Immunization Potpourri 2010 Peter N. Wenger, MD Departments of Preventive Medicine and Community Health/Pediatrics UMDNJ-New Jersey Medical School Newark, NJ

Pandemic Influenza A Virus H1N1 2009

aka Swine Flu, Novel Influenza A H1N1, Swine-Origin Influenza A Virus H1N1, The Pandemic, End of Life as we Know It Flu

CDC Estimates of 2009 H1N1 Cases from April 2009 – March 13, 2010, By Age Group 2009 H1N1 CasesMid-Level RangeEstimated Range 0-17 years~19 million~14 million to ~28 million years~35 million~25 million to ~51 million 65 years and older~6 million~4 million to ~9 million Cases Total~60 million~43 million to ~88 million #Table%20Cumulative

CDC Estimates of 2009 H1N1 Related Hospitalizations from April 2009 – March 13, 2010, By Age Group HospitalizationsMid-Level RangeEstimated Range 0-17 years~86,000~61K to ~127K years~158,000~112K to ~232K 65 years and older~26,000~19K to ~39K Hospitalizations Total ~270,000~192K to ~398K #Table%20Cumulative

CDC Estimates of 2009 H1N1 Related Mortality from April 2009 – March 13, 2010, By Age Group DeathsMid-Level RangeEstimated Range 0-17 years~1,270~900 to ~1, years~9,420~6,700 to ~13, years and older~1,580~1,120 to ~2,320 Deaths Total ~12,270~8,720 to ~18,050 #Table%20Cumulative

Percentage of Visits for Influenza-like Illness (ILI) Reported by the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet) National Summary and Previous Two Seasons Through the week Ending May 22,

National H1N1 Flu Survey* Week of December 6-12, 2009 ~46 million people (15.3%) vaccinated vs 2009 pandemic influenza A virus H1N1 ~46 million people (15.3%) vaccinated vs 2009 pandemic influenza A virus H1N1 28 million adults (13.0%)28 million adults (13.0%) 18 million children (24.0%)18 million children (24.0%) Amount of vaccine distributed to providers Amount of vaccine distributed to providers ~21% of US population~21% of US population 3 of 4 shipped doses administered 3 of 4 shipped doses administered 74% of vaccine went to people in initial target groups74% of vaccine went to people in initial target groups 42% of all vaccine given to children 42% of all vaccine given to children 23% of vaccine doses given were nasal spray23% of vaccine doses given were nasal spray *

Pandemic Influenza A (H1N1) 2009 Monovalent Vaccination Coverage, New Jersey, October 2009 – January 2010* Children aged 6 months to 17 years Children aged 6 months to 17 years 32.7% (95% CI, + 4.6)32.7% (95% CI, + 4.6) Persons aged ≥18 years Persons aged ≥18 years 13.1% (95% CI, + 2.0)13.1% (95% CI, + 2.0) Persons in initial target groups Persons in initial target groups 29.0% (95% CI, + 4.5)29.0% (95% CI, + 4.5) Persons aged years at high risk Persons aged years at high risk 17% (95% CI, + 5.8)17% (95% CI, + 5.8) Persons aged years not included in the initial target groups Persons aged years not included in the initial target groups 9.5% (95% CI, + 2.4)9.5% (95% CI, + 2.4) Persons aged ≥ 65 years Persons aged ≥ 65 years 12.2% (95% CI, + 3.7)12.2% (95% CI, + 3.7) *CDC. MMWR April 2, ;12:363-68

Influenza Vaccine Development

Influenza Strategy to Escape Immune Detection Drift Drift Minor change in HA glycoproteinMinor change in HA glycoprotein Gradual accumulation of amino acid changes Gradual accumulation of amino acid changes Mutations in viral RNA Mutations in viral RNA Occurs continuouslyOccurs continuously Shift Shift Major change in HA glycoproteinMajor change in HA glycoprotein Reassortment (Reassortant) Reassortment (Reassortant) Exchange of gene segmentsExchange of gene segments Direct transmission from a different species to humans without reassortment Direct transmission from a different species to humans without reassortment 1918?1918? 1997 – 2005 Hong Kong; Netherlands; Canada; South Asia; New York1997 – 2005 Hong Kong; Netherlands; Canada; South Asia; New York Occurs infrequentlyOccurs infrequently ~ 33 years ~ 33 years Cox NJ, Subbarao K. Lancet. 1999;354:1277–82.

