Measles Mumps Rubella Varicella Med Ch 401 Lecture

Measles, Mumps, Rubella, Varicella Med. Ch 401 Lecture 6 24 May 06 KL Vadheim Lecture 6 1

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 24 May 06 KL Vadheim Lecture 6 2

Measles • 14 -day incubation period for respiratoryacquired infections • 6 -10 days if acquired parenterally • remains the leading cause of vaccinepreventable death in children 24 May 06 KL Vadheim Lecture 6 3

Measles virus attenuation • Start with attenuated Enders’attenuated Edmonston strain • Propagate in chick embryo cell culture 24 May 06 KL Vadheim Lecture 6 4

Measles vaccine efficacy • 1941 - 894, 134 U. S. cases • 1995 - 288 U. S. cases 24 May 06 KL Vadheim Lecture 6 5

Vaccine failure • Infants vaccinated at <12 m 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 24 May 06 KL Vadheim Lecture 6 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 24 May 06 KL Vadheim Lecture 6 7

Mumps Pathogenesis • Reinfection occurs – usually asymptomatic 24 May 06 KL Vadheim Lecture 6 8

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 24 May 06 KL Vadheim Lecture 6 9

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 24 May 06 KL Vadheim Lecture 6 10

Mumps vaccine efficacy • 1968 - 152, 209 U. S. cases • 1995 - 840 U. S. cases 24 May 06 KL Vadheim Lecture 6 11

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 24 May 06 KL Vadheim Lecture 6 12

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 24 May 06 KL Vadheim Lecture 6 13

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 24 May 06 KL Vadheim Lecture 6 14

UK Mumps epidemic, 2004 -2005 • >70, 000 cases in England 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 24 May 06 KL Vadheim Lecture 6 15

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. 24 May 06 KL Vadheim Lecture 6 16

Rubella • • • Aka ‘German’ measles Discovered in 1841 Virus isolated in 1941 by German scientists Sudden pandemic in 1962 -65 Vaccine developed in 1960 s Vaccine licensed in 1970 (U. S. ) 24 May 06 KL Vadheim Lecture 6 17

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 24 May 06 KL Vadheim Lecture 6 18

Congenital Rubella Syndrome • • Cataracts Deafness Heart malformation Also: – microcephaly – autism – mental retardation – Diabetes – etc. 24 May 06 KL Vadheim Lecture 6 19

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 24 May 06 KL Vadheim Lecture 6 20

Rubella vaccine • Rubella virus RA-27/3 isolated from an infected fetus in 1965 • Culture fluid passaged directly into WI-38 cells – 8 serial passages at 37 C • Seven additional passages at 30 C – human volunteer studies showed attenuation • Ten additional passages to further decrease pathogenicity 24 May 06 KL Vadheim Lecture 6 21

Rubella RA 27/3 vaccine strain • Produced between 25 th and 30 th passage in human diploid cells • Relatively rapid attenuation due to: – cold adaptation (30 C) • Retention of high immunogenicity due to: – relatively low passage number required for attenuation 24 May 06 KL Vadheim Lecture 6 22

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 24 May 06 KL Vadheim Lecture 6 23

Rubella vaccine efficacy • 1969 - 57, 686 U. S. cases • 1995 - 200 U. S. cases 24 May 06 KL Vadheim Lecture 6 24

MMR Vaccines • • • Live Attenuated Subcutaneous administration Lyophilized presentation Licensed 1971 24 May 06 KL Vadheim Lecture 6 25

MMR Vaccines 24 May 06 KL Vadheim Lecture 6 26

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 24 May 06 KL Vadheim Lecture 6 27

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 24 May 06 KL Vadheim Lecture 6 28

Varicella Pathogenicity • Usually a mild disease – can cause severe, life-threatening complications – 1 st trimester infection cause permanent CNS (and other) damage to fetus, or death – 3 rd trimester infectionmay cause severe maternal infection, • Host range limited to humans and some primates 24 May 06 KL Vadheim Lecture 6 29

Varicella Pathogenicity • Latent infection of sensory nerve ganglia common – Some viral infection during latent stage – Suppression of VZV reactivation partially under immunological control 24 May 06 KL Vadheim Lecture 6 30

Varicella Vaccine • Lyophilized • Requires storage at +5 F or below • Live, attenuated virus 24 May 06 KL Vadheim Lecture 6 31

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 24 May 06 KL Vadheim Lecture 6 32