
  sustained antibody levels when later revaccinated
• Primary failure
• No seroconversion
• Secondary failure
• Loss of protection after seroconversion

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Mumps Pathogenesis

• Viremia common, leading to organ involvement
• salivary glands (parotitis), meningitis,
  orchitis, endolymph infection leading to deafness
• A major cause of permanent, bilateral,
  sensorineural deafness in children
• Virus shed in saliva and urine for long periods
  after infection

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Mumps Pathogenesis

• Reinfection occurs
• usually asymptomatic

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Mumps virus attenuation

• Jeryl Lynn (B level) strain
• Cultured from Jeryl Lynn Hillemans throat
• Attenuated by serial passage in
• embryonated hens eggs
• chick embryo cell culture

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Passive immunization against mumps

• Immune globulin ineffective for postexposure
  prophylaxis
• does not prevent disease or reduce complications
• Transplacental maternal antibody appears to
  protect infants for first year of life

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Mumps vaccine efficacy

• 1968 - 152,209 U.S. cases
• 1995 - 840 U.S. cases

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Recent mumps outbreaks

• Started in Dec. 2005 in Iowa
• 2,597 cases Jan. 1- May 2, 2006
• 11 states, all ages affected
• Vaccination clinics initiated

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Theories on outbreak

• College campuses are the perfect environment for
  spreading a disease transmitted through oral
  secretions
• Only 25 states and DC require two doses of MMR
  for college admission

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More theories

• Delayed recognition and diagnosis of disease
• few younger MDs have seen the disease
• Many would not consider the diagnosis in a
  vaccinated individual

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UK Mumps epidemic, 2004-2005

• gt70,000 cases in England and Wales
• Increased susceptibility of unvaccinated cohorts
  who have less exposure to mumps because of a
  decrease in disease circulation after
  implementation of a childhood immunization program

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UK Epidemic

• Importance of ensuring high levels of immunity
  among other age groups when mumps vaccination is
  added to the routine immunization schedule for
  children.

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Rubella

• Aka German measles
• Discovered in 1841
• Virus isolated in 1941 by German scientists
• Sudden pandemic in 1962-65
• Vaccine developed in 1960s
• Vaccine licensed in 1970 (U.S.)

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Congenital Rubella Syndrome

• Infection in first trimester most dangerous
• 90 of fetuses likely to have some type of
  abnormality
• Virus disrupts organogenesis
• plus more destructive on brain, cochlea, lens,
  etc.
• Virus establishes chronic infection in many
  cells/organs
• virus secretion may persist for years

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Congenital Rubella Syndrome

• Cataracts
• Deafness
• Heart malformation
• Also
• microcephaly
• autism
• mental retardation
• Diabetes
• etc.

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Mumps Pandemic 1962-65, Europe and U.S.

• 12.5 million mumps cases
• 20,000 cases CRS
• 11,600 deaf
• 3,580 blind
• 1,800 mental retardation
• 6,250 spontaneous abortions
• 5,000 surgical abortions
• 2,100 stillborn/neonatal deaths

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Rubella vaccine

• Mumps virus RA-27/3 isolated from an infected
  fetus in 1965
• Culture fluid passaged directly into WI-38 cells
• 8 serial passages at 37C
• Seven additional passages at 30C
• human volunteer studies showed attenuation
• Ten additional passages to further decrease
  pathogenicity

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Rubella RA27/3 vaccine strain

• Produced between 25th and 30th passage in human
  diploid cells
• Relatively rapid attenuation due to
• cold adaptation (30C)
• Retention of high immunogenicity due to
• relatively low passage number required for
  attenuation

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Rubella points to remember

• Clinical rubella has been demostrated in
  vaccinees and naturally infected, immune persons
• Reinfection with fetal transmission of wild virus
  in presence of both natural and vaccine-induced
  immunity
• can result in CRS

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Rubella vaccine efficacy

• 1969 - 57,686 U.S. cases
• 1995 - 200 U.S. cases

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MMR Vaccines

• Live
• Attenuated
• Subcutaneous administration
• Lyophilized presentation
• Licensed 1971

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MMR Vaccines
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Varicella zoster

• Causes two separate diseases
• chickenpox (varicella)
• shingles (herpes zoster)
• Generally a benign, self-limiting disease
• Herpes virus
• Highly communicable disease of all ages

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Varicella Transmission

• Airborne
• Skin, Respiratory droplets through conjunctivae
  or mucosa of upper respiratory tract
• Can transmit chickenpox to a susceptible person
  from a person with shingles

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Varicella Pathogenicity

• Usually a mild disease
• can cause severe, life-threatening complications
• 1st trimester infection can cause permanent CNS
  (and other) damage to fetus, or death
• 3rd trimester infectionmay cause severe maternal
  infection,
• Host range limited to humans and some primates

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Varicella Pathogenicity

• Latent infection of sensory nerve ganglia common
• Some viral infection during latent stage
• Suppression of VZV reactivation partially under
  immunological control

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Varicella Vaccine

• Lyophilized
• Requires storage at 5F or below
• Live, attenuated virus

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Varicella attenuation process

• Initial viral isolation from a child with
  varicella
• Adapted to human embryonic lung cell cultures
• Adapted to and propagated in embryonic guinea pig
  cell cultures
• Propagated in human diploid cell cultures (WI-38)
• Further passage in human diploid cell cultures
  (MRC-5) that are free of adventitious agents