Vaccines: The Week in Review

28 December 2009 – 4 January 2010

Center for Vaccine Ethics & Policy
http://www.centerforvaccineethicsandpolicy.org/
A program of
- Center for Bioethics, University of Pennsylvania
http://www.bioethics.upenn.edu/
- The Wistar Institute Vaccine Center
http://www.wistar.org/vaccinecenter/default.html
- Children’s Hospital of Philadelphia, Vaccine Education Center
http://www.chop.edu/consumer/jsp/microsite/microsite.jsp

This weekly summary targets news and events in the global vaccines field gathered
from key governmental, NGO and company announcements, key journals and
events. This summary provides support for ongoing initiatives of the Center for
Vaccine Ethics & Policy, and is not intended to be exhaustive in its coverage.
Vaccines: The Week in Review is now also posted in a blog format at
http://centerforvaccineethicsandpolicy.wordpress.com/. Each item is treated as an individual
post on the blog, allowing for more effective retrospective searching. Given email
system conventions and formats, you may find this alternative more effective. This
blog also allows for RSS feeds, etc.
Comments and suggestions should be directed to David Curry, Editor and
Executive Director of the Center, at
david.r.curry@centerforvaccineethicsandpolicy.org. We also invite you to visit
VaccineEthics.org www.vaccineethics.org/ which complements this weekly review
and is edited by Jason Schwartz, MBE, Center for Bioethics.

Editors Note:
We resume weekly publication after a holiday break. Also, please be aware of
the searchable resource we have been building since last March wherein the
items in each weekly update are treated as a separate “posts”. Over 500 of
these posts are now searchable providing a convenient way to retrieve news
stories, journal article citations/abstracts, etc. Please visit this “blog” version
at http://centerforvaccineethicsandpolicy.wordpress.com/

The WHO continues to issue weekly “updates” and briefing notes on the
H1N1 pandemic at: http://www.who.int/csr/disease/swineflu/en/index.html
The Pandemic (H1N1) 2009 vaccine deployment update - 23
December 2009 notes that “the Director-General has called for international
solidarity to provide equitable access to pandemic influenza vaccine for all
countries. Final preparations are underway to distribute donated pandemic
influenza vaccines to 95 low- and middle-income countries to help prevent
severe disease.”
Current situation:
1. All of the first 35 countries have requested vaccine donations.
2. 23 have signed agreements with WHO.
3. 6 have finalized National Deployment Plans.
Azerbaijan and Mongolia are reported as the first countries actually
scheduled to receive vaccine with estimated delivery dates in January 2010.
http://www.who.int/csr/disease/swineflu/vaccines/h1n1_vaccination_deployme
nt_update_20091223.pdf

The WHO issued “2009 in review: key health issues, December

2009” as a “photo feature.” The overview noted:
“In 2009, the emergence of the new H1N1 influenza virus saw the world
brace itself for the first influenza pandemic since 1968. This was with the
backdrop of the global financial crisis, that could negatively impact spending
on health.
“Yet 2009 also saw H1N1 vaccines becoming available, global responses
under way to support developing countries from the health effects of the
financial crisis, and global action for public health being recognized.
“WHO and UNICEF launched new plans to tackle the two biggest child killers
– pneumonia and diarrhoea, and the number of people receiving antiretroviral
therapy in low- and middle-income countries topped four million. Making
hospitals safe in emergencies, a new look at women’s health, global health
risks, and progress towards tackling malaria also made news in 2009.
http://www.who.int/features/2009/year_review2009/en/index.html

The WHO released the World Malaria Report 2009 on 15 December

2009, noting that “half of the world's population is at risk of malaria, and an
estimated 243 million cases led to nearly 863,000 deaths in 2008. The advent
of long-lasting insecticidal nets and artemisinin-based combination therapy,
plus a revival of support for indoor residual spraying of insecticide, presents a
new opportunity for large-scale malaria control. The World Malaria Report
2009 describes the global distribution of cases and deaths, how WHO-
recommended control strategies have been adopted and implemented in
endemic countries, sources of funding for malaria control, and recent
evidence that prevention and treatment can alleviate the burden of disease.
http://www.who.int/malaria/publications/atoz/9789241563901/en/index.html

