immunization potpourri 2010 peter n. wenger, md departments of preventive medicine and community...

Immunization Potpourri Immunization Potpourri 20102010

Peter N. Wenger, MDPeter N. Wenger, MDDepartments of Preventive Medicine and Departments of Preventive Medicine and

Community Health/PediatricsCommunity Health/PediatricsUMDNJ-New Jersey Medical SchoolUMDNJ-New Jersey Medical School

Newark, NJNewark, NJ

PandemicInfluenza A Virus

H1N1 2009

akaSwine Flu,

Novel Influenza A H1N1,Swine-Origin Influenza A

Virus H1N1,The Pandemic,

End of Life as we Know ItFlu

CDC Estimates of 2009 H1N1 Cases from April 2009 – March 13, 2010, By

Age Group

2009 H1N1 Cases Mid-Level Range Estimated Range

0-17 years ~19 million ~14 million to ~28 million

18-64 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

http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm#Table%20Cumulative

CDC Estimates of 2009 H1N1 Related Hospitalizations from April 2009 –

March 13, 2010, By Age Group

Hospitalizations Mid-Level Range Estimated Range

0-17 years ~86,000 ~61K to ~127K

18-64 years ~158,000 ~112K to ~232K

65 years and older ~26,000 ~19K to ~39K

Hospitalizations Total

~270,000 ~192K to ~398K


CDC Estimates of 2009 H1N1 Related Mortality from April 2009 – March 13,

2010, By Age Group

Deaths Mid-Level Range Estimated Range

0-17 years ~1,270 ~900 to ~1,870

18-64 years ~9,420 ~6,700 to ~13,860

65 years and older ~1,580 ~1,120 to ~2,320

DeathsTotal

~12,270 ~8,720 to ~18,050


Percentage of Visits for Influenza-like Illness (ILI) Percentage of Visits for Influenza-like Illness (ILI) Reported by the U.S. Outpatient Influenza-like Illness Reported by the U.S. Outpatient Influenza-like Illness

Surveillance Network (ILINet) Surveillance Network (ILINet) National Summary 2008-2009 and Previous Two SeasonsNational Summary 2008-2009 and Previous Two Seasons

Through the week Ending May 22, 2010Through the week Ending May 22, 2010

http://www.cdc.gov/h1n1flu/updates/us/

National H1N1 Flu SurveyNational H1N1 Flu Survey**Week of December 6-12, 2009Week of December 6-12, 2009

~46 million people (15.3%) vaccinated vs ~46 million people (15.3%) vaccinated vs 2009 pandemic influenza A virus H1N12009 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 administered3 of 4 shipped doses administered

• 74% of vaccine went to people in initial target 74% of vaccine went to people in initial target groupsgroups

42% of all vaccine given to children42% of all vaccine given to children

• 23% of vaccine doses given were nasal spray23% of vaccine doses given were nasal spray

*http://www.cdc.gov/h1n1flu/in_the_news/influenza_vaccination.htm

Pandemic Influenza A (H1N1) 2009 Monovalent Pandemic Influenza A (H1N1) 2009 Monovalent Vaccination Coverage, Vaccination Coverage,

New Jersey, October 2009 – January 2010New Jersey, October 2009 – January 2010** Children aged 6 months to 17 yearsChildren aged 6 months to 17 years

• 32.7% (95% CI, 32.7% (95% CI, ++ 4.6) 4.6) Persons aged ≥18 yearsPersons aged ≥18 years

• 13.1% (95% CI, 13.1% (95% CI, ++ 2.0) 2.0) Persons in initial target groupsPersons in initial target groups

• 29.0% (95% CI, 29.0% (95% CI, ++ 4.5) 4.5) Persons aged 25-64 years at high riskPersons aged 25-64 years at high risk

• 17% (95% CI, 17% (95% CI, ++ 5.8) 5.8) Persons aged 25-64 years not included in the Persons aged 25-64 years not included in the

initial target groupsinitial target groups• 9.5% (95% CI, 9.5% (95% CI, ++ 2.4) 2.4)