Circulating wild-type strain Master strain - high-growth potential in eggs or cell culture Co-infect cells PB1 PB2 PA HA NA NP M NS PB1 PB2 PA HA NA NP M NS From wild-type strain PB1 PB2 PA HA NA NP M NS Genetic Reassortment To Generate Vaccine Strains From Master strain New high-growth reassortant vaccine strain

Trivalent Inactivated Vaccine (TIV) Live Attenuated Influenza Vaccine (LAIV) FDA-approvedSince 1960sSince 2003 Route of administration IntramuscularIntranasal ImmunityPrimarily humoralMucosal and humoral Virus Split-virus or subunit inactivated virus (HA) Cold-adapted, temperature-sensitive, live attenuated virus Growth MediumChick embryos Indication Persons  6 months Healthy persons 2–49 years Ruben FL. Clin Infect Dis. 2004;38: cdc.gov/nip/publications/pink/flu.pdf. Currently Available Influenza Vaccines

Considerations Include strain that closely match community circulating strains Include strain that closely match community circulating strains May differ in different regionsMay differ in different regions Dose considerations Dose considerations Induces protective immune response in individuals Induces protective immune response in individuals Age-dependent Age-dependent <6 months: inadequate response<6 months: inadequate response Older individuals: less robust responseOlder individuals: less robust response Hemagglutinin antigen (HA)Hemagglutinin antigen (HA) 15 µg in those ≥3 years of age 15 µg in those ≥3 years of age 7.5 µg in those months of age 7.5 µg in those months of age Vaccine-naïve children, 6 months through 8 years of age require a priming doseVaccine-naïve children, 6 months through 8 years of age require a priming dose Priming dose for pandemic (novel) strains? Priming dose for pandemic (novel) strains? Maximizing population coverageMaximizing population coverage Minimizing adverse reactionsMinimizing adverse reactions

Timeline for Vaccine Development Reflect the need to produce and administer vaccine before and during each influenza season Reflect the need to produce and administer vaccine before and during each influenza season Global surveillanceGlobal surveillance Year round in both hemispheres Year round in both hemispheres Trends in viral antigenic changesTrends in viral antigenic changes Collection, analysis, and assessment of circulating strains for selection of appropriate vaccine strains Collection, analysis, and assessment of circulating strains for selection of appropriate vaccine strains Timing is everything!Timing is everything! Too early – significant antigenic changes may be missed Too early – significant antigenic changes may be missed Too late – vaccine output may be affected Too late – vaccine output may be affected

World Health Organization (WHO) Global Influenza Surveillance System ● Established in national influenza centers in 101 countries 130 national influenza centers in 101 countries Analyzed by 4 WHO Collaborating Centers for Reference and Research on InfluenzaAnalyzed by 4 WHO Collaborating Centers for Reference and Research on Influenza CDC; Atlanta, GA, US CDC; Atlanta, GA, US National Institute on Medical Research; London, UK National Institute on Medical Research; London, UK Victoria Infectious Diseases Reference Laboratory; Melbourne, Australia Victoria Infectious Diseases Reference Laboratory; Melbourne, Australia National Institute for Infectious Diseases; Tokyo, Japan National Institute for Infectious Diseases; Tokyo, Japan US Food and Drug Administration (FDA) determines viral components of US-licensed vaccinesUS Food and Drug Administration (FDA) determines viral components of US-licensed vaccines

