Health Economics, Policy and Law 
Volume 6 – Issue 04 – 06 September 2011 http://journals.cambridge.org/action/displayIssue?jid=HEP&tab=currentissue

FirstView Articles
Healthcare policy tools as determinants of health-system efficiency: evidence from the OECD

Preview
Dominika Wranik
Health Economics, Policy and Law / FirstView Articles
Copyright © Cambridge University Press 2011
Published online: 12 December 2011
DOI:10.1017/S1744133111000211

Abstract
This paper assesses which policy-relevant characteristics of a healthcare system contribute to health-system efficiency. Health-system efficiency is measured using the stochastic frontier approach. Characteristics of the health system are included as determinants of efficiency. Data from 21 OECD countries from 1970 to 2008 are analysed. Results indicate that broader health-system structures, such as Beveridgian or Bismarckian financing arrangements or gatekeeping, are not significant determinants of efficiency. Significant contributors to efficiency are policy instruments that directly target patient behaviours, such as insurance coverage and cost sharing, and those that directly target physician behaviours, such as physician payment methods. From the perspective of the policymaker, changes in cost-sharing arrangements or physician remuneration are politically easier to implement than changes to the foundational financing structure of the system.

Nature Reviews Immunology
http://www.nature.com/nri/journal/v11/n12/index.html
December 2011 Vol 11 No 12

Perspectives – Science and society
Vaccines for the twenty-first century society
Rino Rappuoli, Christian W. Mandl, Steven Black & Ennio De Gregorio
1865 | doi:10.1038/nri3085

The childhood vaccination campaigns of the twentieth century represent one of the great success stories of modern medicine. But are we yet to realize the full potential of vaccines? This article discusses the medical needs of the twenty-first century society and proposes that new vaccines will play a major part in addressing these needs.

The Pediatric Infectious Disease Journal
December 2011 – Volume 30 – Issue 12  pp: 1019-1051,e225-e247
http://journals.lww.com/pidj/pages/currenttoc.aspx

Published Ahead-of-Print
Brief Reports
Clinical Presentation of Invasive Pneumococcal Disease in Spain in the Era of Heptavalent Conjugate Vaccine
De Sevilla, Maria F.; Garcí, Juan-José Garcí; Esteva, Cristina; Moraga, Fernando; Hernández, Sergi; Selva, Laura; Coll, Francisco; Ciruela, Pilar; Planes, Ana Maria; Codina, Gemma; Salleras, Luis; Jordan, Iolanda; Domínguez, Angela; Muñoz-Almagro, Carmen
Pediatric Infectious Disease Journal., POST ACCEPTANCE, 14 December 2011
doi: 10.1097/INF.0b013e318241d09e

Abstract:
Background: The aim of this study was to analyze the rate of incidence, clinical presentation, serotype and clonal distribution of invasive pneumococcal disease (IPD) in the era of heptavalent pneumococcal conjugate vaccine (PCV7) in Barcelona, Spain.

Methods: This was a prospective study comprising all children <5 years with IPD who were managed in two tertiary-care pediatric hospitals between January 2007 and December 2009. IPD was defined as the presence of clinical findings of infection together with isolation or detection of DNA of S .pneumoniae in a sterile fluid sample.

Results: 319 patients (53.3% male), mean age 29.6 months, were included. Comparing rates in 2007 and 2009 (76.2 and 109.9 episodes/100,000 population, respectively) an increase of 44% (95% CI, 10%-89%) was observed.

The main clinical presentation was pneumonia (254 episodes, 79.6%), followed by meningitis (29, 9.1%) and bacteremia (25, 7.8%).The diagnosis was made by positive culture in 123 (38.6%) patients and in 196 (61.4%) by real-time PCR. Serotype study was done in 300 episodes and 273 (91%) were non-PCV7 serotypes. The most frequent serotypes were 1 (20.7%), 19A (15.7%) and 3 (12.3%). A minimal inhibitory concentration >= 0.12[mu]g/mL to penicillin was detected in 34.4% of isolates. Sequence type 306 expressing serotype 1 was the most frequent clonal type detected (20.3% of studied strains).

Conclusions: IPD continues to increase in Barcelona and the rate is higher than perviously reported as a result of low sensitivity of bacterial culture. Non-PCV7 serotypes were responsible for 91% of episodes and pneumonia was the main clinical presentation.

Pharmacoeconomics
January 1, 2012 – Volume 30 – Issue 1  pp: 1-81
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Original Research Articles
A Systematic Review of the Cost and Cost Effectiveness of Treatment for Multidrug-Resistant Tuberculosis
Fitzpatrick, Christopher; Floyd, Katherine
Pharmacoeconomics. 30(1):63-80, January 1, 2012.
doi: 10.2165/11595340-000000000-00000

Abstract:
Background: Around 0.4 million cases of multidrug-resistant tuberculosis (MDR-TB) occur each year. Only a small fraction of these cases are treated according to international guidelines. Evidence relevant to decisions about whether to scale-up treatment for MDR-TB includes cost and cost-effectiveness data. Up to 2010, no systematic review of this evidence has been available.

Objective: Our objective was to conduct a systematic review of the cost and cost effectiveness of treatment for MDR-TB and synthesize the available data.

Methods: We searched for papers published or prepared for publication in peer-review journals and grey literature using search terms in five languages: English, French, Portuguese, Russian and Spanish. From an initial set of 420 studies, four were included, from Peru, the Philippines, Estonia and Tomsk Oblast in the Russian Federation. Results on costs, effectiveness and cost effectiveness were extracted. Assessment of the quality of each economic evaluation was guided by two existing checklists around which there is broad consensus. Costs were adjusted to a common year of value (2005) to remove distortions caused by inflation, and calculated in two common currencies: $US and international dollars (I$), to standardize for purchasing power parity.

Data from the four identified studies were then synthesized using probabilistic sensitivity analysis, to appraise the likely cost and cost effectiveness of MDR-TB treatment in other settings, relative to WHO benchmarks for assessing whether or not an intervention is cost effective. Best estimates are provided as means, with 5th and 95th percentiles of the distributions.

Results: The cost per patient for MDR-TB treatment in Estonia, Peru, the Philippines and Tomsk was $US10 880, $US2423, $US3613 and $US14 657, respectively. Best estimates of the cost per disability-adjusted life-year (DALY) averted were $US598 (I$960), $US163 (I$291), $US143 (I$255) and $US745 (I$1059), respectively. The main influences on costs were (i) the model of care chosen (the extent to which hospitalization or ambulatory care were relied upon) and (ii) the second-line drugs included in the treatment regimen. When extrapolated to other settings, the best estimate of the cost of treatment varied from US3401 to US195 078, depending on the region and model of care. The cost per DALY averted was lower than GDP per capita in all 14 WHO sub-regions considered, with better cost effectiveness for outpatient versus inpatient models of care.

Conclusions: Treatment for MDR-TB can be cost effective in low- and middle-income countries. Evidence about the relative cost effectiveness of outpatient versus inpatient models of care is limited and more data are needed from Africa and Asia – especially India and China, which have the largest number of cases. Unless there is strong evidence that hospitalization is necessary to achieve high rates of adherence to treatment, patients with MDR-TB should be treated using mainly ambulatory care.

PLoS One
[Accessed 18 December 2011]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis
Kumanan Wilson, Steven Hawken, Jeffrey C. Kwong, Shelley Deeks, Natasha S. Crowcroft, Carl Van Walraven, Beth K. Potter, Pranesh Chakraborty, Jennifer Keelan, Michael Pluscauskas, Doug Manuel
PLoS ONE: Research Article, published 12 Dec 2011 10.1371/journal.pone.0027897

Abstract
Background
Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months.

Methods
Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine.

Results
Four to 12 days post 12 month vaccination, children had a 1.33 (1.29–1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17–1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months.

Conclusions
There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented.

