The pdf version of Vaccines: The Week in Review  31 October 2011, comprising the posts below for this date, is available here: Vaccines_The Week in Review_31 October 2011

    WHO Europe said that Member States in the WHO European Region “continue to struggle with the uninterrupted spread of measles, reporting more than 26,000 confirmed cases in the first seven months of 2011, representing a 276% increase from a comparable period in 2007. Zsuzsanna Jakab, WHO Regional Director for Europe, said, “We call on countries to respond to this Region-wide epidemic. The Region has set the goal of eliminating measles by 2015, but these outbreaks pose a serious threat to that goal. Measles is not the harmless infection that some people seem to believe it is, and where we can prevent illness and death, we must do so.” From January to July 2011, 40 of the 53 countries in the Region reported 26,025 measles cases, with the largest burden falling on western Europe. Nevertheless, WHO said that the actual number of cases is estimated to be higher, due to delays in reporting and to underreporting. Measles has led to 9 deaths in the Region this year, 7 of them in people over ten years old. The predominant genotype circulating in the European Region is D4, which has been endemic in some countries since 2008.

http://www.euro.who.int/en/what-we-publish/information-for-the-media/sections/latest-press-releases/measles-virus-continues-to-spread-in-the-european-region-who-calls-on-countries-to-step-up-response

UNICEF and partners said that one hundred days since famine was declared in parts of southern Somalia, they “are doing their utmost to prevent a second and potentially more devastating wave of deaths from disease against a background of conflict.” In Mogadishu, a UNICEF and WHO-supported measles vaccination campaign began this week for 750,000 children between six months and 15 years old. Since the declaration of famine in July, more than 1 million children have been vaccinated against measles in Somalia.

     The World Intellectual Property Organization (WIPO) and BIO Ventures for Global Health (BVGH) announced WIPO Re:Search – “an (unprecedented) new consortium where public and private sector organizations share valuable intellectual property (IP) and expertise with the global health research community to promote development of new drugs, vaccines, and diagnostics to treat neglected tropical diseases, malaria, and tuberculosis.” WIPO Director General Francis Gurry commented, “WIPO Re:Search is a ground breaking example of how a multi-stakeholder coalition can put IP to work for social benefit. By joining WIPO Re:Search, companies and researchers commit to making selected intellectual property assets available under royalty-free licenses to qualified researchers anywhere in the world for research and development on neglected tropical diseases, malaria, and tuberculosis. This commitment should accelerate the development of medicines, vaccines, and diagnostics for these diseases.”

WIPO Re:Search involves the following organizations at launch: Alnylam Pharmaceuticals, AstraZeneca, Eisai, GlaxoSmithKline, Merck/MSD, Novartis, Pfizer,    Sanofi, NIH, California Institute of Technology, Center for World Health & Medicine,     Drugs for Neglected Diseases, Fundação Oswaldo Cruz (Fiocruz), Massachusetts Institute of Technology, Medicines for Malaria Venture, PATH, South African Medical Research Council, Swiss Tropical and Public Health Institute, University of California, Berkeley, and University of Dundee (UK). Membership in WIPO Re:Search as “a user, provider, or supporter is open to all organizations that endorse, adhere to, and support the project’s Guiding Principles.” These Guiding Principles include the commitment that IP licensed via WIPO Re:Search will be licensed on a royalty-free basis for research and development on neglected tropical diseases in any country and on a royalty-free basis for sale of neglected tropical disease medicines in, or to, least developed countries.

The WIPO Re:Search database includes “a wide variety of contributions relevant to malaria, tuberculosis, and other neglected tropical diseases, including individual compounds and associated data, screening hits from compound libraries, and expertise and know-how in pharmaceutical research and development. In addition, WIPO Re:Search offers the opportunity for neglected tropical disease researchers to work directly with scientists at pharmaceutical companies to advance R&D on these diseases.”

http://www.wipo.int/pressroom/en/articles/2011/article_0026.html

The Gates Foundation announced that Commonwealth leaders gathered in Perth, Australia to announce new funding for the global fight against polio ahead of this year’s bi-annual Commonwealth Heads of Government Meeting. The Australian government announced a commitment of AUS$50 million to the Global Polio Eradication Initiative (GPEI). The Nigerian government pledged an increase from 2011 of a planned US$17 million to an annual contribution of US$30 million starting in 2012. The Gates Foundation pledged an additional US$40 million to GPEI for the remainder of 2011.

http://www.gatesfoundation.org/press-releases/Pages/commonwealth-contributions-to-polio-111028.aspx

    Merck/MSD announced that the U.S. Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) voted to recommend that boys 11 to 12 years old be vaccinated routinely with GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] to help prevent anal cancer caused by human papillomavirus (HPV) types 16 and 18, anal dysplasias and precancerous lesions caused by HPV types 6, 11, 16 and 18, and genital warts caused by HPV types 6 and 11. Additionally, the Committee recommended that GARDASIL be administered to males 13 to 21 years of age who have not previously been vaccinated or have not completed the three-dose series, and that the vaccination series can be started at age 9 years at the discretion of their physicians. Mark Feinberg, M.D., Ph.D., chief public health and science officer, Merck Vaccines, said, “Today’s ACIP recommendations will help to provide greater access to GARDASIL for males. These new recommendations for use in males mark another important step in helping to protect more people from the HPV-related cancers and disease that GARDASIL is indicated to prevent.”

http://www.businesswire.com/news/home/20111025006830/en/CDC-Advisory-Committee-Immunization-Practices-Votes-Expanded

Pfizer announced that the European Commission has approved Prevenar 13 (pneumococcal polysaccharide conjugate vaccine [13-valent, adsorbed]) for active immunization for the prevention of vaccine-type invasive disease ococcus pneumoniae in adults aged 50 years and older. Emilio Emini, Ph.D., chief scientific officer, Vaccine Research, Pfizer Inc., said, “Prevenar 13, the first and only pneumococcal conjugate vaccine approved by the European Commission for use in adults, has the potential to prevent invasive pneumococcal disease in adults aged 50 and older – a time of life when the risk for contracting the disease begins to increase. It is important that older adults talk to their health care provider about pneumococcal disease prevention and Prevenar 13 as part of a plan for healthy aging.” http://www.businesswire.com/news/home/20111027005499/en/Pfizer-Receives-European-Approval-Extend-Prevenar-13

The Weekly Epidemiological Record (WER) for 28 October 2011, vol. 86, 44 (pp 480–496) includes: Validation of elimination: maternal and neonatal tetanus in Mozambique, 2010; Review of the 2011 winter influenza season, southern hemisphere

http://www.who.int/entity/wer/2011/wer8644.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
#ICYMI check out the #GAVI press conference following announcement of #vaccine funding for 37 more countries- ht.ly/7dr1g

RWJF_PubHealth RWJF PublicHealth
Read more about @RisaLavizzo getting the APHA Presidential Citation award at #APHA11 and download her full speech: bit.ly/rzHKvi

FightingMalaria Malaria Consortium
Not too early to consider funding for distribution of malaria vaccine news-medical.net/news/20111029/…

vaccineethics Vaccine Ethics
by PeterASinger
“The Moral Case for Eradication” — New publication from @mrcglobal –http://bit.ly/tYrbYs
28 Oct

MalariaVaccine PATH MVI
Making vaccines cost-effective: Money is only part of the solution – Forbes article by @sarika008 onforb.es/uHpRyc
28 Oct