Timeline for Vaccine Development From selection to consumer release of trivalent influenza virus vaccine From selection to consumer release of trivalent influenza virus vaccine Six to eight monthsSix to eight months Preparation of each reassortant viral component Preparation of each reassortant viral component Development of high-growth reassortantsDevelopment of high-growth reassortants Capable of high growth in eggs/cell cultures Capable of high growth in eggs/cell cultures PurificationPurification Solvents Solvents Unnecessary viral antigens Unnecessary viral antigens Bacteria Bacteria Standardization and testing of HA components Standardization and testing of HA components Development of appropriate reagentsDevelopment of appropriate reagents Safety and efficacy testing Safety and efficacy testing Production of trivalent vaccine Production of trivalent vaccine PurificationPurification Mass productionMass production Regulatory Issues Regulatory Issues Monovalent pandemic vaccineMonovalent pandemic vaccine Four to six months Four to six months

Production of Influenza Vaccines for Pandemics or Pandemic Alerts Wood, JM. Developing vaccines against pandemic influenza. Phil. Trans. R. Soc. Lond. 2001;356:

To Prime or Not To Prime Minimum Immunogenic Dose of H1N1, H2N2, and H5N3 Vaccines Data from many clinical trials from 1976 to 1999 Wood, JM. Developing vaccines against pandemic influenza. Phil. Trans. R. Soc. Lond. 2001;356:

2010 – 2011 Influenza Vaccine And the winners are…….. A/California/7/2009(H1N1)-like virus A/Perth/16/2009 (H3N2)-like virus B/Brisbane/60/2008-like virus

New Recommendation February 24, 2010 February 24, 2010 Advisory Committee on Immunization Practices (ACIP)Advisory Committee on Immunization Practices (ACIP) Universal immunization for all persons ≥6 months of age Universal immunization for all persons ≥6 months of age Published in the MMWRPublished in the MMWR August 6, 2010 August 6, 2010 Volume 59; RR-08 Volume 59; RR-08

New Recommendation June 24, 2010 June 24, 2010 All children aged 6 months through 8 years of age who did not receive at least 1 dose of the monovalent 2009 Influenza A H1N1 vaccine:All children aged 6 months through 8 years of age who did not receive at least 1 dose of the monovalent 2009 Influenza A H1N1 vaccine: Receive 2 doses of the seasonal influenza vaccine regardless of their previous vaccination history Receive 2 doses of the seasonal influenza vaccine regardless of their previous vaccination history

High-Dose Inactivated Influenza Vaccine for Persons Aged ≥65 Years* 12/23/ /23/2009 FDA licensed an injectable inactivated trivalent influenza vaccine containing an increased amount of viral hemagglutinin antigen compared with other TIVsFDA licensed an injectable inactivated trivalent influenza vaccine containing an increased amount of viral hemagglutinin antigen compared with other TIVs Single dose for persons aged ≥65 yearsSingle dose for persons aged ≥65 years Rationale Rationale Greater risk of hospitalization and mortality from influenzaGreater risk of hospitalization and mortality from influenza Less immunogenic responseLess immunogenic response 04/30/ /30/2010 Advisory Committee on Immunization Practices (ACIP)Advisory Committee on Immunization Practices (ACIP) No preference for new vaccine over other TIVs No preference for new vaccine over other TIVs *CDC. MMWR. Licensure of a high-dose inactivated influenza vaccine for persons aged ≥65 years and guidance for use-US /30/2010;59(16);

New Jersey Attendance at pre-Kindergarten and daycare centers Attendance at pre-Kindergarten and daycare centers Mandatory annual influenza immunizationMandatory annual influenza immunization For those 6 months through 8 years of age For those 6 months through 8 years of age NaïveNaïve 2 doses 2 doses Administered at least 4 weeks apart Administered at least 4 weeks apart

Estimates of Death Associated with Seasonal Influenza, United States, * Annual estimates of influenza- associated deaths Annual estimates of influenza- associated deaths Death certificate dataDeath certificate data Respiratory and circulatory causes (includes pneumonia and influenza causes) Respiratory and circulatory causes (includes pneumonia and influenza causes) Estimated annual average: 23, 607 (range,3,349 [ ] to 48,614 [ ])Estimated annual average: 23, 607 (range,3,349 [ ] to 48,614 [ ]) Average: 9.0 per 100,000 persons (range,1.4 to 16.7) Average: 9.0 per 100,000 persons (range,1.4 to 16.7) *CDC. Estimates of deaths associated with seasonal influenza, US MMWR August 27, 2010;59(33):

