The Weekly Epidemiological Record (WER) for 9 August 2013, vol. 88, 32 (pp. 337–348) includes:
:: Rubella virus nomenclature update: 2013
:: Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca (Hajj)
http://www.who.int/entity/wer/2013/wer8832.pdf

Book: Protecting the World’s Children – Immunisation policies and Practices
Edited by Sidsel Roalkvam, Desmond McNeill, and Stuart Blume
248 pages | 234x156mm
978-0-19-966644-7 | Paperback | 09 May 2013
http://ukcatalogue.oup.com/product/9780199666447.do#.UgWJE234LxM

The strengths and limitations of global immunization programmes
By Desmond McNeill
Excerpt
“…When polio eradication was proposed as a global objective, in the late 1980s, it was vigorously debated. No one doubted the power of the polio vaccine to protect children. But experts differed in how they thought it should best be used. Some have regarded vaccination programmes as a means of strengthening primary health care, whilst others have seen them as likely to divert attention and resources from needed improvements in health services. At issue in such debates is not the immunological properties of a vaccine, but the way in which it should best be used. Taking the health care needs of children, and especially those whose health is most at risk, as the key objective, how should vaccines best be deployed?

The question is even more relevant today, as more and more new vaccines are becoming available, and huge financial resources are being deployed to promote global immunisation. These donor-funded programmes now account for a major part of the effort devoted to improving the health of children in developing countries.

Three distinctive, but interrelated, trends can be identified in international public health in recent years:
:: A growing reliance on health technologies, and on vaccines in particular;
:: A global perspective that is increasingly taken for granted;
:: Quantifiable targets, and especially the Millennium Development Goals (MDGs), play a very important role.

Health policy makers at national level are expected to implement global immunisation programmes in a standard manner and report progress according to standard indicators. Pressures and incentives to meet the targets set are then transmitted down to the community level health worker who actually meets the parents and children to implement these programmes.

Today, despite continuing or even increased talk of ‘country ownership’, there are growing demands for performance accountability, reflected in demands for measurement of performance — not just outputs, but also outcomes and impacts — based on objective quantitative indicators. The MDGs have contributed to the process. One of the attractions of vaccines is precisely their measurability: both as regards specifying targets and measuring achievement. Dividing the number of vaccines distributed by the number of children of the appropriate age in the target population is made to yield two simple but powerful numbers: percentage coverage, and number of lives saved

Although we are not questioning the intentions of global actors who contribute to this situation, we do note that the effect of their actions is to strengthen the ‘verticality’ in the global health system. In this system  money, and vaccines themselves, emanate from the global level and travel down from national to district and to village levels, accompanied by technical advice, exhortation and targets to be achieved. In return — up the chain, emanating from the most local level — come reports on performance, and measures of achievements, expressed in terms of numbers of children vaccinated. In this way, not only is the autonomy of national governments reduced, their accountability may even be reversed. Instead of being accountable ‘downwards’ to their citizens, they become accountable ‘upwards’ to global actors.

The need to show progress can create distortions and lead to the production of misleading data, and an unwillingness to report problems. Vaccines could more effectively serve children’s health needs if immunisation programmes were better understood and acknowledged, and if local knowledge and realities were enabled to inform national and international health policy.

   Desmond McNeill is co-editor, along with Sidsel Roalkvam and Stuart Blume, of Protecting the World’s Children: Immunisation policies and Practices (2013). He is Professor, and former Director, at SUM, the Centre for Development and Environment at the University of Oslo. He heads the research area on Governance for Sustainable Development, and is Director of SUMs Research School. He has worked in over 15 developing countries in Africa, Asia and Latin America and written extensively on aid and global governance.
http://blog.oup.com/2013/08/strengths-limitations-global-immunization-programmes/#sthash.RxooNNRN.dpuf

American Journal of Public Health
Volume 103, Issue 9 (September 2013)
http://ajph.aphapublications.org/toc/ajph/current

Quadrivalent Human Papillomavirus Vaccine Uptake in Adolescent Boys and Maternal Utilization of Preventive Care and History of Sexually Transmitted Infections
Rulin C. Hechter, MD, PhD, Chun Chao, PhD, Lina S. Sy, MPH, Bradley K. Ackerson, MD, Jeff M. Slezak, MS, Margo A. Sidell, ScD, and Steven J. Jacobsen, MD, PhD
All authors are with the Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena.
http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2013.301495

Abstract
Objectives. We examined whether maternal utilization of preventive care and history of sexually transmitted infections (STIs) predicted quadrivalent human papillomavirus vaccine (HPV4) uptake among adolescent boys 1 year following the recommendation for permissive use of HPV4 for males.

