Vaccines: The Week in Review 5 December 2011 Center for Vaccine Ethics & Policy (CVEP)

http://centerforvaccineethicsandpolicy.wordpress.com/ 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 - Childrens Hospital of Philadelphia, Vaccine Education Center http://www.chop.edu/service/vaccine-education-center/home.html
This weekly summary targets news and events in global vaccines ethics and policy gathered from key governmental, NGO and industry sources, key journals and other sources. This summary supports 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 pdf form and as a set of blog posts at http://centerforvaccineethicsandpolicy.wordpress.com/. This blog allows full-texting searching of some 2,000 content items. Comments and suggestions should be directed to David R. Curry, MS Editor and Executive Director Center for Vaccine Ethics & Policy david.r.curry@centerforvaccineethicsandpolicy.org

[Editors Note: World Aids Day was observed on 1 December with announcements from a range of global organizations. In addition to those highlighted, please scan Twitter Watch below for additional content.] 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 Funds 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/2011-1130_Global_Fundsupported_programs_see_strong_results_amid_funding_challenges/ GAVI CEO Seth Berkley, in a statement marking World Aids Day, described GAVIs 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-inachieving-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 HIVinfected 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-themedia/sections/latest-press-releases/european-countries-must-take-actionnow-to-prevent-continued-measles-outbreaks-in-2012

The Bill & Melinda Gates Foundation announced new grants as part of its ongoing support to Pakistans polio eradication program and to assist the governments response to this years 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 years floods and a grant to Save the Children to support relief operations. http://www.gatesfoundation.org/press-releases/Pages/polio-eradication-andflood-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, 20062010 - 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 410, 2011

The Weekly Epidemiological Record (WER) for 2 December 2011, vol. 86, 49 (pp 557564) includes: Fourth meeting of the Global Polio Eradication Initiatives 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 Were not stopping new programs to get us to an HIV-free generation by#2015. Lack of funding is. Were 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

Journal Watch [Editors 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. If you would like to suggest other journal titles to include in this service, please contact David Curry at: david.r.curry@centerforvaccineethicsandpolicy.org Annals of Internal Medicine November 15, 2011; 155 (10) http://www.annals.org/content/current [Reviewed earlier; No relevant content] British Medical Bulletin Volume 99 Issue 1 September 2011 http://bmb.oxfordjournals.org/content/current [Reviewed earlier; No relevant content] 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 doesnt 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 newspaperwhich makes the governments 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 Cost Effectiveness and Resource Allocation (accessed 4 December 2011) http://www.resource-allocation.com/ [No new relevant content] Emerging Infectious Diseases Volume 17, Number 12December 2011 http://www.cdc.gov/ncidod/EID/index.htm [No relevant content] Health Affairs November 2011; Volume 30, Issue 11 http://content.healthaffairs.org/content/current Theme: Linking Community Development & Health [Reviewed earlier; No relevant content] Health Economics, Policy and Law Volume 6 - Issue 04 - 01 October 2011 http://journals.cambridge.org/action/displayIssue?jid=HEP&tab=currentissue [Reviewed earlier]

Health Policy and Planning Volume 26 Issue 6 November 2011 http://heapol.oxfordjournals.org/content/current [Reviewed earlier] 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. 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. 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 homebased 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. Determinants of tetanus and seasonal influenza vaccine uptake in adults living in Germany Merle M. Bhmer, Dietmar Walter, Grard Krause, Stephan Mters, Antje Gwald 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. 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 Indias NIP have been performed. These indicate that universal childhood Hepatitis B immunization in India will be highly costeffective. 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. International Journal of Infectious Diseases Volume 15, Issue 12, Pages e807-e888 (December 2011) http://www.sciencedirect.com/science/journal/12019712 [No relevant content] JAMA November 23/30, 2011, Vol 306, No. 20, pp 2187-2283 http://jama.ama-assn.org/current.dtl [No relevant content]