Harvard_Health HarvardGlobalHealth
Vaccine-Preventable Outbreaks Map bitURL.net/can6 Big Pharma will share drug patents to fight neglected diseases #GlobalHealth #WIPO
28 Oct

cdchep CDC Hepatitis
New ACIP recommendation on #hepatitis B vaccination for persons w diabetes is provisional pending adoption by CDC & pub in MMWR #hepB
27 Oct

Eurovaccine ECDC Eurovaccine
RT @MeaslesInit: “What is driving this epidemic is the failure to vaccinate” – #measles in Ireland… bit.ly/tAwe7W
25 Oct

GAVISeth Seth Berkley
New estimates Rota: 453K deaths children <5, 95% in GAVI eligible countries. 37% diarrhea deaths. Vax rollout critical goo.gl/1zeD5
25 Oct

UNICEF UNICEF
Visit new UNICEF site highlighting social issues & data impacting #polio eradication: bit.ly/ofBwPS – #WPD11 @EndPolioNow @gatespolio
24 Oct

Emerging Infectious Diseases
Volume 17, Number 11—November 2011
http://www.cdc.gov/ncidod/EID/index.htm

THEME ISSUE: CHOLERA IN HAITI
A number of synopses, dispatches, commentaries and letters are part of this theme issue including:

Lessons Learned during Public Health Response to Cholera Epidemic in Haiti and the Dominican Republic
J. W. Tappero and R. V. Tauxe

Rapid Development and Use of a Nationwide Training Program for Cholera Management, Haiti, 2010
R. V. Tauxe et al.

Cholera—Modern Pandemic Disease of Ancient Lineage
J. G. Morris

Considerations for Oral Cholera Vaccine Use during Outbreak after Earthquake in Haiti, 2010−2011
K. A. Date et al.

The Lancet  
Oct 29, 2011  Volume 378  Number 9802  p1527 – 1604 e1 – 2
http://www.thelancet.com/journals/lancet/issue/current

Editorial
A vaccine for malaria: prospects and predicaments
The Lancet

Release of interim results from a phase 3 trial of GlaxoSmithKline’s experimental vaccine against malaria generated much excitement (and even more questions) last week. “Malaria vaccine could save millions of children’s lives”, declared the UK’s Guardian. “Malaria-vaccine trials raise hope of eradicating deadly disease”, proclaimed Canada’s Globe and Mail.

The study, published in the New England Journal of Medicine, showed that the RTS,S/AS01 vaccine roughly halved the risk of clinical and severe malaria in African infants aged 5—17 months a year after vaccination. These results are promising and consistent with findings from phase 2 trials. However, the release of this interim analysis is not without controversy. As Nick White wrote in an accompanying editorial, “…there does not seem to be a clear scientific reason why this trial has been reported with less than half the efficacy results available”. Some observers have suggested that the timing of the publication was political. The results were released at the Bill & Melinda Gates Foundation’s forum on malaria in Seattle, following the same event in 2007 at which they famously called for the eradication of malaria.

But well intentioned political agendas must not obscure the evidence. In terms of side-effects, meningitis and generalised convulsive seizures occurred more frequently in those receiving the RTS,S/AS01 vaccine than in the control group, and the vaccine did not reduce deaths from malaria. Additionally, this vaccine is not a single magic bullet against malaria. It only offers partial protection. Still, modelling studies have suggested that the vaccine could save hundreds of thousands of lives, together with existing control methods.

The key RTS,S/AS01 data are still to come. The ideal population for this vaccine is 6—12-week-old infants who could receive the vaccine at the same time as immunisation against other major childhood illnesses. Data for efficacy in this age group will be released in 2012, and the final combined trial results will be out in 2014. This will provide crucial information about the effect of a booster dose and long-term protection. Although the latest findings are encouraging, we look forward to the full results of the RTS,S/AS01 trial in 3 years time.

New England Journal of Medicine
October 27, 2011  Vol. 365 No. 17
http://content.nejm.org/current.shtml

Original Articles
HPV Vaccine against Anal HPV Infection and Anal Intraepithelial Neoplasia
J.M. Palefsky and Others

Background
The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men.

PLoS One
[Accessed 30 October 2011]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Repeated Assessments of Informed Consent Comprehension among HIV-Infected Participants of a Three-Year Clinical Trial in Botswana
Lelia H. Chaisson, Nancy E. Kass, Bafanana Chengeta, Unami Mathebula, Taraz Samandari of the quality of informed consent in a vaccine field trial … Knowledge about vaccine trials and willingness to participate in an HIV/AIDS vaccine study in the ugandan PLoS ONE: Research Article, published 27 Oct 2011 10.1371/journal.pone.0022696

Abstract 
Background
Informed consent (IC) has been an international standard for decades for the ethical conduct of clinical trials. Yet frequently study participants have incomplete understanding of key issues, a problem exacerbated by language barriers or lack of familiarity with research concepts. Few investigators measure participant comprehension of IC, while even fewer conduct interim assessments once a trial is underway.

Methods and Findings
We assessed comprehension of IC using a 20-question true/false quiz administered in 6-month intervals in the context of a placebo-controlled, randomized trial for the prevention of tuberculosis among HIV-infected adults in Botswana (2004–2009). Quizzes were offered in both Setswana and English. To enroll in the TB trial, participants were required to have ≥16/20 correct responses. We examined concepts understood and the degree to which understanding changed over three-years. We analyzed 5,555 quizzes from 1,835 participants. The participants’ highest education levels were: 28% primary, 59% secondary, 9% tertiary and 7% no formal education. Eighty percent of participants passed the enrollment quiz (Quiz1) on their first attempt and the remainder passed on their second attempt. Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt (adjusted odds ratios and 95% confidence intervals, 3.1 (2.4–4.0) and 1.5 (1.2, 1.9), respectively). The trial’s purpose or procedures were understood by 90–100% of participants, while 44–77% understood randomization, placebos, or risks. Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial. Pass rates improved with quiz re-administration in subsequent years.

Conclusions
Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large, international collaboration and efficiently determined IC comprehension by trial participants. Strategies to improve understanding of concepts like placebos and randomization are needed. Comprehension assessments throughout a study may reinforce key concepts.

PLoS Medicine
(Accessed 30 October 2011)
http://www.plosmedicine.org/article/browse.action?field=date

Measuring the Performance of Vaccination Programs Using Cross-Sectional Surveys: A Likelihood Framework and Retrospective Analysis
Justin Lessler, C. Jessica E. Metcalf, Rebecca F. Grais, Francisco J. Luquero, Derek A. T. Cummings, Bryan T. Grenfell Research Article, published 25 Oct 2011
doi:10.1371/journal.pmed.1001110

Abstract 
Background
The performance of routine and supplemental immunization activities is usually measured by the administrative method: dividing the number of doses distributed by the size of the target population. This method leads to coverage estimates that are sometimes impossible (e.g., vaccination of 102% of the target population), and are generally inconsistent with the proportion found to be vaccinated in Demographic and Health Surveys (DHS). We describe a method that estimates the fraction of the population accessible to vaccination activities, as well as within-campaign inefficiencies, thus providing a consistent estimate of vaccination coverage.

Methods and Findings
We developed a likelihood framework for estimating the effective coverage of vaccination programs using cross-sectional surveys of vaccine coverage combined with administrative data. We applied our method to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone, using data from each country’s most recent DHS survey and administrative coverage data reported to the World Health Organization. We estimate that 93% (95% CI: 91, 94) of the population in Ghana was ever covered by any measles vaccination activity, 77% (95% CI: 78, 81) in Madagascar, and 69% (95% CI: 67, 70) in Sierra Leone. “Within-activity” inefficiencies were estimated to be low in Ghana, and higher in Sierra Leone and Madagascar. Our model successfully fits age-specific vaccination coverage levels seen in DHS data, which differ markedly from those predicted by naïve extrapolation from country-reported and World Health Organization–adjusted vaccination coverage.