Science        
16 December 2011 vol 334, issue 6062, pages 1461-1592
http://www.sciencemag.org/current.dtl
DOI: 10.1126/science.334.6062.1488

News Focus – Infectious Disease
Taking a New Shot At a TB Vaccine
Kai Kupferschmidt

Summary
For many people around the globe, there’s only one line of defense against Mycobacterium tuberculosis: a shot of a 90-year-old problematic vaccine that they get shortly after birth. The emergence and rapid spread of multidrug-resistant strains of M. tuberculosis and the United Nation’s goal of halving TB deaths by 2015 have led to an influx of private and public money to develop a new vaccine. Now the most advanced of these candidates are entering their first human efficacy trials. But with this new hope come challenges. Researchers are wrestling with how to select the best candidates to advance to much larger trials—and they are wondering how to pay for those final rounds of testing. Nor are there any guarantees of success at the end of this road. A human trial of one new tuberculosis vaccine was halted at the end of September because of apparent side effects.

Tropical Medicine & International Health
December 2011  Volume 16, Issue 12  Pages 1465–1561
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-3156/currentissue
[Reviewed earlier; No relevant content]

Early View
Original Articles
Expanding and improving urban outreach immunization in Patna, India
Narottam Pradhan, Tove K. Ryman, Sherin Varkey, Alok Ranjan, Satish K. Gupta, Gopal Krishna, R. P. Swetanki and Randall Young
Article first published online: 14 DEC 2011 | DOI: 10.1111/j.1365-3156.2011.02916.x

Abstract
Objectives We conducted a case study of an urban immunization outreach strategy to determine the feasibility of the intervention and to measure administrative immunization coverage outcomes.

Methods A multipronged strategy for improving immunization coverage in Urban Patna, India, was implemented for 1 year (2009/2010). The strategy was designed to increase immunization sites, shift human resources, plan logistics, improve community mobilization, provide supervision, strengthen data flow and implement special vaccination drives.

Results Over 1 year, the coverage of all primary vaccines of the Universal Immunization Program improved by over 100%.

Conclusion Coverage can be rapidly improved through outreach immunization in low socioeconomic areas if existing opportunities are carefully utilized

The pdf version of Vaccines: The Week in Review  12 December 2011, comprising the posts below for this date, is available, here: Vaccines_The Week in Review_12 December 2011

WHO: The Meningitis Vaccine Project – where we are today
9 December 2011

At the end of 2011, Cameroon, Chad and Nigeria are vaccinating more than 22 million individuals aged 1-29 years with the new meningococcal A conjugate vaccine, MenAfriVac, which has the potential to eliminate the leading cause of meningitis epidemics in Africa. In audio files (in French), four individuals closely involved either in the clinical trials for the vaccine, the organization of mass campaigns, or the health of those living in a rural community participating in the trials, talk about their work and the impact that the vaccine is expected to have on the health of people living in the meningitis belt: Doctor Marie-Pierre Preziosi (Responsible for research and development of meningitis vaccines, WHO, Geneva); Doctor Carol Tevi-Benissan (Responsible for logistics planning of meningitis vaccine campaigns, WHO, Geneva); Doctor Aldiouma Diallo (Principal Investigator, MenAfriVac clinical trials, Institut de recherche pour le développement (IRD), Niakhar, Senega); Doctor Seynabou Gaye (District Medical Officer of Niakhar, Sénégal).

http://www.who.int/immunization/newsroom/multimedia/podcasts_meningitis_vaccine_project/en/index.html

Conference: CSIS Conference on the Strategic Power of Vaccines
Center for Strategic and International Studies
Washington, DC 9 December 2011

“This conference grows out of the remarkable surge of interest in vaccines in public health efforts worldwide. Last year, the Bill & Melinda Gates Foundation committed $10 billion to help research, develop, and deliver vaccines over the next ten years, which it christened the Decade of Vaccines. Recent analyses in The Lancet, Nature, Health Affairs, and elsewhere have portrayed vaccines as a “best buy,” a cost-effective global health tool in a tough fiscal environment. In June, at its first pledging conference, the GAVI Alliance received $4.3 billion in commitments from governments and private donors, surpassing its $3.7 billion target.

Along with this growing awareness of the value of vaccines, there has arisen a heightened grasp of the complexities of global immunization efforts. There is uncertainty about continued funding and sustainable programs, shoring up public trust in immunization, bringing current campaigns to a successful conclusion, creating the market conditions for the research and development of new vaccines, and guaranteeing their availability and delivery to those most in need, particularly in unstable and insecure environments.

Webcast of conference available here the week of 12 December 2011: SmartGlobalHealth.org.

Keynote speeches:
– Rajiv Shah, Administrator, U.S. Agency for International Development
– Anthony Fauci, Director, National Institute of Allergy and Infectious Diseases, NIH

Panelists including:
– Stephen Cochi, CDC
– Helen Evans, GAVI Alliance
– Admiral William Fallon
– Markus Geisser, International Committee of the Red Cross
– Julie Gerberding, Merck Vaccines
– Amanda Glassman, Center for Global Development
– Orin Levine, Johns Hopkins Bloomberg School of Public Health
– Margaret McGlynn, International AIDS Vaccine Initiative
– Regina Rabinovich, Bill & Melinda Gates Foundation
– Anne Schuchat, CDC
– Eric Schwartz, U. of Minnesota Humphrey School of Public Affairs

http://csis.org/event/csis-conference-strategic-power-vaccines

Speech: Adolescent Rights: What Progress? by Anthony Lake, UNICEF Executive Director at the Harvard Conference on Adolescent Rights

Plenary Session: The Social and Political Costs of Inaction
FXB Center for Health and Human Rights, Harvard University
Boston, 8 December 2011

Extract:

The coming of age of the Convention on the Rights of the Child is the ideal time to reflect on the generation of adolescents who have grown up under its auspices … to take stock of progress made in improving their lives … to consider how we can build on that progress … and to confront what could happen if we do not.

The CRC was and is a milestone in promoting the welfare and protection of children everywhere.  It has been more quickly and widely ratified than any human rights treaty to date – and it will be even more effective when it is universally ratified.   I hope sooner rather than later.

The CRC is the foundation of all our work at UNICEF: It provides our mission and our mandate.  The rights of children and our emphasis on equity, in all our advocacy and programs around the world, are inseparable.  Because to the degree children are disadvantaged – for reasons of geography or gender or ethnicity … or because they live with disabilities or disease … or are stigmatized and bullied for any reason – to exactly that degree, their rights are being violated.

So let me here sketch out two propositions for our discussion.

First, that sustainable, tangible progress in children’s global welfare depends – in practice as well as in principle – on a focus on equity.

Second, more broadly, and tentatively, that we should not only advocate for policies that promote equity as an outcome of economic growth, but also –conversely – we should make the case that promoting equity helps produce sustainable growth, a proposition that is supported by a growing body of evidence. …

Full text here: http://www.unicef.org/media/media_60917.html

The MMWR Weekly for December 9, 2011 / Vol. 60 / No. 48 includes:

– Update: Influenza Activity — United States, October 2–November 26, 2011

– Announcements: Clinical Vaccinology Course — March 9–11, 2012

– Announcements: 15th Annual Conference on Vaccine Research

15th Annual Conference on Vaccine Research

The 15th Annual Conference on Vaccine Research, the largest scientific forum devoted exclusively to the research and development of vaccines and related technologies for prevention and treatment of disease through immunization, will be held May 7–9, 2012, at the Hyatt Regency Inner Harbor Hotel in Baltimore, Maryland. The conference brings together the diverse fields of human and veterinary vaccinology to encourage collaboration and multidisciplinary approaches among disease-specific and methodologic experts.

Clinical developments in vaccine discovery, rotavirus, meningococcal vaccine, vaccines for enteric diseases, food safety vaccines, vaccine adjuvants, and adverse events are among topics scheduled for discussion during the conference. In addition, a preconference workshop, Creating Outstanding Scientific Communications: Talks, Abstracts, and Posters, will be offered by expert faculty.

Applications for travel grants to subsidize attendees from countries with limited resources must be submitted by December 16, 2011. The deadline for online submission of general abstracts is January 6, 2012. Abstracts from eligible authors may be designated for consideration for the Maurice R. Hilleman Early-Stage Career Investigator Award, which provides $10,000 for research expenses and a travel stipend and    registration for the 2013 conference.

