Adult Immunization:

The Need for Enhanced Utilization

By Steven Marks
November 2009
The American Council on
Science and Health
ACSH, 1995 Broadway 2nd floor,
New York, NY 10023
 THE AMERICAN COUNCIL ON SCIENCE AND HEALTH
GRATEFULLY ACKNOWLEDGES THE
CONTRIBUTIONS OF THE REVIEWERS
NAMED BELOW.

Bruce Gellin, M.D., MPH David R. Smith, M.D.

Director, National Vaccine President, SUNY Upstate
Program Office Medical University
U.S. Department of Health Prof. of Pediatrics, U.
and Human Services of Cincinnati College of
Medicine
William Paul Glezen,
M.D. Raymond A. Strikas,
Department of Microbiology M.D., FACP
and Immunology Captain, U.S. Public Health
Baylor College of Medicine Service National Vaccine
Program Office, HHS
Paul A. Offit, M.D.
The Children’s Hospital of Litjen Tan, Ph.D.
Philadelphia Director of Medicine and
University of Pennsylvania Public Health
American Medical
William Schaffner, M.D. Association
Professor and Chair, Dept.
of Preventive Medicine
Vanderbilt University
School of Medicine

ACSH accepts unrestricted grants on the condition

that it is soley responsible for the conduct of its research
and the dissemination of its work to the public. The
organization does not perform proprietary research, nor
does it accept support from individual corporations for
specific research projects. All contributions to ACSH – a
publicly funded organization under Section 501(c)(3)
of the Internal Revenue Code–are tax deductable.

Copyright © 2009 by American Council on Science

and Health. This book may not be reproduced in
whole or in part without permission. Inquire for bulk
purchases of hard copies: [email protected].
 CONTENTS

Abstract..............................................................................................................................................1

Introduction.........................................................................................................................................1

Raising Awareness, improving Access...................................................................................................2

VPDs: Characteristics, Health Impact, and Vaccination Schedules............................................................3

Influenza...........................................................................................................................................3

Pneumococcal Infections................................................................................................................... 4

Herpes Zoster...................................................................................................................................5

Human Papillomavirus....................................................................................................................... 6

Hepatitis B........................................................................................................................................7

Tetanus, Diphtheria, and Pertussis......................................................................................................8

Improving the Delivery of Adult Vaccines................................................................................................9

Toward the Future............................................................................................................................. 10

Conclusion........................................................................................................................................ 10

References........................................................................................................................................11
 Adult Immunization: The Need for Enhanced Utilization

ABSTRACT takes the lives of over 30,000 Americans, cover-

Immunization against vaccine preventable diseases age is erratic: rates of coverage range from 37% in
is one of the most important and beneficial public younger adults to almost 70% of those age 65 or
health measures available. However, utilization rates older. Among racial and ethnic minorities, utilization
among adults remain low, well below Department is even lower (Schiller 2009). These figures fall well
of Health and Human Services’ target levels. Nearly short of the goals established by the Department of
50,000 adults die each year in the U.S. from one of Health and Human Services’ (HHS) Healthy People
the 10 vaccine preventable diseases identified by 2010 program (Schaffner 2008, HHS 2001)
the Advisory Committee on Immunization Practices
of the Centers for Disease Control and Prevention. Table 1.
Adult vaccination rates and Healthy People 2010 targets
Each year, the direct (medical) and indirect (lost pro-
ductivity) costs of influenza alone top $87 billion, Disease Recent Vaccination Health People 2010
Rate (%) Goals (%)
while medical expenditures and productivity losses
Influenza
associated with hepatitis B reach $700 million. The >65 years of age 64 90
barriers to adult immunization are high and involve 18-64 years 31 60
a number of financial, informational, and operational Pneumococcal 57 90
obstacles. Vaccines are now available to prevent Tetanus, diphtheria,
pertussis
the most common diseases, including influenza, – Td 44 90
pneumococcal infections, herpes zoster, human – Tdap 2 *
papillomavirus, hepatitis B, and tetanus, diphtheria, Herpes zoster 2 *
and pertussis, although vaccination remains a low Human papilloma-
priority for both physicians and patients. To address virus 10 *
these problems, new public–private partnerships Hepatitis B
have been formed to increase awareness of the im- Dialysis patients 56 90
portance of immunization, and additional initiatives Men who have sex
are under consideration to reduce the financial and with men 13 60
operational barriers to broader vaccine delivery. Healthcare workers 75 93
*Vaccines approved subsequent to report.
INTRODUCTION Adapted from Schaffner 2008.
Although vaccination is acknowledged to be one of
Vaccine–preventable diseases cause substantial mor-
the most cost–effective public health strategies avail-
bidity and mortality, and contribute to excess health-
able to prevent many communicable viral and bacte-
care spending for medical treatment and hospitaliza-
rial infections, large numbers of Americans above
tions. Nearly 50,000 adults die each year from one
the age of 18 remain vulnerable to vaccine–prevent-
of the 10 VPDs identified by the ACIP (CMMS Adult
able diseases (VPDs). Whereas upwards of 90% of
Immunization Overview 2008). More than 6 million
children receive most of the vaccines recommended
young women are infected annually with HPV (Wein-
by the Advisory Committee on Immunization Prac-
stock 2004), and more than 1 million older Ameri-
tices (ACIP) of the Centers for Disease Control and
cans every year get herpes zoster, or shingles (CDC
Prevention (CDC) (NFID 2009), variable and gener-
2008). Furthermore, the direct and indirect costs
ally low rates of coverage are the norm for adults.
of an average seasonal outbreak of influenza alone
are estimated to be close to $10 billion (Thompson
For example, only 10% of women in the target popula-
2004) and $87 billion (Molinari 2007), respectively
tion of 18 to 26 years have been vaccinated against
(the costs of a pandemic could be even higher),
human papilloma virus (HPV), a major cause of cervi-
while medical expenditures and productivity losses
cal cancer (CDC Nat Immun Survey 2008). The rate
associated with hepatitis B reach $700 million an-
is not much higher for tetanus and diphtheria toxi-
nually (HHS 2007). Despite the ready availability of
oids; only 44% of American adults have been vacci-
clinically proven interventions to prevent a host of
nated (CDC Nat Immun Survey 2008). Even for influ-
potentially life–threatening illnesses, utilization rates
enza, the illness for which the value of immunization
by adults continue to be disappointing.
is best recognized by the public, and which annually
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 Adult Immunization: The Need for Enhanced Utilization