Journal of Infectious Diseases Volume 204 Issue 12 December 15, 2011 http://www.journals.uchicago.edu/toc/jid/current [No relevant content] 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 2122, 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. 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'CallaghanGordo, 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 Simes, 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 49162 million) new cases of influenza (data from nine studies), 20 million (1332 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (12 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 000111 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. 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. The Lancet Infectious Disease

Dec 2011 Volume 11 Number 12 p887 - 970 http://www.thelancet.com/journals/laninf/issue/current [Reviewed earlier] Medical Decision Making (MDM) November/December 2011; 31 (6) http://mdm.sagepub.com/content/current [No relevant content] Nature Volume 480 Number 7375 pp5-144 1 December 2011 http://www.nature.com/nature/current_issue.html [No relevant content] Nature Medicine November 2011, Volume 17 No 11 http://www.nature.com/nm/index.html [No relevant content] 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] The Pediatric Infectious Disease Journal December 2011 - Volume 30 - Issue 12 pp: 1019-1051,e225-e247 http://journals.lww.com/pidj/pages/currenttoc.aspx [No relevant content] 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 Schdel 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. 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 > 38C), 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. 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 20062009 National Immunization SurveyTeen, 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. 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 privatepractice 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 nonage-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. Welfare, Maternal Work, and On-Time Childhood Vaccination Rates Min-Woong Sohn, Joan Yoo, Elissa H. Oh, Laura B. Amsden, and Jane L. Holl Pediatrics 2011; 128:1109-1116 Abstract OBJECTIVE: To examine effects of Temporary Assistance for Needy Families welfare cash assistance and maternal work requirements on on-time childhood vaccination rates. METHODS: A stratified random sample of Illinois children from low-income families affected by welfare reform was monitored from 1997 to 2004. Medical records from pediatricians' offices and Medicaid claims data were used to identify the timeliness of 18 recommended vaccinations. Randomintercept logistic models were used to estimate on-time vaccine administration as a function of welfare receipt and maternal work with adjustment for characteristics of the children and mothers and time-varying covariates pertaining to the administration window for each recommended vaccine dose. RESULTS: Of all recommended vaccinations, 55.9% were administered on time. On-time vaccination rates were higher when families were receiving welfare than not (57.4% vs 52.8%). Children in families that either were receiving welfare or had working mothers were 1.7 to 2.1 times more likely to receive vaccinations on time compared with children in families that were not receiving welfare and did not have working mothers. When vaccine doses were stratified according to welfare status, maternal work was associated with decreased on-time vaccination rates (odds ratio: 0.73 [95% confidence interval: 0.590.90]) when families received welfare but increased on-time vaccination rates (odds ratio: 1.68 [95% confidence interval: 1.272.22]) when they did not receive welfare. CONCLUSIONS: These results indicate that maternal work requirements of Temporary Assistance for Needy Families had negative effects on timely administration of childhood vaccinations, although receipt of welfare itself was associated with increased on-time rates.

Commentaries Reflections on US Immunization Challenges: Lady Montague, Where Are You? Edgar K. Marcuse Pediatrics 2011; 128:1192-1194 Extract Dickens' oft-quoted words describe well the opportunities and challenges of US immunization programs: the best of times the worst of times the age of wisdom the age of foolishness .1 Vaccine-preventable disease rates are low, and immunization rates are high, but the broad societal consensus that supported the US immunization program has eroded.2 Our new understanding of immunology, along with new technologies, has launched a renaissance in vaccine research that holds real promise of preventing more infections and their sequelae, but not all US children are yet ensured timely access to all recommended vaccines. The transfer of most immunization from public clinics to physicians' offices has resulted in the cross-subsidy of public health by primary care, which, because of the economics of vaccine administration, is unsustainable. In the world of adult medicine, the gap between what we have and what we could achieve if we fully used the vaccines now in hand is even greater. As a nation, we talk of the value of prevention, of reining in health care costs, but we fail to walk the talk. We seem to have lost sight of the interface between public health and the individual health of all the members of our communities.3 Today there Pharmacoeconomics December 1, 2011 - Volume 29 - Issue 12 pp: 1011-1014 http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx [Reviewed earlier] PLoS One [Accessed 4 December 2011] http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DA A533C413369CD6F3.ambra01?field=date Do People Taking Flu Vaccines Need Them the Most? Qian Gu, Neeraj Sood PLoS ONE: Research Article, published 02 Dec 2011 10.1371/journal.pone.0026347 Abstract Background A well targeted flu vaccine strategy can ensure that vaccines go to those who are at the highest risk of getting infected if unvaccinated. However, prior research has not explicitly examined the association between the risk of flu infection and vaccination rates. Purpose This study examines the relationship between the risk of flu infection and the probability of getting vaccinated. Methods

