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

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

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

Measles vaccine efficacy 1941 - 894,134 U.S. cases 1995 - 288 U.S. cases 24May06 KL Vadheim Lecture 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

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

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

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

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 24May06 KL Vadheim Lecture 6

Mumps vaccine efficacy 1968 - 152,209 U.S. cases 1995 - 840 U.S. cases 24May06 KL Vadheim Lecture 6

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 24May06 KL Vadheim Lecture 6

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 24May06 KL Vadheim Lecture 6

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 24May06 KL Vadheim Lecture 6

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

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

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.) 24May06 KL Vadheim Lecture 6

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

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

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

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

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

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

Rubella vaccine efficacy 1969 - 57,686 U.S. cases 1995 - 200 U.S. cases 24May06 KL Vadheim Lecture 6

MMR Vaccines Live Attenuated Subcutaneous administration Lyophilized presentation Licensed 1971 24May06 KL Vadheim Lecture 6

MMR Vaccines 24May06 KL Vadheim Lecture 6

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

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 24May06 KL Vadheim Lecture 6

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

Varicella Pathogenicity Latent infection of sensory nerve ganglia common Some viral infection during latent stage Suppression of VZV reactivation partially under immunological control 24May06 KL Vadheim Lecture 6

Varicella Vaccine Lyophilized Requires storage at +5F or below Live, attenuated virus 24May06 KL Vadheim Lecture 6

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