istics, health impact, and current immunization rec-

Table 2.
Immunizations for adults ommendations. Next, the paper describes a number
Disease Vaccines Age Group Frequency of educational and informational initiatives designed
Influenza Injectable All adults >50 yrs 1 dose to reduce the barriers to adult vaccination. Finally,
•Fluarix annually
•FluLava the report takes a brief look at new vaccines now in
•Affuria Adults age 19 – 49
with risk factors clinical development. As we shall see, the evidence
Intranasal spray
•FluMist
is overwhelming that increasing adult immunization
Pneumonia Pneumovax 23 All adults >65 yrs 1 dose
rates can improve public health, even as they reduce
and other the enormous expense of these serious, and pre-
streptococccus Adults age 19-64 1 or 2 doses
infections with risk factors ventable, diseases.
Herpes zoster Zostavax All adults >60 yrs 1 dose
(shingles)
Human Gardasil All females age 3 doses
RAISING AWARENESS, IMPROVING ACCESS
papillomavirus 19 – 25
Hepatitis B Recombivax HB
Engerix – B
All adults age 19
and above
3 doses Why do so many adults remain unvaccinated against
Tetanus, Tdap All adults age 1-time dose of
the most common VPDs? There are several barriers
diphtheria, •Boostrix
•Adacel
19 – 64 Tdap for Td to immunization; they may best be grouped as finan-
pertussis booster, then
(Whooping cough) boost with Td cial, informational, and operational.
every 10 years
All adults >65 yrs Td booster
every 10 yrs Financing. Payment for the cost and admin-
istration of adult vaccinations is frequently un-
available. Although most private insurance plans
One reason for the difference in child and adult cover-
cover recommended vaccines, many do not.
age is that vaccination regimens are well entrenched
Moreover, high deductibles and co–payments
in routine pediatric care. Another is that insurance
often discourage people from following the rec-
programs cover pediatric vaccine costs, while gov-
ommended schedules. Public sector financing is
ernment support is available for the uninsured. A third
subject to the vagaries of state and local politics.
explanation is that public schools require proof of im-
Unpublished data from the CDC showed that in
munization for enrollment. The barriers for adults,
2006, only 22 states used their resources to
on the other hand, are high. For example, adult vac-
purchase vaccines for adults (Orenstein 2007).
cination is not a high priority for many primary care
And even though upwards of 90% of Medicaid
physicians. Many people are unaware of their need
plans provide coverage of the recommended
for immunization, and providers often fail to rec-
adult vaccines, physician reimbursements vary
ommend vaccination even when indicated (Ahmed
widely between the states, ranging from $2 to
2007). Further, insurance coverage by public and
$18 per dose (Orenstein 2007). Consequently,
private payers is erratic. As a result, adults are need-
compensation often falls short of the total cost
lessly vulnerable to illness, diminished quality of life,
of the vaccine, plus back–office expenses (eg,
and death, even though new vaccines are now avail-
ordering, storage, record keeping, and adminis-
able for HPV, shingles, and combination tetanus,
tration). For seniors, although Medicare part B or
diphtheria, and pertussis (or “whooping cough”), and
D covers the recommended vaccines (influenza,
others are in the pipeline. Adults may perceive that
hepatitis A and B, shingles, and pneumoccocus)
VPDs are a matter for infants and children, and that
for adults at 65 years and above, payments fail
the health risks from common transmissible viral and
to meet the administrative costs of delivery.
bacterial infections are high only for children. The
Medicare also does not pay for establishing or
weight of epidemiological evidence, however, sug-
maintaining inventories, and physicians must pur-
gests otherwise.
chase vaccines in advance (Orenstein 2007).
This report will examine the current status of VPDs
Information. There is a general lack of aware-
in the US. It begins with an explanation of the causes
ness of the need for, and merits of, adult im-
for low rates of use and continues with a description
munization. Physicians are often unaware of the
of the most common VPDs, including their character-
recommendations, and health professionals have
2
 Adult Immunization: The Need for Enhanced Utilization

not been effective in educating the public about nizations, consumer groups, the mainstream me-
the benefits of vaccination. As a consequence, dia, and alternative delivery sites such as drug-
opportunities to inform adults about the merits of stores and supermarkets, have educated adults,
immunization and then provide vaccinations or a particularly those age 65 and above, about the
referral are missed frequently during office visits. need for immunization (NFID 2009). Supplies are
In fact, a 2007 National Foundation of Infectious usually available at an affordable price. As a re-
Diseases survey reported that although 87% of sult, utilization for seniors now approaches 70%,
respondents said they would be vaccinated if a rate substantially higher than those for most
their doctors recommended it, only 41% indicat- other VPDs.
ed they would ask to be immunized on their own
(NFID 2007). VPDs: CHARACTERISTICS, HEALTH IMPACT,
AND VACCINATION SCHEDULES
In addition, adults are often ignorant of the se- What follows is a brief description of the 8 most com-
rious health and medical problems associated mon adult VPDs and their impact on society. It also
with VPDs. At the same time, many question the includes a discussion of risk factors, health conse-
safety of available vaccines. Furthermore, the im- quences, and the ACIP’s most recent immunization
munization schedule can be difficult for some pa- recommendations. A short discussion of the relevant
tients – and even some providers – to fully com- vaccines is offered as well. For suggestions about
prehend. Those with language barriers and the sources of more information, see the sidebar “Other
elderly have particular trouble deciphering the Reliable Sources” near the end of this booklet.
recommendations. And patients are often sur-
prised to learn that booster doses are required Influenza
to maintain maximum protection. The economic and health burdens from influenza are
substantial. In addition to the direct medical costs
Operational. The American healthcare system, of more than $10 billion spent each flu season, an-
which emphasizes acute treatment, is poorly other $16 billion in lost earnings due to illness has
equipped to deliver preventive medicine to the been attributed to influenza (Molinari 2006). Among
population as a whole, especially to adults. Ac- adults over the age of 50, about 226,000 people
cess to preventive services, when they are in are hospitalized, and somewhere between 30,000
place, is limited, and neither the government nor and 40,000 Americans die as a result of pneumonia
the private sector has been able to develop a or other complications from the disease (Thompson
sustained adult–vaccine delivery infrastructure. JAMA 2003).
In particular, primary–care practices, including
those specializing in prenatal care, can be bet- Most of these serious illnesses and deaths occur in
ter used as points of vaccination. And, unlike those over the age of 65 and in the immune compro-
schools, which require immunizations records mised, the populations at the highest risk (Thomp-
as a condition of enrollment, few employers de- son JAMA 2003). Vaccination can prevent most flu–
mand the same coverage of their workers. Medi- related complications, including the exacerbation of
care and Medicaid do not require immunization coexisting illnesses.
protection as a criterion for protection as well.
Influenza is characterized by the abrupt onset of
Thus, multiple structural problems must be re- constitutional and respiratory symptoms such as
solved before immunization rates begin to ap- fever, myalgia, headache, malaise, nonproductive
proach the targets established by public health cough, sore throat, and rhinitis (CDC 2008). These
officials. Yet there is one exception to this bleak symptoms typically resolve in a few days, although
analysis – influenza – and the relatively high vac- cough and malaise may linger for several weeks or
cination rates reported year in and year out can more. Influenza viral infections can lead to primary
serve as a model for how a concerted public/ influenza viral pneumonia or aggravate pre–existing
private partnership can function successfully. medical conditions, such as pulmonary or cardiac
Working together, the government, medical orga- disease. It also can lead to a number of serious com-
3
 Adult Immunization: The Need for Enhanced Utilization