The conference is being sponsored by the National Foundation for Infectious Diseases (NFID), in collaboration with CDC and 13 other national and international agencies and organizations. Additional information is available at http://www.nfid.org

The Weekly Epidemiological Record (WER) for 9 December 2011, vol. 86, 50 (pp 565–580) includes: Validation of elimination: maternal and neonatal tetanus – Uganda, 2011; Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2011; Monthly report on dracunculiasis cases, January–October 2011

http://www.who.int/entity/wer/wer8650.pdf

Twitter Watch
A selection of items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and by no means intended to be exhaustive.

PIH Partners In Health
“Poverty doesn’t need to be the chief determinant of whether or not someone gets health care” -Paul Farmer ow.ly/7QJb0
2 hours ago

UNICEF UNICEF
On 11 December, UNICEF celebrates our 65th anniversary ~~~ bit.ly/rDiVQG ~~~ Thank you all for your support over the years ~~~ @UN

unfoundation UN Foundation
63 years ago today, the #UN adopted Universal Declaration of #HumanRights. #CelebrateRights by learning about yours: ow.ly/7Vdrc
10 Dec

pahowho PAHO/WHO
#PAHO launches new human rights report, honors leaders on the right to health bit.ly/vHBXEo
9 Dec

globalfundnews The Global Fund
ICASA conference: Global Fund: We’re here to stay – Dr. Debrework Zewdie, Deputy Executive Director icasa2011addis.org/home/205-globa…
9 Dec

sabinvaccine Sabin Vaccine Inst.
Help @Global_Network see the end of 7 diseases by 2020 – check out their new @END_7 campaign! ow.ly/7TjsD
8 Dec

DrFriedenCDC Dr. Tom Frieden
Healthcare workers: Gotten a flu shot yet? Get it today for Natl Flu Vaccination Week. Stop, not spread the flu go.usa.gov/56s #NIVW
8 Dec

unfoundation UN Foundation
RT @shotatlife: @unfoundation CEO shares what u can do to support @ShotAtLife & give kids a shot at holiday magic! bit.ly/tqBNru
8 Dec

AIDSvaccine IAVI
#ICASA2011 ends w hopeful, positive closing ceremony. 10,000 ppl from 103 countries took part in conf. #HIV #vaccine #endofAIDS @ICASA2011
8 Dec

JeffDSachs Jeffrey D. Sachs
American Society of Tropical Medicine and Hygiene: “Sachs issues call to action on Global Fund slowdown” bit.ly/v3aT9T
7 Dec

MalariaVaccine PATH MVI
RTS,S malaria vaccine candidate named 2nd biggest medical breakthrough of the year by TIME

Annals of Internal Medicine
December 6, 2011; 155 (11)
http://www.annals.org/content/current

Original Research
Maternal Immune Response and Neonatal Seroprotection From a Single Dose of a Monovalent Nonadjuvanted 2009 Influenza A(H1N1) Vaccine: A Single-Group Trial
Vassilis Tsatsaris, Catherine Capitant, Thomas Schmitz, Corine Chazallon, Sophie Bulifon, Didier Riethmuller, Olivier Picone, Patrice Poulain, Fanny Lewin, Fabrice Lainé, Evelyne Jacqz-Aigrain, Jean-Pierre Aboulker, and Odile Launay, for the Inserm C09-33 PREFLUVAC (Immunogenicity and Safety of an Inactivated Nonadjuvanted A[H1N1v] Influenza Vaccine in Pregnant Women) Study Group
Ann Intern Med December 6, 2011 155:733-741;

Summary
Pregnant women and infants who get influenza are at increased risk for severe illness. In this prospective, multicenter, single-group clinical trial from France, nearly all women who received a single dose of a nonadjuvant 2009 influenza A(H1N1) vaccine in their second and third trimesters had antibody titers that were considered protective. Antibody titers in cord blood samples from 95% of the infants were also at a level considered protective. A single dose of influenza vaccine administered to women during pregnancy should protect both mothers and their newborns.

The Lancet  
Dec 10, 2011  Volume 378  Number 9808  p1975 – 2048  e19 – 21
http://www.thelancet.com/journals/lancet/issue/current

Editorial
What constitutes full access to data in industry-funded trials?
The Lancet

Preview
Open any medical journal and you are likely to find significant results outnumbering those that are non-significant. Novel, positive findings evoke greater interest than do confirmatory or “negative” trials, although the latter are equally as important. Such publication bias at a journal level has long been judged problematic. But might selective data reporting at a study level be even more sinister? The answer is yes.

The Lancet  
http://www.thelancet.com/journals/lancet/issue/current

Online First
Comment
Dec 09, 2011

Why we need a Commission on Global Governance for Health
Ministers of Foreign Affairs of Brazil, France, Indonesia, Norway, Senegal, and Thailand

Preview
5 years ago, the foreign ministers of Brazil, France, Indonesia, Norway, Thailand, Senegal, and South Africa, launched the Global Health and Foreign Policy Initiative1 in recognition of the central importance of health and its connection to multiple global governance processes. In many ways, protecting and enhancing the health of its population is one of the most important goals and duties of any state. With globalisation and increased interdependency among countries, health issues have become even more central to states’ interests.

Medical Decision Making (MDM)
http://mdm.sagepub.com/content/current

Online First
November 29, 2011
Jeffrey T. Vietri, Meng Li, Alison P. Galvani, and Gretchen B. Chapman
Vaccinating to Help Ourselves and Others
Med Decis Making 0272989X11427762, first published on November 29, 2011 as doi:10.1177/0272989X11427762

Abstract
Background. Many behaviors affect not only the self but also others. The utility of a vaccination to each individual depends on population immunity, the cumulative result of individual vaccination decisions. However, little is known about how the benefit to others influences vaccination decisions.

Methods. In a series of 3 experiments (N = 292, 316, and 299) using hypothetical scenarios and college student respondents, we tested whether the vaccination decisions of individuals were sensitive to the level of immunity in the population when it had implications for either altruistic or free-riding vaccination behavior.

Results. Our findings indicate that decisions of individuals were sensitive to opportunities both to free ride by refusing vaccination and to vaccinate altruistically. Although individuals were most willing to get vaccinated when they were at risk themselves, they were also sensitive to the amount of good they could do for others. This altruistic sensitivity was strongest when individuals were not vulnerable to the disease themselves.

Conclusions. The most effective vaccination strategies, from a public health perspective, often entail vaccinating the disease transmitters rather than those who are most vulnerable. Consequently, those who bear the burden of vaccination and those who benefit are not the same individuals. Thus, effective vaccination campaigns require that disease transmitters vaccinate even when it is not in their self-interest to do so. Our results suggest that it may be possible to encourage vaccination by appealing to altruistic motives.

Nature  
Volume 480 Number 7376 pp151-284  8 December 2011
http://www.nature.com/nature/current_issue.html

Specials
Outlook Influenza
Herb Brody

Epidemiology: Racing against the flu
Duncan Graham-Rowe

Q&A: The flu catcher
Richard Webby

Prevention: Vaccine for all seasons
Jana Schlütter

Drugs: Lines of defence
Roxanne Palmer

Public health: Life lessons
Laura Vargas Parada

Morbidity: A personal response
Christine Junge

Nature Medicine
December 2011, Volume 17 No 12
http://www.nature.com/nm/index.html

Commentary
Improving the efficacy of translational medicine by optimally integrating health care, academia and industry – pp1567 – 1569
Stefan R Bornstein & Julio Licinio
doi:10.1038/nm.2583

Preview
Translational medicine has become a global priority, but there is still a major gap between the arrival of new treatments and the investment that many countries have made on this front. Here we discuss often unrecognized roadblocks in the translational process and offer potential solutions for further advancement through enhanced integration of health care, academia and industry.