Persons aged ≥ 65 yearsPersons aged ≥ 65 years• 12.2% (95% CI, 12.2% (95% CI, ++ 3.7) 3.7)

*CDC. MMWR April 2, 2010. 59;12:363-68

Influenza VaccineDevelopment

http://www.ifpma.org/Influenza/index.aspx?000_The_Influenza_Virus/001a_Influenza_Virus.html

InfluenzaInfluenzaStrategy to Escape Immune DetectionStrategy to Escape Immune Detection

DriftDrift• Minor change in HA glycoproteinMinor change in HA glycoprotein

Gradual accumulation of amino acid changesGradual accumulation of amino acid changes Mutations in viral RNAMutations in viral RNA

• Occurs continuouslyOccurs continuously ShiftShift

• 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 Direct transmission from a different species to humans without

reassortmentreassortment• 1918?1918?• 1997 – 2005 Hong Kong; Netherlands; Canada; South Asia; New York 1997 – 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 cellsPB1PB2PAHANANPMNS

PB1PB2PAHANANPMNS

From wild-type strain

PB1PB2PAHANANPMNS

Genetic Reassortment To Generate Genetic Reassortment To Generate Vaccine StrainsVaccine Strains

From Masterstrain

New high-growth reassortant vaccine strain

Trivalent Inactivated

Vaccine (TIV)

Live Attenuated Influenza Vaccine

(LAIV)

FDA-approved Since 1960s Since 2003

Route of administration

Intramuscular Intranasal

Immunity Primarily humoral Mucosal and humoral

VirusSplit-virus or subunit inactivated virus (HA)

Cold-adapted, temperature-sensitive, live attenuated virus

Growth Medium Chick embryos Chick embryos

Indication Persons 6 monthsHealthy persons 2–49

years

Ruben FL. Clin Infect Dis. 2004;38:689-91. cdc.gov/nip/publications/pink/flu.pdf.

Currently Available Influenza Vaccines

ConsiderationsConsiderations Include strain that closely match community Include strain that closely match community

circulating strainscirculating strains• May differ in different regionsMay differ in different regions

Dose considerationsDose considerations• Induces protective immune response in individualsInduces protective immune response in individuals

Age-dependentAge-dependent• <6 months: inadequate response<6 months: inadequate response• Older individuals: less robust response Older individuals: less robust response • Hemagglutinin antigen (HA)Hemagglutinin antigen (HA)

15 µg in those ≥3 years of age15 µg in those ≥3 years of age 7.5 µg in those 6 - 35 months of age7.5 µg in those 6 - 35 months of age

• Vaccine-naïve children, 6 months through 8 years of age Vaccine-naïve children, 6 months through 8 years of age require a priming doserequire 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 DevelopmentTimeline for Vaccine Development

Reflect the need to produce and Reflect the need to produce and administer vaccine before and during each administer vaccine before and during each influenza seasoninfluenza season• Global surveillanceGlobal surveillance

Year round in both hemispheresYear round in both hemispheres• Trends in viral antigenic changesTrends in viral antigenic changes

Collection, analysis, and assessment of circulating Collection, analysis, and assessment of circulating strains for selection of appropriate vaccine strainsstrains for selection of appropriate vaccine strains

• Timing is everything!Timing is everything! Too early – significant antigenic changes may be Too early – significant antigenic changes may be

missedmissed Too late – vaccine output may be affectedToo late – vaccine output may be affected

World Health Organization (WHO)World Health Organization (WHO)Global Influenza Surveillance Global Influenza Surveillance

SystemSystem● ● Established in 1948Established in 1948

• • 130 national influenza centers in 101 countries130 national influenza centers in 101 countries• Analyzed by 4 WHO Collaborating Centers for Reference Analyzed by 4 WHO Collaborating Centers for Reference

and Research on Influenzaand Research on Influenza CDC; Atlanta, GA, USCDC; Atlanta, GA, US National Institute on Medical Research; London, UKNational Institute on Medical Research; London, UK Victoria Infectious Diseases Reference Laboratory; Victoria Infectious Diseases Reference Laboratory;