Nationally representative data from the US and multivariate regression models were used to estimate what individual characteristics are associated with (1) the risk of flu infection when unvaccinated and (2) flu vaccination rates. These results were used to estimate the correlation between the probability of infection and the probability of getting vaccinated. Separate analyses were performed for the general population and the high priority population that is at increased risk of flu related complications. Results We find that the high priority population was more likely to get vaccinated compared to the general population. However, within both the high priority and general populations the risk of flu infection when unvaccinated was negatively correlated with vaccination rates (r = 0.067, p<0.01). This negative association between the risk of infection when unvaccinated and the probability of vaccination was stronger for the high priority population (r = 0.361, p<0.01). Conclusions There is a poor match between those who get flu vaccines and those who have a high risk of flu infection within both the high priority and general populations. Targeting vaccination to people with low socioeconomic status, people who are engaged in unhealthy behaviors, working people, and families with kids will likely improve effectiveness of flu vaccine policy. Using the Indirect Cohort Design to Estimate the Effectiveness of the Seven Valent Pneumococcal Conjugate Vaccine in England and Wales Nick Andrews, Pauline A. Waight, Ray Borrow, Shamez Ladhani, Robert C. George, Mary P. E. Slack, Elizabeth Miller PLoS ONE: Research Article, published 02 Dec 2011 10.1371/journal.pone.0028435 Abstract Background The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2,3 and 13month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD. Methods and Findings We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine type (n = 919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we

estimated that effectiveness estimates may be overestimated by about 2 to 5%. Conclusions This study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine. PLoS Medicine (Accessed 4 December 2011) http://www.plosmedicine.org/article/browse.action?field=date [No new relevant content] Proceedings of the National Academy of Sciences of the United States of America (Accessed 4 December 2011) http://www.pnas.org/content/early/recent [No new relevant content] Science 2 December 2011 vol 334, issue 6060, pages 1173-1312 http://www.sciencemag.org/current.dtl [No relevant content] Science Translational Medicine 30 November 2011 vol 3, issue 111 http://stm.sciencemag.org/content/current [No relevant content] Tropical Medicine & International Health December 2011 Volume 16, Issue 12 Pages 14651561 http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-3156/currentissue [No relevant content] Vaccine http://www.sciencedirect.com/science/journal/0264410X Volume 30, Issue 1 pp. 1-102 (9 December 2011) Regular Papers Progress in newborn hepatitis B vaccination by birth year cohorts 19982007, USA