Although understanding of biological mechanisms is on the rise, the process of translating fundamental knowledge to the clinic remains disappointing. Essential issues that have been widely recognized to account for the transitional gap include the need for increased investment in early-stage research and, in preclinical and early clinical work, the need for the capacity to stretch out beyond the boundaries of individual disciplines, for a more transparent dialogue between companies and regulators, for an approval process that does not always sacrifice efficacy in the name of safety and for other considerations that ultimately prevent new drugs from making it to the market1, 2, 3, 4, 5, 6, 7, 8. However, there are additional problems that have not received sufficient attention and need to be addressed to improve success in translational medicine…

PLoS One
[Accessed 11 December 2011]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

The Increasing Burden of Imported Chronic Hepatitis B — United States, 1974–2008
Tarissa Mitchell, Gregory L. Armstrong, Dale J. Hu, Annemarie Wasley, John A. Painter PLoS ONE: Research Article, published 07 Dec 2011 10.1371/journal.pone.0027717

Abstract 
Background
Without intervention, up to 25% of individuals chronically infected with hepatitis B virus (HBV) die of late complications, including cirrhosis and liver cancer. The United States, which in 1991 implemented a strategy to eliminate HBV transmission through universal immunization, is a country of low prevalence. Approximately 3,000–5,000 U.S.-acquired cases of chronic hepatitis B have occurred annually since 2001. Many more chronically infected persons migrate to the United States yearly from countries of higher prevalence. Although early identification of chronic HBV infection can reduce the likelihood of transmission and late complications, immigrants are not routinely screened for HBV infection during or after immigration.

Methods
To estimate the number of imported cases of chronic hepatitis B, we multiplied country-specific prevalence estimates by the yearly number of immigrants from each country during 1974–2008.

Results
During 1974–2008, 27.9 million immigrants entered the U.S. Sixty-three percent were born in countries of intermediate or high chronic hepatitis B prevalence (range 2%–31%). On average, an estimated 53,800 chronic hepatitis B cases were imported to the U.S. yearly from 2004 through 2008. The Philippines, China, and Vietnam contributed the most imported cases (13.4%, 12.5%, and 11.0%, respectively). Imported cases increased from an estimated low of 105,750 during the period 1974–1977 to a high of 268,800 in 2004–2008.

Conclusions
Imported chronic hepatitis B cases account for approximately 95% of new U.S. cases. Earlier case identification and management of infected immigrants would strengthen the U.S. strategy to eliminate HBV transmission, and could delay disease progression and prevent some deaths among new Americans.

PLoS Medicine
(Accessed 11 December 2011)
http://www.plosmedicine.org/article/browse.action?field=date

The Primacy of Public Health Considerations in Defining Poor Quality Medicines
Paul N. Newton, Abdinasir A. Amin, Chris Bird, Phillip Passmore, Graham Dukes, Göran Tomson, Bright Simons, Roger Bate, Philippe J. Guerin, Nicholas J. White Essay, published 06 Dec 2011
doi:10.1371/journal.pmed.1001139

Summary Points
– Poor quality essential medicines, both substandard and counterfeit, are serious but neglected public health problems. Anti-infective medicines are particularly afflicted.

– Unfortunately, attempts to improve medicine quality have been hampered by confusion and controversy over definitions. For counterfeit (or falsified) medicines, this has arisen from perceived differences between public health and intellectual property approaches to the problem.

– We argue that public health, and not intellectual property or trade issues, should be the prime consideration in defining and combating counterfeit medicines, and that the World Health Organization (WHO) should be encouraged and supported to take a more prominent role in improving the world’s medicine quality and supply.

– An international treaty on medicine quality, under WHO auspices, could be an important step forward in the struggle against both substandard and counterfeit (or falsified) medicines.

Science        
9 December 2011 vol 334, issue 6061, pages 1313-1460
http://www.sciencemag.org/current.dtl
Vol. 334 no. 6061 pp. 1362-1366
DOI: 10.1126/science.1213199

AAAS Affairs
Presidential Address
[Free full-text: http://www.sciencemag.org/content/334/6061/1362.full ]

Passions
Alice S. Huang

Extract
What is the secret to success in science or anything else? Hard work alone is not enough. It is being passionate about something, enough to make a whole-hearted commitment of creativity, rigor, and determination. Let me share my lifelong passions. Foremost, I am passionate about investigating viruses and finding ways to control their growth. Along the way, I have also developed other passions: using science to build international bridges, improving science education, and maximizing access to science for diverse populations, especially women and minorities….

Science        
9 December 2011 vol 334, issue 6061, pages 1313-1460
http://www.sciencemag.org/current.dtl

Research Articles
Imaging of Plasmodium Liver Stages to Drive Next-Generation Antimalarial Drug Discovery
Stephan Meister, David M. Plouffe, Kelli L. Kuhen, Ghislain M. C. Bonamy, Tao Wu, S. Whitney Barnes, Selina E. Bopp, Rachel Borboa, A. Taylor Bright, Jianwei Che, Steve Cohen, Neekesh V. Dharia, Kerstin Gagaring, Montip Gettayacamin, Perry Gordon, Todd Groessl, Nobutaka Kato, Marcus C. S. Lee, Case W. McNamara, David A. Fidock, Advait Nagle, Tae-gyu Nam, Wendy Richmond, Jason Roland, Matthias Rottmann, Bin Zhou, Patrick Froissard, Richard J. Glynne, Dominique Mazier, Jetsumon Sattabongkot, Peter G. Schultz, Tove Tuntland, John R. Walker, Yingyao Zhou, Arnab Chatterjee, Thierry T. Tiagana, and Elizabeth A. Winzeler
Science 9 December 2011: 1372-1377.
Published online 17 November 2011 [DOI:10.1126/science.1211936]

Abstract
Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.

Value in Health
http://www.valueinhealthjournal.com/home

Articles in Press
Modeling the Effects of H1N1 Influenza Vaccine Distribution in the United States
05 December 2011
Richard C. Larson, Anna Teytelman

Abstract 
Objective: We analyzed the effects of the timing of vaccine distribution in 11 US states during the 2009 H1N1 influenza pandemic.

Methods: By using reported data on the fraction of patients presenting with flu-related symptoms, we developed a transformation that allowed estimation of the state-specific temporal flu wave curve, representing the number of new infections during each week. We also utilized data describing the weekly numbers of vaccine doses delivered and administered. By using a simple difference equations model of flu progression, we developed two influenza wave curves: first, an “observable” curve that included the beneficial effects of vaccinations, and second, an unobservable curve that depicted how the flu would have progressed with no vaccine administered. We fit the observable curve to match the estimated epidemic curve and early exponential growth associated with R0, the reproductive number. By comparing the number of infections in each scenario, we estimated the infections averted by the administration of vaccine.

Results: Southern states experienced peak infection several weeks before northern states, and most of the vaccine was delivered well after the peak of the southern flu wave. Our models suggest that the vaccine had minimal ameliorative impact in the southern states and measurable positive impact in the northern states. Vaccine delivery after peak also results in a smaller fraction of the population’s seeking the vaccine.

Conclusions: Our analysis suggests that current Centers for Disease Control and Prevention policy of allocating flu vaccine over time in direct proportion to states’ populations may not be best in terms of averting nationally the maximum possible number of infections.