Conclusions
Combining administrative data with survey data substantially improves estimates of vaccination coverage. Estimates of the inefficiency of past vaccination activities and the proportion not covered by any activity allow us to more accurately predict the results of future activities and provide insight into the ways in which vaccination programs are failing to meet their goals.

Science        
28 October 2011 vol 334, issue 6055, pages 421-552
http://www.sciencemag.org/current.dtl

Research Articles
Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity
J. E. Epstein, K. Tewari, K. E. Lyke, B. K. L. Sim, P. F. Billingsley, M. B. Laurens, A. Gunasekera, S. Chakravarty, E. R. James, M. Sedegah, A. Richman, S. Velmurugan, S. Reyes, M. Li, K. Tucker, A. Ahumada, A. J. Ruben, T. Li, R. Stafford, A. G. Eappen, C. Tamminga, J. W. Bennett, C. F. Ockenhouse, J. R. Murphy, J. Komisar, N. Thomas, M. Loyevsky, A. Birkett, C. V. Plowe, C. Loucq, R. Edelman, T. L. Richie, R. A. Seder, and S. L. Hoffman
Science 28 October 2011: 475-480.
Published online 8 September 2011 [DOI:10.1126/science.1211548]
The efficacy of a sporozoite-based malaria vaccine is tested in humans, nonhuman primates, and mice.

Abstract
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8+ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8+, IFN-γ–producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 49 pp. 9123-9288 (15 November 2011)

Short Communications
Rubella revisited: Where are we on the road to disease elimination in Central Europe?
Pages 9141-9147
Vytautas Usonis, Ioana Anca, Francis André, Roman Chlibek, Milan Čižman, Inga Ivaskeviciene, Atanas Mangarov, Zsófia Mészner, Penka Perenovska, Marko Pokorn, Roman Prymula, Darko Richter, Nuran Salman, Pavol Šimurka, Eda Tamm, Goran Tešović, Ingrid Urbančíková

Abstract
Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing.

Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015.

This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory-confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 49 pp. 9123-9288 (15 November 2011)

Reviews
Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC)
Pages 9171-9176
Faruque Ahmed, Jonathan L. Temte, Doug Campos-Outcalt, Holger J. Schünemann, for the ACIP Evidence Based Recommendations Work Group (EBRWG)

Abstract
The Advisory Committee on Immunization Practices (ACIP) provides expert external advice and guidance to the Director of the Centers for Disease Control and Prevention and the Secretary of the U.S. Department of Health and Human Services on use of vaccines and related agents for control of vaccine-preventable disease in the United States. During the October 2010 ACIP meeting, the ACIP voted to adopt a new framework for developing evidence-based recommendations that is based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Key factors considered in the development of recommendations include the balance of benefits and harms, type of evidence, values and preferences of the people affected, and health economic analyses. Category A recommendations will be made for all persons in an age- or risk-factor-based group. Category B recommendations will be made for individual clinical decision making; category B recommendations do not apply to all members of an age- or risk-factor-based group, but in the context of a clinician–patient interaction, vaccination may be found to be appropriate for a person. Evidence tables will be used to summarize the benefits and harms and the strengths and limitations of the body of evidence. The new evidence framework will enhance the ACIP’s decision-making process by making it more transparent, consistent and systematic.

The pdf version of Vaccines: The Week in Review 24 October 2011 comprising the posts below for this date is available here: Vaccines_The Week in Review_24 Oct 2011

[Editor’s Note: Please consult New England Journal of Medicine article for the results of the RTS,S malaria vaccine trial and an NEJM editorial on malaria vaccines in separate posts below]

   WHO and other partners announced promising results from a large-scale phase 3 clinical trial of the most advanced malaria vaccine candidate, RTS,S/AS01 at the Global Malaria Forum in Seattle. http://www.who.int/immunization/newsroom/newsstory_malaria_vaccine_trial_results/en/index.html

Speech: WHO Director-General Dr Margaret Chan assesses prospects for malaria control. Keynote address at the Bill and Melinda Gates Foundation 2011 Malaria Forum: Optimism and Urgency; Seattle, Washington, United States of America
17 October 2011

http://www.who.int/dg/speeches/2011/malaria_forum_17_10/en/index.html

In a PATH media release, a number of partner comments were captured including:

Andrew Witty, CEO, GSK:

“These data bring us to the cusp of having the world’s first malaria vaccine, which has the potential to significantly improve the outlook for children living in malaria endemic regions across Africa. The addition of a malaria vaccine to existing control interventions such as bed nets and insecticide spraying could potentially help prevent millions of cases of this debilitating disease. It could also reduce the burden on hospital services, freeing up much needed beds to treat other patients who often live in remote villages, with little or no access to healthcare. Today’s results are a testament to the dedication and tenacity of many scientists, led at GSK by Jean Stéphenne and his vaccine team, including Joe Cohen, the co-inventor of RTS,S, in partnership with many others from across the world. Development is however only half the task, but GSK remains committed to further research into malaria and most importantly, to ensuring that this vaccine will reach those who need it.”

Christopher Elias, president and CEO of PATH:

“This trial represents a powerful example of the high-quality science that is moving us toward controlling and someday potentially eliminating malaria. The results made public today are encouraging and certainly something to feel good about, but let’s also remember the human dimension. The PATH Malaria Vaccine Initiative’s mission is to deliver a vaccine to the children of Africa so that instead of carrying near lifeless babies to crowded pediatric wards, mothers will carry their infants past noisy school playgrounds to bustling immunization clinics. Today, we are an important step closer to realizing that vision, and we look forward to continuing our drive, together with our partners, to bring this vaccine home to the children of Africa.”

The release also noted that “GSK and MVI are committed to making this vaccine available to those who need it most, should it be approved and recommended for use. In January 2010, GSK announced that the eventual price of RTS,S will cover the cost of manufacturing the vaccine together with a small return that will be reinvested in research and development for second-generation malaria vaccines or vaccines against other neglected tropical diseases.

“If the required public health information, including safety and efficacy data from the Phase III programme, is deemed satisfactory, the WHO has indicated that a policy recommendation for the RTS,S malaria vaccine candidate is possible as early as 2015, paving the way for decisions by African nations regarding large scale implementation of the vaccine through their national immunisation programmes.”

http://www.path.org/news/pr111018-rtss-results.php

Speech: WHO Director-General Dr Margaret Chan addresses first World Conference on Social Determinants of Health, Rio de Janeiro, Brazil -19 October 2011 http://www.who.int/dg/speeches/2011/social_determinants_19_10/en/index.html

   Speech: Anthony Lake, UNICEF Executive Director, at Institute of Medicine Annual Meeting: “Reaching the Fifth Child: Immunization and Equity” Washington, DC, 17 October 2011 http://www.unicef.org/media/media_60115.html

    WHO Europe reported on a meeting of over 100 experts and policy-makers from 42 countries and 7 partner organizations in Istanbul, Turkey to discuss the prevention of cervical cancer in the WHO European Region. This cancer kills 30 000 women in Europe every year. Gauden Galea, Director of the Division of Noncommunicable Diseases and Health Promotion at WHO/Europe, said, “We must be explicit in the message that vaccination and screening are about preventing cancer and saving lives. Given the technology and the level of development in our Region, women in Europe have a right to be protected from this cancer. It is not just a matter of public health; this is a matter of women’s rights.”

http://www.euro.who.int/en/what-we-publish/information-for-the-media/sections/latest-press-releases/deaths-of-30-000-women-can-be-prevented-whoeurope-calls-for-more-action-on-cervical-cancer

   The Kaiser Family Foundation released a new report: Innovative Financing Mechanisms for Global Health: Overview & Considerations for U.S. Government Participation. The synopsis:

“When leaders from the world’s 20 major economies gather for the upcoming G-20 Summit in France, one of their priorities will be finding new ways to maintain and expand the impact of global development programs in the wake of an international financial crisis and mounting efforts to control public spending and debt. The previous decade saw significant increases in support for global health, but there is growing pressure on traditional funding channels. As a result, greater attention is now being paid to what are called “innovative financing mechanisms” – a broad category of proposed approaches to supplement traditional funding for global health.
“This report examines some of the most prominent new financing mechanisms for global health across a range of categories, with particular attention to the current level of U.S. government involvement. While these financing mechanisms are not meant to be a substitute for traditional sources of health assistance, they do have the potential to generate additional revenues or extend the impact of existing resources. The report explores the status of U.S. government participation in these financing mechanisms and identifies the potential opportunities and challenges for further engagement by the U.S. as part of its global health effort.”

