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

   The International Finance Facility for Immunisation (IFFIm) announced the renewal of its Treasury Management Agreement with the World Bank for a five year period. Alan Gillespie, IFFIm Board Chair, said, “this has been an effective partnership that has positioned IFFIm exceptionally well in markets and contributed greatly to the GAVI Alliance’s role in vaccinating children in developing countries against serious, but preventable diseases.” Under the agreement, the World Bank manages IFFIm’s finances according to prudent policies and standards. This includes IFFIm’s funding strategy and its implementation in the capital markets, rating agency and investor outreach, hedging transactions and investment management. The World Bank also coordinates with IFFIm’s donors and manages their pledges and payments as well as IFFIm’s disbursements for immunisation and health programmes through the GAVI Alliance. IFFIm was set up in 2006, to help save millions of children’s’ lives by increasing funding for the purchase and delivery of vaccines and by strengthening health services in developing countries through the GAVI Alliance. IFFIm’s donors are the United Kingdom, France, Italy, Spain, Australia, the Netherlands, Sweden, Norway and South Africa. Brazil has also announced that it will become an IFFIm donor.

http://www.gavialliance.org/library/news/press-releases/2011/iffim-and-world-bank-renew-commitment-to-raise-funds-for-gavi-programmes/

WHO Meeting Announcement: World Conference on Social Determinants of Health

Place: Rio de Janeiro, Brazil
Date: 19–21 October 2011

This conference will bring together Member States and stakeholders to build support for the implementation of action on social determinants of health to reduce inequities. The conference is being organized in accordance with a 2009 World Health Assembly Resolution (WHA62.14) and will be hosted by the Government of Brazil.

The event will provide a global platform for dialogue on how the 2008 recommendations of the WHO Commission on Social Determinants of Health could be taken forward. Specifically, the conference will provide a process for the sharing of national experiences and technical knowledge on addressing social determinants of health.

The conference will aim to catalyse coordinated global action in five key areas:

governance to tackle the root causes of health inequities: implementing action on social determinants of health; the role of the health sector, including public health programmes, in reducing health inequities; promoting participation: community leadership for action on social determinants; global action on social determinants: aligning priorities and stakeholders; monitoring progress: measurement and analysis to inform policies on social determinants.

Member States are expected to endorse the Rio Declaration, thereby strengthening their political commitment to reducing health inequities

http://www.who.int/mediacentre/events/meetings/2011/social_determinants_health/en/index.html

The MMWR for October 14, 2011 / Vol. 60 / No. 40
– Progress Toward Implementation of Human Papillomavirus Vaccination — the Americas, 2006–2010

– Establishment of a Viral Hepatitis Surveillance System — Pakistan, 2009–2011

– Recommendation of the Advisory Committee on Immunization Practices (ACIP) for Use of Quadrivalent Meningococcal Conjugate Vaccine (MenACWY-D) Among Children Aged 9 Through 23 Months at Increased Risk for Invasive Meningococcal Disease

The Weekly Epidemiological Record (WER) for 14 October 2011, vol. 86, 42 (pp 457–468) includes: Recommended composition of influenza vaccines for use in the 2012 southern hemisphere influenza season

http://www.who.int/entity/wer/2011/wer8642.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
First child in Ethiopia receives pneumococcal vaccine…millions more to follow
11 hours ago

GAVIAlliance GAVI Alliance
Ethiopia is 1 of 10 pilots where #GAVI funds civil society organisations to help with immunisation- ht.ly/6Ywkd
15 Oct

pahowho PAHO/WHO
World Conference on Social Determinants of Health who.int/sdhconference/…
14 Oct

PublicHealth APHA
Cervical cancer kills 36,000+ women each yr in the Americas. HPV vaccination varies widely, says MMWR study: goo.gl/aTZZZ
14 Oct

WHO_Europe WHO/Europe
by Eurovaccine
Investment in building relations with media, parent communities, and other stakeholders helps in #vaccine safety events bit.ly/reIO2q
13 Oct

JAMA   
October 12, 2011, Vol 306, No. 14, pp 1513-1614
http://jama.ama-assn.org/current.dtl

Commentaries
A Model for Dissemination and Independent Analysis of Industry Data
Harlan M. Krumholz, Joseph S. Ross
JAMA. 2011;306(14):1593-1594.doi:10.1001/jama.2011.1459