The pdf version of Vaccines: The Week in Review  5 December 2011, comprising the posts for ths date below, is available here: Vaccines_The Week in Review_5 December 2011

    WHO noted “global progress in both preventing and treating HIV in a new report by WHO, UNICEF and UNAIDS: Report on the global HIV/AIDS response http://www.who.int/entity/hiv/pub/progress_report2011/en/index.html. The report emphasizes the benefits of sustaining investment in HIV/AIDS over the longer term and ”indicates that increased access to HIV services resulted in a 15% reduction of new infections over the past decade, and a 22% decline in AIDS-related deaths in the last five years.” Gottfried Hirnschall, Director of WHO’s HIV Department, said, “It has taken the world ten years to achieve this level of momentum. There is now a very real possibility of getting ahead of the epidemic. But this can only be achieved by both sustaining and accelerating this momentum over the next decade and beyond.”

http://www.who.int/mediacentre/news/releases/2011/hiv_20111130/en/index.html

The Global Fund to Fight AIDS, Tuberculosis and Malaria announced that “countries that benefit from its support are putting more people on life-saving AIDS treatment and preventing more babies from being born with HIV than ever before amid severe funding constraints stemming from the economic crisis.” The Global Fund’s Executive Director Professor Michel Kazatchkine “appealed to donors to increase funding, saying that while the latest results showed that programs supported by the Global Fund were delivering remarkable results, far more could be achieved with additional resources.” Professor Kazatchkine noted, “Millions of people in poor countries are relying on the Global Fund to stay alive and healthy so that they can lead normal, productive lives. But millions of others may not be reached by treatment because we lack the financial resources further to expand health programs on the scale that is required. The poor and the vulnerable must not be made to pay the price for the global financial crisis.”

http://www.theglobalfund.org/en/mediacenter/pressreleases/2011-11-30_Global_Fund-supported_programs_see_strong_results_amid_funding_challenges/

GAVI CEO Seth Berkley, in a statement marking World Aids Day, described GAVI’s role in “achieving world free from AIDS” –

“As we mark World AIDS Day this year, let there be no doubt that the world is making great progress in tackling HIV and AIDS, and with continued focus and work the end of the pandemic could be in sight.

“As the Founder, President and CEO of the International AIDS Vaccine Initiative (IAVI) and now the CEO of the GAVI Alliance, I have spent my professional life working to create prevention tools to defeat HIV/AIDS and to help people all over the world live in good health.

“We are in a renaissance in AIDS vaccine development and I hope that one day the GAVI Alliance will play its part in rolling such a vaccine out to the people we serve in developing countries.

“In the meantime, GAVI is funding vaccines that provide important protection for people living with HIV/AIDS.  Studies have shown that children with HIV/AIDS are up to 40 times more likely to contract pneumococcal disease than HIV-negative children, and may be more likely to contract antibiotic-resistant strains of the disease. Pneumococcal disease is the leading cause of pneumonia which is, in turn, the most common infection leading to hospitalization among HIV-infected children.

“This year, GAVI has successfully introduced pneumococcal vaccines in 15 developing countries and we are on track to reach 58 countries by 2015.

“Over the last four decades, so much progress has been made to defeat AIDS and now is the time to press ahead to achieve our collective vision of a world free from AIDS.

“No one should die of a disease that is preventable and we at the GAVI Alliance stand ready, willing and able to play our role in achieving a world with zero new HIV infections, zero discrimination and zero AIDS-related deaths.”

http://www.gavialliance.org/library/news/statements/2011/gavi-role-in-achieving-world-free-from-aids/

NIH Statement on World AIDS Day 2011

Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases
Jack Whitescarver, Ph.D., Director, NIH Office of AIDS Research
Francis S. Collins, M.D., Ph.D., Director, NIH

“This year, we commemorate World AIDS Day during the 30th year since the first reported cases of AIDS, a milestone that has led many to reflect on how far we have come since those dark days when HIV infection was almost always fatal. Remarkably, three decades of scientific progress in HIV/AIDS prevention and treatment have brought us to a time when we can begin to imagine an AIDS-free generation…

“…Yet we know that to end the HIV/AIDS pandemic, we must not only treat HIV infection but also prevent new infections from occurring. No single HIV prevention modality will suffice. Rather, a combination of scientifically proven HIV prevention tools will be required to end the pandemic. In collaboration with our sister agencies of the Department of Health and Human Services, other governments, nongovernmental organizations and scientists around the world, the National Institutes of Health is leading the effort to develop the scientific basis for an HIV prevention toolkit robust enough to support the goal of realizing a generation without AIDS.

As a result of NIH-sponsored research, we have known for some time that the use of antiretroviral drugs during pregnancy can prevent HIV transmission from mother to child. More recently, medically supervised adult male circumcision was shown to decrease by more than half the risk of female-to-male sexual transmission in communities where men are not circumcised. We also have long known that correct and consistent condom use can prevent sexual transmission of the virus.

“But an extraordinary burst of new scientific advances in HIV prevention during the past 18 months is fueling additional prevention research that could accelerate the pace toward our ultimate goal of ending the HIV/AIDS pandemic. For example, several clinical trials have shown that taking an antiretroviral pill as pre-exposure prophylaxis (PrEP) once a day could reduce the risk of HIV infection in certain HIV-negative populations. In addition, scientists are beginning to uncover the mechanisms behind the modest first success of a vaccine regimen against HIV infection.

“Moreover, a carefully controlled clinical trial conducted this past summer by the NIH HIV Prevention Trials Network demonstrated that treating an HIV-infected person with antiretroviral drugs can dramatically reduce the likelihood that the individual will transmit HIV to his or her heterosexual partner. This study provided further evidence that HIV treatment is prevention and can be a critical component of the HIV prevention toolkit…”

“…With great anticipation, we plan to gather with our colleagues from around the world next summer at the XIX International AIDS Conference in Washington, D.C., to determine the next steps in research that will help translate the recent advances in HIV prevention into action toward ending the pandemic. NIH will eagerly participate in this international dialogue and will continue to support and promote the discovery, development and scientific validation of HIV treatment and prevention tools until we achieve a world without HIV/AIDS….”

http://www.nih.gov/news/health/dec2011/niaid-01.htm

WHO Europe noted that “European countries must take action now to prevent continued measles outbreaks in 2012.” A report in the current Weekly Epidemiological Record http://www.who.int/entity/wer/2011/wer8649.pdf “emphasizes the urgent actions European countries should take to prevent measles outbreaks in 2012 and beyond, particularly with the approaching high season for measles transmission. More than 26,000 cases of measles occurred in 36 European countries from January-October 2011, with more than 14,000 of those in France.  Despite strong health systems, Western European countries have reported 83% of these cases. These outbreaks have caused nine deaths, including six in France, and 7288 hospitalizations.”

Ms Zsuzsanna Jakab, WHO Regional Director for Europe, said, “The increase in measles in European countries reveals a serious challenge to achieving the regional measles elimination goal by 2015. Every country in the European Region must take the opportunity now to raise coverage amongst susceptible populations, improve surveillance and severely reduce measles virus circulation before the approaching measles high season. ” The peak months for measles outbreaks in Europe are typically from February through to May. The majority of European cases (90%) were amongst adolescents and adults who had not been vaccinated or for whom vaccination history was not reported.

http://www.euro.who.int/en/what-we-publish/information-for-the-media/sections/latest-press-releases/european-countries-must-take-action-now-to-prevent-continued-measles-outbreaks-in-2012

The Bill & Melinda Gates Foundation announced new grants as part of its ongoing support to Pakistan’s polio eradication program and to assist the government’s response to this year’s floods. The grants “will fund initiatives aiming to provide assistance to polio survivors as well as address the urgent needs of families affected by the floods in parts of Sindh province.” Sindh province experienced a significant polio outbreak following the floods and currently accounts for nearly 20% of cases reported in the country. So far this year Pakistan has reported 161 cases of polio, more than any other country in the world. The Gates Foundation said it allocated more than 198 million rupees in grants for additional support to Pakistan in 2011, including a grant to WHO to support the physical rehabilitation of more than 200 children paralyzed by polio; a grant to the Government of Sindh to directly support more than 4,400 families in Umerkot and one other district affected by this year’s floods and a grant to Save the Children to support relief operations.

http://www.gatesfoundation.org/press-releases/Pages/polio-eradication-and-flood-response-pakistan-111130.aspx

The U.S. Agency for International Development unveiled a new global health strategy “to assist in its implementation of President Obama’s Global Health Initiative to address major health challenges worldwide. The Global Health Bureau’s Assistant Administrator, Dr. Ariel Pablos-Mendez, said a key component of the strategy is producing efficient results, even during times of fiscal challenges. Other components include aligning programs, partnering with wide range of actors, and countries and more investments in technological innovation.”