Report pdf here: http://www.kff.org/globalhealth/upload/8247.pdf

http://www.kff.org/globalhealth/8247.cfm

The MMWR for October 21, 2011 / Vol. 60 / No. 41 includes:
– Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (Tdap) in Pregnant Women and Persons Who Have or Anticipate Having Close Contact with an Infant Aged <12 Months — Advisory Committee on Immunization Practices (ACIP), 2011

– Addition of History of Intussusception as a Contraindication for Rotavirus Vaccination

The Weekly Epidemiological Record (WER) for 21 October 2011, vol. 86, 43 (pp 469–480) includes: Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness; Standardization of terminology of the pandemic A(H1N1) 2009 virus

http://www.who.int/entity/wer/2011/wer8643.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
We are this close to eradicating #polio! Join us tomorrow to honor World Polio Day with our partners- ht.ly/764b4
9 hours ago

PIH Partners In Health
#Cholera #vaccine in #Haiti will be limited: hopes to slow pandemic down: ow.ly/74WsO via @haitimphise
22 Oct

gatesfoundation Gates Foundation
Bill Gates issues a call to action on World #Polio Day: gates.ly/rdUR9x #WPD11
21 Oct

ImmunizeAction IAC
Studies dig into physicians’ views on vaccine issues cidrap.umn.edu/cidrap/content…
21 Oct

Eurovaccine ECDC Eurovaccine
Register for free to view #Eurovaccine 2011 live and recorded webcasts: bit.ly/qOUkyb

globalfundnews The Global Fund
#Sweden thank you for your support! 2011 contribution to the Global Fund in full and 11% increase for 2011-2013! bit.ly/pNynsN
21 Oct

DofVC DoV Collaboration
Just finished video interview with @PATHtweets CEO Chris Elias around our mission and role of citizens in the process. pic.twitter.com/HJBWeMML
20 Oct

BillGates Bill Gates
by DofVC
Malaria eradication is an ambitious, long-term goal—but a goal @melindagates and I are 100% committed to. #endmalaria b-gat.es/qX03eS
19 Oct

British Medical Journal
22 October 2011 Volume 343, Issue 7828
http://www.bmj.com/content/current

Letter
Comparing HPV vaccines
HPV vaccine prices in Italy
Livio Garattini, Katelijne van de Vooren, Gianluigi Casadei

Extract
In contrast to what was reported in the editorial, both the bivalent (Cervarix) and the quadrivalent (Gardasil) vaccines are used in Italy for the campaign against cervical cancer. Most of the 20 Italian regions, which fund and implement vaccination programmes on their territory, ran single tenders to exploit potential competition between the two …

Letter
HPV vaccines
UK needs vaccine to protect against HPV types causing recurrent respiratory papillomatosis
Michael P Rothera, David M Albert, Owain R Hughes,

Extract
We are pleased that the Department of Health is reviewing which human papillomavirus (HPV) vaccine to use in the national immunisation programme. 1 As Jit and colleagues state, deciding between the bivalent and the quadrivalent vaccine is not straightforward. We would like to contribute to the decision making process by highlighting our experience of treating …

Letter
Comparing HPV vaccines
Changing face of HPV related cancer in the UK

Andrew G Schache, Richard Simcock, Duncan C Gilbert, Richard J Shaw

Extract
As the UK nears a decision on continuation of the national human papillomavirus (HPV) vaccination programme, Jit and colleagues’ economic evaluation of the available vaccines makes compelling reading. 1

When developing arguments for cost effectiveness of the bivalent and quadrivalent vaccines, the analysis bears heavily on available data for cervical cancer, …

JAMA   
October 19, 2011, Vol 306, No. 15, pp 1625-1723
http://jama.ama-assn.org/current.dtl

Commentaries
Mandatory HPV Vaccination and Political Debate
Lawrence O. Gostin
JAMA. 2011;306(15):1699-1700.Published online October 6, 2011. doi:10.1001/jama.2011.1525

Extract
Vaccinations are among the most cost-effective and widely used public health interventions but have provoked popular resistance, with compulsory vaccination framed as an unwarranted state interference. When the US Food and Drug Administration (FDA) approved a human papillomavirus (HPV) vaccine in 2006, conservative religious groups strongly opposed a mandate, arguing it would condone premarital sex and undermine parental rights. Yet Governor Rick Perry signed an executive order in 2007 making Texas the first state to enact a mandate—later revoked by the state legislature.

Mandatory HPV vaccination received additional attention during a recent debate among Republican presidential candidates. Michele Bachmann, US representative from Minnesota, Rick Santorum, former US senator from Pennsylvania, and Governor Perry had spirited exchanges about the executive order that Perry issued in 2007. Bachmann called the vaccine “a dangerous drug” and Santorum added, “There is no government purpose served for having little girls inoculated at the force and …

JAMA   
October 19, 2011, Vol 306, No. 15, pp 1625-1723
http://jama.ama-assn.org/current.dtl

Commentaries
Lessons From the US Rotavirus Vaccination Program
Roger I. Glass, Manish Patel, Umesh Parashar
JAMA. 2011;306(15):1701-1702.doi:10.1001/jama.2011.1475

The Lancet  
Oct 22, 2011  Volume 378  Number 9801  p1439 – 1526
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Global funding for infectious diseases: TB or not TB?
The Lancet

Preview
WHO’s sixteenth annual report on global tuberculosis control, released on Oct 11, presents detailed and encouraging statistics, carefully interwoven with words of caution about the perils of failing to maintain disease-specific funding. Taking a global view, the numbers are undoubtedly sobering, with 8·8 million new cases of tuberculosis estimated in 2010, and about 1·45 million deaths from tuberculosis across populations with and without HIV. In 2009, 9·7 million children are thought to have been orphaned by parental deaths caused by tuberculosis (whether or not accompanied by HIV).

The Lancet  
Oct 22, 2011  Volume 378  Number 9801  p1439 – 1526
http://www.thelancet.com/journals/lancet/issue/current

Articles
Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis
Mohammad H Forouzanfar, Kyle J Foreman, Allyne M Delossantos, Rafael Lozano, Alan D Lopez, Christopher J L Murray, Mohsen Naghavi

Summary
Background
Breast and cervical cancer are important causes of mortality in women aged ≥15 years. We undertook annual age-specific assessments of breast and cervical cancer in 187 countries.