Pages 14-20 Zhen Zhao, Trudy V. Murphy, Lisa Jacques-Carroll Abstract Background In 1999, the American Academy of Pediatrics (AAP) and the U.S. Public Health Service (USPHS) issued a joint statement on thimerosal in vaccines, which advised clinicians to temporarily postpone the first dose of hepatitis B vaccine for infants born to hepatitis B surface antigen (HBsAg)-negative women. In 2005, the Advisory Committee on Immunization Practices (ACIP) updated the strategy to improve prevention of perinatal and early childhood hepatitis B virus (HBV) transmission. Objectives To evaluate the progress in hepatitis B birth dose vaccination coverage in birth year cohort from 1998 to 2007 and assess the impact of changes in ACIP recommendations on the birth dose coverage. Methods Birth year cohort study of hepatitis B birth dose vaccination status of 200,865 children aged 1935 months in the United States and by selected sociodemographic factors; percentage increases of hepatitis B birth dose vaccination coverage between two consecutive birth year cohorts from 1998 to 2007. Results From 1998 to 1999, hepatitis B birth dose vaccination coverage declined overall in the United States and among selected socio-demographic groups (P < 0.001). Conversely, from 1999 to 2007 hepatitis B birth dose vaccination coverage increased significantly by birth year cohort (P < 0.001), from approximately 30% in the 1999 birth year cohort to approximately 60% in the 2007 birth year cohort. The first significant increase in hepatitis B birth dose vaccination coverage occurred from 2000 to 2001 birth year cohort. Coverage increases ranged from 8.4% to 11.9% (P < 0.001) in the U.S. and across all socio-demographic strata. The second largest increase in hepatitis B birth dose vaccination coverage occurred from 2005 to 2006 birth year cohort in the U.S. and among almost all socio-demographic strata, ranging from 5.6% to 8.7% (P < 0.001). Forty-one of the 50 states and the District of Columbia (80%) in the U.S. had increases in hepatitis B birth dose vaccination coverage from 2005 to 2006 birth year cohort. Conclusions The United States has made substantial progress in increasing hepatitis B birth dose vaccination and recovered from coverage declines associated with temporary postponement of the birth dose in 1999. The hepatitis B birth dose coverage in the U.S. remains substantially below the Healthy People 2020 target of 85%. Vaccine Volume 29, Issue 52 pp. 9573-9722 (6 December 2011) http://www.sciencedirect.com/science/journal/0264410X Editorial Methods in vaccine effectiveness and safety studies: A critical need for vaccine confidence

Pages 9573-9574 Steven J. Jacobsen, Gregory A. Poland Reviews School-based vaccination: A systematic review of process evaluations Pages 9588-9599 Spring Chenoa Cooper Robbins, Kirsten Ward, S. Rachel Skinner Abstract Objective School-based vaccination is becoming a more widely used method of vaccine delivery. However, evaluations of school-based vaccination program implementation have not been systematically reviewed. This paper describes the results of a systematic review of the literature on process (or implementation) evaluations of school-based vaccination delivery. Methods Search terms: school based vaccination OR ((schools OR school) AND (immunisation OR immunization OR vaccination)). Limits: Humans; English language; Age: 618 (school-age children and adolescents); No editorials; No letters. Databases: PUBMED; ; Cochrane Database of Systematic Reviews; Cinahl; Web of Science; PsycINFO. Inclusions: Articles must have originated from an advanced economic developed country, be peer-reviewed, available in English, randomised or non-randomised controlled design, published from 1970 to August 2010 and focused on vaccinations provided in the school setting and during school time which reported one or more outcomes. Exclusions: qualitative or descriptive papers without any evaluation component; papers that only reported on impact evaluation (i.e. number of students vaccinated); and those published before 1970. Results A total of 14 articles were identified as including some element of a process evaluation of a school-based vaccination program. Nurses, parents, teachers, and adolescents were involved in measures of procedural factors related to school-based vaccination implementation. Outcomes included return rates of consent forms; knowledge about the specific vaccine offered; attitudes toward vaccination and school-based vaccination; reasons for nonvaccination; resources, support, and procedures related to implementation; and environmental factors within the school that may impact vaccination success. Vaccination coverage was also reported in the majority of papers. Regular Papers Financing and systems barriers to seasonal influenza vaccine delivery in community settings Pages 9632-9639 Robert B. Penfold, Donna Rusinak, Tracy A. Lieu, Abigail Shefer, Mark Messonnier, Grace M. Lee Abstract Background Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings.