Estimates of Death Associated with Seasonal Influenza, United States, * Age-specfic estimates Age-specfic estimates <19 years of age<19 years of age Estimated annual average: 124 (range, 57 [ ] to 197 [ ]) Estimated annual average: 124 (range, 57 [ ] to 197 [ ]) Rate: 0.2 deaths per 100,000 (range, ) Rate: 0.2 deaths per 100,000 (range, ) years of age19-64 years of age Estimated annual average: 2,385 (range, 504 [ ] to 4,752 [ ]) Estimated annual average: 2,385 (range, 504 [ ] to 4,752 [ ]) Rate: 1.5 per 100,000 persons (range, ) Rate: 1.5 per 100,000 persons (range, ) ≥65 years of age≥65 years of age Estimated annual average: 21,098 (range, 2,344 [ ] to 43,727 [ ] Estimated annual average: 21,098 (range, 2,344 [ ] to 43,727 [ ] Rate: 66.1 per 100,000 persons (range, 8.0 – 121.1) Rate: 66.1 per 100,000 persons (range, 8.0 – 121.1) 89.4% of influenza-associated mortality 89.4% of influenza-associated mortality *CDC. Estimates of deaths associated with seasonal influenza, US MMWR August 27, 2010;59(33):

Estimates of Death Associated with Seasonal Influenza, United States, * Wide variation in the estimated mortality from season to season associated with predominant influenza type and subtypes Wide variation in the estimated mortality from season to season associated with predominant influenza type and subtypes ≥20% of all isolates tested during season≥20% of all isolates tested during season Influenza A(H3N2)Influenza A(H3N2) 2.7 times higher 2.7 times higher 22 seasons 22 seasons *CDC. Estimates of deaths associated with seasonal influenza, US MMWR August 27, 2010;59(33):

Estimates of Death Associated with Seasonal Influenza, United States, * Substantial variability in influenza- associated mortality estimates Substantial variability in influenza- associated mortality estimates Year (season to season)Year (season to season) Age groupAge group Influenza type/subtypeInfluenza type/subtype A single estimate cannot be used to summarize influenza-associated mortality A single estimate cannot be used to summarize influenza-associated mortality A range of estimates should be usedA range of estimates should be used Age groups Age groups Circulating types/subtypes Circulating types/subtypes *CDC. Estimates of deaths associated with seasonal influenza, US MMWR August 27, 2010;59(33):

Intradermal Influenza Vaccine Sanofi Aventis submitted FDA application for approval Sanofi Aventis submitted FDA application for approval Becton DickinsonBecton Dickinson Short, thin needle Short, thin needle 1/10 th size of regularly used needle1/10 th size of regularly used needle 1.5 mm vs 25 to 40 mm 1.5 mm vs 25 to 40 mm 1/5 th antigen dose1/5 th antigen dose Stimulates the dendritic cells Stimulates the dendritic cells Extends vaccine supplyExtends vaccine supply Less discomfortLess discomfort Less expensive?Less expensive? Approval in early 2011?Approval in early 2011?

13-valent Pneumococcal Conjugate Vaccine (PCV13)

Transition from PCV7 to PCV 13 Since introduction of PCV7 in 2000 Since introduction of PCV7 in 2000 Dramatic overall decrease in invasive pneumococcal disease (IPD)Dramatic overall decrease in invasive pneumococcal disease (IPD) IPD due to serotypes not included in PCV7 have increased IPD due to serotypes not included in PCV7 have increased February 24, 2010 February 24, 2010 FDA approved a new 13-valent pneumococcal conjugate vaccine (PCV13)FDA approved a new 13-valent pneumococcal conjugate vaccine (PCV13) ACIP recommended transition from PCV7 to PCV 13ACIP recommended transition from PCV7 to PCV 13

