Transcript Immunization Update 2010

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 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
http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm
#Table%20Cumulative
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
Deaths
Total
~12,270
~8,720 to ~18,050
http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm
#Table%20Cumulative
Percentage of Visits for Influenza-like Illness (ILI)
Reported by the U.S. Outpatient Influenza-like Illness
Surveillance Network (ILINet)
National Summary 2008-2009 and Previous Two Seasons
Through the week Ending May 22, 2010
http://www.cdc.gov/h1n1flu/updates/us/
National H1N1 Flu Survey*
Week of December 6-12, 2009

~46 million people (15.3%) vaccinated vs
2009 pandemic influenza A virus H1N1
• 28 million adults (13.0%)
• 18 million children (24.0%)

Amount of vaccine distributed to providers
• ~21% of US population

3 of 4 shipped doses administered
• 74% of vaccine went to people in initial target
groups

42% of all vaccine given to children
• 23% of vaccine doses given were nasal spray
*http://www.cdc.gov/h1n1flu/in_the_news/influenza_vaccination.htm
Pandemic Influenza A (H1N1) 2009 Monovalent
Vaccination Coverage,
New Jersey, October 2009 – January 2010*

Children aged 6 months to 17 years
• 32.7% (95% CI, + 4.6)

Persons aged ≥18 years
• 13.1% (95% CI, + 2.0)

Persons in initial target groups
• 29.0% (95% CI, + 4.5)

Persons aged 25-64 years at high risk
• 17% (95% CI, + 5.8)

Persons aged 25-64 years not included in the
initial target groups
• 9.5% (95% CI, + 2.4)

Persons aged ≥ 65 years
• 12.2% (95% CI, + 3.7)
*CDC. MMWR April 2, 2010. 59;12:363-68
Influenza Vaccine
Development
http://www.ifpma.org/Influenza/index.aspx?000_The_Influenza_Virus/001a_Influenza_Virus.html
Influenza
Strategy to Escape Immune Detection

Drift
• Minor change in HA glycoprotein



Gradual accumulation of amino acid changes
Mutations in viral RNA
• Occurs continuously
Shift
• Major change in HA glycoprotein

Reassortment (Reassortant)
• Exchange of gene segments

Direct transmission from a different species to humans without
reassortment
• 1918?
• 1997 – 2005 Hong Kong; Netherlands; Canada; South Asia; New York
• Occurs infrequently

~ 33 years
Cox NJ, Subbarao K. Lancet. 1999;354:1277–82.
Genetic Reassortment To Generate
Vaccine Strains
Master strain high-growth potential in eggs
or cell culture
PB1
PB2
PA
HA
NA
NP
M
NS
Circulating wild-type strain
Co-infect cells
From Master
strain
PB1
PB2
PA
HA
NA
NP
M
NS
PB1
PB2
PA
HA
NA
NP
M
NS
From wild-type
strain
New high-growth reassortant vaccine strain
Currently Available Influenza Vaccines
Trivalent Inactivated
Vaccine (TIV)
Live Attenuated
Influenza Vaccine
(LAIV)
FDA-approved
Since 1960s
Since 2003
Route of
administration
Intramuscular
Intranasal
Primarily humoral
Mucosal and humoral
Split-virus or subunit
inactivated virus (HA)
Cold-adapted,
temperature-sensitive,
live attenuated virus
Chick embryos
Chick embryos
Persons 6 months
Healthy persons 2–49
years
Immunity
Virus
Growth Medium
Indication
Ruben FL. Clin Infect Dis. 2004;38:689-91. cdc.gov/nip/publications/pink/flu.pdf.
Considerations

Include strain that closely match community
circulating strains
• May differ in different regions

Dose considerations
• Induces protective immune response in individuals

Age-dependent
• <6 months: inadequate response
• Older individuals: less robust response
• Hemagglutinin antigen (HA)
 15 µg in those ≥3 years of age
 7.5 µg in those 6 - 35 months of age
• Vaccine-naïve children, 6 months through 8 years of age
require a priming dose

Priming dose for pandemic (novel) strains?
• Maximizing population coverage
• Minimizing adverse reactions
Timeline for Vaccine Development

Reflect the need to produce and
administer vaccine before and during each
influenza season
• Global surveillance

Year round in both hemispheres
• Trends in viral antigenic changes

Collection, analysis, and assessment of circulating
strains for selection of appropriate vaccine strains
• Timing is everything!
 Too early – significant antigenic changes may be
missed
 Too late – vaccine output may be affected
World Health Organization (WHO)
Global Influenza Surveillance
System
● Established in 1948
• 130 national influenza centers in 101 countries
• Analyzed by 4 WHO Collaborating Centers for Reference
and Research on Influenza




