1. Measles, Mumps, Rubella, Varicella
MedCh 401
Lecture 6
24May06
KL Vadheim Lecture 6

2. 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
24May06
KL Vadheim Lecture 6

3. 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
24May06
KL Vadheim Lecture 6

4. Measles virus attenuation
Start with attenuated Enders’attenuated Edmonston strain
Propagate in chick embryo cell culture
24May06
KL Vadheim Lecture 6

5. Measles vaccine efficacy
,134 U.S. cases
U.S. cases
24May06
KL Vadheim Lecture 6

6. Vaccine failure
Infants vaccinated at <12m 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
24May06
KL Vadheim Lecture 6

7. 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
24May06
KL Vadheim Lecture 6

8. Mumps Pathogenesis Reinfection occurs usually asymptomatic 24May06
KL Vadheim Lecture 6

9. Mumps virus attenuation
Jeryl Lynn (B level) strain
Cultured from Jeryl Lynn Hilleman’s throat
Attenuated by serial passage in
embryonated hen’s eggs
chick embryo cell culture
24May06
KL Vadheim Lecture 6

10. 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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KL Vadheim Lecture 6

11. Mumps vaccine efficacy
,209 U.S. cases
U.S. cases
24May06
KL Vadheim Lecture 6

12. Recent mumps outbreaks
Started in Dec in Iowa
2,597 cases Jan. 1- May 2, 2006
11 states, all ages affected
Vaccination clinics initiated
24May06
KL Vadheim Lecture 6

13. 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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KL Vadheim Lecture 6

14. 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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KL Vadheim Lecture 6

15. UK Mumps epidemic, 2004-2005 >70,000 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
24May06
KL Vadheim Lecture 6

16. 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.
24May06
KL Vadheim Lecture 6

17. Rubella Aka ‘German’ measles Discovered in 1841
Virus isolated in 1941 by German scientists
Sudden pandemic in
Vaccine developed in 1960s
Vaccine licensed in 1970 (U.S.)
24May06
KL Vadheim Lecture 6

18. 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
24May06
KL Vadheim Lecture 6

19. Congenital Rubella Syndrome
Cataracts
Deafness
Heart malformation
Also:
microcephaly
autism
mental retardation
Diabetes
etc.
24May06
KL Vadheim Lecture 6

20. 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
24May06
KL Vadheim Lecture 6

21. 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
24May06
KL Vadheim Lecture 6

22. 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
24May06
KL Vadheim Lecture 6

23. 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
24May06
KL Vadheim Lecture 6

24. Rubella vaccine efficacy
,686 U.S. cases
U.S. cases
24May06
KL Vadheim Lecture 6

25. MMR Vaccines Live Attenuated Subcutaneous administration
Lyophilized presentation
Licensed 1971
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KL Vadheim Lecture 6

26. MMR Vaccines
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KL Vadheim Lecture 6

27. 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
24May06
KL Vadheim Lecture 6

28. 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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KL Vadheim Lecture 6

29. 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
24May06
KL Vadheim Lecture 6

30. 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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KL Vadheim Lecture 6

31. Varicella Vaccine Lyophilized Requires storage at +5F or below
Live, attenuated virus
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KL Vadheim Lecture 6

32. 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
24May06
KL Vadheim Lecture 6