24May06KL Vadheim Lecture 61 Measles, Mumps, Rubella, Varicella MedCh 401 Lecture 6.

24May06 KL Vadheim Lecture 6 1

Measles, Mumps, Rubella, Varicella

MedCh 401

Lecture 6


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


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


Measles virus attenuation

• Start with attenuated Enders’attenuated Edmonston strain

• Propagate in chick embryo cell culture


Measles vaccine efficacy

• 1941 - 894,134 U.S. cases

• 1995 - 288 U.S. cases


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


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


Mumps Pathogenesis

• Reinfection occurs – usually asymptomatic


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


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


Mumps vaccine efficacy

• 1968 - 152,209 U.S. cases

• 1995 - 840 U.S. cases


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


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


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


UK Mumps epidemic, 2004-2005

• >70,000 cases in England and Wales>70,000 cases in England and Wales

• Increased susceptibility of unvaccinated Increased susceptibility of unvaccinated cohorts who have less exposure to mumps cohorts who have less exposure to mumps because of a decrease in disease circulation because of a decrease in disease circulation after implementation of a childhood after implementation of a childhood immunization programimmunization program


UK Epidemic

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


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.)


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


Congenital Rubella Syndrome• Cataracts

• Deafness

• Heart malformation

• Also:– microcephaly– autism– mental retardation– Diabetes– etc.


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


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


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


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


Rubella vaccine efficacy

• 1969 - 57,686 U.S. cases

• 1995 - 200 U.S. cases


MMR Vaccines

• Live

• Attenuated

• Subcutaneous administration

• Lyophilized presentation

• Licensed 1971


MMR VaccinesComponent,per 0.5 ml dose

Measles(Attenuvax)Merck

MumpsJeryl Lynn StrainMerck

Rubella(Meruvax)Merck

MMR-IIMerck

Measles virus >1,000TCID50

>1,000TCID50

Mumps virus >20,000 TCID50 >20,000TCID50

Rubella virus >1,000TCID50

>1,000TCID50

Sorbitol 14.5 mg 14.5 mg 14.5 mg 14.5 mgSodiumphosphateSucrose 1.9 mg 1.9 mg 1.9 mg 1.9 mgNaClGelatin 14.5 mg 14.5 mg 14.5 mg 14.5 mgHumanalbumin

0.3 mg 0.3 mg 0.3 mg 0.3 mg

Fetal bovineserum

<1 ppm <1 ppm <1 ppm <1 ppm

Neomycin ~25g ~25g ~25g ~25g


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


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


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


Varicella Pathogenicity

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

under immunological control


Varicella Vaccine

• Lyophilized

• Requires storage at +5F or below

• Live, attenuated virus


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

24May06KL Vadheim Lecture 61 Measles, Mumps, Rubella, Varicella MedCh 401 Lecture 6.

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