Pneumococcal Serotypes in PCV7 and PCV 13

Invasive Pneumococcal Disease (IPD) in Newark Residents* December 1, 2007 – November 30, /72 (2.8%) were serotypes included in the PCV7 2/72 (2.8%) were serotypes included in the PCV7 Reflected success of PCV7 in decreasing IPD due to vaccine serotypesReflected success of PCV7 in decreasing IPD due to vaccine serotypes 32/72 (44.4%) were covered by PCV13 32/72 (44.4%) were covered by PCV13 Serotypes 3 (6), 6A (3), and 19A (19)Serotypes 3 (6), 6A (3), and 19A (19) Serotype 19A was dominant Serotype 19A was dominant 19/72 (26.4%)19/72 (26.4%) Serotype 19A was most closely associated with penicillin-resistanceSerotype 19A was most closely associated with penicillin-resistance Consistent with trends reported in USConsistent with trends reported in US A significantly higher proportion was found in children compared with adults and the elderlyA significantly higher proportion was found in children compared with adults and the elderly *Tasslimi A, et al. Clinical and Vaccine Immunology. August ;8:1256

Pneumococcal Immunization with PCV13 Advisory Committee on Immunization Practices (ACIP) Recommendations Infants and children under 2 years of age Infants and children under 2 years of age 4-dose regimen4-dose regimen 2, 4, 6, and months2, 4, 6, and months Older children and adolescents Older children and adolescents Healthy between 2 nd and 5 th birthdaysHealthy between 2 nd and 5 th birthdays Not completed PCV7 or PCV13 series before age 2 Not completed PCV7 or PCV13 series before age 2 1 dose1 dose Children at high risk between 2 nd and 6 th birthdayChildren at high risk between 2 nd and 6 th birthday Received 3 doses of PCV7/PCV13 before 2 years Received 3 doses of PCV7/PCV13 before 2 years 1 dose1 dose Received ≤2 doses of PCV7/PCV13 before 2 years Received ≤2 doses of PCV7/PCV13 before 2 years 2 doses2 doses Children and adolescents at high risk 6 through 18 yearsChildren and adolescents at high risk 6 through 18 years 1 dose 1 dose Even if previous recipient of PCV7 or PPSV23 Even if previous recipient of PCV7 or PPSV23 Children who have completed the 4-dose series with PCV7 and are healthy and <5 years or at high risk and <6 yearsChildren who have completed the 4-dose series with PCV7 and are healthy and <5 years or at high risk and <6 years 1 dose 1 dose

Risk Factors for Invasive Pneumococcal Disease Sickle cell disease Sickle cell disease Functional or anatomical asplenia Functional or anatomical asplenia Cochlear implants Cochlear implants CSF leaks CSF leaks Diabetes Diabetes Chronic heart and lung disease Chronic heart and lung disease Immunocompromised conditions Immunocompromised conditions HIV infection and congenital immunodeficienciesHIV infection and congenital immunodeficiencies Chronic renal failure and nephrotic syndromeChronic renal failure and nephrotic syndrome Diseases associated with treatment with immunosuppressive medications or radiation therapyDiseases associated with treatment with immunosuppressive medications or radiation therapy Solid organ transplantation Solid organ transplantation Lymphomas, leukemias, malignant neoplasms Lymphomas, leukemias, malignant neoplasms Asthma if treated with prolonged, high-dose oral corticosteroids Asthma if treated with prolonged, high-dose oral corticosteroids

Mumps Outbreak New York and New Jersey

Mumps RNA virus RNA virus Systemic disease Systemic disease Swelling of ≥1 salivary glandsSwelling of ≥1 salivary glands Parotids Parotids ~1/3 of patients do not demonstrate salivary gland swelling~1/3 of patients do not demonstrate salivary gland swelling Respiratory tract symptoms Respiratory tract symptoms >50% of patients have CSF pleocytosis>50% of patients have CSF pleocytosis <10% have CNS symptomology<10% have CNS symptomology