Merck announced that Dr. Julie Gerberding will become president

of Merck Vaccines effective January 25, 2010. Dr. Gerberding led the
Centers for Disease Control and Prevention (CDC) as director from 2002 to
2009. Merck chairman and CEO Richard T. Clark commented, “Vaccines are a
cornerstone of Merck's commitment to health and wellness. We are delighted
to welcome an expert of Dr. Gerberding's caliber to Merck. As a preeminent
authority in public health, infectious diseases and vaccines, Dr. Gerberding is
the ideal choice to lead Merck's engagement with organizations around the
world that share our commitment to the use of vaccines to prevent disease
and save lives." Merck said that in her new role, Dr. Gerberding will lead the
company's $5 billion global vaccine business. Merck “currently markets a
broad range of pediatric, adolescent and adult vaccines and is a leading
provider of vaccines in countries around the world; in the U.S., Merck markets
vaccines for 12 of the 17 diseases for which the U.S. Advisory Committee for
Immunization Practices currently recommends vaccines.”

http://www.businesswire.com/portal/site/home/permalink/?
ndmViewId=news_view&newsId=20091221005649&newsLang=en

The MMWR for December 25, 2009 / Vol. 58 / No. 50 includes:

Intent to Receive Influenza A (H1N1) 2009 Monovalent and Seasonal
Influenza Vaccines
Two Counties, North Carolina, August 2009
To assess intent to receive influenza vaccines among children and adults,
during August 2009, the North Carolina Center for Public Health Preparedness
conducted a community assessment in two counties to measure knowledge
of and intent to receive H1N1 and seasonal influenza vaccines. The results
determined that 64% of adults reported intent to receive H1N1 vaccine. In
addition, 65% of parents reported intent to have all their children vaccinated
for H1N1, whereas 51% said they would have all their children vaccinated for
both H1N1 and seasonal influenza.
Impact of Seasonal Influenza-Related School Closures on Families ---
Southeastern Kentucky, February 2008

Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues its weekly scanning of key journals
to identify and cite articles, commentary and editorials, books reviews and
other content supporting our focus on vaccine ethics and policy. Journal
Watch is not intended to be exhaustive, but indicative of themes and
issues the Center is actively tracking. We selectively provide full text of
some editorial and comment articles that are specifically relevant to our
work. Successful access to some of the links provided may require
subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles,
please write to David Curry at
david.r.curry@centerforvaccineethicsandpolicy.org

JAMA
Vol. 302 No. 24, pp. 2625-2722, December 23/30, 2009
http://jama.ama-assn.org/current.dtl
Letters
Adverse Events and Quadrivalent Human Papillomavirus Recombinant
Vaccine
Vicky Debold; Eric Hurwitz
JAMA. 2009;302(24):2657.
Adverse Events and Quadrivalent Human Papillomavirus Recombinant
Vaccine—Reply
John Iskander; Claudia Vellozzi; Barbara A. Slade
JAMA. 2009;302(24):2657-2658.
Efficacy Data and HPV Vaccination Studies
Norman W. Baylor; Melinda Wharton
JAMA. 2009;302(24):2658-2659.
Efficacy Data and HPV Vaccination Studies
Rebecca B. Perkins
JAMA. 2009;302(24):2659.
Efficacy Data and HPV Vaccination Studies—Reply
Charlotte Haug
JAMA. 2009;302(24):2659-2660.
Marketing and the HPV Vaccine
L. Stewart Massad
JAMA. 2009;302(24):2660.
Marketing and the HPV Vaccine
Marisol Betensky
JAMA. 2009;302(24):2660-2661.
Marketing and the HPV Vaccine—Reply
Sheila M. Rothman; David J. Rothman
JAMA. 2009;302(24):2661.