CDC; Atlanta, GA, US
National Institute on Medical Research; London, UK
Victoria Infectious Diseases Reference Laboratory;
Melbourne, Australia
National Institute for Infectious Diseases; Tokyo, Japan
• US 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
• Six to eight months

Preparation of each reassortant viral component
• Development of high-growth reassortants

Capable of high growth in eggs/cell cultures
• Purification

Solvents

Unnecessary viral antigens

Bacteria

Standardization and testing of HA components
• Development of appropriate reagents


Safety and efficacy testing
Production of trivalent vaccine
• Purification
• Mass production

Regulatory Issues
• Monovalent pandemic vaccine

Four to six months
Production of Influenza Vaccines for Pandemics or
Pandemic Alerts
1957 - 1998
Wood, JM. Developing vaccines against pandemic influenza. Phil. Trans. R.
Soc. Lond. 2001;356:1953-60.
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;356:1953-60.
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
• Advisory Committee on Immunization
Practices (ACIP)

Universal immunization for all persons ≥6
months of age
• Published in the MMWR


August 6, 2010
Volume 59; RR-08
New Recommendation

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:

Receive 2 doses of the 2010-11 seasonal
influenza vaccine regardless of their
previous vaccination history
High-Dose Inactivated Influenza
Vaccine for Persons Aged ≥65 Years*

12/23/2009
• FDA 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 years

Rationale
• Greater risk of hospitalization and mortality from
influenza
• Less immunogenic response

04/30/2010
• Advisory Committee on Immunization Practices (ACIP)

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 2010.
04/30/2010;59(16);485-86.
New Jersey

Attendance at pre-Kindergarten and
daycare centers
• Mandatory annual influenza
immunization

For those 6 months through 8 years of age
• Naïve
 2 doses
 Administered at least 4 weeks apart
Estimates of Death Associated with
Seasonal Influenza,
United States, 1976-2007*

Annual estimates of influenzaassociated deaths
• Death certificate data

Respiratory and circulatory causes (includes
pneumonia and influenza causes)
• Estimated annual average: 23, 607
(range,3,349 [1986-87] to 48,614
[2003-04])
• Average: 9.0 per 100,000 persons
(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.
Estimates of Death Associated with
Seasonal Influenza,
United States, 1976-2007*

Age-specfic estimates
• <19 years of age


Estimated annual average: 124 (range, 57 [1981-82]
to 197 [1977-78])
Rate: 0.2 deaths per 100,000 (range, 0.1-0.3)
• 19-64 years of age


Estimated annual average: 2,385 (range, 504 [198182] to 4,752 [2003-04])
Rate: 1.5 per 100,000 persons (range, 0.4-3.1)
• ≥65 years of age



Estimated annual average: 21,098 (range, 2,344
[1986-87] to 43,727 [2004-04]
Rate: 66.1 per 100,000 persons (range, 8.0 – 121.1)
89.4% of influenza-associated mortality
*CDC. Estimates of deaths associated with seasonal influenza, US.
1976-2007. MMWR August 27, 2010;59(33):1057-62.
Estimates of Death Associated with
Seasonal Influenza,
United States, 1976-2007*

Wide variation in the estimated
mortality from season to season
associated with predominant
influenza type and subtypes
• ≥20% of all isolates tested during
season
• Influenza A(H3N2)


2.7 times higher
22 seasons
*CDC. Estimates of deaths associated with seasonal influenza, US.
1976-2007. MMWR August 27, 2010;59(33):1057-62.
Estimates of Death Associated with
Seasonal Influenza,
United States, 1976-2007*

Substantial variability in influenzaassociated mortality estimates
• Year (season to season)
• Age group
• Influenza type/subtype

A single estimate cannot be used to
summarize influenza-associated mortality
• A range of estimates should be used


Age groups
Circulating types/subtypes
*CDC. Estimates of deaths associated with seasonal influenza, US.
1976-2007. MMWR August 27, 2010;59(33):1057-62.
Intradermal Influenza Vaccine

Sanofi Aventis submitted FDA application
for approval
• Becton Dickinson

Short, thin needle
• 1/10th size of regularly used needle
 1.5 mm vs 25 to 40 mm
• 1/5th antigen dose
 Stimulates the dendritic cells
•
•
•
•
Extends vaccine supply
Less discomfort
Less expensive?
Approval in early 2011?
13-valent
Pneumococcal
Conjugate
Vaccine
(PCV13)
Transition from PCV7 to PCV 13