Mumps

Mumps Systemic Disease (continued) Systemic Disease (continued) OrchitisOrchitis Post-pubertal complication Post-pubertal complication Sterility is rareSterility is rare Rare complicationsRare complications Arthritis, thyroiditis, mastitis, glomerularnephritis, myocarditis, endocardial fibroelastosis, pancreatitis, oophoritis, hearing impairment Arthritis, thyroiditis, mastitis, glomerularnephritis, myocarditis, endocardial fibroelastosis, pancreatitis, oophoritis, hearing impairment Infections in adults more likely to be severeInfections in adults more likely to be severe Death, though rare, occurs most often in adults Death, though rare, occurs most often in adults Infection in first trimester associated with increased risk of spontaneous abortionInfection in first trimester associated with increased risk of spontaneous abortion

Mumps Epidemiology Epidemiology Transmission via infected respiratory tract secretionsTransmission via infected respiratory tract secretions Incubation periodIncubation period 12–25 days (usually days) 12–25 days (usually days) Period of maximum communicabilityPeriod of maximum communicability 1 to 2 days prior to parotid swelling 1 to 2 days prior to parotid swelling 5 days after onset of swelling 5 days after onset of swelling Virus has been isolated in salivia from 7 days prior to swelling onset to 9 days after onset of swellingVirus has been isolated in salivia from 7 days prior to swelling onset to 9 days after onset of swelling Reported incidence in US in 1967Reported incidence in US in , ,000

Mumps Vaccine Vaccine Licensed in US in 1967Licensed in US in 1967 Recommended for routine childhood immunization in 1977Recommended for routine childhood immunization in 1977 One-dose schedule One-dose schedule Disease incidence fell to very low levels Disease incidence fell to very low levels Outbreaks occurred between Outbreaks occurred between Two-dose schedule recommended in 1989Two-dose schedule recommended in : <300 reported cases/year : <300 reported cases/year 2006: Mumps outbreak: 6584 cases 2006: Mumps outbreak: 6584 cases years of age18-24 years of age Many received 2 doses MMRMany received 2 doses MMR Mumps least effective component of MMRMumps least effective component of MMR 73%-91% after 1 dose 73%-91% after 1 dose 79%-95% after 2 doses 79%-95% after 2 doses

Mumps Immunization Advisory Committee on Immunization Practices (ACIP) Recommendations Two doses of mumps-containing vaccine (in US – MMR) Two doses of mumps-containing vaccine (in US – MMR) All school-aged children (K-12)All school-aged children (K-12) 1 st dose: months 1 st dose: months 2 nd dose: 4-6 years 2 nd dose: 4-6 years Adults at high-risk for infectionAdults at high-risk for infection i.e., person who work in healthcare facilities, international travelers, students at post-high school educational institutions, etc.) i.e., person who work in healthcare facilities, international travelers, students at post-high school educational institutions, etc.) For healthcare workers born before 1957 without laboratory evidence of immunityFor healthcare workers born before 1957 without laboratory evidence of immunity Consider receiving 1 dose Consider receiving 1 dose During outbreaks During outbreaks Children aged 1-4 yearsChildren aged 1-4 years Offer 2 nd dose Offer 2 nd dose Confirm 2-doses in othersConfirm 2-doses in others

Mumps Outbreak New York and New Jersey * June 17, 2009: 11-year old boy returns from United Kingdom June 17, 2009: 11-year old boy returns from United Kingdom ~7,400 reports of laboratory confirmed mumps in 2009~7,400 reports of laboratory confirmed mumps in 2009 Symptomatic by June 28 Symptomatic by June 28 At camp for tradition-observant Jewish boysAt camp for tradition-observant Jewish boys Subsequent transmission to other camp attendees and staff member Subsequent transmission to other camp attendees and staff member 25 cases reported from June 28 th –September 8th 25 cases reported from June 28 th –September 8th Transmission occurred in multiple locations when campers returned home Transmission occurred in multiple locations when campers returned home As of January 29, 2010: 1,521 cases reportedAs of January 29, 2010: 1,521 cases reported *CDC. MMWR. Update: mumps outbreak-New York and New Jersey, June 2009-January February 12, 2010;59(5):

