Download A 25 Gauge View of Prevention

A 25 Gauge View of Prevention:
Adult Vaccinations
Shobhina Chheda, M.D., M.P.H
Laurel Romer, M.D.
Primary Care Conference
September 14, 2005
Learning Objectives
1. Understand epidemiology of vaccine
preventable diseases.
2. Review recommendations for common
adult vaccinations.
3. Offer vaccination to appropriate patients.
4. Answer patient questions regarding
upcoming vaccines.
Influenza
• Epidemiology
• Hospitalizations (From 1979/80 to 2000/01)
• 54,000 to 430,000 per epidemic
• 226,000 influenza-related hospitalizations/year
• 63% of these among patients > 65 years old
• Deaths
• 19,000 per season from 1976-1990
• 36,000 per season from 1990-1999
MMWR 13 June 2005;54:1-40.
Influenza
• Virus characteristics
– Influenza A
• Envelope glycoproteins/Hemagglutinins 1,2,3/
Neuraminidases 1,2
• Antigenic shift (epidemics/pandemics)
• Antigenic drift (localized outbreaks)
– Influenza B
• Antigenic drift
Influenza
• Vaccine Characteristics
– Changes yearly to approximate currently circulating
strains of Influenza A/B
– Trivalent inactivated influenza vaccine
• intramuscular
– Trivalent live-attenuated, cold-adapted influenza
vaccine
• Intranasal
– Protection conferred by induction of antibodies
(mainly against the hemagglutinin)
Influenza
• Vaccine Efficacy
– Greater reduction in serologically confirmed
cases than in clinical influenza
– Healthy adults ages 14-65 years:
• 68% reduction in serologically confirmed influenza
– 48% reduction with intranasal vaccine
• 24% reduction in clinical influenza
– 13% reduction with intranasal vaccine
Demichelli V, et al. Cochrane Database Syst Rev 2001; CD001269.
Influenza
• Vaccine efficacy
– Elderly
• > 90% of influenza-related deaths occur among
those > age 60
Influenza
• Vaccine Recommendations for 2005-2006
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Persons age > 65 with comorbid conditions
Residents of long-term care facilities
Persons aged 2-64 with comorbid conditions
Persons age > 65 without comorbid conditions
Children age 6-23 months
Pregnant women
Health-care personnel who provide direct patient care
Household contacts and out-of-home caregivers of
children < 6 months
CDC
Pneumococcus
• Epidemiology
– Illness
• 150,000 - 570,000 cases per year
• 36% of community-acquired pneumonias in adults
– Deaths
• 6,000–12,000 per year
• Case-fatality rate 5%-7%, higher in elderly
• Risk highest in
– Older adults
– Any age with certain underlying chronic diseases
CDC/Fishbein
Pneumococcus
• Vaccine characteristics
– First used in 1945
– First vaccine developed from a capsular
polysaccharide
– 23-valent formulation created in 1983 (PPV23)
– Intramuscular injection
Pneumococcus
• Efficacy: Cochrane database
– Review of all RCT from 1/66 to 6/03
• Combined results fail to show PPV is effective in
preventing pneumonia (OR 0.77) or death (OR 0.90)
– Review of all case-control studies for same
interval
• Combined results show significant efficacy in
preventing invasive pneumococcal disease (OR
0.47), corresponding to an efficacy of 53%
Dear KB, et al. Cochrane Database Syst Rev;3: 2005.
Pneumococcus
• Recommendations for use
– Adults age 65 or older
– Persons age >2
• with chronic disease (similar to influenza)
• No spleen
• Compromised immunity (HIV, malignancy, chronic
renal disease, organ transplant, chemotherapy)
– Second dose of vaccine if patient received
vaccine > 5 years previously and was < 65
MMWR 2003;52:965
MMWR 2002;51:931
Hepatitis B
• Incidence
– In endemic areas, ~70% of adult population
positive for prior infection
• 8-15% with chronic Hep B
– Globally
• 2 billion with evidence of prior Hep B infection
• 350 million chronic carriers
• 1 million deaths annually due to
cirrhosis/hepatocellular carcinoma
Poland GA and Jacobson RM. NEJM;351(27):2004.