Melbourne, AustraliaMelbourne, Australia National Institute for Infectious Diseases; Tokyo, JapanNational Institute for Infectious Diseases; Tokyo, Japan

• US Food and Drug Administration (FDA) determines viral US Food and Drug Administration (FDA) determines viral components of US-licensed vaccinescomponents of US-licensed vaccines

Timeline for Vaccine DevelopmentTimeline for Vaccine Development

From selection to consumer release of trivalent influenza virus From selection to consumer release of trivalent influenza virus vaccinevaccine• Six to eight months Six to eight months

Preparation of each reassortant viral componentPreparation of each reassortant viral component• Development of high-growth reassortantsDevelopment of high-growth reassortants

Capable of high growth in eggs/cell culturesCapable of high growth in eggs/cell cultures• PurificationPurification

SolventsSolvents Unnecessary viral antigensUnnecessary viral antigens Bacteria Bacteria

Standardization and testing of HA componentsStandardization and testing of HA components• Development of appropriate reagentsDevelopment of appropriate reagents

Safety and efficacy testingSafety and efficacy testing Production of trivalent vaccineProduction of trivalent vaccine

• PurificationPurification• Mass productionMass production

Regulatory IssuesRegulatory Issues• Monovalent pandemic vaccineMonovalent pandemic vaccine

Four to six monthsFour to six months

Production of Influenza Vaccines for Pandemics or Production of Influenza Vaccines for Pandemics or Pandemic AlertsPandemic Alerts

1957 - 19981957 - 1998

Wood, JM. Developing vaccines against pandemic influenza. Phil. Trans. R.Soc. Lond. 2001;356:1953-60.

To Prime or Not To PrimeTo Prime or Not To PrimeMinimum 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;356:1953-60.

2010 – 2011 Influenza Vaccine2010 – 2011 Influenza Vaccine

And the winners are……..

A/California/7/2009(H1N1)-like virusA/Perth/16/2009 (H3N2)-like virus

B/Brisbane/60/2008-like virus

New RecommendationNew Recommendation

February 24, 2010February 24, 2010• Advisory Committee on Immunization Advisory Committee on Immunization

Practices (ACIP)Practices (ACIP) Universal immunization for all persons ≥6 Universal immunization for all persons ≥6

months of agemonths of age

• Published in the MMWRPublished in the MMWR August 6, 2010August 6, 2010 Volume 59; RR-08Volume 59; RR-08

New RecommendationNew Recommendation

June 24, 2010June 24, 2010• All children aged 6 months through 8 All children aged 6 months through 8

years of age who did not receive at least years of age who did not receive at least 1 dose of the monovalent 2009 1 dose of the monovalent 2009 Influenza A H1N1 vaccine:Influenza A H1N1 vaccine:

Receive 2 doses of the 2010-11 seasonal Receive 2 doses of the 2010-11 seasonal influenza vaccine regardless of their influenza vaccine regardless of their previous vaccination historyprevious vaccination history

High-Dose Inactivated Influenza High-Dose Inactivated Influenza Vaccine for Persons Aged Vaccine for Persons Aged ≥65 Years*≥65 Years*

12/23/200912/23/2009• FDA licensed an injectable inactivated trivalent influenza FDA licensed an injectable inactivated trivalent influenza

vaccine containing an increased amount of viral vaccine containing an increased amount of viral hemagglutinin antigen compared with other TIVshemagglutinin antigen compared with other TIVs

• Single dose for persons aged ≥65 yearsSingle dose for persons aged ≥65 years RationaleRationale

• Greater risk of hospitalization and mortality from Greater risk of hospitalization and mortality from influenza influenza

• Less immunogenic responseLess immunogenic response 04/30/201004/30/2010

• Advisory Committee on Immunization Practices (ACIP)Advisory Committee on Immunization Practices (ACIP) No preference for new vaccine over other TIVsNo 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 2010. 04/30/2010;59(16);485-86.