Extract
Each day, patients and their physicians make treatment decisions with access to only a fraction of the relevant clinical research data. Many clinical studies, including randomized clinical trials, are never published in the biomedical literature. 1, 2 Among those that are published, key information is often not presented, such as data on specific outcomes and safety end points. 3, 4 Moreover, patient-level data from clinical trials are rarely publicly available, leaving investigators to conduct meta-analyses of summary-level data, an approach with limitations. 5

Current clinical research standards lack sufficiently strong requirements for transparency and availability. There are no uniform international standards requiring that study protocols, statistical analysis plans, and study results be made available, and there are no requirements that completed clinical trial data be publicly available or posted for independent analysis. Even data submitted to the US Food and Drug Administration are not made publicly available

Pharmacoeconomics
November 1, 2011 – Volume 29 – Issue 11  pp: 913-1009
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

The Importance of the Comparator in Economic Evaluations: Working on the Efficiency Frontier
Neyt, Mattias; Van Brabandt, Hans
Pharmacoeconomics. 29(11):913-916, November 1, 2011.
doi: 10.2165/11595260-000000000-00000

[No abstract]

Pharmacoeconomics
November 1, 2011 – Volume 29 – Issue 11  pp: 913-1009
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Rotavirus Vaccine RIX4414 (Rotarix™): A Pharmacoeconomic Review of its Use in the Prevention of Rotavirus Gastroenteritis in Developing Countries
Plosker, Greg L.
Pharmacoeconomics. 29(11):989-1009, November 1, 2011.
doi: 10.2165/11207210-000000000-00000

Abstract:
This article provides an overview of the clinical profile of rotavirus vaccine RIX4414 (Rotarix™) in the prevention of rotavirus gastroenteritis (RVGE) in developing countries, followed by a comprehensive review of pharmacoeconomic analyses with the vaccine in low- and middle-income countries.

RVGE is associated with significant morbidity and mortality among children <5 years of age in developing countries. The protective efficacy of a two-dose oral series of rotavirus vaccine RIX4414 has been demonstrated in several well designed clinical trials conducted in developing countries, and the ‘real-world’ effectiveness of the vaccine has also been shown in naturalistic and case-control trials after the introduction of universal vaccination programmes with RIX4414 in Latin American countries. The WHO recommends universal rotavirus vaccination programmes for all countries.

Numerous modelled cost-effectiveness analyses have been conducted with rotavirus vaccine RIX4414 across a wide range of low- and middle-income countries. Although data sources and assumptions varied across studies, results of the analyses consistently showed that the introduction of the vaccine as part of a national vaccination programme would be very (or highly) cost effective compared with no rotavirus vaccination programme, according to widely used cost-effectiveness thresholds for developing countries. Vaccine price was not known at the time the analyses were conducted and had to be estimated. In sensitivity analyses, rotavirus vaccine RIX4414 generally remained cost effective at the highest of a range of possible vaccine prices considered.    Despite these favourable results, decisions regarding the implementation of universal vaccination programmes with RIX4414 may also be contingent on budgetary and other factors, underscoring the importance of subsidized vaccination programmes for poor countries through the GAVI Alliance (formerly the Global Alliance for Vaccines and Immunization).

PLoS One
[Accessed 16 October 2011]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

7-Valent Pneumococcal Conjugate Vaccination in England and Wales: Is It Still Beneficial Despite High Levels of Serotype Replacement?
Yoon Hong Choi, Mark Jit, Nigel Gay, Nick Andrews, Pauline A. Waight, Alessia Melegaro, Robert George, Elizabeth Miller
PLoS ONE: Research Article, published 14 Oct 2011 10.1371/journal.pone.0026190

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 46 pp. 8175-8470 (26 October 2011)

Regular Papers
Reasons related to non-vaccination and under-vaccination of children in low and middle income countries: Findings from a systematic review of the published literature, 1999–2009
Pages 8215-8221
Jeanette J. Rainey, Margaret Watkins, Tove K. Ryman, Paramjit Sandhu, Anne Bo, Kaushik Banerjee

Abstract
Objective
Despite increases in routine vaccination coverage during the past three decades, the percent of children completing the recommended vaccination schedule remains below expected targets in many low and middle income countries. In 2008, the World Health Organization Strategic Advisory Group of Experts on Immunization requested more information on the reasons that children were under-vaccinated (receiving at least one but not all recommended vaccinations) or not vaccinated in order to develop effective strategies and interventions to reach these children.