28 Nov 2011

http://www.c-spanvideo.org/program/HealthStr

The MMWR for December 2, 2011 / Vol. 60 / No. 47 includes:
– Increased Transmission and Outbreaks of Measles — European Region, 2011

– Progress in the Introduction of Rotavirus Vaccine — Latin America and the Caribbean, 2006–2010

– Limited Human-to-Human Transmission of Novel Influenza A (H3N2) Virus — Iowa, November 2011

– Vital Signs: HIV Prevention Through Care and Treatment — United States

– Announcement: National Influenza Vaccination Week — December 4–10, 2011

The Weekly Epidemiological Record (WER) for 2 December 2011, vol. 86, 49 (pp 557–564) includes: Fourth meeting of the Global Polio Eradication Initiative’s Independent Monitoring Board; Increased transmission and outbreaks of measles, European Region, 2011

http://www.who.int/entity/wer/2011/wer8649.pdf

Twitter Watch
A selection of items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and by no means intended to be exhaustive.

GAVIAlliance GAVI Alliance
@WHOnews estimates that over 450,000 children under 5 die from rotavirus infection- nearly 1,200 each day- ht.ly/7NnvP
3 Dec

gatesfoundation Gates Foundation
Reflecting on #WorldAIDSDay: Education and treatment provide hope for the future: gates.ly/u8gua9 #WAD11
2 Dec

GAVIAlliance GAVI Alliance
@gatesfoundation announced new grants in response of #polio eradication and flood response in Pakistan- ht.ly/7MSGG #globalhealth
2 Dec

AIDSvaccine IAVI
Susan Blumenthal op/ed: US investment in #research saves lives & provides hope for an #AIDS-free generation huff.to/sW4kpa #EndofAIDS
2 Dec

CDCFlu CDC Flu
Next week, Dec. 4-10 is National Influenza Vaccination Week! Join our Twitter chat: Dec 8, 1pm EST @ CDCFlu, #NIVW. go.usa.gov/5B2
2 Dec

pahowho PAHO/WHO
#PAHO Marks 109th Anniversary – bit.ly/u5lxtI
2 Dec

globalfundnews The Global Fund
Reading @Kazatchkine #WorldAIDSDay blog: No Funding, No #AIDS Free Generation – via @Huffpost huff.to/tu3fLr
2 Dec

WHOnews WHO
With antiretroviral drugs, patients can control HIV virus & enjoy healthy, productive lives bit.ly/s57xCg #WorldAIDSDay
1 Dec

PEPFAR PEPFAR
In honor of #WorldAIDSDay, retweet if you are thankful that an AIDS-free generation is within reach. #WAD11 #AIDSFreeGeneration
1 Dec

UNICEF UNICEF
Special Report for #WorldAIDSDay: Meeting the challenges of #AIDS with fewer financial resources bit.ly/u6Shei ~~~ #endofAIDS
1 Dec

IHME_UW IHME at UW
Nearly 300 HIV-related datasets cataloged in #GHDxData. bit.ly/tqZhbT #WorldAIDSDay
1 Dec

globalfundnews The Global Fund
We’re not stopping new programs to get us to an HIV-free generation by#2015. Lack of funding is. We’re too close to stop now! #WorldAIDSDay
1 Dec

GAVIAlliance GAVI Alliance
#GAVI CEO Seth Berkley’s #WorldAIDSDay statement ‘GAVI role in achieving world free from AIDS’ – ht.ly/7Lwgx Via @GAVISeth
1 Dec

ImmunizeAction IAC
CDC recently updated Vaccine Information Statements (VISs) for MCV/MPSV, HepA, & IPV, translations available at immunize.org/vis
1 Dec

Kazatchkine Michel Kazatchkine
We can only achieve an AIDS-free generation and end the AIDS epidemic if donors increase their committments, including to the Global Fund
1 Dec

SigridKaag Sigrid Kaag
At # Busan #HLF4 civil society, donor states, fragile countries, new donors & pvt. sector all promise to work together for aid effectiveness
30 Nov
Retweeted by UNDP

GAVIAlliance GAVI Alliance
#ICYMI:Under the GAVI Matching Fund, @DFID_UK & @gatesfoundation will match contributions from corporations&foundations ht.ly/7KaMj
30 No

globalfundnews The Global Fund
Our latest results: 3.3m on ARVs, 1.3m mothers getting PMTCT, 230m bednets delivered, 8.6m cases TB treated. bit.ly/sGZ8uL
30 Nov

British Medical Journal
03 December 2011 (Vol 343, Issue 7834)
http://www.bmj.com/content/current

Observations
Warts and all at last: HPV vaccination
Phil Hammond
BMJ 2011;343:d7779 (Published 30 November 2011)

Extract
The UK at last follows other countries in providing the Gardasil vaccine

Health campaigning, like much of public health, can be a slow, repetitive business. The media will break a big story once and then tend to lose interest unless a fresh scandal surfaces. But to change culture, opinion, or behaviour the same message may have to be drip fed over many years. And if the story doesn’t lend itself to a cute front page photo the chance of success is remote. Genital warts will never make the headlines in the Daily Mail or indeed any other newspaper—which makes the government’s decision to switch to a multipurpose vaccine against human papillomavirus all the more remarkable.1

The Lancet kicked off the campaign in October 2006, with an editorial titled “Should HPV vaccines be mandatory for all adolescents?”2 It argued that Gardasil, which protects against HPV types 6, 11, 16, and 18, could dramatically reduce not just the incidence of cervical cancer but unpleasant conditions such as genital warts, anal cancer, and other malignancies affecting both sexes. It concluded, “EU member states should lead by making the vaccinations mandatory for …

Human Vaccines
Volume 7, Issue 12  December 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/11/

Reviews
Acceptance on the move: Public reaction to shifting vaccination realities
Baruch Velan

Abstract
This review examines four events related to vaccination that have occurred in recent years: (a) the ongoing recovery from the MMR/Autism scare in the UK, (b) the upgrading of the Varicella vaccine to a universal childhood vaccine, (c) the major effort of authorities to provide a vaccine for A/H1N1 influenza and its rejection by the public, and, d) the current attempts to change the HPV vaccine target from girls only to boys and girls. All of these changes have been met with shifts in the public acceptance of the relevant vaccine. These shifts are characterized not only by the number of people willing to be vaccinated, but also by the attitudes and the motives related to acceptance. Examination of the interrelationship between changes in vaccination realities, and changes in acceptance patterns suggests that today, the public has a better understanding of vaccination, is acting in a more reflexive way, and is capable of changing attitudes and behavior. All together, changes in vaccination enhance debates and dialogues about vaccines, and lead to higher awareness and more conscious acceptance.

Human Vaccines
Volume 7, Issue 12  December 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/11/

Reviews
Rotavirus vaccines: Update on global impact and future priorities
Catherine Yen, Jacqueline E. Tate, Manish M. Patel, Margaret M. Cortese, Benjamin Lopman, Jessica Fleming, Kristen Lewis, Baoming Jiang, Jon Gentsch, Duncan Steele and Umesh D. Parashar

Abstract
Early rotavirus vaccine adopter countries in the Americas, Europe, and in Australia have documented substantial declines in rotavirus disease burden following the introduction of vaccination.  However, the full public health impact of rotavirus vaccines has not been realized as they have not been introduced into routine immunization programs in countries of Africa and Asia with the highest rotavirus disease morbidity and mortality burden.  In this article, we review the epidemiology of rotavirus disease, the development and current status of rotavirus vaccines including newly available vaccine impact data from early-introducer countries, and future priorities for implementation and monitoring of rotavirus vaccination programs in developing countries.