New JerseyNew Jersey

Attendance at pre-Kindergarten and Attendance at pre-Kindergarten and daycare centersdaycare centers• Mandatory annual influenza Mandatory annual influenza

immunizationimmunization For those 6 months through 8 years of ageFor those 6 months through 8 years of age

• NaïveNaïve 2 doses 2 doses Administered at least 4 weeks apartAdministered at least 4 weeks apart

Estimates of Death Associated with Estimates of Death Associated with Seasonal Influenza, Seasonal Influenza,

United States, 1976-2007United States, 1976-2007**

Annual estimates of influenza-Annual estimates of influenza-associated deathsassociated deaths• Death certificate dataDeath certificate data

Respiratory and circulatory causes (includes Respiratory and circulatory causes (includes pneumonia and influenza causes)pneumonia and influenza causes)

• Estimated annual average: 23, 607 Estimated annual average: 23, 607 (range,3,349 [1986-87] to 48,614 [2003-(range,3,349 [1986-87] to 48,614 [2003-04])04])

• Average: 9.0 per 100,000 persons Average: 9.0 per 100,000 persons (range,1.4 to 16.7) (range,1.4 to 16.7)

*CDC. Estimates of deaths associated with seasonal influenza, US. 1976-2007. MMWR August 27, 2010;59(33):1057-62.


United States, 1976-2007United States, 1976-2007** Age-specfic estimatesAge-specfic estimates

• <19 years of age<19 years of age Estimated annual average: 124 (range, 57 [1981-82] Estimated annual average: 124 (range, 57 [1981-82]

to 197 [1977-78])to 197 [1977-78]) Rate: 0.2 deaths per 100,000 (range, 0.1-0.3)Rate: 0.2 deaths per 100,000 (range, 0.1-0.3)

• 19-64 years of age19-64 years of age Estimated annual average: 2,385 (range, 504 [1981-Estimated annual average: 2,385 (range, 504 [1981-

82] to 4,752 [2003-04])82] to 4,752 [2003-04]) Rate: 1.5 per 100,000 persons (range, 0.4-3.1)Rate: 1.5 per 100,000 persons (range, 0.4-3.1)

• ≥≥65 years of age65 years of age Estimated annual average: 21,098 (range, 2,344 Estimated annual average: 21,098 (range, 2,344

[1986-87] to 43,727 [2004-04][1986-87] to 43,727 [2004-04] 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 mortality89.4% of influenza-associated mortality



United States, 1976-2007United States, 1976-2007** Wide variation in the estimated Wide variation in the estimated

mortality from season to season mortality from season to season associated with predominant associated with predominant influenza type and subtypes influenza type and subtypes • ≥≥20% of all isolates tested during 20% of all isolates tested during

seasonseason• Influenza A(H3N2) Influenza A(H3N2)

2.7 times higher2.7 times higher 22 seasons22 seasons



United States, 1976-2007United States, 1976-2007** Substantial variability in influenza-Substantial variability in influenza-

associated mortality estimatesassociated 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 A single estimate cannot be used to summarize influenza-associated mortalitysummarize influenza-associated mortality• A range of estimates should be usedA range of estimates should be used

Age groupsAge groups Circulating types/subtypesCirculating types/subtypes


Intradermal Influenza VaccineIntradermal Influenza Vaccine

Sanofi Aventis submitted FDA application Sanofi Aventis submitted FDA application for approvalfor approval• Becton DickinsonBecton Dickinson

Short, thin needleShort, thin needle• 1/101/10thth size of regularly used needle size of regularly used needle

1.5 mm vs 25 to 40 mm1.5 mm vs 25 to 40 mm• 1/51/5thth antigen dose antigen dose

Stimulates the dendritic cellsStimulates the dendritic cells

• Extends vaccine supplyExtends vaccine supply• Less discomfortLess discomfort• Less expensive?Less expensive?• Approval in early 2011?Approval in early 2011?