Methods
A systematic review of the peer-reviewed literature published from 1999 to 2009 was conducted to aggregate information on reasons and factors related to the under-vaccination and non-vaccination of children. A standardized form was used to abstract information from relevant articles identified from eight different medical, behavioural and social science literature databases.

Findings
Among 202 relevant articles, we abstracted 838 reasons associated with under-vaccination; 379 (45%) were related to immunization systems, 220 (26%) to family characteristics, 181 (22%) to parental attitudes and knowledge, and 58 (7%) to limitations in immunization-related communication and information. Of the 19 reasons abstracted from 11 identified articles describing the non-vaccinated child, 6 (32%) were related to immunization systems, 8 (42%) to parental attitudes and knowledge, 4 (21%) to family characteristics, and 1 (5%) to communication and information.

Conclusions
Multiple reasons for under-vaccination and non-vaccination were identified, indicating that a multi-faceted approach is needed to reach under-vaccinated and unvaccinated children. Immunization system issues can be addressed through improving outreach services, vaccine supply, and health worker training; however, under-vaccination and non-vaccination linked to parental attitudes and knowledge are more difficult to address and likely require local interventions.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 46 pp. 8175-8470 (26 October 2011)

Regular Papers
Attitudes and perceptions of private pediatricians regarding polio immunization in India
Pages 8317-8322
Panna Choudhury, Naveen Thacker, Lisa M. Gargano, Paul S. Weiss, Vipin M. Vashishtha, Tanmay Amladi, Karen Pazol, Walter A. Orenstein, Saad B. Omer, James M. Hughes

Abstract
Background
India has faced considerable challenges in eradicating polio. Uttar Pradesh (UP) and Bihar are the two states in India where transmission of polio has never been interrupted. Private pediatricians are important stakeholders for vaccine delivery and maintaining public confidence in vaccines. The purpose of this study was to investigate the attitudes and perceptions of pediatricians in India regarding polio immunization and their opinions about various strategies regarding polio eradication in the country.

Methods
A random sample of 785 pediatricians belonging to the Indian Academy of Pediatrics (IAP) were selected for the survey with over sampling of members located in Bihar and UP. Potential participants were either contacted by phone or sent a self-administered anonymous questionnaire by mail. For this analysis both sets of responses were combined. Surveys were conducted from June 2009 to June 2010.

Results
A total of 398 surveys were completed (51%). Nearly all respondents indicated that polio eradication is still an important priority (99.7%). Ninety-six percent of pediatricians believed that strengthening routine immunization efforts remains the best way to eradicate polio in endemic areas. Other measures thought to be important in eradicating polio are mass campaigns with IPV (73%) and mass campaigns with bivalent OPV (59%). Pediatricians also identified several barriers to polio eradication which included parents’ lack of awareness of the importance of polio vaccination (88.8%), parents’ lack of confidence in polio vaccine (64.0%), religious beliefs (59.2%), fear of side effects (59.2%), lack of time or priority (56.6%), superstition (50.3%) and cultural beliefs (46.4%).

Conclusion
There is still strong support for polio eradication efforts among IAP members. Pediatricians in India strongly believe that improving the coverage of routine immunization remains the best way to eradicate polio. There is an urgent need to improve awareness, build confidence in the program, and remove barriers among parents.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 46 pp. 8175-8470 (26 October 2011)

Regular Papers
The cost-effectiveness of male HPV vaccination in the United States
Pages 8443-8450
Harrell W. Chesson, Donatus U. Ekwueme, Mona Saraiya, Eileen F. Dunne, Lauri E. Markowitz

Abstract
Introduction
The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12–26 years in the United States.

Methods
We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers.

Results
The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated.

Conclusions
HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population.

The pdf version of Vaccines: The Week in Revoew  10 October 2011, comprising the posts below for this date, is available here: Vaccines_The Week in Review_10 Oct 2011

 WHO reported on measles outbreak in Member States in the European and African regions, with several reported outbreaks in the Americas linked to Europe or Africa.