plications, including: ranges from 70–90% when the match between the
antigen and the epidemic virus is high to 0–50% when
• Secondary bacterial pneumonia; it is low (Glezen 2006). Vaccine effectiveness also
• Sinusitis; is indirectly related to age: although the clinical ef-
• Otitis media; ficacy of influenza vaccines ranges from 70–90% in
• Other bacterial or viral co–infections. young adults, depending on the circulating viruses, it
falls to 17–53% in the elderly because of their dimin-
Distinguishing respiratory illnesses caused by influ- ished antibody response (Goodwin 2006). Efforts to
enza from those triggered by other pathogens us- increase the efficacy of influenza vaccines in adults
ing disease signs and symptoms is challenging. The over age 65 are focusing on such as proposed strat-
positive predictive value of clinical definitions for in- egies as the use of higher doses and adjuvants to
fluenza range from about 30% in the community to improve immune function. Overall, both the intramus-
50% in hospitalized patients (CDC 2008), although cular shot and intranasal spray are well tolerated.
one recent study from the University of Michigan
School of Public Health reported that symptoms Although influenza vaccination coverage for older
such as cough and fever positively predicted influ- adults now approaches 70%, mortality and hospital-
enza virus in 79% of those evaluated (Ohmit 2006). ization rates remain high enough to pose an ongoing
For this reason, people with respiratory symptoms public health concern (Glezen 2006). Infectious dis-
during flu season should be considered for a diagno- ease researchers have offered a variety of theories
sis of influenza and undergo laboratory confirmation for this paradox, ranging from selection bias in the
(CDC MMWR 2008). studies of vaccine effectiveness to waning immune
response in the elderly (Jackson 2006a, Jackson
The current ACIP guidelines recommend that all 2006b, Goodwin 2006). Although the controversy
adults 50 years or older receive an annual influenza remains unresolved, the fact that high morbidity and
vaccination (MMWR Guidelines 2009). Yearly vacci- mortality from influenza are reported when effective
nation also is advised for individuals between 19 and vaccines are available points to the need to develop
50 years at high risk due to medical, occupational, improved strategies for delivering influenza vac-
or lifestyle factors (including those with pre–exist- cines to the most vulnerable elderly patients (Glezen
ing heart or lung conditions), household contacts of 2006).
those at high risk. Healthcare workers, residents of
long–term care facilities, and pregnant women. Two Pneumococcal Infections
types of vaccines are available, an injectable (ie, “flu Streptococcus pneumoniae bacteria colonize the
shot”) formulation containing inactivated (killed) virus upper respiratory tract. They can be spread from
(Fluarix, GlaxoSmithKline [GSK]; FluLava, GSK; and person–to–person through contact with respira-
Affuria, CSL Biotherapies; Fluzone, Sanofi Aventis; tory droplets transmitted by coughing, sneezing, or
Fluvirin, Novartis) and a nasal spray containing live skin–to–skin contact. Autoinoculation in individuals
attenuated influenza vaccine (FluMist, MedImmune). carrying pneumococci in the upper respiratory tract
Each vaccine contains antigens from three influenza also is common. Pneumococci are the leading cause
viruses, two type A and one type B virus : an A(H3N2) of community–acquired pneumonias, bacteremia,
virus, an A(H1N1) virus, and a B virus. (The 2009 meningitis, otitis media, sinusitis, and other bacte-
swine–origin influenza is an A(H1N1) type virus.) The rial infections. Although the precise immunologic
precise formula varies from year to year, based on mechanism involved in the onset of these illnesses
the recommendation of international surveillance sci- is unknown, most patients have a predisposing con-
entists, who estimate the type and strain of virus dition, particularly chronic pulmonary, heart, or re-
likely to circulate in a given flu season. Changes in nal disease; smoking; or impaired immune function
the viral strain during each annual influenza epidemic (CDC Pink Book 2009).
explain why annual vaccinations are necessary. An-
tibodies that provide protection develop about two The most common clinical presentation of pneumo-
weeks following inoculation and persist through the coccal disease leading to hospitalization is pneumo-
influenza season (CDC 2009). Vaccine effectiveness nia. Following a short (1–3 day) incubation period,
4
 Adult Immunization: The Need for Enhanced Utilization

patients experience a rapid onset of fever and chills. highly efficacious: more than 80% of healthy adults
Other typical symptoms include chest pain, produc- develop antibodies against the vaccine serotypes
tive cough, rusty sputum, dyspnea (shortness of within two weeks. Although estimates vary, the CDC
breath), hypoxia (poor oxygenation) tachypnea (rapid reports that the vaccine prevents 60% to 70% of
breathing), tachycardia (rapid heart rate), malaise, cases of invasive disease (CDC Pink Book 2009).
and weakness (CDC Pink Book 2009).
Herpes Zoster
Even though the use of the pneumococcal vaccine Infection by the varicella zoster virus causes two dis-
in children, which is designed to protect against 7 crete clinical conditions, varicella and herpes zoster.
important pneumoccocal strains, has helped indi- The former, also known as “chicken pox,” is a con-
rectly protect their parents and grandparents (an tagious rash that typically infects children, while the
effect called “herd immunity”), pneumococcal infec- latter, commonly called “shingles,” usually emerges
tions still occur frequently in adults. About 175,000 in adults decades following an initial varicella infec-
patients are hospitalized annually for community–ac- tion as the body’s natural immunity begins to wane.
quired pneumonia, while 50,000 cases of bacte- Shingles is characterized by a localized, unilateral,
remia and 6000 of meningitis are reported each and painful skin rash, accompanied by blistering.
year (NFID Fact Sheet 2002). More important, the Clinical signs of the disease are usually preceded by
case–fatality rate from pneumococcal disease is a prodromal period marked by headache, light sen-
high, ranging from 5–7% for community–acquired sitivity, malaise, abnormal skin sensations, itching,
pneumonia to 30–80% for bacterial meningitis. Each and pain of varying severity. The rash begins with the
year about 6000 people with invasive pneumococ- appearance of erythematous lesions that develop
cal disease die; experts estimate that vaccination into clusters of clear vesicles, most commonly local-
could have prevented more than half of those deaths ized on the chest, neck, and ophthalmic regions. The
(see below). Unless vaccination utilization improves, rash typically lasts 7–10 days, with complete reso-
the mortality rate is expected to rise in the future lution occurring within 2–4 weeks in most cases.
as the incidence of antibiotic resistance increases. However, changes in pigmentation and scarring may
Although the current rate of coverage has reached be permanent. The primary risk factor for shingles
nearly 60% among adults above age 65 as a result is increasing age (above 60 years). Women, Cauca-
of efforts to raise awareness, that figure is still far sians, and individuals with a pre–existing inflamma-
too short of the 2010 goal of 90%. tory or immunodeficiency condition, such as human
immunodeficiency virus (HIV) or cancer, also have an
All adults above age 65 without evidence of immu- elevated risk (CDC MMWR 2008).
nity (ie, documentation of prior immunization or evi-
dence of prior infection) should receive the 23–valent The most debilitating complication of shingles is
polysaccharide pneumococcal vaccine (PPSV23 or postherpetic neuralgia (PHN), a persistent pain that
Pneumovax 23, Merck) (see Table 1, above). Vacci- follows the resolution of the rash. PHN is believed to
nation is also recommended for younger adults (<65 be a consequence of neuronal (axonal) cell damage
years) who are immunocompromised, residents of in the central nervous system stemming from ongo-
long–term care facilities, or those at high risk for ing viral replication. Pain related to PHN may con-
pneumococcal disease (eg, people with chronic car- tinue for weeks, months, and even years. Shingles
diovascular, liver, or pulmonary diseases; diabetes patients with severe pain, an extreme rash, or most
mellitus; functional or anatomic asplenia [eg, sickle important, advanced age have the greatest likelihood
cell disease]; or other immunocompromising condi- of developing PHN. Between 10% and 25% of her-
tion). Although antibody levels decline after 5–10 pes zoster patients may also have eye involvement,
years, the current evidence does not demonstrate a condition known as “herpes zoster ophthalmicus,”
a benefit from revaccination except for selected per- which includes various ocular disorders (CDC MMWR
sons with rapid antibody loss or at very high risk of 2008). In some cases, herpes zoster eye infection
pneumococcal infection (CDC MMWR 2009). may cause vision loss due to corneal scarring.