Journal of Infectious Diseases

1 January 2010 Volume 201, Number 1
http://www.journals.uchicago.edu/toc/jid/current
Major Articles and Brief Reports: Viruses
Evidence of Bias in Studies of Influenza Vaccine Effectiveness in
Elderly Patients
Roger Baxter, Janelle Lee, and Bruce Fireman
Although studies have shown influenza vaccines to be effective in preventing
death in the elderly population, these findings may be the result of selection
bias. We examined the relationship between vaccination, age, underlying
morbidity, and probability of death in the upcoming year. Vaccination
coverage varied in a curvilinear fashion with age, morbidity, and risk of
death. Forgoing vaccination predicted death in those who had received
vaccinations in the previous 5 years, but it predicted survival in patients who
had never before received a vaccination. We conclude that bias is inherent in
studies of influenza vaccination and death among elderly patients.

The Lancet
Jan 02, 2010 Volume 375 Number 9708 Pages 1 - 92
http://www.thelancet.com/journals/lancet/issue/current
Comment
Large trials confirm immunogenicity of H1N1 vaccines
Heath Kelly, Ian Barr
Preview
Since the recognition of a novel influenza A H1N1 virus, in March, 2009, the
virus has spread throughout the world to cause the first influenza pandemic
of this century, resulting in a cumulative incidence of death of 5–14 per
million in populous southern hemisphere countries.1 In view of the high
likelihood that pandemic H1N1 will circulate as a dominant strain for several
years, a vaccine will be the most effective long-term mitigation measure. The
Lancet today includes three studies of candidate vaccines against pandemic
H1N1 that report on several separate randomised trials in China, Hungary,
and the USA.
Immune response after a single vaccination against 2009 influenza
A H1N1 in USA: a preliminary report of two randomised controlled
phase 2 trials
Eric Plennevaux, Eric Sheldon, Mark Blatter, Mary-Kate Reeves-Hoché,
Martine Denis
Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine
when administered alone or simultaneously with the seasonal influenza
vaccine for the 2009–10 influenza season: a multicentre, randomised
controlled trial
Zoltan Vajo, Ferenc Tamas, Laszlo Sinka, Istvan Jankovics
Safety and immunogenicity of 2009 pandemic influenza A H1N1
vaccines in China: a multicentre, double-blind, randomised, placebo-
controlled trial
Xiao-Feng Liang, Hua-Qing Wang, Jun-Zhi Wang, Han-Hua Fang, Jiang Wu,
Feng-Cai Zhu, Rong-Cheng Li, Sheng-Li Xia, Yu-Liang Zhao, Fang-Jun Li, Shao-
Hong Yan, Wei-Dong Yin, Kang An, Duo-Jia Feng, Xuan-Lin Cui, Feng-Chun Qi,
Chang-Jun Ju, Yu-Hui Zhang, Zhi-Jun Guo, Ping-Yu Chen, Ze Chen, Kun-Ming
Yan, Yu Wang
Defining the safety profile of pandemic influenza vaccines
Dina Pfeifer, Claudia Alfonso, David Wood
Preview
Vaccines have side-effects. When making decisions about regulatory approval
and public health use of vaccines, authorities need to be convinced that the
benefits of reduced disease outweigh actual and potential risks of
vaccination. The side-effect profiles of influenza vaccines are well known due
to more than 50 years of large-scale use. However, influenza vaccines
uniquely undergo changes in their strain composition virtually every year.
Critical evaluation of the safety profile of the vaccines manufactured to
respond to the 2009 H1N1 pandemic is of the highest priority.
Series
Programmes, partnerships, and governance for elimination and
control of neglected tropical diseases
Bernhard Liese, Mark Rosenberg, Alexander Schratz
Preview
Neglected tropical diseases represent one of the most serious burdens to
public health. Many can be treated cost-effectively, yet they have been
largely ignored on the global health policy agenda until recently. In this first
paper in the Series we review the fragmented structure of elimination and
control programmes for these diseases, starting with the ambiguous
definition of a neglected tropical disease. We describe selected international
control initiatives and present their effect, governance arrangements, and
financing mechanisms, including substantial drug-donation programmes.