Methods
We systematically collected cancer registry data on mortality and incidence, vital registration, and verbal autopsy data for the period 1980—2010. We modelled the mortality-to-incidence (MI) ratio using a hierarchical model. Vital registration and verbal autopsy were supplemented with incidence multiplied by the MI ratio to yield a comprehensive database of mortality rates. We used Gaussian process regression to develop estimates of mortality with uncertainty by age, sex, country, and year. We used out-of-sample predictive validity to select the final model. Estimates of incidence with uncertainty were also generated with mortality and MI ratios.

Findings
Global breast cancer incidence increased from 641 000 (95% uncertainty intervals 610 000—750 000) cases in 1980 to 1 643 000 (1 421 000—1 782 000) cases in 2010, an annual rate of increase of 3·1%. Global cervical cancer incidence increased from 378 000 (256 000—489 000) cases per year in 1980 to 454 000 (318 000—620 000) cases per year in 2010—a 0·6% annual rate of increase. Breast cancer killed 425 000 (359 000—453 000) women in 2010, of whom 68 000 (62 000—74 000) were aged 15—49 years in developing countries. Cervical cancer death rates have been decreasing but the disease still killed 200 000 (139 000—276 000) women in 2010, of whom 46 000 (33 000—64 000) were aged 15—49 years in developing countries. We recorded pronounced variation in the trend in breast cancer mortality across regions and countries.

Interpretation
More policy attention is needed to strengthen established health-system responses to reduce breast and cervical cancer, especially in developing countries.

Funding
Susan G Komen for the Cure and the Bill & Melinda Gates Foundation

New England Journal of Medicine
October 20, 2011  Vol. 365 No. 16
http://content.nejm.org/current.shtml

Editorial
A Vaccine for Malaria
Nicholas J. White, F.R.S.
October 18, 2011 (10.1056/NEJMe1111777)

It’s been a long time coming, and indeed we are still not there yet, but it is becoming increasingly clear that we really do have the first effective vaccine against a parasitic disease in humans. If there are no unforeseen disasters, the RTS,S/AS01 Plasmodium falciparum malaria vaccine should become available in just over 3 years. The World Health Organization (WHO) has already taken the unusual step of indicating that it could recommend this first malaria vaccine for use in some African countries as early as 2015, depending on the full phase 3 trial results that will become available in 2014.1 The vaccine has been developed by a public–private partnership between GlaxoSmithKline and the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative, supported by the Bill and Melinda Gates Foundation, primarily for use in infants and young children in sub-Saharan Africa. RTS,S/AS01 is a hybrid construct of the hepatitis B surface antigen fused with a recombinant antigen derived from part of the circumsporozoite protein. This is the protein coat of the sporozoite, the parasite stage that is inoculated by the feeding anopheline mosquito, which then invades liver cells and multiplies there before entering the bloodstream. Keys to the success of the vaccine are the immunogenic polymeric nature of RTS,S particles and the proprietary adjuvant AS01. A large number of other potential malaria vaccines are in various stages of development, but the RTS,S/AS01 vaccine is considerably further along the path to registration and potential deployment than the others.

In this issue of the Journal, the RTS,S Clinical Trials Partnership provides an interim report of a large, multicenter phase 3 trial of this vaccine.2 A total of 15,460 children in two age categories — 6 to 12 weeks and 5 to 17 months — were enrolled. The report describes vaccine efficacy against P. falciparum malaria in the first 6000 of 8923 children in the older age category, together with an evaluation of the first 250 cases of severe malaria from the two age groups. It is not usual practice to publish the results of trials in pieces, and there does not seem to be a clear scientific reason why this trial has been reported with less than half the efficacy results available. The target population for this vaccine is young infants who would receive the malaria vaccine together with routine immunizations, but the critical efficacy results in this subgroup will not be reported for another year. Even then, only results on short-term efficacy will be available, findings that will be insufficient to assess the public health role of this vaccine.

The interim results are broadly in line with those reported previously in extended phase 2 studies.3-5 Protective efficacy against P. falciparum malaria (55% protection against all malaria episodes) was at the upper end of expectations from earlier studies, whereas the overall reduction in severe malaria (35% protection) was slightly less than anticipated.

Trials often throw up unexpected findings. In this trial, there were significantly more cases of meningitis among children receiving the RTS,S/AS01 vaccine than among those receiving the comparator vaccines. There seems to be no plausible explanation for this, and it may well turn out to be a chance finding, but it cannot be ignored. On the other hand, the increased risk of febrile reactions or seizures among RTS,S/AS01 recipients may be real, reflecting the reactogenicity of this highly immunogenic vaccine. Such questions highlight the importance of phase 4 studies of both safety and effectiveness with active surveillance if this vaccine is deployed.

What does this vaccine mean for the future of the control and elimination of malaria? The considerable increase in global funding is paying dividends. In places where effective interventions (insecticide-treated bed nets, insecticides, and artemisinin-combination treatments) are being intensively deployed, malaria morbidity and mortality are falling. Several new, simple, affordable interventions, such as seasonal chemoprevention among young children in areas of seasonally high malaria transmission and the use of artesunate in patients with severe malaria, can also provide substantial reductions in mortality. The very low rate of death from malaria in this large trial (only 10 deaths directly attributed to malaria) testifies to the benefits of providing early diagnosis and effective antimalarial treatment. But there are real dangers ahead. How will the necessary funding be sustained in the face of a global economic downturn, along with a reduction in political pressure associated with declining mortality from malaria? In addition, artemisinin resistance in malaria parasites and pyrethroid resistance in anopheline mosquito vectors pose very serious threats.

All the investigators who have labored long and hard in the development and evaluation of this malaria vaccine deserve congratulations. It is a great achievement and an important advance, but they know that this partially protective vaccine is not the sole solution to the control and elimination of malaria. After registration, the definitive WHO guidance, expected in 2015, may recommend that the inclusion of RTS,S/AS01 in the multipronged attack against malaria is justified. The key question of how long the protection against malaria lasts, particularly in the anticipated context of declining malaria transmission, remains open. An assessment of an 18-month booster dose will not be available until 2014. Another key issue is whether efficacy varies according to the intensity of transmission. We also do not know yet how much the vaccine will cost. All these factors are essential components of the objective assessments of cost-effectiveness that should form the basis of future global and national policy decisions.

New England Journal of Medicine
October 20, 2011  Vol. 365 No. 16
http://content.nejm.org/current.shtml

Original Article
First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children
The RTS,S Clinical Trials Partnership
October 18, 2011 (10.1056/NEJMoa1102287)

Abstract
An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries.

Methods
From March 2009 through January 2011, we enrolled 15,460 children in two age categories — 6 to 12 weeks of age and 5 to 17 months of age — for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories.

Results
In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64).

Conclusions
The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.)

PLoS One
[Accessed 23 October 2011]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior
Liang Mao
PLoS ONE: Research Article, published 17 Oct 2011
10.1371/journal.pone.002470

Abstract 
Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment.

PLoS Medicine
(Accessed 23 October 2011)
http://www.plosmedicine.org/article/browse.action?field=date

Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in The Gambia: A Cluster-Randomized Trial
Anna Roca, Philip C. Hill, John Townend, Uzo Egere, Martin Antonio, Abdoulie Bojang, Abiodun Akisanya, Teresa Litchfield, David E. Nsekpong, Claire Oluwalana, Stephen R. C. Howie, Brian Greenwood, Richard A. Adegbola
Research Article, published 18 Oct 2011
doi:10.1371/journal.pmed.1001107

Abstract 
Background
Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.

Methods and Findings
A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4–6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively).

A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04–0.57] and OR = 0.32 [95% CI 0.10–0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15–0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small.

Conclusions
Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a “herd effect” in non-vaccinated older children and adults. No significant serotype replacement was detected.