In general, the PPSV23 vaccine is well tolerated and Postherpetic neuralgia can have pronounced effects
5
 Adult Immunization: The Need for Enhanced Utilization

on quality of life, disturbing daily activities and alter- insurance plans still fail to cover this vaccine and its
ing one’s mental and physical health and well being. inclusion under Medicare Part D presents great dif-
Although antiviral therapy can minimize the severity of ficulties in providing the vaccine.
shingles if used immediately after the rash appears,
the treatment does not prevent PHN. Other drugs Human Papillomavirus
that are used for PHN, such as anticonvulsants, an- Human papillomavirus (HPV) is the most common
tidepressants, and topical ointments, provide only sexually transmitted infection in the US and the pri-
partial relief and are associated with side effects of mary cause of cervical cancer in women. About 20
their own, especially in older adults. million Americans are already infected and, each
year, about 6.2 million people acquire HPV. The in-
Although not a reportable disease, shingles is esti- fection is most common in adolescents and young
mated to affect about 1 million American adults each adults, with up to 75% of new infections occurring
year (CDC MMWR 2008). Difficulties in distinguishing among persons from 15 to 24 years of age. Over-
cases in which zoster was the cause of or incidental all, about 65% of women and 27% of men are in-
to hospital admission make precise hospitalization fected with the virus (CDC MMWR 2008), The CDC
rates hard to determine. Mortality is rarely seen in estimates that about $4 billion a year is spent on
healthy adults; those deaths that do occur are found managing the medical consequences of HPV infec-
mainly in patients above age 65. tion, a figure greater than the economic burden of
all other sexually transmitted infections save for HIV
The herpes zoster vaccine (Zostavax, Merck) can re- (CDC MMWR 2008)
duce the risk of shingles, PHN, disfiguring scarring, Different types of HPV carry different risks, so the vi-
bacterial superinfections, vision–altering complica- rus is classified according to its oncogenic (cancer–
tions of the eye, as well as the severity and duration causing) potential: high–risk or low–risk. The two
of the disease. The vaccine has a favorable side–ef- most common types of high–risk HPV (types 16 and
fect profile (the most common adverse events are in- 18) trigger many cervical, anogenital (vulvar, anal,
jection–site reactions and headaches) and has been penile), and oral cancers. For instance, squamous
shown to reduce the burden of illness by more than cell carcinoma and adenocarcinoma, the two leading
60% and incidence of PHN by 67% (Oxman 2005). types of cervical cancer, are both caused by HPV,
Current guidelines recommend vaccination for all and 90% of anal cancers have been attributed to the
individuals age 60 or above (CDC MMWR 2009). virus (CDC MMWR 2008. Lower–risk HPV strains are
However, people who are seriously immunocompro- associated with the vast majority of cases of genital
mised (eg, those with leukemia, lymphoma, or other warts and other low–grade cervical abnormalities
bone–marrow malignancies; people with AIDS; or (Schaffner 2008).
individuals taking immunosuppressive drugs) should
not receive Zostavax. The HPV vaccine is the first to be developed explic-
itly to prevent cancer. Multiple large–scale clinical
At present, the durability of protection of Zostavax is trials have shown the quadrivalent HPV vaccine (Gar-
unknown. Ongoing longitudinal studies are expected dasil, Merck), which protects against viral types 6,
to determine whether a booster dose will be neces- 11, 16, and 18, is safe and highly immunogenic in
sary. Current rates of immunization are low, about young women (FUTURE II 2007, Garland 2007). In
2% (see Table 1, above), although experts expect these trials, vaccine efficacy ranged from 95% to
this figure to improve once patients and physicians 100%, depending on the viral type or cervical can-
become more familiar with the vaccine, which was cer precursor lesions studied. Although the trials
approved for use in 2006 (Schaffner personal com- demonstrated that Gardasil is effective in uninfect-
munication). Worth noting, too, is the recent finding ed women, they offered no evidence of efficacy in
that Zostavax can be administered in conjunction women with pre–existing infection. The vaccine also
with influenza vaccines without compromising the is safe and effective in males. Although no clinical
immune effect of either agent (Kertzner 2007). In efficacy data are available at present, clinical studies
the future, co–administration may improve coverage in young men are now underway and an application
rates in eligible patients. Unfortunately, many private for FDA approval may be filed in 2009. The most
6
 Adult Immunization: The Need for Enhanced Utilization

common side effects seen in the clinical trials were

mild–to–moderate injection–site reactions, such as The initial clinical manifestation of acute hepatitis B
pain, swelling, and erythema (FUTURE II 2007, Gar- infection is jaundice, which Is usually preceded by a
land 2007). Nausea, dizziness, myalgia, and malaise 3–10 day prodromal phase that is marked by such
also were reported, although the rates for those re- symptoms as malaise, anorexia, nausea, vomiting,
ceiving vaccine and placebo were the same. fever, headache, and right upper–quadrant abdomi-
nal pain. The icteric (jaundice) phase lasts from 1–3
Current ACIP guidelines recommend a 3–dose weeks and is characterized by the presence of light
course of HPV vaccine for all girls and women be- or gray stools and hepatic tenderness and enlarge-
tween the ages of 11 and 26, although immunization ment. Feelings of malaise and fatigue often persist
can begin as early as age 9 (see Table 1, above). for weeks and months during the recovery period,
The vaccine can be administered at the same time while other symptoms (eg, jaundice and anorexia)
as others suggested for this cohort (eg, Tdap, me- resolve (CDC Pink Book 2009).
ningococcal conjugate, hepatitis B). Older women up
to age 45 who are sexually active might also benefit Most acute HBV infections result in full recovery. In
from vaccination, although the vaccine is not yet ap- these cases, anti–HBs antibodies are produced, pro-
proved for these adults. All women receiving Gardasil viding lifetime immunity. However, 1–2% of patients
should be given the second and third doses at 2 and with acute infection develop fulminant hepatitis, 63–
6 months, respectively, following the initial injection. 93% of whom (200–300 Americans) die from the dis-
A bivalent HPV vaccine, developed by GSK, Cervarix, ease. About 5% of acute HBV infections develop into
has proven effective and been approved in the EU; chronic hepatitis B, with the highest risk occurring
it is expected to be distributed here within the next in younger patients. In fact, nearly 90% of infants
year or so. who are infected perinatally will become chronically
infected. As noted above cirrhosis and liver cancer
Hepatitis B are the most serious consequences of chronic HBV
Hepatitis B is a leading cause of liver diseases, includ- infection; thus the HBV vaccine should be seen as
ing chronic hepatitis, cirrhosis, and liver cancer. HBV another vaccine to prevent cancer. Up to 25% of
is transmitted through the blood and serous fluids via chronic carriers of HBV will die prematurely from ei-
sexual activity, exposure to contaminated needles, ther of these conditions, an estimated 1000 to 1500
transfusions, and from mother to child at birth. In- persons a year in the US (CDC MMWR 2008)
deed, perinatal transmission is highly efficient – 70–
90% of all infants born to mothers who are positive There is no cure for chronic hepatitis B. Thus, com-
for two hepatitis B antigens (HBsAg and HBeAg) will pletion of the 3–dose HBV vaccination series (Re-
become infected without postnatal vaccination (pro- combivax HB, Merck; Engerix–B, GSK) is the best
phylaxis) (CDC MMWR 2008), Healthcare workers, means of prevention; more than 90% of healthy
people getting tattoos, and household contacts of adults who complete the course develop antibody
people with chronic HBV are also at increased risk, responses. Immunogenicity declines with age, how-
as are those who engage in sexual intercourse with ever, so that by age 60, only 75% of vaccinated
multiple partners and inadequate protection. Public individuals develop protective antibody titers (CDC
health officials estimate that more than 1.25 million MMWR 2008). The first two doses should be given
Americans are infected with HBV, with 5000 to 8000 at least 4 weeks apart, followed by the final injection
new cases reported each year (CDC 2007). Thanks 4 to 6 months later. Booster doses are not recom-
to mandatory infant and child vaccination, as well as mended for adults with normal immune status. The
measures to decrease HIV/AIDS transmission, the most common side effects of vaccination are injec-
incidence of acute hepatitis B has declined by 75% tion–site reactions and mild fatigue, headache, and
since 1990. The highest rate of new hepatitis B in- irritability (CDC Pink Book 2009).
fections occurs in adults aged 25 – 45 years, nearly
80% of whom are known to engage in the high–risk At present, only 35% of adults in the critical 18–to–
sexual behaviors or use injection drugs (CDC MMWR 49 age group have been immunized. Higher rates of
2008). coverage (about 45%) (Schaffner 2008) are seen in
7
 Adult Immunization: The Need for Enhanced Utilization