13-valentPneumococcal

ConjugateVaccine(PCV13)

Transition from PCV7 to PCV 13Transition from PCV7 to PCV 13

Since introduction of PCV7 in 2000Since introduction of PCV7 in 2000• Dramatic overall decrease in invasive Dramatic overall decrease in invasive

pneumococcal disease (IPD) pneumococcal disease (IPD) IPD due to serotypes not included in PCV7 have IPD due to serotypes not included in PCV7 have

increasedincreased

February 24, 2010February 24, 2010• FDA approved a new 13-valent pneumococcal FDA approved a new 13-valent pneumococcal

conjugate vaccine (PCV13)conjugate vaccine (PCV13)• ACIP recommended transition from PCV7 to ACIP recommended transition from PCV7 to

PCV 13PCV 13

Pneumococcal Serotypes in PCV7 Pneumococcal Serotypes in PCV7 and PCV 13and PCV 13

Invasive Pneumococcal Disease (IPD) in Invasive Pneumococcal Disease (IPD) in Newark ResidentsNewark Residents**

December 1, 2007 – November 30, 2008December 1, 2007 – November 30, 2008 2/72 (2.8%) were serotypes included in the PCV72/72 (2.8%) were serotypes included in the PCV7

• Reflected success of PCV7 in decreasing IPD due to Reflected success of PCV7 in decreasing IPD due to vaccine serotypesvaccine serotypes

32/72 (44.4%) were covered by PCV1332/72 (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 Serotype 19A was most closely associated with

penicillin-resistancepenicillin-resistance• Consistent with trends reported in USConsistent with trends reported in US• A significantly higher proportion was found in children A significantly higher proportion was found in children

compared with adults and the elderlycompared with adults and the elderly

*Tasslimi A, et al. Clinical and Vaccine Immunology. August 2009. 16;8:1256

Pneumococcal Immunization with PCV13 Pneumococcal Immunization with PCV13 Advisory Committee on Immunization Practices (ACIP) Advisory Committee on Immunization Practices (ACIP)

RecommendationsRecommendations

Infants and children under 2 years of ageInfants and children under 2 years of age• 4-dose regimen4-dose regimen• 2, 4, 6, and 12-15 months2, 4, 6, and 12-15 months

Older children and adolescentsOlder children and adolescents• Healthy between 2Healthy between 2ndnd and 5 and 5thth birthdays birthdays

Not completed PCV7 or PCV13 series before age 2Not completed PCV7 or PCV13 series before age 2• 1 dose1 dose

• Children at high risk between 2Children at high risk between 2ndnd and 6 and 6thth birthday birthday Received 3 doses of PCV7/PCV13 before 2 yearsReceived 3 doses of PCV7/PCV13 before 2 years

• 1 dose1 dose Received ≤2 doses of PCV7/PCV13 before 2 yearsReceived ≤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 dose1 dose Even if previous recipient of PCV7 or PPSV23Even if previous recipient of PCV7 or PPSV23

• Children who have completed the 4-dose series with PCV7 and are Children who have completed the 4-dose series with PCV7 and are healthy and <5 years or at high risk and <6 yearshealthy and <5 years or at high risk and <6 years

1 dose1 dose

Risk Factors for Invasive Risk Factors for Invasive Pneumococcal DiseasePneumococcal Disease

Sickle cell diseaseSickle cell disease Functional or anatomical aspleniaFunctional or anatomical asplenia Cochlear implantsCochlear implants CSF leaksCSF leaks DiabetesDiabetes Chronic heart and lung diseaseChronic heart and lung disease Immunocompromised conditionsImmunocompromised 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 Diseases associated with treatment with immunosuppressive

medications or radiation therapymedications or radiation therapy Solid organ transplantationSolid organ transplantation Lymphomas, leukemias, malignant neoplasmsLymphomas, leukemias, malignant neoplasms Asthma if treated with prolonged, high-dose oral corticosteroidsAsthma if treated with prolonged, high-dose oral corticosteroids