Mumps Outbreak New York and New Jersey * Confined primarily to the tradition- observant Jewish community Confined primarily to the tradition- observant Jewish community New York City {Brooklyn} (44%); Orange County, NY (24%); Rockland County, NY (20%); Four counties in New Jersey (10%)New York City {Brooklyn} (44%); Orange County, NY (24%); Rockland County, NY (20%); Four counties in New Jersey (10%) Camp-associated cases in Sullivan County, NY (2%)Camp-associated cases in Sullivan County, NY (2%) <3% of cases occurring outside the community<3% of cases occurring outside the community Reported regular contact with members of the affected community Reported regular contact with members of the affected community *CDC. MMWR. Update: mumps outbreak-New York and New Jersey, June 2009-January February 12, 2010;59(5):

Mumps Outbreak New York and New Jersey * 61% of cases occurred in persons aged years of age 61% of cases occurred in persons aged years of age 4.9% in children aged 1-4 years4.9% in children aged 1-4 years Range, 3 months-90 yearsRange, 3 months-90 years 76% were male76% were male Among patients in which vaccination status was known (n=1,115) Among patients in which vaccination status was known (n=1,115) 88% received at least 1 dose of mumps- containing vaccine (MCV)88% received at least 1 dose of mumps- containing vaccine (MCV) 75% received 2 doses of MCV75% received 2 doses of MCV *CDC. MMWR. Update: mumps outbreak-New York and New Jersey, June 2009-January February 12, 2010;59(5):

Mumps Outbreak New York and New Jersey * Complications Complications 65 reports65 reports Orchitis: 55 cases (85%) Orchitis: 55 cases (85%) Pancreatitis: 5 cases (8%) Pancreatitis: 5 cases (8%) Aseptic meningitis: 2 cases (3%) Aseptic meningitis: 2 cases (3%) Transient deafness: 1 case (1.5%) Transient deafness: 1 case (1.5%) Bell’s palsy: 1 case (1.5%) Bell’s palsy: 1 case (1.5%) Oophoritis: 1 case (1.5%) Oophoritis: 1 case (1.5%) 19 reported hospitalizations19 reported hospitalizations No deaths No deaths *CDC. MMWR. Update: mumps outbreak-New York and New Jersey, June 2009-January February 12, 2010;59(5):

Mumps Outbreak New York and New Jersey * Mumps outbreak in a highly vaccinated population Mumps outbreak in a highly vaccinated population Most cases occur in vaccinated peopleMost cases occur in vaccinated people Why????? Why????? Specific close-knit, closed communitySpecific close-knit, closed community No sustained transmission outside the specific community No sustained transmission outside the specific community Congregate settingCongregate setting Prolonged close contact Prolonged close contact Large household sizeLarge household size Mean household size in the affected community was 5.7 versus mean US household size of 2.6 Mean household size in the affected community was 5.7 versus mean US household size of 2.6 Effectiveness of mumps component of MMREffectiveness of mumps component of MMR *CDC. MMWR. Update: mumps outbreak-New York and New Jersey, June 2009-January February 12, 2010;59(5):

Mumps Outbreak New York and New Jersey * Public Health Response Public Health Response Health-care providers notifiedHealth-care providers notified Verify children are completely vaccinated Verify children are completely vaccinated Offer 2 nd dose in children aged 1-4 yearsOffer 2 nd dose in children aged 1-4 years Offer vaccine to adults Offer vaccine to adults Unknown immunity or vaccine statusUnknown immunity or vaccine status State and local health departmentsState and local health departments Affected schools Affected schools Enhance vaccination policiesEnhance vaccination policies Exclude unvaccinated children from school during outbreak Exclude unvaccinated children from school during outbreak Home isolation for 5 days after onset of parotitis Home isolation for 5 days after onset of parotitis Orange County, New York beginning 01/19/2010 Orange County, New York beginning 01/19/ rd dose of MMR in 3 schools3 rd dose of MMR in 3 schools Continued transmission of infection despite high level of 2-dose coverage Continued transmission of infection despite high level of 2-dose coverage Institutional Review Board-approval protocol that includes evaluation of intervention Institutional Review Board-approval protocol that includes evaluation of intervention *CDC. MMWR. Update: mumps outbreak-New York and New Jersey, June 2009-January February 12, 2010;59(5):