Since introduction of PCV7 in 2000
• Dramatic overall decrease in invasive
pneumococcal disease (IPD)


IPD due to serotypes not included in PCV7 have
increased
February 24, 2010
• FDA approved a new 13-valent pneumococcal
conjugate vaccine (PCV13)
• ACIP 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, 2008

2/72 (2.8%) were serotypes included in the PCV7
• Reflected success of PCV7 in decreasing IPD due to
vaccine serotypes

32/72 (44.4%) were covered by PCV13
• Serotypes 3 (6), 6A (3), and 19A (19)

Serotype 19A was dominant
• 19/72 (26.4%)
• Serotype 19A was most closely associated with
penicillin-resistance
• Consistent with trends reported in US
• A significantly higher proportion was found in children
compared with adults and the elderly
*Tasslimi A, et al. Clinical and Vaccine Immunology. August 2009. 16;8:1256
Pneumococcal Immunization with PCV13
Advisory Committee on Immunization Practices (ACIP)
Recommendations

Infants and children under 2 years of age
• 4-dose regimen
• 2, 4, 6, and 12-15 months

Older children and adolescents
• Healthy between 2nd and 5th birthdays

Not completed PCV7 or PCV13 series before age 2
• 1 dose
• Children at high risk between 2nd and 6th birthday

Received 3 doses of PCV7/PCV13 before 2 years
• 1 dose

Received ≤2 doses of PCV7/PCV13 before 2 years
• 2 doses
• Children and adolescents at high risk 6 through 18 years


1 dose
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 years

1 dose
Risk Factors for Invasive
Pneumococcal Disease







Sickle cell disease
Functional or anatomical asplenia
Cochlear implants
CSF leaks
Diabetes
Chronic heart and lung disease
Immunocompromised conditions
• HIV infection and congenital immunodeficiencies
• Chronic renal failure and nephrotic syndrome
• Diseases associated with treatment with immunosuppressive
medications or radiation therapy



Solid organ transplantation
Lymphomas, leukemias, malignant neoplasms
Asthma if treated with prolonged, high-dose oral corticosteroids
Mumps Outbreak
New York and New
Jersey
2009-2010
Mumps


RNA virus
Systemic disease
• Swelling of ≥1 salivary glands

Parotids
• ~1/3 of patients do not demonstrate
salivary gland swelling

Respiratory tract symptoms
• >50% of patients have CSF pleocytosis
• <10% have CNS symptomology
Mumps
Mumps

Systemic Disease (continued)
• Orchitis

Post-pubertal complication
• Sterility is rare
• Rare complications

Arthritis, thyroiditis, mastitis, glomerularnephritis,
myocarditis, endocardial fibroelastosis, pancreatitis,
oophoritis, hearing impairment
• Infections in adults more likely to be severe

Death, though rare, occurs most often in adults
• Infection in first trimester associated with
increased risk of spontaneous abortion
Mumps

Epidemiology
• Transmission via infected respiratory tract
secretions
• Incubation period

12–25 days (usually 16-18 days)
• Period of maximum communicability


1 to 2 days prior to parotid 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 swelling
• Reported incidence in US in 1967

186,000
Mumps

Vaccine
• Licensed in US in 1967
• Recommended for routine childhood immunization in
1977


One-dose schedule
Disease incidence fell to very low levels
• Outbreaks occurred between 1986-1991
• Two-dose schedule recommended in 1989


2000-2005: <300 reported cases/year
2006: Mumps outbreak: 6584 cases
• 18-24 years of age
• Many received 2 doses MMR
• Mumps least effective component of MMR


73%-91% after 1 dose
79%-95% after 2 doses
Mumps Immunization
Advisory Committee on Immunization
Practices (ACIP) Recommendations

Two doses of mumps-containing vaccine (in US – MMR)
• All school-aged children (K-12)


1st dose: 12-15 months
2nd dose: 4-6 years
• Adults at high-risk for infection

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 immunity


Consider receiving 1 dose
During outbreaks
• Children aged 1-4 years

Offer 2nd dose
• Confirm 2-doses in others
Mumps Outbreak
New York and New Jersey
2009-2010*

June 17, 2009: 11-year old boy returns
from United Kingdom
• ~7,400 reports of laboratory confirmed mumps
in 2009