Methods Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n = 65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach. Results Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-tostate variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a trusted broker to overcome existing challenges. Conclusions Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public health partners at the federal, state, and local levels are well-positioned to facilitate the engagement of all stakeholders in this important and complex vaccine delivery system. Pharmacoeconomic assessment of implementing a universal PCV-13 vaccination programme in the Valencian public health system (Spain) Pages 9640-9648 Javier Dez-Domingo, Manuel Ridao-Lpez, M. Victoria Gutirrez-Gimeno, Joan Puig-Barber, Jose A. Lluch-Rodrigo, Eliseo Pastor-Villalba Abstract Background Heptavalent pneumococcal conjugate vaccine (PCV-7) was licensed to provide immunity against pneumococcal disease caused by seven serotypes of S. pneumoniae. Thirteen-valent pneumococcal conjugate vaccine (PCV-13) includes 6 additional serotypes for preventing invasive pneumococcal disease. Objective The objective of this study was to estimate the potential health benefits, costs, and cost-effectiveness of vaccination with PCV-13 in the Community of Valencia and to generate valuable information for policy makers at regional and country levels. Methods A decision tree was designed to determine the health and economic outcomes in hypothetical cohorts of vaccinated and unvaccinated children followed over their lifetime. Information about disease incidence and

serotype distribution were gathered from local databases and from published and unpublished local records. PCV-13 effectiveness was extrapolated from PCV-7 efficacy data. A 5% of herd effect and a serotype replacement of 25% were considered for the base case scenario. Only direct costs were taken into account and results were expressed in terms of life-years gained (LYG) and quality adjusted life years (QALY). Results Implementing a universal PCV-13 vaccination program in the Community of Valencia would decrease the number of hospital admitted pneumonia to less than 4571 cases while avoiding 310 cases of IPD and 82,596 cases of AOM throughout the cohort lifetime. A total of 190 S. pneumoniae related deaths would be averted over the same period. Total medical costs of nonvaccinating the cohort of newborns would reach up to 403,850.859 compared to 438,762.712 that would represent vaccinating the cohort. The incremental cost of vaccinating the children was estimated in 12,794 /LYG and 10,407 /QALY, respectively. Uptake of the human papillomavirus-vaccination within the free-ofcharge childhood vaccination programme in Denmark Pages 9663-9667 Katarina Widgren, Jacob Simonsen, Palle Valentiner-Branth, Kre Mlbak Abstract Background Persistent infection with human papillomavirus (HPV) is a prerequisite for cervical cancer, which causes 175 yearly deaths and substantial morbidity in Denmark. In January 2009, HPV-vaccination for 12 year-old girls was introduced into the free-of-charge childhood vaccination programme. Due to concerns about potential poor compliance we determined the uptake and identified determinants for vaccination after the first year of the programme. Methods All vaccinations given within the vaccination programme are reported to a central register, which we linked to demographic information found in the Danish civil register. We calculated vaccination uptake and used Cox regression survival analysis to compare the uptake rates between demographic subgroups in the population, e.g. by number of siblings, age of mother (at the daughter's birth) and place of origin. Results The uptake among the 33,838 eligible girls was 80%, 75% and 62% respectively for the three HPV-doses. All subgroups had uptake above 68% for the first HPV-vaccination. Girls with mothers younger or older than the reference group of 2534 years had a lower uptake rate (adjHR 0.94, 95% CI 0.910.97 and adjHR 0.91, 95% CI 0.880.94 respectively). Girls with 5 or more siblings had lower uptake rate than girls without siblings (adjHR 0.79, 95% CI 0.710.87). Girls born in other EU/EFTA-countries had lower uptake rate than Danish-born girls with Danish-born parents (adjHR 0.74, 95% CI 0.670.82). Conclusions The introduction of routine HPV-vaccination in Denmark resulted in a relatively high uptake, indicating little reason for major concern about barriers towards the vaccination in Denmark. Population groups with reduced uptake were identified, but as they were small in number their effect on the

overall vaccination coverage was marginal. Nonetheless, these groups should be targeted in future acceptance studies and vaccination awareness campaigns. Value in Health November 2011, Vol. 14, No. 7 http://www.valueinhealthjournal.com/home [Reviewed earlier; No relevant content]