Rotavirus Vaccine Contamination

Contamination of Rotavirus Vaccine March 22, 2010 March 22, 2010 FDA recommends temporary suspension of use of Rotarix® (GlaxoSmithKline Biologicals)FDA recommends temporary suspension of use of Rotarix® (GlaxoSmithKline Biologicals) Porcine circovirus 1 (PCV1) DNA, particles, infectious virus are present in vaccine Porcine circovirus 1 (PCV1) DNA, particles, infectious virus are present in vaccine May 6, 2010 May 6, 2010 Preliminary studies by Merck identified PCV1 and PCV2 DNA at low levels in Rotateq® (Merck & Co, Inc.)Preliminary studies by Merck identified PCV1 and PCV2 DNA at low levels in Rotateq® (Merck & Co, Inc.)

Porcine Circovirus (PCV) Types 1 and 2 Small viruses Small viruses Single strand of circular DNASingle strand of circular DNA Commonly found in pigsCommonly found in pigs PCV2 may cause disease in pigs PCV2 may cause disease in pigs Neither PCV1 or PCV2 are known to infect or cause disease in humansNeither PCV1 or PCV2 are known to infect or cause disease in humans

FDA Recommendations May 14, 2010 It is appropriate for clinicians and healthcare professionals to resume the use of Rotarix® (GSK Biologicals) and to continue to use Rotateq® (Merck & Co, Inc.) It is appropriate for clinicians and healthcare professionals to resume the use of Rotarix® (GSK Biologicals) and to continue to use Rotateq® (Merck & Co, Inc.) Considerations Considerations Strong safety recordsStrong safety records Clinical trials Clinical trials Tens of thousands of participantsTens of thousands of participants Post-licensure clinical experience Post-licensure clinical experience Millions of recipientsMillions of recipients No evidence the PCV1 or PCV2 poses a safety risk to humans No evidence the PCV1 or PCV2 poses a safety risk to humans Benefits of vaccination outweigh the risks which are theoreticalBenefits of vaccination outweigh the risks which are theoretical

Next Steps FDA and manufacturers are updating labeling for both vaccines to include information concerning presence of PCV1 and PCV2 FDA and manufacturers are updating labeling for both vaccines to include information concerning presence of PCV1 and PCV2 Planning appropriate follow-up studies Planning appropriate follow-up studies Continuing investigation into the findings of PCV in rotavirus vaccines Continuing investigation into the findings of PCV in rotavirus vaccines GSK plans to rederive its vaccine in consultation with the FDAGSK plans to rederive its vaccine in consultation with the FDA Merck is in early stages of its investigation and has not determined as yet its next steps in this regardMerck is in early stages of its investigation and has not determined as yet its next steps in this regard

Guillain-Barré Syndrome (GBS) and Conjugated Meningococcal Vaccine (MCV4) June 24, 2010 June 24, 2010 Studies have not demonstrated an increased risk of GBS associated with the meningococcal vaccineStudies have not demonstrated an increased risk of GBS associated with the meningococcal vaccine Removed precautionary warning from the sanofi pasteur MCV4 labelRemoved precautionary warning from the sanofi pasteur MCV4 label

Religious Exemptions* New Jersey New Jersey Eightfold increase since school yearEightfold increase since school year 3,865 student exemptions this school year 3,865 student exemptions this school year New York New York Double the amount seen in 1999Double the amount seen in ,615 student exemptions in ,615 student exemptions in 2008 Connecticut Connecticut 455 student exemptions in 2009 versus 248 in student exemptions in 2009 versus 248 in 1999 *The Wall Street Journal. More parents seek vaccine exemption. July

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