Symptomatic by June 28
• At camp for tradition-observant Jewish boys



Subsequent transmission to other camp attendees
and staff member
25 cases reported from June 28th–September 8th
Transmission occurred in multiple locations
when campers returned home
• As 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.
Mumps Outbreak
New York and New Jersey
2009-2010*

Confined primarily to the traditionobservant Jewish community
• 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%)
• <3% of cases occurring outside the community

Reported regular contact with members of the
affected community
*CDC. MMWR. Update: mumps outbreak-New York and New Jersey,
June 2009-January 2010. February 12, 2010;59(5):125-29.
Mumps Outbreak
New York and New Jersey
2009-2010*

61% of cases occurred in persons aged 718 years of age
• 4.9% in children aged 1-4 years
• Range, 3 months-90 years
• 76% were male

Among patients in which vaccination
status was known (n=1,115)
• 88% received at least 1 dose of mumpscontaining vaccine (MCV)
• 75% received 2 doses of MCV
*CDC. MMWR. Update: mumps outbreak-New York and New Jersey,
June 2009-January 2010. February 12, 2010;59(5):125-29.
Mumps Outbreak

New York and New Jersey
2009-2010*
Complications
• 65 reports






Orchitis: 55 cases (85%)
Pancreatitis: 5 cases (8%)
Aseptic meningitis: 2 cases (3%)
Transient deafness: 1 case (1.5%)
Bell’s palsy: 1 case (1.5%)
Oophoritis: 1 case (1.5%)
• 19 reported hospitalizations

No deaths
*CDC. MMWR. Update: mumps outbreak-New York and New Jersey,
June 2009-January 2010. February 12, 2010;59(5):125-29.
Mumps Outbreak
New York and New Jersey
2009-2010*

Mumps outbreak in a highly vaccinated
population
• Most cases occur in vaccinated people

Why?????
• Specific close-knit, closed community

No sustained transmission outside the specific
community
• Congregate setting

Prolonged close contact
• Large household size

Mean household size in the affected community was
5.7 versus mean US household size of 2.6
• Effectiveness of mumps component of MMR
*CDC. MMWR. Update: mumps outbreak-New York and New Jersey,
June 2009-January 2010. February 12, 2010;59(5):125-29.
Mumps Outbreak
New York and New Jersey
2009-2010*

Public Health Response
• Health-care providers notified

Verify children are completely vaccinated
• Offer 2nd dose in children aged 1-4 years

Offer vaccine to adults
• Unknown immunity or vaccine status
• State and local health departments

Affected schools
• Enhance vaccination policies
 Exclude unvaccinated children from school during outbreak
 Home isolation for 5 days after onset of parotitis

Orange County, New York beginning 01/19/2010
• 3rd dose of MMR in 3 schools
 Continued transmission of infection despite high level of 2-dose
coverage
 Institutional Review Board-approval protocol that includes
evaluation of intervention
*CDC. MMWR. Update: mumps outbreak-New York and New Jersey,
June 2009-January 2010. February 12, 2010;59(5):125-29.
Rotavirus
Vaccine
Contamination
Contamination of Rotavirus Vaccine

March 22, 2010
• FDA recommends temporary suspension
of use of Rotarix® (GlaxoSmithKline
Biologicals)


Porcine circovirus 1 (PCV1) DNA, particles,
infectious virus are present in vaccine
May 6, 2010
• 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
• Single strand of circular DNA
• Commonly found in pigs

PCV2 may cause disease in pigs
• Neither 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.)
Considerations
• Strong safety records

Clinical trials
• Tens of thousands of participants

Post-licensure clinical experience
• Millions of recipients

No evidence the PCV1 or PCV2 poses a safety risk to
humans
• Benefits 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
Planning appropriate follow-up studies
Continuing investigation into the findings
of PCV in rotavirus vaccines
• GSK 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
regard
Guillain-Barré Syndrome (GBS) and
Conjugated Meningococcal Vaccine
(MCV4)

June 24, 2010
• Studies have not demonstrated an
increased risk of GBS associated with
the meningococcal vaccine
• Removed precautionary warning from
the sanofi pasteur MCV4 label
Religious Exemptions*

New Jersey
• Eightfold increase since 2005-06 school year


3,865 student exemptions this school year
New York
• Double the amount seen in 1999


3,615 student exemptions in 2008
Connecticut
• 455 student exemptions in 2009 versus 248 in
1999
*The Wall Street Journal. More parents seek vaccine exemption. July 6. 2010
Thank You
For
All you Do!!!