healthcare workers or in those with an elevated risk The incidence of tetanus and diphtheria in the US
due to lifestyle choices, but the numbers are still far is very low due to the availability of effective vac-
below public health goals (see Table 1, above). In cines. Since 2000, the number of cases of tetanus
an effort to improve utilization, the ACIP now rec- reported yearly has been about 30, 73% of which
ommends vaccination for: (a) all sexually active in- followed acute injury or wounds. For diphtheria, the
dividuals who are not in a long–term monogamous corresponding figure is 1 (CDC MMWR 2008). In con-
relationship, or (b) for those seeking evaluation or trast, the annual incidence of pertussis reached a
treatment for a sexually transmitted disease (MMWR low of 2,900 cases during the period 1980–1990.
2009). Since then, the rate has been increasing, reaching a
high of 25,827 cases in 2004, the largest number
Tetanus, Diphtheria, and Pertussis since 1959. The reasons for the rising frequency are
Although unrelated, these three bacterial diseases uncertain, although waning immunity may be a con-
will be discussed together, as all can be prevented tributing factor. Although many pertussis patients
by the same combination vaccine, Tdap (Boostrix, are infants or young children, about 60% of reported
GSK; Adacel, sanofi pasteur). The two approved ap- cases occur in persons above age 11. The higher
proved formulations will be reviewed below as well. incidence in older individuals has been attributed to
Tetanus is an acute, often fatal illness caused by a increased recognition and diagnosis in this cohort
toxin produced by the bacterium Clostridium tetani (CDC MMWR 2008).
(“lockjaw”). The disease is characterized by general-
ized rigidity and convulsive muscle spasms, initially Vaccination with either Tdap vaccine – Boostrix or
involving the jaw and neck and then descending Adacel – is the best way to prevent these 3 bacterial
downward through the body. Other symptoms in- infections. The vaccines are effective and extremely
clude fever, elevated heart rate and blood pressure, well tolerated, with the most common side effects
and sweating. Tetanus can interfere with breathing, being local reactions at the injection site (eg, pain,
produce bone fractures from sustained convulsions, redness, swelling), mild fever, and headache. Boost-
and lead to essential hypertension (CDC MMWR rix and Adacel are FDA approved for a single booster
2008). dose for older children and adults (10–64 years for
Boostrix, 11–64 for Adacel) who completed the rec-
Diphtheria is another acute toxin–mediated illness ommended childhood DTP/DTaP vaccination series.
provoked by the microbe Cornybacterium diphthe- The ACIP recommends that adults aged 19 to 64
riae. Toxigenic bacilli typically are acquired in the na- years receive a single dose of Tdap for booster im-
sopharynx and then absorbed into the bloodstream, munization against tetanus, diphtheria, and pertus-
whence they are disseminated throughout the body. sis after a period of no more than 10 years following
The toxin produced by these bacilli are responsible administration of the last tetanus toxoid–containing
for the major complications of diphtheria, including vaccine (MMWR 2009). This schedule is especially
myocarditis, neuritis, proteinuria, and thrombocyto- important for adults who have close contact with in-
penia (low platelet count) (CDC MMWR 2008). fants, such as childcare or healthcare workers and
parents. In sum, all adolescents and adults should
The third disease covered by the combination Tdap have documented completion of at least 3 doses of
vaccine is pertussis (whooping cough), an infec- tetanus and diphtheria toxoids during their lifetime.
tion caused by the bacterium Bordetella pertussis. Individuals without this documentation should be
The bacteria bind with cilia on lung epithelial cells, given a 3–dose course, the first of which should be
leading to inflammation of the respiratory tract and Boosterix or Adacel and the remaining two should
impaired clearance of pulmonary secretions. Pertus- be adult formulation Td (tetanus/diphtheria) (MMWR
sis is highly communicable, with secondary attack 2009).
rates of 80% in susceptible household contacts,
and is most severe in younger adults and children. IMPROVING THE DELIVERY OF
The most common complication of pertussis, and ADULT VACCINES
the leading cause of death, is secondary pneumonia As we have seen, even though effective and safe
(CDC MMWR 2008). vaccines are available, the system for immunizing
8
 Adult Immunization: The Need for Enhanced Utilization

adults is less than ideal. On the demand side, pa- site, www.adultvaccination.com, includes portals
tients do not request vaccinations during visits to with links to fact sheets, immunization schedules,
their doctors, and physicians do not aggressively along with other background information on the
promote their use. Employers do not require proof role of vaccines in improving health and quality of
of immunization as a condition of work. Private in- life.
surance coverage is inconsistent, and public sector
financing often falls below the cost of the vaccine • The US Preventive Services Task Force, which
plus back–office expenses. On the supply side, the has issued recommendations to improve vacci-
availability of vaccines, particularly those for influen- nation uptake (http://www.thecommunityguide.
za, can be erratic, and when supplies are on hand, org/vaccines/universally/index.html). These in-
physicians often lack the facilities (eg, refrigerators clude the use of such tactics as standing orders,
and supply space) to store them. There is substan- reminder recall, and home medical visits to in-
tial wastage as well. For instance, each year, many crease utilization rates.
millions of doses of influenza vaccine are returned
to the manufacturer for credit or scrapped as medi- These initiatives are the first wave of novel programs
cal waste. In 2008, about 29 million vials had to be developed to overhaul the adult immunization infra-
discarded (Aleccia 2009). structure. Other approaches under consideration in-
clude model insurance contracts providing payment
To help address these issues, a number of medical for all ACIP vaccines, vouchers to patients to guaran-
professional societies have endorsed programs and tee payment, liability protection for pharmaceutical
protocols to heighten awareness of the importance companies, new research to gather data on the true
of adult immunization. Among them are: costs of vaccine delivery, deferred payment plans
for vaccine purchasers, and manufacturer/govern-
• The Institute of Medicine, which published a ment “buy–back” of unused influenza vaccine fol-
set of recommendations to improve the vaccine lowing flu season. Several of the current legislative
infrastructure, enhance government funding and proposals to re–structure US health care guarantee
purchasing of adult vaccines, and assess public “first–dollar” coverage for adult immunizations, as
and private sector immunization performance. recommended by the ACIP.