PLoS Medicine
(Accessed 23 October 2011)
http://www.plosmedicine.org/article/browse.action?field=date

A Statistical Model of the International Spread of Wild Poliovirus in Africa Used to Predict and Prevent Outbreaks
Kathleen M. O’Reilly, Claire Chauvin, R. Bruce Aylward, Chris Maher, Sam Okiror, Chris Wolff, Deo Nshmirimana, Christl A. Donnelly, Nicholas C. Grassly Research Article, published 18 Oct 2011
doi:10.1371/journal.pmed.1001109

Abstract 
Background
Outbreaks of poliomyelitis in African countries that were previously free of wild-type poliovirus cost the Global Polio Eradication Initiative US$850 million during 2003–2009, and have limited the ability of the program to focus on endemic countries. A quantitative understanding of the factors that predict the distribution and timing of outbreaks will enable their prevention and facilitate the completion of global eradication.

Methods and Findings
Children with poliomyelitis in Africa from 1 January 2003 to 31 December 2010 were identified through routine surveillance of cases of acute flaccid paralysis, and separate outbreaks associated with importation of wild-type poliovirus were defined using the genetic relatedness of these viruses in the VP1/2A region. Potential explanatory variables were examined for their association with the number, size, and duration of poliomyelitis outbreaks in 6-mo periods using multivariable regression analysis. The predictive ability of 6-mo-ahead forecasts of poliomyelitis outbreaks in each country based on the regression model was assessed. A total of 142 genetically distinct outbreaks of poliomyelitis were recorded in 25 African countries, resulting in 1–228 cases (median of two cases). The estimated number of people arriving from infected countries and <5-y childhood mortality were independently associated with the number of outbreaks. Immunisation coverage based on the reported vaccination history of children with non-polio acute flaccid paralysis was associated with the duration and size of each outbreak, as well as the number of outbreaks. Six-month-ahead forecasts of the number of outbreaks in a country or region changed over time and had a predictive ability of 82%.

Conclusions
Outbreaks of poliomyelitis resulted primarily from continued transmission in Nigeria and the poor immunisation status of populations in neighbouring countries. From 1 January 2010 to 30 June 2011, reduced transmission in Nigeria and increased incidence in reinfected countries in west and central Africa have changed the geographical risk of polio outbreaks, and will require careful immunisation planning to limit onward spread.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 48 pp. 8767-9122 (8 November 2011)

Discussions
Safe landing for global polio eradication: A perspective
Pages 8827-8834
Isao Arita, Donald P. Francis

Abstract
After over two decades of immense efforts, the global polio eradication initiative may be approaching its final phase. With leadership from WHO, great efforts of national programs and support from its collaborators, combined with the recent use of mono and bivalent oral polio vaccines, success may be at hand. For a “safe landing” of this global program, it is important once more to recall the key role of routine vaccination as the foundation on which mass vaccination campaigns can be successful. Continued effective routine vaccination programs are essential to reduce the ill effects of high population density in formerly endemic countries. Considering the large number of subclinical poliovirus infections, failing to reduce the number of unvaccinated persons per km2 could severely impact the final stage of eradication. Here the authors, from their personal perspectives, discuss how the current program will be viewed from 2012 onwards. The authors will highlight the epidemiological importance of circulating vaccine-derived poliovirus, the problem of biosecurity as well as the use of inactivated polio vaccine and how each of these may affect the post eradication era and how research into each of these must continue to ensure success.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 48 pp. 8767-9122 (8 November 2011)

Building on the success of the Expanded Programme on Immunization: Enhancing the focus on disease prevention and control
Pages 8835-8837
T.J. John, S.A. Plotkin, W.A. Orenstein

Abstract
The Expanded Programme on Immunization (EPI) has succeeded in establishing a vaccine delivery system in all low and middle income (LMI) countries. Because EPI has focused on immunization delivery, its major outcome is measured in many countries only as vaccine coverage, not as disease reduction, the real goal of EPI. Monitoring disease reduction requires real-time case-based disease surveillance and appropriate interventions, for which a functional public health infrastructure is needed. If the highest priority for assessing impact of EPI shifts to disease prevention and control from vaccine coverage, the programme may be transformed to one of control of childhood communicable diseases (CCCD), with the potential of expanding the range of diseases of children and adults for control and of integrating all other current vertical (single disease) control efforts with it. EPI provides the essential platform on which CCCD can be built to create a public health infrastructure.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 48 pp. 8767-9122 (8 November 2011)

“Once I begin to participate, people will run away from me”: Understanding stigma as a barrier to HIV vaccine research participation in Kenya
Pages 8924-8928
Laura Nyblade, Sagri Singh, Kim Ashburn, Laura Brady, Joyce Olenja

Abstract
Purpose
Participation of volunteers in clinical research is essential to the development of effective HIV prevention methods, including an HIV vaccine. This study expands current knowledge of stigma and discrimination related to participation in HIV vaccine research in sub-Saharan Africa by exploring the perception of stigma and discrimination as a barrier to participation in HIV vaccine research in Kenya.

Methods
Eighteen focus groups with a total of 133 participants and 82 individual interviews were conducted with a range of respondents at two centers in Nairobi, Kenya: a preventive AIDS vaccine trial center; and a preparatory clinical and epidemiological study center. Respondents included peer leaders, community advisory board members, former and current volunteers in clinical research, study staff, community leaders and community members. Data were analyzed using an iterative coding process.

Results
Four prominent stigma-related barriers to participation emerged among all respondent groups, across both centers: (1) volunteers are often assumed by family and community members to be HIV positive because of their participation in vaccine research; (2) HIV-related stigma is perceived as pervasive and damaging in the communities where volunteers live, thus they fear consequent stigma if people believe them to be HIV positive; (3) potential volunteers fear being tested for HIV, a prerequisite for participation, because of possible disclosure of HIV status in communities with high perceived HIV-related stigma; and (4) volunteers must carefully manage information about their participation because of misperceptions and assumptions about vaccine research volunteers.

Conclusions
HIV-related stigma and discrimination influence people’s decisions to join HIV-vaccine related research. Findings underscore a need for integration of stigma-reduction programming into education and outreach activities for volunteers, and the communities in which they live. This is particularly critical for trials recruiting individuals with higher HIV risk, who are often already highly stigmatized.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 48 pp. 8767-9122 (8 November 2011)

The clinical benefit and cost-effectiveness of human papillomavirus vaccination for adult women in the Netherlands
Pages 8929-8936
Johannes A. Bogaards, Veerle M.H. Coupé, Chris J.L.M. Meijer, Johannes Berkhof

Abstract
Background
The use of human papillomavirus (HPV) vaccines has been universally approved for women from age 12 to 25 years, but those older than 16 years receive no reimbursement for the cost of the vaccine in the Netherlands. Reductions in the vaccine price as well as new insights in the efficacy of HPV vaccines offer renewed arguments to consider HPV vaccination in adult women. We calculated the clinical benefit and cost-effectiveness of vaccinating women aged 17–25 years in 2010.

Methods
The calculations were based on an individual-based simulation model for cervical carcinogenesis, with HPV infection risks obtained from a type-specific HPV transmission model. The indirect protective effect from vaccinating 12 to 16 year-old girls was adjusted for. Cervical screening in the model was incorporated according Dutch screening guidelines, i.e. 7 cytology-based rounds at 5-year intervals from the age of 30. As base-case, we assumed the vaccine to offer full protection against HPV16/18 only if no prior exposure to that type had occurred before vaccination. In sensitivity analyses, we considered partial cross-protection against types 31/33/45/58 and efficacy against all future infections, irrespective of previous or current infection status.