Mumps OutbreakNew York and New

Jersey2009-2010

MumpsMumps

RNA virusRNA virus Systemic diseaseSystemic disease

• Swelling of ≥1 salivary glandsSwelling of ≥1 salivary glands ParotidsParotids

• ~1/3 of patients do not demonstrate ~1/3 of patients do not demonstrate salivary gland swellingsalivary gland swelling

Respiratory tract symptomsRespiratory tract symptoms

• >50% of patients have CSF pleocytosis>50% of patients have CSF pleocytosis• <10% have CNS symptomology<10% have CNS symptomology

MumpsMumps

MumpsMumps

Systemic Disease (continued)Systemic Disease (continued)• OrchitisOrchitis

Post-pubertal complicationPost-pubertal complication• Sterility is rareSterility is rare

• Rare complicationsRare complications Arthritis, thyroiditis, mastitis, glomerularnephritis, Arthritis, thyroiditis, mastitis, glomerularnephritis,

myocarditis, endocardial fibroelastosis, pancreatitis, myocarditis, endocardial fibroelastosis, pancreatitis, oophoritis, hearing impairmentoophoritis, hearing impairment

• Infections in adults more likely to be severeInfections in adults more likely to be severe Death, though rare, occurs most often in adultsDeath, though rare, occurs most often in adults

• Infection in first trimester associated with Infection in first trimester associated with increased risk of spontaneous abortionincreased risk of spontaneous abortion

MumpsMumps EpidemiologyEpidemiology

• Transmission via infected respiratory tract Transmission via infected respiratory tract secretionssecretions

• Incubation periodIncubation period 12–25 days (usually 16-18 days)12–25 days (usually 16-18 days)

• Period of maximum communicabilityPeriod of maximum communicability 1 to 2 days prior to parotid swelling1 to 2 days prior to parotid swelling 5 days after onset of swelling5 days after onset of swelling

• Virus has been isolated in salivia from 7 days prior to Virus has been isolated in salivia from 7 days prior to swelling onset to 9 days after onset of swellingswelling onset to 9 days after onset of swelling

• Reported incidence in US in 1967Reported incidence in US in 1967 186,000186,000

MumpsMumps

VaccineVaccine• Licensed in US in 1967Licensed in US in 1967• Recommended for routine childhood immunization in Recommended for routine childhood immunization in

19771977 One-dose scheduleOne-dose schedule Disease incidence fell to very low levelsDisease incidence fell to very low levels

• Outbreaks occurred between 1986-1991Outbreaks occurred between 1986-1991• Two-dose schedule recommended in 1989Two-dose schedule recommended in 1989

2000-2005: <300 reported cases/year2000-2005: <300 reported cases/year 2006: Mumps outbreak: 6584 cases2006: Mumps outbreak: 6584 cases

• 18-24 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 dose73%-91% after 1 dose 79%-95% after 2 doses79%-95% after 2 doses

Mumps Immunization Mumps Immunization Advisory Committee on Immunization Advisory Committee on Immunization Practices (ACIP) RecommendationsPractices (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)

11stst dose: 12-15 months dose: 12-15 months 22ndnd dose: 4-6 years dose: 4-6 years

• Adults at high-risk for infectionAdults at high-risk for infection i.e., person who work in healthcare facilities, international i.e., person who work in healthcare facilities, international

travelers, students at post-high school educational institutions, travelers, students at post-high school educational institutions, etc.)etc.)