• The Infectious Diseases Society of America Taken together, these proposals have several objec-
(IDSA) and American College of Physicians (ACP), tives. In addition to bolstering the immunization of
which issued a joint statement to their members adults against VPDs, they also have a broader pur-
stressing the importance of adult immunization pose – to shift our thinking about healthcare delivery
against VPDs. from one grounded in acute–care treatment to one
focused on disease prevention. Such a change in
• The Partnership for Prevention, a group of emphasis will undeniably contribute to lower rates
corporations, non–profit organizations, medi- of morbidity and mortality. However, the short–term
cal and health professional societies, and gov- costs of such care may be considerable, even if the
ernment agencies active in promoting disease long–term savings justify the change. Whether such
prevention, which has developed a set of policy an approach will prove viable may well depend on
recommendations to improve the vaccine infra- the contours of the debate on healthcare reform now
structure; underway and the shape of the legislation that ulti-
mately emerges from Congress.
• The National Foundation for Infectious Dis-
eases, along with several other interest groups,
governmental agencies (eg, the CDC), and the
lobbying group American Association of Retired TOWARD THE FUTURE
Persons, recently launched a public and health Newer vaccines, such as those for HPV, HBV, and
professional education program on adult immuni- herpes zoster, have the potential to reduce morbid-
zation called “Saving Lives.” The program’s Web- ity and mortality from a host of serious infectious
9
 Adult Immunization: The Need for Enhanced Utilization

diseases and their sequelae. Looking ahead, phar- sons, our system does a poor job of delivering them
maceutical companies are exploring the safety and to the populations in need of vaccination.
effectiveness of a number of additional vaccine can-
didates and strategies. First to arrive will likely be The pharmaceutical industry has brought to market
improved influenza vaccines. These could include a wide array of vaccines to prevent a number of seri-
more potent vaccines to better protect high–risk ous infectious diseases, and new and improved prod-
adults and people who are immunocompromised, ucts are on the way. Although the pediatric vaccine
as well as those that trigger a stronger immune re- infrastructure is not perfect, it has been highly effec-
sponse. Also on the horizon is the availability of im- tive, although a few parents still refuse to vaccinate
proved pneumococcal conjugate vacccines that will their children due to unwarranted concerns about
allow protection against more bacterial strains. For vaccine safety (Omer 2009). For adults, the story
example, Wyeth is developing a new formulation that is dramatically different, with gaps in perception, un-
will provide coverage against the 13 most prevalent derstanding, delivery, administration, and financing
serotypes associated with pneumococcal disease causing low rates of coverage that fall well short of
(Wyeth 2009); FDA licensing is anticipated in the current public health targets. Today, infectious dis-
near future. At earlier stages of development are ease specialists from the public and private sectors
vaccines to protect against herpes simplex; staph- are joining together to try to resolve some of these
ylococcal (S. aureus) infections, including possibly outstanding issues. If these programs are success-
methicillin–resistant staphylococcus aureus (MRSA); ful, a growing number of adults may come to benefit
and traveler’s diarrhea. Unfortunately, a vaccine to from the protection afforded them by these safe and
prevent HIV remains elusive, as are those against potent vaccines.
malaria and tuberculosis, two diseases that continue
to ravage the developing world.

CONCLUSION
Despite serving as the pharmaceutical foundry of
the world and the leader in the development of new
medical technologies, the US often fails to allocate
its healthcare resources efficiently. This observation
is especially apt in the case of adult immunization.
The vaccines are available. But for a variety of rea-

Figure 1. Recommended adult immunization schedule by vaccine and age group – United States, 2009
Vaccine Age Group 19 – 26 27 – 49 50 – 59 60 – 64 >64
1,* Td booster
Tetanus, diphtheria, pertussis (Td/Tdap) Substitute 1 – time dose of Tdap or Td booster; then boost with Td for 10 years every 10 yrs
2,*
Human papillomavirus (HPV) 3 doses (females)

Varicella
3,* 2 doses

Zoster
4 1 dose
5,*
Measles, Munps, Rubella (MMR) 1 or 2 doses 1 dose
6,*
Influenza 1 dose annually
7,8
Pneumoccal 1 or 2 doses 1 dose
9,*
Hepatitis A 2 doses
10,*
Hepatitis B 3 doses
11,*
Menningococcal 1 or more doses
For all persons in this catagory who meet the age Recommended if some other risk factor is
*Covered by the Vaccine Inquiry No recommendation
requirements and who lack evidence of immunity present (e.g., on the basis of medical,
Compensation Program
(e.g., lack documentation of vaccination or have occupational, lifestyle, or other indications)
no evidence of prior infection)

10
 Adult Immunization: The Need for Enhanced Utilization

OTHER RELIABLE SOURCES Steven Marks would like to thank

Litjen (LJ) Tan, William Schaffner, Lisa Jack-
The Website of the Centers for Disease Control and Preven- son, and W. Paul Glezen, four leaders in the
tion (CDC) is an excellent source of reliable information on field of infectious diseases, who offered their
adult vaccination. time, shared their perspectives, and thus
helped ensure that this report would be accu-
http://www.cdc.gov/vaccines rate and useful for readers.
Once there, you can also click on the CDC’s vaccination
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 Adult Immunization: The Need for Enhanced Utilization