Results
In base-case analyses, vaccinating 17 year-olds reduced their lifetime risk of treatment for precancerous lesions from 7.77% to 3.48% and their lifetime cervical cancer risk from 0.52% to 0.24%. These risks were 6.12% and 0.45%, respectively, for a 25 year-old vaccinee. The incremental cost-effectiveness ratio (ICER) for vaccinating 17–25 year-olds was €22,526 per quality-adjusted life-year (QALY) at a vaccine price of €65 per dose, a 50% reduction of the 2010 pharmacy price in the Netherlands. If cross-protection against types 31/33/45/58 was included, the ICER decreased to €14,734 per QALY. Results were robust to efficacy assumptions with respect to previous or current infection status.

Conclusion
The clinical benefit of HPV vaccination of women up to 25 years moderately depends on cross-protection to non-vaccine types. Refunding the cost of the vaccine to 17–25 year-old women in the Netherlands can be considered cost-effective at anticipated price reductions.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 48 pp. 8767-9122 (8 November 2011)

Preparing for the next public debate: Universal vaccination against hepatitis B
Pages 8960-8964
Hans Houweling, Marina Conyn-van Spaendonck, Theo Paulussen, Marcel Verweij, E. Joost Ruitenberg

Abstract
WHO have long called for universal vaccination against hepatitis B worldwide. However, in north-western Europe low incidence of the disease has fueled debate whether targeted or universal vaccination strategies are the way to go for. Careful assessment has made it clear that the extensive targeted hepatitis B vaccination programmes in the Netherlands nevertheless fail to reach a significant part of the risk groups and have not succeeded in eliminating the disease. Modelling suggests that the public health benefits obtained through targeted programmes could be augmented considerably by universal vaccination. Therefore, the Minister of Health of the Netherlands has decided to implement universal vaccination by October 2011. We illustrate the case of the Netherlands and explore lessons, which can be learnt from the vaccination programmes against HPV and influenza A/H1N1 and how to prepare for a potential public debate that might arise when implementing universal vaccination against hepatitis B.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 48 pp. 8767-9122 (8 November 2011)

The cost-effectiveness of rotavirus vaccination in Armenia
Pages 9104-9111
Mark Jit, Ruzanna Yuzbashyan, Gayane Sahakyan, Tigran Avagyan, Liudmila Mosina

Abstract
The cost-effectiveness of introducing infant rotavirus vaccination in Armenia in 2012 using Rotarix(R) was evaluated using a multiple birth cohort model. The model considered the cost and health implications of hospitalisations, primary health care consultations and episodes not leading to medical care in children under five years old. Rotavirus vaccination is expected to cost the Ministry of Health $220,000 in 2012, rising to $830,000 in 2016 following termination of GAVI co-financing, then declining to $260,000 in 2025 due to vaccine price maturity. It may reduce health care costs by $34,000 in the first year, rising to $180,000 by 2019. By 2025, vaccination may be close to cost saving to the Ministry of Health if the vaccine purchase price declines as expected. Once coverage has reached high levels, vaccination may prevent 25,000 cases, 3000 primary care consultations, 1000 hospitalisations and 8 deaths per birth cohort vaccinated. The cost per disability-adjusted life year (DALY) saved is estimated to be about $650 from the perspective of the Ministry of Health, $850 including costs accrued to both the Ministry and to GAVI, $820 from a societal perspective excluding indirect costs and $44 from a societal perspective including indirect costs. Since the gross domestic product per capita of Armenia in 2008 was $3800, rotavirus vaccination is likely to be regarded as “very cost-effective” from a WHO standpoint. Vaccination may still be “very cost-effective” if less favourable assumptions are used regarding vaccine price and disease incidence, as long as DALYs are not age-weighted.

Vaccine
Volume 29, Issue 47 pp. 8471-8766 (3 November 2011)

Meeting Reports
Researching routine immunization–do we know what we don’t know?
Pages 8477-8482
C. John Clements, Margaret Watkins, Ciro de Quadros, Robin Biellik, James Hadler, Deborah McFarland, Robert Steinglass, Elizabeth Luman, Karen Hennessey, Vance Dietz

Abstract
Background
The Expanded Programme on Immunization (EPI), launched in 1974, has developed and implemented a range of strategies and practices over the last three decades to ensure that children and adults receive the vaccines they need to help protect them against vaccine-preventable diseases. Many of these strategies have been implemented, resulting in immunization coverage exceeding 80% among children one year of age in many countries. Yet millions of infants remain under-immunized or unimmunized, particularly in poorer countries. In November 2009, a panel of external experts met at the United States Centers for Disease Control and Prevention (CDC) to review and identify areas of research required to strengthen routine service delivery in developing countries.

Methods
Research opportunities were identified utilizing presentations emphasizing existing research, gaps in knowledge and key questions. Panel members prioritized the topics, as did other meeting participants.

Findings
Several hundred research topics covering a wide range were identified by the panel members and participants. However there were relatively few topics for which there was a consensus that immediate investment in research is warranted. The panel identified 28 topics as priorities. 18 topics were identified as priorities by at least 50% of non-panel participants; of these, five were also identified as priorities by the panel. Research needs included identifying the best ways to increase coverage with existing vaccines and introduce new vaccines, integrate other services with immunizations, and finance immunization programmes.

Interpretation
There is an enormous range of research that could be undertaken to support routine immunization. However, implementation of strategic plans, rather than additional research will have the greatest impact on raising immunization coverage and preventing disease, disability, and death from vaccine-preventable diseases. The panel emphasized the importance of tying operational research to programmatic needs, with a focus on efforts to scale up proven best practices in each country, facilitating the full implementation of immunization strategies.

Vaccine
Volume 29, Issue 47 pp. 8471-8766 (3 November 2011)

Reviews
Planning for influenza vaccination in health care workers: An Intervention Mapping approach
Pages 8512-8519
Gerjo Kok, Gerrit A. van Essen, Sabine Wicker, Anna Llupià, Guillermo Mena, Raquel Correia, Robert A.C. Ruiter

Abstract
Influenza vaccination uptake by health care workers (HCWs) decreases the transmission of influenza to vulnerable patients and prevents influenza-related absenteeism. Vaccination is effective, easy, and generally without serious side-effects. However, vaccination rates of HCWs are too low. This paper’s objective is to apply Intervention Mapping (IM), a planning process for the systematic theory- and evidence-based development of health promotion interventions, to the development of voluntary educational interventions to promote influenza vaccination in HCWs. IM consists of the following six steps: needs assessment, program objectives, methods and applications, program development, planning for program implementation, and planning for program evaluation. Examples are provided to illustrate the activities associated with these steps. It is concluded that applying IM in the (influenza) vaccination field may help the development of effective behavior change interventions.

Vaccine
Volume 29, Issue 47 pp. 8471-8766 (3 November 2011)

Regulars Papers
Economic evaluation of second generation pneumococcal conjugate vaccines in Norway
Pages 8564-8574
Bjarne Robberstad, Carl R. Frostad, Per E. Akselsen, Kari J. Kværner, Aud K.H. Berstad

Abstract
Background
A seven valent pneumococcal conjugate vaccine (PCV7) was introduced in the Norwegian childhood immunization programme in 2006, and since then the incidence of invasive pneumococcal disease has declined substantially. Recently, two new second generation pneumococcal conjugate vaccines have become available, and an update of the economic evidence is needed. The aim of this study was to estimate incremental costs, health effects and cost-effectiveness of the pneumococcal conjugate vaccines PCV7, PCV13 and PHiD-CV in Norway.