Human Vaccines
Volume , Issue 12  December 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/11/

Research Papers
Social and cultural determinants of anticipated acceptance of an oral cholera vaccine prior to a mass vaccination campaign in Zanzibar
Christian Schaetti, Claire-Lise Chaignat, Raymond Hutubessy, Ahmed M. Khatib, Said M. Ali, Christian Schindler and Mitchell G. Weiss

Abstract
Despite improvements in sanitation and water supply, cholera remains a serious public health burden. Vaccination is included among recommendations for cholera control. Cultural concepts of illness are likely to affect vaccine acceptance. This study examined social and cultural determinants of anticipated acceptance of an oral cholera vaccine (OCV) prior to a mass vaccination campaign in Zanzibar. Using a cultural epidemiological approach, 356 unaffected adult residents were studied with vignette-based semi-structured interviews. Anticipated acceptance was high for a free OCV (94%), but declined with increasing price. Logistic regression models examined social and cultural determinants of anticipated acceptance at low (USD 0.9), medium (USD 4.5) and high (USD 9) price. Models including somatic symptoms (low and high price), social impact (low and medium) and perceived causes (medium and high) explained anticipated OCV acceptance better than models containing only socio-demographic characteristics. Identifying thirst with cholera was positively associated with anticipated acceptance of the low-priced OCV, but acknowledging the value of home-based rehydration was negatively associated. Concern about spreading the infection to others was positively associated at low price among rural respondents. Confidence in the health system response to cholera outbreaks was negatively associated at medium price among peri-urban respondents. Identifying witchcraft as cause of cholera was negatively associated at medium and high price. Anticipated acceptance of free OCVs is nearly universal in cholera-endemic areas of Zanzibar; pre-intervention assessments of community demand for OCV should not only consider the social epidemiology, but also examine local socio-cultural features of cholera-like illness that explain vaccine acceptance.

Human Vaccines
Volume 7, Issue 12  December 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/11/

Research Papers
Determinants of tetanus and seasonal influenza vaccine uptake in adults living in Germany
Merle M. Böhmer, Dietmar Walter, Gérard Krause, Stephan Müters, Antje Gößwald and Ole Wichmann

Abstract
The primary objective of this study was to assess determinants of vaccine uptake in adults living in Germany exemplified by one standard vaccination (tetanus) and one vaccination targeting specific risk-groups (seasonal influenza). Data from 21,262 telephone household-interviews representative of the adult population in Germany were collected in 2009 and analysed. A total 73.1% of the adult population had a sufficient tetanus vaccination status according to national recommendations (i.e. last tetanus shot ≤10 years ago). Influenza vaccination coverage in the target population (i.e. persons ≥60 years, chronically ill, healthcare workers) was 44.1%. Persons who received professional vaccination advice within the past five years were more frequently vaccinated against tetanus and influenza than persons without (p<0.001). Private physicians were identified as the most important source for vaccination advice. Having a statutory health insurance, last physician contact <1 year ago, and living in the eastern part of Germany were independently associated with higher tetanus and influenza vaccine uptake. Low socio-economic status, two-sided migration background, and the feeling of being insufficiently informed on the benefits of vaccination were independently associated with low uptake of tetanus but not influenza vaccines. Our results show that tetanus vaccination coverage in the general adult population and influenza vaccination coverage in the target population are unsatisfactorily low in Germany. Since physicians’ advice has a major impact on the vaccination decision, physician reminder systems could provide a method to increase vaccination coverage in adults. For tetanus, information activities should target population groups with an increased risk of being undervaccinated.

Human Vaccines
Volume 7, Issue 12  December 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/11/

COMMENTARIES
Hepatitis B Vaccine in national immunization schedule: A preventive step in India
Ramesh Verma, Pardeep Khanna, Shankar Prinja, Meena Rajput, Suraj Chawla and Mohan Bairwa

Abstract
Hepatitis B is a disease of the liver caused by Hepatitis B virus (HBV) infection. HBV is transmitted through contact with infected blood or body fluids, unprotected sexual intercourse and the perinatal route but not through casual contact. About two billion people worldwide have been infected with the virus, an estimated 360 million live with chronic infection, and at least 600,000 people die annually from acute or chronic consequences of Hepatitis B, such that Hepatitis B is a major public health problem worldwide. HBV is 50 to 100 times more infectious than HIV. It has been estimated that, of the 25 million infants born every year in India, over one million run the lifetime risk of developing chronic HBV infection. Every year over 100,000 Indians die due to illnesses related to HBV infection. Following the launch of the Global Alliance for Vaccines and Immunization (GAVI) to intensify National Immunization Programs (NIPs) in developing countries worldwide. World Health Organization (WHO) recommends that Hepatitis B vaccine should be given to all infants. Several cost-effectiveness analyses of inclusion of Hepatitis B vaccine in India’s NIP have been performed. These indicate that universal childhood Hepatitis B immunization in India will be highly cost-effective. The Government of India is also supporting planned state programs for introducing new vaccines as part of routine immunization. The current immunization schedule for hepatitis B vaccine includes a dose given as early as possible after birth, preferably within 24 hours for all institutional deliveries because the birth dose of Hepatitis B vaccine is effective in preventing perinatal transmission of Hepatitis B. Irrespective of the birth dose, 3 doses are to be given at 6, 10, 14 weeks at the same time as DPT and OPV.

The Lancet  
Dec 03, 2011  Volume 378  Number 9807  p1895 – 1974  e12 – 18
http://www.thelancet.com/journals/lancet/issue/current

Editorial
The Global Fund and a new modus operandi
The Lancet

Preview
On Nov 21–22, the Global Fund to Fight AIDS, Tuberculosis and Malaria held its 25th Board meeting in Accra, Ghana. Tensions were high as the Fund had to make difficult decisions in a year that has been plagued by financial shortfalls, corruption, and calls for organisational reforms. In view of the financial challenges presented by the US budget environment and the Euro crisis, the Fund has now decided to cancel grant funding for round 11, which will be a huge setback to these disease programmes worldwide.

The Lancet  
Dec 03, 2011  Volume 378  Number 9807  p1895 – 1974  e12 – 18
http://www.thelancet.com/journals/lancet/issue/current

Articles
Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis
Harish Nair, W Abdullah Brooks, Mark Katz, Anna Roca, James A Berkley, Shabir A Madhi, James Mark Simmerman, Aubree Gordon, Masatoki Sato, Stephen Howie, Anand Krishnan, Maurice Ope, Kim A Lindblade, Phyllis Carosone-Link, Marilla Lucero, Walter Ochieng, Laurie Kamimoto, Erica Dueger, Niranjan Bhat, Sirenda Vong, Evropi Theodoratou, Malinee Chittaganpitch, Osaretin Chimah, Angel Balmaseda, Philippe Buchy, Eva Harris, Valerie Evans, Masahiko Katayose, Bharti Gaur, Cristina O’Callaghan-Gordo, Doli Goswami, Wences Arvelo, Marietjie Venter, Thomas Briese, Rafal Tokarz, Marc-Alain Widdowson, Anthony W Mounts, Robert F Breiman, Daniel R Feikin, Keith P Klugman, Sonja J Olsen, Bradford D Gessner, Peter F Wright, Igor Rudan, Shobha Broor, Eric AF Simões, Harry Campbell

Summary
Background

The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years.

Methods
We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality.

Findings
We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49—162 million) new cases of influenza (data from nine studies), 20 million (13—32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1—2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28 000—111 500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting.

Interpretation
Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available.

Funding
WHO; Bill & Melinda Gates Foundation.

The Lancet  
Dec 03, 2011  Volume 378  Number 9807  p1895 – 1974  e12 – 18
http://www.thelancet.com/journals/lancet/issue/current

Review
Serotype replacement in disease after pneumococcal vaccination
Daniel M Weinberger, Richard Malley, Marc Lipsitch

Summary
Vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of pneumococcal disease and has had an important public health benefit. Because this vaccine targets only seven of the more than 92 pneumococcal serotypes, concerns have been raised that non-vaccine serotypes (NVTs) could increase in prevalence and reduce the benefits of vaccination. Indeed, among asymptomatic carriers, the prevalence of NVTs has increased substantially, and consequently, there has been little or no net change in the bacterial carriage prevalence. In many populations, pneumococcal disease caused by NVT has increased, but in most cases this increase has been less than the increase in NVT carriage. We review the evidence for serotype replacement in carriage and disease, and address the surveillance biases that might affect these findings. We then discuss possible reasons for the discrepancy between near-complete replacement in carriage and partial replacement for disease, including differences in invasiveness between vaccine serotypes. We contend that the magnitude of serotype replacement in disease can be attributed, in part, to a combination of lower invasiveness of the replacing serotypes, biases in the pre-vaccine carriage data (unmasking), and biases in the disease surveillance systems that could underestimate the true amount of replacement. We conclude by discussing the future potential for serotype replacement in disease and the need for continuing surveillance.