W. Lawrence Beeson, Morris E. Chafetz, M.D. Merle L. Diamond, M.D.

ACSH BOARD OF TRUSTEES Dr.P.H. Health Education Foundation Diamond Headache Clinic
Loma Linda University
Sam K. C. Chang, Ph.D. Seymour Diamond, M.D.
Nigel Bark, M.D. Elizabeth McCaughey, Ph.D. Elizabeth Rose Sir Colin Berry, D.Sc., Ph.D., North Dakota State University Diamond Headache Clinic
Albert Einstein College of Medicine Committee to Reduce Infection Aim High Productions M.D.
Deaths Institute of Pathology, Royal Bruce M. Chassy, Ph.D. Donald C. Dickson, M.S.E.E.
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University of Michigan Medical Henry I. Miller, M.D. Princeton University Urbana-Champaign
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School The Hoover Institution University of Arizona Martha A. Churchill, Esq. Houston, TX
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M.P.H The New York Academy of Kaiser-Permanente Vaccine Study Emil William Chynn, M.D., National Council Against Health
University of California, Los Sciences, President Emeritus Harold D. Stratton, Jr., J.D. Center FACS., M.B.A. Fraud
Angeles Dykema New York Eye & Ear Infirmary
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Moody’s Corporation Kenneth M. Prager, M.D. The Menninger Clinic (ret.) University of California, Davis
Columbia University Medical Center Hinrich L. Bohn, Ph.D. Theron W. Downes, Ph.D.
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Massachusetts Institute of George A. Bray, M.D. University of Pittsburgh
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Center John J. Cohrssen, Esq. Toronto Center
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Consultants, Inc. Center
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Julie A. Albrecht, Ph.D. University of California, San International Medical Consultation Ercole L. Cavalieri, D.Sc. University of Illinois, Edward A. Emken, Ph.D.
University of Nebraska, Lincoln Francisco Services University of Nebraska Urbana-Chamaign Midwest Research Consultants
Philip Alcabes, Ph.D. Karl E. Anderson, M.D. Stephen Barrett, M.D. Russell N. A. Cecil, M.D., Peter C. Dedon, M.D., Ph.D. Nicki J. Engeseth, Ph.D.
Hunter College, CUNY University of Texas Medical Branch, Pittsboro, NC Ph.D. Massachusetts Institute of University of Illinois
Galveston Albany Medical College Technology
James E. Alcock, Ph.D. Thomas G. Baumgartner, Stephen K. Epstein, M.D.,
Glendon College, York University Jerome C Arnett, Jr., M.D. Pharm.D., M.Ed. Rino Cerio, M.D. Robert M. Devlin, Ph.D. M.P.P., FACEP
Elkins, WV University of Florida Barts and The London Hospital University of Massachusetts Beth Israel Deaconess Medical
Institute of Pathology Center

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 Adult Immunization: The Need for Enhanced Utilization

Myron E. Essex, D.V.M., Jay A. Gold, M.D., J.D., Robert B. Helms, Ph.D. William M. P. Klein, Ph.D. Scott O. Lilienfeld, Ph.D. Richard K. Miller, Ph.D.
Ph.D. M.P.H. American Enterprise Institute University of Pittsburgh Emory University University of Rochester
Harvard School of Public Health Medical College of Wisconsin
Zane R. Helsel, Ph.D. Ronald E. Kleinman, M.D. Floy Lilley, J.D. William J. Miller, Ph.D.
Terry D. Etherton, Ph.D. Roger E. Gold, Ph.D. Rutgers University, Cook College Massachusetts General Hospital/ Fernandina Beach, FL University of Georgia
Pennsylvania State University Texas A&M University Harvard Medical School
James D. Herbert, Ph.D. Paul J. Lioy, Ph.D. Grace P. Monaco, J.D.
R. Gregory Evans, Ph.D., Reneé M. Goodrich, Ph.D. Drexel University Leslie M. Klevay, M.D., S.D. UMDNJ-Robert Wood Johnson Medical Care Ombudsman Program
M.P.H. University of Florida in Hyg. Medical School
St. Louis University Center for the Richard M. Hoar, Ph.D. University of North Dakota School Brian E. Mondell, M.D.
Study of Bioterrorism and Emerging Frederick K. Goodwin, M.D. Williamstown, MA of Medicine and Health Sciences William M. London, Ed.D., Baltimore Headache Institute
Infections The George Washington University M.P.H.
Medical Center Theodore R. Holford, Ph.D. David M. Klurfeld, Ph.D. California State University, Los John W. Morgan, Dr.P.H.
William Evans, Ph.D. Yale University School of Medicine U.S. Department of Agriculture Angeles California Cancer Registry
University of Alabama Timothy N. Gorski, M.D.,
F.A.C.O.G. Robert M. Hollingworth, Kathryn M. Kolasa, Ph.D., Frank C. Lu, M.D., BCFE Stephen J. Moss, D.D.S.,
Daniel F. Farkas, Ph.D., University of North Texas Ph.D. R.D. Miami, FL M.S.
M.S., P.E. Michigan State University East Carolina University New York University College of
Oregon State University Ronald E. Gots, M.D., Ph.D. William M. Lunch, Ph.D. Dentistry/ Health Education
International Center for Toxicology Edward S. Horton, M.D. James S. Koopman, M.D, Oregon State University Enterprises, Inc.
Richard S. Fawcett, Ph.D. and Medicine Joslin Diabetes Center/Harvard M.P.H.
Huxley, IA Medical School University of Michigan School of Daryl B. Lund, Ph.D. Brooke T. Mossman, Ph.D.
Henry G. Grabowski, Ph.D. Public Health University of Wisconsin-Madison University of Vermont College of
Owen R. Fennema, Ph.D. Duke University Joseph H. Hotchkiss, Ph.D. Medicine
University of Wisconsin, Madison Cornell University Alan R. Kristal, Dr.P.H. John R. Lupien, M.Sc.
James Ian Gray, Ph.D. Fred Hutchinson University of Massachusetts Allison A. Muller, Pharm.D
Frederick L. Ferris, III, M.D. Michigan State University Clifford A. Hudis, M.D. Cancer Research Center The Childrenís Hospital of
National Eye Institute Memorial Sloan-Kettering Cancer Howard D. Maccabee, Ph.D., Philadelphia
William W. Greaves, M.D., Center Stephen B. Kritchevsky, M.D.
David N. Ferro, Ph.D. M.S.P.H. Ph.D. Alamo, CA Ian C. Munro, F.A.T.S.,
University of Massachusetts Medical College of Wisconsin Peter Barton Hutt, Esq. Wake Forest University Baptist Ph.D., FRCPath
Covington & Burling, LLP Medical Center Janet E. Macheledt, M.D., Cantox Health Sciences
Madelon L. Finkel, Ph.D. Kenneth Green, D.Env. M.S., M.P.H. International
Weill Medical College American Interprise Institute Susanne L. Huttner, Ph.D. Mitzi R. Krockover, M.D. Houston, TX
of Cornell University University of California, Berkeley SSB Solutions Harris M. Nagler, M.D.
Laura C. Green, Ph.D., Henry G. Manne, J.S.D. Beth Israel Medical Center/ Albert
Kenneth D. Fisher, Ph.D. D.A.B.T. Lucien R. Jacobs, M.D. Manfred Kroger, Ph.D. George Mason Einstein College of Medicine
Office of Dietary Supplements Cambridge Environmental, Inc. University of California, Pennsylvania State University University Law School
Los Angeles Daniel J. Ncayiyana, M.D.
Leonard T. Flynn, Ph.D., Richard A. Greenberg, Ph.D. Sandford F. Kuvin, M.D. Karl Maramorosch, Ph.D. Benguela Health
M.B.A. Hinsdale, IL Alejandro R. Jadad, M.D., University of Miami School of Rutgers University, Cook College
Morganville, NJ D.Phil., F.R.C.P.C. Medicine/ Hebrew University of Philip E. Nelson, Ph.D.
Sander Greenland, Dr.P.H., University of Toronto Jerusalem Judith A. Marlett, Ph.D., Purdue University
William H. Foege, M.D., M.S., M.A. R.D.
M.P.H. UCLA School of Public Health Rudolph J. Jaeger, Ph.D. Carolyn J. Lackey, Ph.D., University of Wisconsin, Madison Joyce A. Nettleton, D.Sc.,
Seattle, WA Environmental Medicine, Inc. R.D. R.D.
Gordon W. Gribble, Ph.D. North Carolina State University Lawrence J. Marnett, Ph.D. Denver, CO
Ralph W. Fogleman, D.V.M. Dartmouth College William T. Jarvis, Ph.D. Vanderbilt University
Savannah, GA Loma Linda, CA J. Clayburn LaForce, Ph.D. John S. Neuberger, Dr.P.H.
William Grierson, Ph.D. University of California, Los James R. Marshall, Ph.D. University of Kansas
Christopher H. Foreman, Jr., University of Florida Elizabeth H. Jeffery, Ph.D. Angeles Roswell Park Cancer Institute School of Medicine
Ph.D. University of Illinois, Urbana
University of Maryland F. Peter Guengerich, Ph.D. Robert G. Lahita, M.D., Roger O. McClellan, D.V.M., Gordon W. Newell, Ph.D.,
Vanderbilt University School of Geoffrey C. Kabat, Ph.D., Ph.D. M.M.S., DABT, DABVT, FATS M.S., F.-A.T.S.
Glenn W. Froning, Ph.D. Medicine M.S. Mount Sinai School of Medicine Toxicology and Risk Analysis Cupertino, CA
University of Nebraska, Lincoln Albert Einstein College of Medicine
Caryl J. Guth, M.D. James C. Lamb, IV, Ph.D., Mary H. McGrath, M.D., Thomas J. Nicholson, Ph.D.,
Vincent A. Fulginiti, M.D. Advance, NC Michael Kamrin, Ph.D. J.D., D.A.B.T. M.P.H. M.P.H.
Tucson, AZ Michigan State University The Weinberg Group University of California, San Western Kentucky University
Philip S. Guzelian, M.D. Francisco
Robert S. Gable, Ed.D., University of Colorado John B. Kaneene, D.V.M., Lawrence E. Lamb, M.D. Robert J. Nicolosi, Ph.D.
Ph.D., J.D. M.P.H., Ph.D. San Antonio, TX Alan G. McHughen, D.Phil. University of Massachusetts, Lowell
Claremont Graduate University Terryl J. Hartman, Ph.D., Michigan State University University of California, Riverside
M.P.H., R.D. William E. M. Lands, Ph.D. Steven P. Novella, M.D.
Shayne C. Gad, Ph.D., The Pennsylvania State University P. Andrew Karam, Ph.D., College Park, MD James D. McKean, D.V.M., Yale University School of Medicine
D.A.B.T., A.T.S. CHP J.D.
Gad Consulting Services Clare M. Hasler, Ph.D. MJW Corporation Lillian Langseth, Dr.P.H. Iowa State University James L. Oblinger, Ph.D.
The Robert Mondavi Institute of Lyda Associates, Inc. North Carolina State University
William G. Gaines, Jr., M.D., Wine and Food Science, University Kathryn E. Kelly, Dr.P.H. Joseph P. McMenamin,
M.P.H. of California, Davis Delta Toxicology Brian A. Larkins, Ph.D. M.D., J.D. Paul A. Offit, M.D.
College Station, TX University of Arizona McGuireWoods, LLP The Childrenís Hospital of
Virgil W. Hays, Ph.D. George R. Kerr, M.D. Philadelphia
Charles O. Gallina, Ph.D. University of Kentucky University of Texas, Houston Larry Laudan, Ph.D. Patrick J. Michaels, Ph.D.
Professional Nuclear Associates National Autonomous University of University of Virginia John Patrick OíGrady, M.D.
Cheryl G. Healton, Dr.PH. George A. Keyworth II, Ph.D. Mexico Tufts University School of Medicine
Raymond Gambino, M.D. Mailman School of Public Health of Progress and Freedom Foundation Thomas H. Milby, M.D.,
Quest Diagnostics Incorporated Columbia University Tom B. Leamon, Ph.D. M.P.H. James E. Oldfield, Ph.D.
F. Scott Kieff, J.D. Liberty Mutual Insurance Company Walnut Creek, CA Oregon State University
J. Bernard L. Gee, M.D. Clark W. Heath, Jr., M.D. Washington University School of
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K. H. Ginzel, M.D. Brown University Michael Kirsch, M.D. Enterprises, Inc. Durham, NH University of Nevada, Reno
University of Arkansas for Medical Highland Heights, OH
Science Robert Heimer, Ph.D. Brian C. Lentle, MD., Richard A. Miller, M.D. Michael T. Osterholm,
Yale School of Public Health John C. Kirschman, Ph.D. FRCPC, DMRD Pharmacyclics, Inc. Ph.D., M.P.H.
William Paul Glezen, M.D. Allentown, PA University of British Columbia University of Minnesota
Baylor College of Medicine