• For healthcare workers born before 1957 without laboratory For healthcare workers born before 1957 without laboratory evidence of immunityevidence of immunity

Consider receiving 1 doseConsider receiving 1 dose During outbreaksDuring outbreaks

• Children aged 1-4 yearsChildren aged 1-4 years Offer 2Offer 2ndnd dose dose

• Confirm 2-doses in others Confirm 2-doses in others

Mumps Outbreak Mumps Outbreak New York and New JerseyNew York and New Jersey

2009-20102009-2010**

June 17, 2009: 11-year old boy returns June 17, 2009: 11-year old boy returns from United Kingdomfrom United Kingdom• ~7,400 reports of laboratory confirmed mumps ~7,400 reports of laboratory confirmed mumps

in 2009in 2009 Symptomatic by June 28Symptomatic by June 28

• At camp for tradition-observant Jewish boysAt camp for tradition-observant Jewish boys Subsequent transmission to other camp attendees Subsequent transmission to other camp attendees

and staff memberand staff member 25 cases reported from June 2825 cases reported from June 28thth–September 8th–September 8th

Transmission occurred in multiple Transmission occurred in multiple locations when campers returned homelocations 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 2010. February 12, 2010;59(5):125-29.


2009-20102009-2010**

Confined primarily to the tradition-Confined primarily to the tradition-observant Jewish communityobservant Jewish community• New York City {Brooklyn} (44%); Orange New York City {Brooklyn} (44%); Orange

County, NY (24%); Rockland County, NY (20%); County, NY (24%); Rockland County, NY (20%); Four counties in New Jersey (10%)Four counties in New Jersey (10%)

• Camp-associated cases in Sullivan County, NY Camp-associated cases in Sullivan County, NY (2%)(2%)

• <3% of cases occurring outside the community<3% of cases occurring outside the community Reported regular contact with members of the Reported regular contact with members of the

affected communityaffected community



2009-20102009-2010** 61% of cases occurred in persons aged 7-61% of cases occurred in persons aged 7-

18 years of age18 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 Among patients in which vaccination status was known (n=1,115)status was known (n=1,115)• 88% received at least 1 dose of mumps-88% received at least 1 dose of mumps-

containing vaccine (MCV)containing vaccine (MCV)• 75% received 2 doses of MCV 75% received 2 doses of MCV



2009-20102009-2010** ComplicationsComplications

• 65 reports 65 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



2009-20102009-2010** Mumps outbreak in a highly vaccinated Mumps outbreak in a highly vaccinated

populationpopulation• 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 No sustained transmission outside the specific communitycommunity

• Congregate settingCongregate setting Prolonged close contactProlonged close contact

• Large household sizeLarge household size Mean household size in the affected community was Mean household size in the affected community was

5.7 versus mean US household size of 2.65.7 versus mean US household size of 2.6• Effectiveness of mumps component of MMREffectiveness of mumps component of MMR



2009-20102009-2010** Public Health ResponsePublic Health Response

• Health-care providers notifiedHealth-care providers notified Verify children are completely vaccinatedVerify children are completely vaccinated

• Offer 2Offer 2ndnd dose in children aged 1-4 years dose in children aged 1-4 years Offer vaccine to adultsOffer vaccine to adults

• Unknown immunity or vaccine statusUnknown immunity or vaccine status• State and local health departmentsState and local health departments

Affected schoolsAffected schools• Enhance vaccination policiesEnhance vaccination policies

Exclude unvaccinated children from school during outbreakExclude unvaccinated children from school during outbreak Home isolation for 5 days after onset of parotitisHome isolation for 5 days after onset of parotitis

Orange County, New York beginning 01/19/2010Orange County, New York beginning 01/19/2010• 33rdrd dose of MMR in 3 schools dose of MMR in 3 schools

Continued transmission of infection despite high level of 2-dose Continued transmission of infection despite high level of 2-dose coveragecoverage

Institutional Review Board-approval protocol that includes Institutional Review Board-approval protocol that includes evaluation of interventionevaluation of intervention


RotavirusVaccine

Contamination

Contamination of Rotavirus Contamination of Rotavirus VaccineVaccine

March 22, 2010March 22, 2010• FDA recommends temporary suspension FDA recommends temporary suspension

of use of Rotarix® (GlaxoSmithKline of use of Rotarix® (GlaxoSmithKline Biologicals)Biologicals)

Porcine circovirus 1 (PCV1) DNA, particles, Porcine circovirus 1 (PCV1) DNA, particles, infectious virus are present in vaccineinfectious virus are present in vaccine

May 6, 2010May 6, 2010• Preliminary studies by Merck identified Preliminary studies by Merck identified

PCV1 and PCV2 DNA at low levels in PCV1 and PCV2 DNA at low levels in Rotateq® (Merck & Co, Inc.)Rotateq® (Merck & Co, Inc.)