The Lancet Infectious Disease

Jan 2010 Volume 10 Number 1 Pages 1 - 66
http://www.thelancet.com/journals/laninf/issue/current
Reflection and Reaction
Mandatory influenza immunisation of health-care workers
Gwendolyn L Gilbert, Ian Kerridge, Paul Cheung
Preview
Seasonal influenza imposes an enormous but poorly defined burden of excess
deaths, hospital admissions, and health-care costs, and often spreads within
health-care facilities. Hospital patients with influenza are a potential source of
infection for health-care workers that are not immunised, with attack rates
among health-care workers of 18–24%.1 Unfortunately, health-care workers
infected with influenza often continue to work, despite symptoms, with
potentially devastating consequences for high-risk patients, including those
who are very young, elderly, or immunocompromised—for example, patients
receiving bone-marrow transplants have a high risk of pneumonia and death
from influenza.

Nature
Volume 462 Number 7276 pp957-1088 24 December 2009
http://www.nature.com/nature/journal/v462/n7276/
[No relevant content]

New England Journal of Medicine

Volume 361 — December 31, 2009 — Number 27
http://content.nejm.org/current.shtml
[No relevant content]
Volume 361 — December 24, 2009 — Number 26
Editorial
The Need for Science in the Practice of Public Health
N. Lurie
[Free Full-text]
When H5N1 avian influenza emerged in 1997, much of the world began
planning for an eventual pandemic. Most planners expected the pandemic to
begin in Asia and believed the virus would be highly lethal. In the United
States, planning efforts for pandemic influenza escalated again in November
2005, with the publication of the National Strategy for Pandemic Influenza.1
The H1N1 pandemic that emerged in the spring of 2009 did not conform to
prior planning assumptions. It began in Mexico rather than Asia and to date
has not been as lethal as first feared.
Since 2005, global influenza surveillance has vastly improved. Many
countries, including China, markedly increased disease-surveillance efforts
after the outbreak of severe acute respiratory syndrome (SARS) in 2003. The
report by Cao and colleagues in this issue of the Journal2 demonstrates the
progress China has made in developing robust surveillance in a relatively
short period. Surveillance has also improved in the United States, where
detection of the first two cases of H1N1 infection was the result of
investments leading to experimental diagnostic tests and enhanced border
surveillance.
 The planners involved in efforts to contain pandemics called for a layered
approach to protecting the population, including steps to prevent or slow the
spread of disease, communication with the public, and treatment with
antiviral medications until a vaccine could be manufactured and made widely
available. The world's response to this pandemic is far better than it would
have been without the aggressive planning that has been done since 1997,
but experience with the H1N1 virus to date reminds us that even though we
have made great strides, additional science is needed to better inform public
health responses.
By the time the H1N1 virus was recognized, infection was already
widespread in Mexico and in several sites in the United States. From the
perspective of many in the public health community, it made little sense to
try to close the border with Mexico, since doing so would not stop the spread
of disease within the United States. In addition to the preventive measures
recommended for the individual person (e.g., hand washing, covering one's
cough), early prevention efforts focused on isolation of infected persons,
early detection, and postexposure prophylaxis. As local outbreaks
progressed, some communities closed their schools. Unfortunately, we still
have little science to tell us whether and under what circumstances measures
such as school closures are most effective, but we do know the closures were
disruptive to children's learning and to working parents and their employers.
China built on its post-SARS disease-surveillance capability and focused
first on early detection and postexposure prophylaxis. China also
implemented a strict isolation and quarantine policy in the hope of preventing
or slowing the spread of disease. But as Cao and colleagues remind us,
further data are needed to inform screening and the actions based on it. For
example, the accuracy of large-scale thermal screening is variable. As noted
by Cao and colleagues and by other investigators, roughly one quarter of
those infected are afebrile.3,4 Hence, screening that relies on the presence
of fever will mean that many infected persons will be overlooked. Testing
with real-time reverse transcriptase–polymerase chain reaction (RT-PCR) is
important in making a diagnosis, but it is both expensive and of limited
practicality on a very large scale. Since people are likely to remain PCR-