[full text]
Europe: As of 20 September 2011, 40 of 53 Member States in the WHO European Region have reported 26,025 confirmed measles cases for the period January – July 2011 to the WHO European Regional Office through routine surveillance and outbreak reports. The highest number of cases was reported from France with 14,025 cases for the first six months of the year. In addition, eleven of all cases in the Region were lethal (6 in France and one in each of Germany, Kyrgyzstan, Romania, the Former Yugoslav Republic of Macedonia and the United Kingdom). The predominant genotype currently circulating in the European Region is D4, the same endemic genotype from the United Kingdom in 2008. The most recent outbreak was reported from Israel in September, with 12 cases. Member States have responded to the outbreak by modifying the vaccination schedule, like France, or by offering vaccination free of charge or in schools, to increase accessibility to and availability of vaccines.

Africa: The Regional Office reports that as of September 2011 large measles outbreaks are being reported by the Democratic Republic of the Congo, with over 103,000 cases, Nigeria, with 17,428 cases, and Zambia, with 5,397 cases, and Ethiopia, with 2 902 cases. Even though deaths are not routinely reported to the Regional Office, the WHO Country Office in the Democratic Republic of the Congo reports over 1100 measles-associated deaths in the country during 2011.

Americas: The last case of endemic measles was reported from the region in 2002. In 2011 the Region has received reports of several outbreaks linked to importation of measles virus from other regions. The largest, in Quebec, Canada, involves 742 reported cases, 89 requiring hospitalization, but no measles-associated deaths. Other outbreaks have been reported from the United States (213 cases), Ecuador (41 cases), Brazil (18 cases), Columbia (7 cases), Mexico (3 cases), and Chile (6 cases). Most of these outbreaks are linked to importations from Europe, except for outbreaks in the United States and Chile linked to cases from Malaysia and the outbreak in Ecuador, linked to Kenya.

Measles is a highly infectious disease that causes complications and deaths, even in previously-healthy individuals, but is fully preventable by vaccination. Countries need to ensure that they reach 95% coverage with two doses of measles vaccine across all age groups up to 15 years of age. Otherwise the country will experience measles outbreaks with large numbers of cases, associated hospitalizations and deaths. The recent outbreaks in countries with high volumes of international travellers can lead to measles exportation to regions previously free of measles, such as the Region of the Americas or certain African countries. These exportations can lead to large outbreaks and associated deaths.

These outbreaks should remind travellers that they should ensure that they have had two doses of measles-containing vaccine before their trip.

http://www.who.int/csr/don/2011_10_07/en/index.html

   The Nobel Prize in Physiology or Medicine 2011 was awarded jointly to Bruce A. Beutler and Jules A. Hoffmann “for their discoveries concerning the activation of innate immunity” and to Ralph M. Steinman (posthumously) “for his discovery of the dendritic cell and its role in adaptive immunity”.

Extract from press release:

Jules Hoffmann made his pioneering discovery in 1996, when he and his co-workers investigated how fruit flies combat infections. They had access to flies with mutations in several different genes including Toll, a gene previously found to be involved in embryonal development by Christiane Nüsslein-Volhard (Nobel Prize 1995). When Hoffmann infected his fruit flies with bacteria or fungi, he discovered that Toll mutants died because they could not mount an effective defense. He was also able to conclude that the product of the Toll gene was involved in sensing pathogenic microorganisms and Toll activation was needed for successful defense against them.

Bruce Beutler was searching for a receptor that could bind the bacterial product, lipopolysaccharide (LPS), which can cause septic shock, a life threatening condition that involves overstimulation of the immune system. In 1998, Beutler and his colleagues discovered that mice resistant to LPS had a mutation in a gene that was quite similar to the Toll gene of the fruit fly. This Toll-like receptor (TLR) turned out to be the elusive LPS receptor. When it binds LPS, signals are activated that cause inflammation and, when LPS doses are excessive, septic shock. These findings showed that mammals and fruit flies use similar molecules to activate innate immunity when encountering pathogenic microorganisms. The sensors of innate immunity had finally been discovered.

The discoveries of Hoffmann and Beutler triggered an explosion of research in innate immunity. Around a dozen different TLRs have now been identified in humans and mice. Each one of them recognizes certain types of molecules common in microorganisms. Individuals with certain mutations in these receptors carry an increased risk of infections while other genetic variants of TLR are associated with an increased risk for chronic inflammatory diseases…

Ralph Steinman discovered, in 1973, a new cell type that he called the dendritic cell. He speculated that it could be important in the immune system and went on to test whether dendritic cells could activate T cells, a cell type that has a key role in adaptive immunity and develops an immunologic memory against many different substances. In cell culture experiments, he showed that the presence of dendritic cells resulted in vivid responses of T cells to such substances. These findings were initially met with skepticism but subsequent work by Steinman demonstrated that dendritic cells have a unique capacity to activate T cells.