Porcine Circovirus (PCV) Types 1 Porcine Circovirus (PCV) Types 1 and 2and 2

Small virusesSmall viruses• Single strand of circular DNASingle strand of circular DNA• Commonly found in pigsCommonly found in pigs

PCV2 may cause disease in pigsPCV2 may cause disease in pigs

• Neither PCV1 or PCV2 are known to Neither PCV1 or PCV2 are known to infect or cause disease in humansinfect or cause disease in humans

FDA RecommendationsFDA RecommendationsMay 14, 2010May 14, 2010

It is appropriate for clinicians and healthcare It is appropriate for clinicians and healthcare professionals to resume the use of Rotarix® (GSK professionals to resume the use of Rotarix® (GSK Biologicals) and to continue to use Rotateq® Biologicals) and to continue to use Rotateq® (Merck & Co, Inc.)(Merck & Co, Inc.)

ConsiderationsConsiderations• Strong safety recordsStrong safety records

Clinical trialsClinical trials• Tens of thousands of participantsTens of thousands of participants

Post-licensure clinical experiencePost-licensure clinical experience• Millions of recipientsMillions of recipients

No evidence the PCV1 or PCV2 poses a safety risk to No evidence the PCV1 or PCV2 poses a safety risk to humanshumans

• Benefits of vaccination outweigh the risks which are Benefits of vaccination outweigh the risks which are theoreticaltheoretical

Next StepsNext Steps FDA and manufacturers are updating FDA and manufacturers are updating

labeling for both vaccines to include labeling for both vaccines to include information concerning presence of PCV1 information concerning presence of PCV1 and PCV2and PCV2

Planning appropriate follow-up studiesPlanning appropriate follow-up studies Continuing investigation into the findings Continuing investigation into the findings

of PCV in rotavirus vaccinesof PCV in rotavirus vaccines• GSK plans to rederive its vaccine in GSK plans to rederive its vaccine in

consultation with the FDAconsultation with the FDA• Merck is in early stages of its investigation and Merck is in early stages of its investigation and

has not determined as yet its next steps in this has not determined as yet its next steps in this regardregard

Guillain-BarrGuillain-Barré Syndrome (GBS) and é Syndrome (GBS) and Conjugated Meningococcal Vaccine Conjugated Meningococcal Vaccine

(MCV4)(MCV4)

June 24, 2010June 24, 2010• Studies have not demonstrated an Studies have not demonstrated an

increased risk of GBS associated with increased risk of GBS associated with the meningococcal vaccinethe meningococcal vaccine

• Removed precautionary warning from Removed precautionary warning from the sanofi pasteur MCV4 labelthe sanofi pasteur MCV4 label

Religious ExemptionsReligious Exemptions**

New JerseyNew Jersey• Eightfold increase since 2005-06 school yearEightfold increase since 2005-06 school year

3,865 student exemptions this school year3,865 student exemptions this school year

New YorkNew York• Double the amount seen in 1999Double the amount seen in 1999

3,615 student exemptions in 20083,615 student exemptions in 2008

ConnecticutConnecticut• 455 student exemptions in 2009 versus 248 in 455 student exemptions in 2009 versus 248 in

19991999

*The Wall Street Journal. More parents seek vaccine exemption. July 6. 2010

Thank YouFor

All you Do!!!

immunization potpourri 2010 peter n. wenger, md departments of preventive medicine and community...

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