positive for several days after they stop shedding viable virus and are
infectious,5 the practice of basing either community mitigation or social
distancing policies on PCR-positivity could result in unnecessary interventions
for people who are no longer able to transmit the virus. This speaks to the
need to better understand the practical aspects of transmission and the need
for simple, accurate tests with rapidly produced results that can be used to
guide decisions about diagnosis, treatment, and social distancing.
Many observers think that China's isolation and quarantine policy, like the
school closures in the United States, was disruptive. Unfortunately, we do not
yet have adequate data to help us understand whether any of these
measures worked, nor do we have a good understanding of the levels of
individual or social disruption that are acceptable to different people,
communities, and countries. Clarifying the benefits of social distancing and
mitigation measures will be critical to understanding whether the burdens to
society are worth bearing.
The ultimate way to protect individual persons and populations from
disease is with vaccination, and the rapid development and manufacture of
the H1N1 vaccine represent a triumph of modern science. Even so, the United
States, which was one of the first countries to mount a large-scale
vaccination campaign, has not yet reached the aspirational goal articulated in
the pandemic preparedness plan published in November 2005 — that is, to
attain within 5 years the domestic manufacturing capacity to produce
sufficient pandemic vaccine for the U.S. population within 6 months of
pandemic onset. Additional breakthroughs in the development of safe cell-
based, plant-based, and recombinant vaccines, combined with large-scale
manufacturing capacity, are needed to reach this goal. Analogous global
goals — and plans for achieving them — are badly needed.
Once vaccine is widely available, it must rapidly reach those who need it.
Comparatively little research has been conducted in operations and logistics
to inform us of how best to do this. Although methods of reaching high-risk
patients are admittedly country-specific and health system–specific, a
substantial effort in operations research would be likely to help us better
understand how to accomplish more rapid delivery of vaccine — or any other
countermeasure — to those who most need it anywhere in the world.
Effective communication with the public is central to any public health
emergency response. The widespread misunderstanding of vaccine safety
and effectiveness speaks to the need to improve not only safety science but
also communication science — to enhance our ability to reach and educate
the public, especially those who are at highest risk for disease.
We will all have the opportunity to learn lessons from the 2009 pandemic
H1N1 virus. Although we would like to believe that pandemics occur rarely
and that we have plenty of time until the next one, new infectious diseases,
as well as other kinds of threats, can emerge at any time. One challenge will
be to continue to invest in science — whether that means basic virology;
surveillance; mitigation measures; vaccine development, manufacture, and
distribution; operations and logistics; or communication — so that when the
next pandemic or other emerging infectious disease appears, we will have
the data we need to make informed decisions about how to confront it. A
second challenge will be to strengthen the nation's public health
infrastructure so that we can rapidly turn scientific knowledge into action.
Financial and other disclosures provided by the author are available with the full text of this article at
NEJM.org.
The views expressed here are those of the author and do not necessarily reflect the policies of the
Department of Health and Human Services.
Source Information
Dr. Lurie is the Assistant Secretary for Preparedness and Response, Department of Health and Human
Services.
This article (10.1056/NEJMe0911050) was published on December 9, 2009, at NEJM.org.
References
National strategy for pandemic influenza. Washington, DC: United States Homeland Security Council,
2005.
Cao B, Li X-W, Mao Y, et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus
infection in China. N Engl J Med 2009;361:2507-2517. [Free Full Text]
Carrat F, Vergu E, Ferguson NM, et al. Time lines of infection and disease in human influenza: a review of
volunteer challenge studies. Am J Epidemiol 2008;167:775-785. [Free Full Text]
Introduction and transmission of 2009 pandemic influenza A (H1N1) virus -- Kenya June-July 2009. MMWR
Morb Mortal Wkly Rep 2009;58:1143-1146. [Medline]
Witkop CT, Duffy MR, Macias EA, et al. Novel influenza A (H1N1) outbreak at the U.S. Air Force Academy:
epidemiology and viral shedding duration. Am J Prev Med 2009 October 21 (Epub ahead of print).