New England Journal of Medicine
December 1, 2011  Vol. 365 No. 22
http://content.nejm.org/current.shtml

Correspondence
2137-2138
Intussusception Risk of Rotavirus Vaccination
[Free Full Text]

Intussusception after Rotavirus Vaccination — Spontaneous Reports
[Free Full Text]

Pediatrics
December 2011, VOLUME 128 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Articles
Immunogenicity and Safety of MMRV and PCV-7 Administered Concomitantly in Healthy Children
Michael Leonardi, Kenneth Bromberg, Roger Baxter, Julie L. Gardner, Stephanie Klopfer, Ouzama Nicholson, Michael Brockley, James Trammel, Vicky Leamy, Wendy Williams, Barbara Kuter, and Florian Schödel
Pediatrics 2011; 128:e1387-e1394

Abstract
OBJECTIVE: We assessed the immunogenicity and safety of a combination measles, mump, rubella, and varicella vaccine (MMRV) (ProQuad [Merck & Co, Inc, West Point, PA]) administered to healthy children concomitantly with a pneumococcal 7-valent conjugate vaccine (PCV-7) (Prevnar [Pfizer, Philadelphia, PA]).

PATIENTS AND METHODS: Healthy 12- to 15-month-old children who lacked vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster but had written documentation of receipt of a 3-dose primary series of PCV-7 were randomly assigned in a 2:1:1 ratio to receive either the MMRV and PCV-7 (group 1), PCV-7 followed 6 weeks later by MMRV (group 2), or MMRV followed 6 weeks later by PCV-7 (group 3). The primary safety analysis was 56 days (28 days after each visit). Immunogenicity was evaluated 6 weeks after each vaccination.

RESULTS: A total of 1027 children were enrolled (group 1: 510; group 2: 258; group 3: 259). For all 3 groups, the antibody response rate was ≥96.8% for measles, mumps, and rubella, ≥88.0% for varicella-zoster virus, and ≥98.3% for all of the 7 Streptococcus pneumoniae serotypes. The immune responses to all antigens present in MMRV and PCV-7 were similar whether administered concomitantly or sequentially. The incidence of local and systemic adverse experiences (AEs) was comparable between group 1 and groups 2 and 3 combined. No vaccine-related serious AEs were reported.

CONCLUSIONS: Concomitant administration of the MMRV and PCV-7 is highly immunogenic and generally well tolerated. Similar immune responses between the groups support concomitant administration of the MMRV and PCV-7 to healthy children 12 to 15 months of age.

Pediatrics
December 2011, VOLUME 128 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Articles
Varicella in Infants After Implementation of the US Varicella Vaccination Program
Sandra S. Chaves, Adriana S. Lopez, Tureka L. Watson, Rachel Civen, Barbara Watson, Laurene Mascola, and Jane F. Seward
Pediatrics 2011; 128:1071-1077

Abstract
OBJECTIVE: To describe varicella disease in infants since implementation of the varicella vaccination program in the United States.

PATIENTS AND METHODS: From 1995 to 2008, demographic, clinical, and epidemiologic data on cases of varicella in infants were collected prospectively through a community-based active surveillance project. We examined disease patterns for infants in 2 age groups: 0 to 5 and 6 to 11 months.

RESULTS: Infant varicella disease incidence declined 89.7% from 1995 to 2008. Infants aged 0 to 5 months had milder clinical disease than those aged 6 to 11 months: ≥50 lesions, 49% vs 58% (P = .038); fever (body temperature > 38°C), 12% vs 21% (P = .014); and varicella-related complications, 6% vs 14% (P = .009), respectively. Age was an independent predictor of the occurrence of complications.

CONCLUSIONS: The varicella vaccination program has resulted in substantial indirect benefits for infants, who are not eligible for vaccination. Presence of maternal varicella-zoster virus antibodies might explain attenuated disease in very young infants likely born to mothers with history of varicella. Although varicella disease incidence has declined, exposure to varicella-zoster virus continues to occur. Improving varicella vaccination coverage in all age groups will further reduce the risk of varicella exposure and protect those not eligible for varicella vaccination.

Pediatrics
December 2011, VOLUME 128 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Articles
Adolescent Vaccination-Coverage Levels in the United States: 2006–2009
Shannon Stokley, Amanda Cohn, Christina Dorell, Susan Hariri, David Yankey, Nancy Messonnier, and Pascale M. Wortley
Pediatrics 2011; 128:1078-1086

Abstract
BACKGROUND: From 2005 through 2007, 3 vaccines were added to the adolescent vaccination schedule: tetanus-diphtheria-acellular pertussis (TdaP); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) for girls.

OBJECTIVE: To assess implementation of new adolescent vaccination recommendations.

METHODS: Data from the 2006–2009 National Immunization Survey–Teen, an annual provider-verified random-digit-dial survey of vaccination coverage in US adolescents aged 13 to 17 years, were analyzed. Main outcome measures included percentage of adolescents who received each vaccine according to survey year; potential coverage if all vaccines were administered during the same vaccination visit; and, among unvaccinated adolescents, the reasons for not receiving vaccine.

RESULTS: Between 2006 and 2009, ≥1 TdaP and ≥1 MenACWY coverage increased from 11% to 56% and 12% to 54%, respectively. Between 2007 and 2009, ≥1 HPV coverage among girls increased from 25% to 44%; between 2008 and 2009, ≥3 HPV coverage increased from 18% to 27%. In 2009, vaccination coverage could have been >80% for Td/TdaP and MenACWY and as high as 74% for the first HPV dose if providers had administered all recommended vaccines during the same vaccination visit. For all years, the top reported reasons for not vaccinating were no knowledge about the vaccine, provider did not recommend, and vaccine is not needed/necessary (for TdaP and MenACWY) and adolescent is not sexually active, no knowledge about the vaccine, and vaccine is not needed/necessary (for HPV).

CONCLUSIONS: Adolescent vaccination coverage is increasing but could be improved. Strategies are needed to increase parental knowledge about adolescent vaccines and improve provider recommendation and administration of all vaccines during the same visit.

Pediatrics
December 2011, VOLUME 128 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Articles
Financial Impact to Providers Using Pediatric Combination Vaccines
Angela K. Shen, Elizabeth Sobczyk, Lone Simonsen, Farid Khan, Allahna Esber, and Margie C. Andreae
Pediatrics 2011; 128:1087-1093

Abstract
OBJECTIVE: To understand the financial impact to providers for using a combination vaccine (Pediarix [GlaxoSmithKline Biologicals, King of Prussia, PA]) versus its equivalent component vaccines for children aged 1 year or younger.

METHODS: Using a subscription remittance billing service offered to private-practice office-based physicians, we analyzed charge and payment information submitted by providers to insurance payers from June 2007 through July 2009. We analyzed provider and payer characteristics, payer comments, and the ratio of vaccine product to immunization administration (IA) codes and computed total charges and payments to providers for both arms of the study.

RESULTS: Most providers in our data set were pediatricians (74%), and most payers were commercial (75%), primarily managed care. The ratio of the number of vaccine products to the number of IAs was 1:1 in the majority of the claims. Twenty percent of claims were paid with no adjustment by the payer, whereas 76% of the claims were adjusted for charges that exceeded the contract arrangement or the fee schedule. Providers received $23 less from commercial payers and $13 less from Medicaid for the use of Pediarix compared with the equivalent component vaccines. The mean commercial payment was greater for age-specific Current Procedural Terminology IA codes 90465 and 90466 than for non–age-specific codes 90471 and 90472, whereas the reverse was true for Medicaid.

CONCLUSIONS: Providers who administer vaccines to children face a reduction in payment when choosing to provide combination vaccines. The new IA codes should be monitored for correction of financial barriers to the use of combination vaccines.