Further studies by Steinman and other scientists went on to address the question of how the adaptive immune system decides whether or not it should be activated when encountering various substances. Signals arising from the innate immune response and sensed by dendritic cells were shown to control T cell activation. This makes it possible for the immune system to react towards pathogenic microorganisms while avoiding an attack on the body’s own endogenous molecules.

From fundamental research to medical use

The discoveries that are awarded the 2011 Nobel Prize have provided novel insights into the activation and regulation of our immune system. They have made possible the development of new methods for preventing and treating disease, for instance with improved vaccines against infections and in attempts to stimulate the immune system to attack tumors. These discoveries also help us understand why the immune system can attack our own tissues, thus providing clues for novel treatment of inflammatory diseases…

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2011/press.html

     The GAVI Alliance “praised ‘la Caixa’ Foundation’s leadership and generosity in donating € 4 million (US$5.7 million) to GAVI’s new Matching Fund.” GAVI described the matching programme as ” a major new effort with the private sector to raise US$260 million for immunisation by the end of 2015. Under the programme, the Gates Foundation has pledged US$50 million to match contributions to GAVI from primarily private sector companies, their customers and employees. In addition, pledges to the Matching Fund by UK companies and their customers and employees are being matched by the £ 50 million pledge from the UK Department for International Development (DFID).”  The “la Caixa” pledge – € 2 million in 2011 and € 2 million in 2012 — specifically goes toward the purchase of pneumococcal vaccine for GAVI-supported countries in Latin America.   http://www.gavialliance.org/library/news/press-releases/2011/la-caixa-donation-matching-fund/

   The Bill & Melinda Gates Foundation announced a new initiative for Nigeria’s Executive Governors “challenging them to deliver a dramatic improvement in polio and routine immunization by the end of 2012.” The program “will recognize those Executive Governors whose states pass a pre-defined threshold to improve routine immunization coverage and end polio. The states that meet the threshold criteria will be awarded a $500,000 grant from the Bill & Melinda Gates Foundation to support their top health priorities.” The award will support winning governors’ priority initiatives in public health, such as malaria and tuberculosis, improving immunization, HIV prevention and treatment, or safe drinking water and hygiene promotion. In addition to the grant, “those governors who achieve the goals will receive special recognition from Mr. Gates for their contribution to the elimination of polio. Winning governors will be highlighted in foundation communications, such as Mr. Gates’ annual letter or the foundation’s annual report, social media materials and Mr. Gates’ public engagements globally.” In addition, “if Governors choose, they also may contribute $250,000 to their chosen health project and the foundation will match that contribution, meaning a potential total $1 million towards improving health in their state.”

http://www.gatesfoundation.org/press-releases/Pages/governors-immunization-leadership-challenge-111004.aspx

The Gates Foundation announced that it is accepting nominations for the first Gates Vaccine Innovation Award “to recognize, celebrate, and spur transformative ideas for achieving impact through the delivery of vaccines.” Nominations will be accepted through 17 November 2011. The Gates Vaccine Innovation Award “seeks to reward those who have achieved significant improvements in the prevention, control, or elimination of vaccine preventable disease through imaginative and pioneering approaches,” and is “unique in that it complements other awards already focused on scientific research and development. The winning person or team will receive $250,000 and earn special recognition by foundation leadership for their contribution.” The Gates Vaccine Innovation Award application process is open to any individual or team from any discipline – academic institutions, governments, health care facilities, research institutions, non-profit organizations and for-profit companies. Nominations are being accepted online now at: www.gatesfoundation.org/gates-vaccine-innovation-award.

http://www.gatesfoundation.org/press-releases/Pages/gates-vaccine-innovation-award-111006.aspx

The Weekly Epidemiological Record (WER) for 7 October 2011, vol. 86, 41 (pp 445–456) includes: Hepatitis C; Monkeypox; Nipah virus;
http://www.who.int/entity/wer/2011/wer8641.pdf