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 Adult Immunization: The Need for Enhanced Utilization

Michael W. Pariza, Ph.D. Steven T. Rosen, M.D. Anne M. Smith, Ph.D., R.D., Willard J. Visek, M.D., Ph.D. Steven D. Wexner, M.D. Carl K. Winter, Ph.D.
University of Wisconsin, Madison Northwestern University L.D. University of Illinois Cleveland Clinic Florida University of California, Davis
Medical School Ohio State University College of Medicine
Stuart Patton, Ph.D. Joel Elliot White, M.D., James J. Worman, Ph.D.
Pennsylvania State University Stanley Rothman, Ph.D. Gary C. Smith, Ph.D. Lynn Waishwell, Ph.D., F.A.C.R. Rochester Institute of Technology
Smith College Colorado State University C.H.E.S. Danville, CA
James Marc Perrin, M.D. University of Medicine Russell S. Worrall, O.D.
Mass General Hospital for Children Stephen H. Safe, D.Phil. John N. Sofos, Ph.D. and Dentistry of New Jersey, John S. White, Ph.D. University of California, Berkeley
Texas A&M University Colorado State University School of Public Health White Technical Research
Jay Phelan, M.D. S. Stanley Young, Ph.D.
Wyle Integrated Science and Wallace I. Sampson, M.D. Laszlo P.Somogyi, Ph.D. Brian Wansink, Ph.D. Kenneth L. White, Ph.D. National Institute of Statistical
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Leonard T. Sperry, M.D., Christopher F. Wilkinson,
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Ph.D. Purdue University Florida Atlantic University New York Medical College Wilmington, NC Nutrition Institute,
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Sally L. Satel, M.D. Robert A. Squire, D.V.M., Janet S. Weiss, M.D. Mark L. Willenbring, M.D.,
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University of Illinois, Johns Hopkins University National Institute on Alcohol Abuse University of Iowa
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Gary P. Posner, M.D.
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David W. Ramey, D.V.M. Patrick J. Shea, Ph.D. University of Minnesota
Ramey Equine Group University of Nebraska, Lincoln
Dick Taverne
R.T. Ravenholt, M.D., M.P.H. Michael B. Shermer, Ph.D. House of Lords, UK
Population Health Imperatives Skeptic Magazine
Steve L. Taylor, Ph.D.
Russel J. Reiter, Ph.D. Sidney Shindell, M.D., LL.B. University of Nebraska, Lincoln
University of Texas, San Antonio Medical College of Wisconsin
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William O. Robertson, M.D. Sarah Short, Ph.D., Ed.D., Townsend and Townsend
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The United States Pharmacopeia University of Arizona
Michael S. Simon, M.D.,
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Michigan State University Wayne State University Mark J. Utell, M.D.
S. Fred Singer, Ph.D. University of Rochester
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