Hepatitis B
• Viral source
– Blood or blood-derived body fluids
• Transmission
– Percutaneous, mucosal
• Sex, injection drug use, mother-child, health care
• 100x more infectious than HIV
Hepatitis B
• Vaccine characteristics
– First generation HBV vaccine was plasma derived
– Current vaccines are recombinant HBV
– Schedule: 3 doses, intramuscular injection
• 0, 1-2 months, 4-6 months
• Combined form with Hepatitis A
– Safety
• Soreness at injection site (25%)
• Fever, malaise, headache, myalgia, joint pain (1-3%)
Hepatitis B
• Efficacy
– After completing the 3 dose course of vaccine
• 90% of adults have protective serum antibody
concentrations
• 95% of infants, children and adolescents
Mast E, et al. In: Vaccines, 2004. 299-337.
Hepatitis B
• Vaccine recommendations
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All infants
Catch-up vaccination
Pregnant women
Homosexual/bisexual men
Multiple sexual partners (4 or more/lifetime)
Household contacts of patients with Hep B
Injection drug users
Healthcare workers
Patients on hemodialysis (recipients of frequent transfusion)
Patients with chronic illness
Immunocompromised patients
Hepatitis A
• Significant decrease in incidence with
vaccine
• Most occurs in community wide epidemics
• Higher disease incidence in West and
Southwest
• Highest incidence in children ages 5-14
• Children – reservoir
Hepatitis A
• Transmission: Fecal-oral
• 70% children asymptomatic or nonspecific
symptoms
• > 70% adults have jaundice
– Liver failure rare
• Chronic infection doesn’t occur
Hepatitis A and Hurricane
Katrina
• No transmission from contaminated water
in US since 1980’s
• No outbreak seen in other recent
hurricane/floods
• < 10 cases of hepatitis A in New Orleans in
past 3 months
CDC
Hepatitis A
• Inactivated vaccine
• 2 brands licensed for children>2 and adults
• Different pediatric and adult formulations
Hepatitis A
• 2 doses – 6 months apart
– 97% immunogenic with first dose
– 100% with second dose- long term immunity
• No severe/adverse reactions
• Side effects
– Soreness/tenderness –50%
– Headache-15%
– Malaise-7%
Hepatitis A
• Not routine pediatric immunization
• Adult recommendations
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Certain international travelers
Men who have sex with men
Illicit drug users
Chronic liver disease
Persons receiving clotting factor concentrates
Persons working with laboratory HAV
• Not routinely recommended for healthcare
workers
Combined Hepatitis A and B
vaccine
• FDA approved for > age 18
• Immunogencity/safety similar to single
antigen vaccines
• Schedule 0, 1, 6 months (same as Hep B)
• Total 3 injections instead of 5
Meningococcal disease
• 1,400-2,800 cases/yr
• Rate 0.5-1.1/100,000
• College freshman*
– 1.9/100,000
– Living in dorms 5.1/100,000
• Leading cause of bacterial meningitis
– Dramatic reductions of Strep Pneumoniae and HIB
meningitis from universal vaccination of children
*Bruce et al. JAMA 2001 286:688-93
Meningococcal disease
• Three clinical forms
– Meningitis (49%)
– Bacteremia (33%)
– Pneumonia (9%)
• High case- fatality ratio (10-14%)
• High morbidity
– 11-19% of survivors have sequelae
• Transmission: direct contact with large droplet
respiratory secretions
– 5-10% carries bacteria
Meningococcal disease
• Disease caused by 5 serogroups worldwide
– A, B, C, Y W-135
• United States
– B, C, Y
• Serogroup B (no vaccine available)
– > 50% cases in age <1
– < 25% cases age >11
Meningococcal vaccines
• MCPV4 – licensed 1981
– Polysaccharide vaccine
– Mature B-lymphocyte response, no T-cell stimulation
– Not long lasting, no amnestic response
• MCV4 – licensed 2005 for ages 11-55
– Polysaccharide protein conjugate vaccine
– T-cell dependent immune response
– Longer lasting and stronger amnestic response
Meningococcal disease:
MCV4 use
• Universal vaccination
– Ages 11-12
– Adolescents at age 15 if not previously vaccinated
• Groups at elevated risk
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College freshman in dorms
Military recruits
Certain microbiologists
Certain travelers
Asplenia/Terminal complement component deficiencies
• Single dose IM
Meningococcal disease:
MCV4 use (continued)
• Adverse reactions
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Mild injection site pain and tenderness
Brief fever 5%
Severe allergic reaction (<0.1/100,000)
Neurological reaction (<0.1/100,000)
Meningococcal disease:
MPSV4 use
• Groups at elevated risk ages 2-10; >55
• Groups at elevated risk if MSV4 not
available
• No longer recommended for routine
vaccination
• Single dose IM
• Adverse reactions similar to MCV4
Pertussis: Secular Trends
• Incidence
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1940 (Prior to vaccination): 150 cases /100,000
1960: 8 cases/100,000
1980-90: 1 cases/100,000 (2,900 cases/yr)
2003: 11,647 cases
Only disease for which universal immunization is
recommended that incidence is on the rise !