Methods
We used a Markov model to estimate costs and epidemiological burden of pneumococcal- and NTHi-related diseases (invasive pneumococcal disease (IPD), Community Acquired Pneumonia (CAP) and acute otitis media (AOM)) for a specific birth cohort. Using the most relevant evidence and assumptions for a Norwegian setting, we calculated incremental costs, health effects and cost-effectiveness for different vaccination strategies. In addition we performed sensitivity analyses for key parameters, tested key assumptions in scenario analyses and explored overall model uncertainty using probabilistic sensitivity analysis.

Results
The model predicts that both PCV13 and PHiD-CV provide more health gains at a lower cost than PCV7. Differences in health gains between the two second generation vaccines are small for invasive pneumococcal disease but larger for acute otitis media and myringotomy procedures. Consequently, PHiD-CV saves more disease treatment costs and indirect costs than PCV13.

Conclusion
This study predicts that, compared to PVC13, PHiD-CV entails lower costs and greater benefits if the latter is measured in terms of quality adjusted life years. PVC13 entails more life years gained than PHiD-CV, but those come at a cost of NOK 3.1 million (∼€0.4 million) per life year. The results indicate that PHiD-CV is cost-effective compared to PCV13 in the Norwegian setting.

Vaccine
Volume 29, Issue 47 pp. 8471-8766 (3 November 2011)

Regulars Papers
Adolescents’ awareness of HPV infections and attitudes towards HPV vaccination 3 years following the introduction of the HPV vaccine in Hungary
Pages 8591-8598
Erika Marek, Timea Dergez, Gabor Rebek-Nagy, Antal Kricskovics, Krisztina Kovacs, Szabolcs Bozsa, Istvan Kiss, Istvan Ember, Peter Gocze

Abstract
Hungary takes the fourth place regarding the incidence and the fifth regarding the mortality of cervical cancer among the member countries of the European Union, with 500 deaths due to this preventable illness and nearly 1200 new cases diagnosed every year. Although the vaccines have been available for 3 years, the estimated rate of the female population vaccinated against HPV is approximately 10% in the 12–26-year-age cohort. The aim of this study was to determine factors and motivations affecting the uptake of HPV vaccination among Hungarian adolescents. Examining the effects of some possible sociodemographic predictors (age and gender) and the exposure to health information on HPV vaccine acceptability were also focused on, as well as assessing the most trusted sources of information about sexually transmitted diseases (STDs).

A nationwide anonymous questionnaire survey with a sample of 1769 students attending public primary or secondary schools was organised by the authors in 16 Hungarian cities and towns. Data were analysed using the Statistical Package for the Social Sciences (SPSS).

Adolescents’ awareness of HPV was relatively low. Only 35% of the participants reported they had heard about HPV prior to the survey. Almost 70% of the potentially affected study population had not heard about the vaccine previously. Every fourth student did not believe that vaccination against HPV can prevent cervical cancer. If the vaccination was available free of charge, almost 80% of respondents would request it, but in case they had to pay for it, this number would significantly decrease. Significantly better knowledge and also more positive attitudes towards HPV vaccination was found in relation to the number of information sources. The majority of respondents (62–83%) were open for further information about STDs. The main trusted mediators were school-health services (61.3%), education on health at school (49.2%), health professionals (42.2%) and electronic media (24.6%).

Since Hungarian adolescent students expect guidance about STDs principally from school health education, an urgent need for well-designed, HPV-focused educational programmes emerges. Launching such programmes would be especially important for the adolescent population to increase their awareness of the risks associated with HPV infection thus reducing the high incidence of cervical cancer in Hungary in the future.

Vaccine

Volume 29, Issue 47 pp. 8471-8766 (3 November 2011)

Regular Papers

Missed clinical opportunities: Provider recommendations for HPV vaccination for 11–12 year old girls are limited
Pages 8634-8641
Susan T. Vadaparampil, Jessica A. Kahn, Daniel Salmon, Ji-Hyun Lee, Gwendolyn P. Quinn, Richard Roetzheim, Karen Bruder, Teri L. Malo, Tina Proveaux, Xiuhua Zhao, Neal Halsey, Anna R. Giuliano

Abstract

Objective

The purpose of this study was to determine the prevalence of physician recommendation of human papillomavirus (HPV) vaccination in early (ages 11–12), middle (13–17), and late adolescent/young adult (18–26) female patients by physician specialty, and to identify factors associated with recommendation in early adolescents.

Methods

A 38-item survey was conducted April 2009 through August 2009 among a nationally representative random sample of 1538 Family Physicians, Pediatricians, and Obstetricians and Gynecologists obtained from the American Medical Association Physician Masterfile. A multivariable model was used to assess factors associated with frequency of physician recommendation of HPV vaccination (“always” = 76–100% of the time vs. other = 0–75%) within the past 12 months.

Results

Completed surveys were received from 1013 physicians, including 500 Family Physicians, 287 Pediatricians, and 226 Obstetricians and Gynecologists (response rate = 67.8%). Across the specialties, 34.6% of physicians reported they “always” recommend the HPV vaccine to early adolescents, 52.7% to middle adolescents, and 50.2% to late adolescents/young adults. The likelihood of “always” recommending the HPV vaccine was highest among Pediatricians for all age groups (P < 0.001). Physician specialty, age, ethnicity, reported barriers, and Vaccines for Children provider status were significantly associated with “always” recommending HPV vaccination for early adolescents.

Conclusions

Findings suggest missed clinical opportunities for HPV vaccination, and perceived barriers to vaccination may drive decisions about recommendation. Results suggest the need for age and specialty targeted practice and policy level interventions to increase HPV vaccination among US females.

The pdf version of Vaccines: The Week in Review  17 October 2011 comprising the posts for this date below is available here: Vaccines_The Week in Review_17 Oct 2011

    WHO released the WHO 2011 global tuberculosis control report, noting that for the first time that the number of people falling ill with tuberculosis (TB) each year is declining. New data also show that the number of people dying from the disease fell to its lowest level in a decade. The new report noted:

– the number of people who fell ill with TB dropped to 8.8 million in 2010, after peaking at nine million in 2005;

– TB deaths fell to 1.4 million in 2010, after reaching 1.8 million in 2003;

– the TB death rate dropped 40% between 1990 and 2010, and all regions, except Africa, are on track to achieve a 50% decline in mortality by 2015;

– in 2009, 87% of patients treated were cured, with 46 million people successfully treated and seven million lives saved since 1995. However, a third of estimated TB cases worldwide are not notified and therefore it is unknown whether they have been diagnosed and properly treated. The report is available in various formats here:

http://www.who.int/entity/tb/publications/global_report/en/index.html

http://www.who.int/mediacentre/news/releases/2011/tb_20111011/en/index.html

NIH said it awarded five-year contracts which could total $150 million to four companies to develop broad-spectrum therapeutics. The NIAID awards will support research on antibiotics, antivirals and an antitoxin “to prevent or treat diseases caused by multiple types of bacteria or viruses. The contracts “are designed to support essential research and development activities to enable promising investigational therapies to move toward early-phase clinical studies and, if successful in clinical studies, on to eventual licensure. The ultimate goal is to develop products that the U.S. government can stockpile to protect the public in the event of a bioterror attack or public health crisis.” NIH said the contracts are to focus “on candidate therapies that can be used against classes of pathogens rather than being agent-specific. Such broad-spectrum therapeutics would improve preparedness for all infectious threats, whether they occur naturally or are deliberately introduced.” More on the companies involved and their research focus areas here:

http://www.nih.gov/news/health/oct2011/niaid-13.htm