Pediatrics
January 2010 / VOLUME 125 / ISSUE 1
http://pediatrics.aappublications.org/current.shtml
Empyema Hospitalizations Increased in US Children Despite
Pneumococcal Conjugate Vaccine
Su-Ting T. Li, MD, MPH and Daniel J. Tancredi, PhD
Department of Pediatrics, University of California at Davis, Sacramento,
California
OBJECTIVE: To determine if the incidence of empyema among children in the
United States has changed since the introduction of the pneumococcal
conjugate vaccine in 2000.
METHODS: We used the nationally representative Kids' Inpatient Database to
estimate the annual total number of hospitalizations of children 18 years of
age that were associated with empyema in 1997, 2000, 2003, and 2006.
Using US Census data, estimated counts were converted into annual
incidence rates per 100000 children. Incidence rates were compared between
1997 and later years to determine the impact of pneumococcal conjugate
vaccine on hospitalization rates.
RESULTS: During 2006, an estimated total of 2898 (95% confidence interval
[CI]: 2532–3264) hospitalizations of children 18 years of age in the United
States were associated with empyema. The empyema-associated
hospitalization rate was estimated at 3.7 (95% CI: 3.3–4.2) per 100000
children, an increase of almost 70% from the 1997 empyema hospitalization
rate of 2.2 (95% CI: 1.9–2.5) per 100000. The rate of complicated pneumonia
(empyema, pleural effusion, or bacterial pneumonia requiring a chest tube or
decortication) similarly increased 44%, to 5.5 (95% CI: 4.8–6.1) per 100000.
The rate of bacterial pneumonia decreased 13%, to 244.3 (95% CI: 231.1–
257.5) per 100000. The rate of invasive pneumococcal disease (pneumonia,
sepsis, or meningitis caused by Streptococcus pneumoniae) decreased 50%,
to 6.3 (95% CI: 5.7–6.9) per 100000.
CONCLUSIONS: Among children 18 years of age, the annual empyema-
associated hospitalization rates increased almost 70% between 1997 and
2006, despite decreases in the bacterial pneumonia and invasive
pneumococcal disease rates. Pneumococcal conjugate vaccine is not
decreasing the incidence of empyema.
Health Care Utilization by Adolescents on Medicaid: Implications for
Delivering Vaccines
Amanda F. Dempsey, MD, PhD, MPH and Gary L. Freed, MD, MPH
Child Health Evaluation and Research Unit, Department of Pediatrics and
Communicable Diseases, University of Michigan, Ann Arbor, Michigan
OBJECTIVE: To examine the degree to which current health care utilization
patterns of Medicaid-enrolled adolescents living in Michigan would allow
opportunities for adolescent immunizations to be provided.
METHODS: Outpatient claims data from 2001–2005 were analyzed for 11- to
18-year-old Medicaid-enrolled adolescents living in Michigan. Visits were
classified as either health-maintenance examinations (HMEs) or problem
focused by using diagnostic and procedural codes. Data were divided into 4
overlapping 2-year time periods, and the age-specific proportion of
adolescents who attended these 2 visit types was calculated for each. 2
tests were used to evaluate associations of visit patterns with gender.
RESULTS: Of the 718847 adolescents included in the study, <50% had 1
HME visit within any 2-year time period, and substantially fewer (<15%) had
annual HMEs. In contrast, at least 75% of the adolescents had 1 problem-
focused visit in any given 2-year period, and approximately half had
participated in at least 2 problem-focused visits. Problem-focused, but not
HME, visit utilization was significantly associated with gender, with girls
increasing, but boys decreasing, visit utilization as they aged.
CONCLUSIONS: Similar to privately insured adolescents, most Medicaid-
enrolled adolescents do not have annual preventive-care visits, which calls
into question the feasibility of providing immunizations primarily at annual
HMEs. Participation in problem-focused encounters was generally high in our
study. However, even problem-focused visit utilization was low among older
adolescent boys. This suggests that in addition to strengthening
immunization within the medical home, alternative venues for reaching
certain subpopulations of adolescents should also be developed.

PLoS Medicine
(Accessed 4 January 2010)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1
&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1
c2a2501181c#results
[No relevant articles]

Science
1 January 2010 Vol 327, Issue 5961, Pages 10-100
http://www.sciencemag.org/current.dtl
[No relevant content]

Vaccine
Volume 28, Issue 3, Pages 583-868 (8 January 2010)
http://www.sciencedirect.com/science?
_ob=PublicationURL&_cdi=5188&_pubType=J&_acct=C000050221&_version
=1&_urlVersion=0&_userid=10&md5=06a70dff873c73731f4a31331c8deee2
&jchunk=28#28
[Reviewed earlier]