Pertussis: Why the increase?
• Increase in reporting vs. actual disease
– True burden is at least 10x > reported
• Waning immunity
– Less passive Ab transmitted to newborns
– Decreased herd immunity
– Aging cohort
• ? Under-vaccination in childhood
Pertussis: Important to internists?
• Number of cases high in adults
– Rate, morbidity and mortality higher in < age 1
• Adults are source of infection for children
– 80% secondary attack rate
• Wisconsin with high number of cases
Pertussis
Children
• Catarrhal stage 1-2 weeks
• Paroxysmal cough stage 1-6 weeks
• Convalescent stage weeks-months
Pertussis
Adults
• Accounts for 7% of all cough illnesses per
year
• Mild disease
– No phases
– Persistent cough >21d
• Often not diagnosed/treated until after
maximum transmission
Pertussis
•
•
•
•
*
Aerobic gram negative rod
Attaches to cilia
Local tissue damage
Decreased ability to clear secretions
Challenging to diagnose
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Gold standard-culture (Low sensitivity)
PCR (Sensitivity highly age dependent)
DFA (now rarely used)
Serology (not practical)
Pertussis: Vaccine
• Acellular (DTaP)
– Licensed 1996 for primary series
– Replaced whole- cell vaccine for children
– More effective and fewer side effects
• Purified subunit vaccine
– Varies between 2 and 4 subunit components
Immunogenicity and Safety Study
• Prospective, randomized, double blinded trial
comparing safety and efficacy of dT and DTaP
• 4480 participants enrolled
– Ages 11-64
Results:
• Elicited robust immune responses to all antigens
• No differences observed in side effects in 2
vaccines groups
Pinchicherio et al. JAMA 2005:293(24) 3003
Immunogenicity and Safety Study
• Prospective, randomized, double blinded trial
comparing safety and efficacy of dT and DTaP
• 4480 participants enrolled
– Ages 11-64
– 39 US centers
• Results
– Elicited robust immune responses to all antigens
Pinchicherio et al. JAMA 2005:293(24) 3003
Pertussis: Bottom line
• DTaP – 2 vaccines licensed 2005 by FDA
– Adcel* ages 11 to 65
– Boostrix ages 11-19
• ACIP recommendations/most cost effective
– Ages 11-12 give DTaP instead of dT
– Ages 11-18 give DTaP even if dT given
• 5 year interval recommended
* Used in JAMA study
Pertussis: Bottom line (cont.)
Watch for ACIP recommendations for older
adults
– Universal (using DTaP instead of dT for all) vs.
“High risk-groups” (health care workers, those
in contact with infants)
– Economic issue
Hurricane Katrina: Evacuees in
crowded settings
• Influenza -all > 6 months
– < 8 years old need 2 doses
• Hepatitis A -all > 6 months
• Varicella, MMR, dT (DTaP) ,
meningococcal, pneumococcus
– Usual recommendations
Hurricane Katrina
• Evacuees not in crowded settings
– Usual recommendations
• Responders
– dT and Hepatitis B
Varicella
• Vaccine recommendations
– Who:
• Age >18 lacking history of chicken pox or
documentation of prior vaccination
– Schedule:
• 2 doses
• 0, 4-8 weeks
– Characteristics:
• Oka/Merck VZV vaccine – 1350 plaque-forming units
• IM injection
Varicella Zoster
• Epidemiology
– Prevalence
• 15% of the population
– Incidence
• 74 per 100,000 age < 10
• 300 per 100,000 age 35-44
• 1200 per 100,000 age >75
Donahue JG, et al. Arch Intern Med 1995;155: 1605-1609.
Varicella Zoster
• Epidemiology
– Incidence and severity increase with advancing
age
• Half of those who develop zoster are > 60 years old
• 36.6% of those > 60 have persistent pain > 1 year
• 47.5% of those > 70 have persistent pain > 1 year
De Moragas JM and Kierland RR. AMA Arch Derm 1957;75:193-196.
Varicella Zoster
• Clinical Features
– Unilateral radicular pain and vesicular rash
usually limited to a single dermatome
– Results from reactivation of latent VZV within
the sensory ganglia
Varicella Zoster
• Vaccine administration:
– Live attenuated VZV vaccine
• 18,700 to 60,000 plaque-forming units of virus
– (1350 p-f units in VZV vaccine for children)
– Higher dosage necessary to elicit a significant increase in
cell-mediated immunity to VZV among older adults
– One subcutaneous injection
Varicella Zoster
• Efficacy
– Recent Randomized Controlled Trial in NEJM:
• 38,546 adults age 60 or older
• Administered adult VZV vaccine
• Primary endpoint: burden of illness due to herpes
zoster (incidence, severity and duration of pain)
• Secondary endpoint: incidence of postherpetic
neuralgia
Oxman MN, et al. NEJM;352(22):2271-2284.
Results
Vaccine
Cases of Zoster
315
Placebo
642
51.3%
Cases of Postherpetic Neuralgia
27
80
66.5 %
Oxman MN, et al. NEJM;352(22):2271-2284.
Varicella Zoster
• Safety
– Adverse events equal between placebo and
vaccine groups
– Greater chance of adverse events at injection
site with vaccine (48% vaccine, 17% placebo)
•
•
•
•
Erythema – 35.8%
Pain – 34.5%
Swelling – 26.2%
Pruritis – 7.1%
Oxman MN, et al. NEJM;352(22):2271-2284.
Varicella Zoster
• Vaccine recommendations
– Pending FDA approval
• Submitted in April 2005
– No current recommendations to use existing
Varivax for prevention of Zoster
– Unclear whether the higher dosage vaccine is
necessary for zoster prevention
Human Papillomavirus
Cervical cancer
• United states
– 10,000+ cases
– 3700 deaths
• In women worldwide…
– Third most common cancer
– Most common cause of cancer death
Age –adjusted SEER
Cervical Cancer 1996-2000
Race/Ethnicity
Incidence*
Mortality*
All races
9.6
3.0
White Non-Hispanic
7.6
2.6
Black
12.4
5.9
Asian/Pacific Islander
10.2
2.9
Amer Ind/Alaska Nat
6.9
2.9
Hispanic
16.8
3.7
On the horizon: HPV vaccine
• Two vaccines in phase 3 trials
– Cervarix- bivalent
• HPV 16 and 18 (cervical and anogenital cancer)
• women ages 15-25
– Gardasil- quadrivalent
•
•
•
•
HPV 16 and 18
HPV 6 and 11 (anogenital warts)
Men and women ages 15-25
Possibly submit FDA request October 2005
HPV vaccines
• Phase 2 trial bivalent HPV vaccine (16/18)
• 1,113 women for 18 months
• Results
– Efficacy persistent infection type 16: 93.9%
• Decreased cytological changes 95.2%
– Efficacy persistent infection type 18: 100%
• Decreased cytological changes 91.2%
Harper et al. Lancet 2004;364:1757
HPV vaccines
• Phase 2 trial quadrivalent HPV vaccine
(16/18/6/11)
• 552 women
• Results
– Persistent infection, cervical atypia or external
genital lesions was decreased by 90% compared
to control group
Villa et al. Lancet Onc 2005; 6:5: 271
HPV vaccine
• Likely primary preventive efforts will target
pre-adolescent (age 11)
– Age 15- median age of sexual activity in US
• Both vaccines require 3 doses in 6 months
On the horizon: HIV vaccine
• February 2003 failed Phase 3 trial
• Currently two phase 2 trials are underway
– Not primary prevention
– Prevent/limit viral replication and delay disease
progression
How long it takes…..
Disease
Years from organism
identification to vaccine
Typhoid
105
Haemophilus influenza
92
Pertussis
89
Polio
47
Measles
42
Hepatitis B
16
Markel NEJM 2005 353;8: 753