Methods. We linked maternal information with electronic health records of 254 489 boys aged 9 to 17 years who enrolled in Kaiser Permanente Southern California health plan from October 21, 2009, through December 21, 2010. We used multivariable Poisson regression with robust error variance to examine whether HPV4 initiation was associated with maternal uptake of influenza vaccine, Papanicolaou (Pap) screening, and history of STIs.

Results. We identified a modest but statistically significant association between initiation of HPV4 series and maternal receipt of influenza vaccine (rate ratio [RR] = 1.16; 95% confidence interval [CI] = 1.07, 1.26) and Pap screening (RR = 1.13; 95% CI = 1.01, 1.26). Boys whose mothers had a history of genital warts were more likely to initiate HPV4 (RR = 1.47; 95% CI = 0.93, 2.34), although the association did not reach statistical significance (P = .1).

Conclusions. Maternal utilization of preventive care and history of genital warts may influence HPV4 uptake among adolescent boys. The important role of maternal health characteristics and health behaviors needs be considered in intervention efforts to increase vaccine uptake among boys.

British Medical Journal
10 August 2013 (Vol 347, Issue 7920)
http://www.bmj.com/content/347/7920

Editorial
Human to human transmission of H7N9
BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f4730 (Published 6 August 2013)
Cite this as: BMJ 2013;347:f4730
http://www.bmj.com/content/347/bmj.f4730
James W Rudge, lecturer1, Richard Coker, professor12
Limited transmission between humans is not surprising
Since the new avian influenza virus, H7N9, first emerged in China, a primary concern has been whether it might spread between humans. The vast majority of the 133 confirmed cases reported so far seem to be epidemiologically unconnected, with many patients reporting a recent history of exposure to live poultry, which are suspected to be a main reservoir for the virus. Although an earlier study did report two family clusters of H7N9 cases, it was unclear whether these clusters resulted from person to person transmission or simply from exposure to a common animal source of infection.1

In the linked paper (doi:10.1136/bmj.f4752) by Qi and colleagues, a detailed investigation into one of these clusters provides the strongest evidence yet of H7N9 transmission between humans.2 The index case, a 60 year old man, was likely to have been infected at a nearby live poultry market, and subsequently developed a severe and ultimately fatal respiratory illness. His 32 year old daughter, who provided prolonged bedside care for her father before his admission to intensive care, later also became fatally infected. With no indication that the daughter was exposed to live poultry within the days before becoming sick, along with almost 100% genetic similarity between the viruses isolated from each patient, the evidence points to transmission from father to daughter.

As the authors acknowledge, there are some limitations to the study but, on balance, human to human transmission looks probable. So does this imply that H7N9 has come one step closer towards adapting fully to humans? Probably not. Crucially, there is still no evidence of sustained transmission among humans—all 43 close contacts of these two patients, including a son in law who also helped care for the father, tested negative for infection. In addition, the receptor binding sites of the viruses from the two patients are no more adapted towards humans than those of other available H7N9 isolates. In many ways, the evidence corroborates, rather than challenges, previous assertions that the transmissibility of H7N9 between humans is currently low.

Indeed, the occasional transmission event from human to human appears to be the norm rather than the exception for influenza viruses that sporadically cross the species barrier into humans. Limited human to human transmission has been reported for highly pathogenic avian influenza H5N1,3 4 which continues to cause (usually fatal) infections in humans, as well as another bird flu subtype, H7N7, which caused an outbreak of mostly mild infections in the Netherlands in 2003.5 To observe some transmission of H7N9 from human to human is therefore not surprising, and does not necessarily indicate that the virus is on course to develop sustained transmission among humans.

Nevertheless, several traits of H7N9 are of particular concern. The linked paper2 comes close on the heels of studies showing airborne transmissibility of H7N9 between ferrets in the laboratory, a mammalian model.6 7 Also, it is now well documented that owing to its non-lethality in birds, H7N9 can spread undetected through avian populations. In addition, Chinese surveillance data suggest that the number of confirmed human cases is just the tip of the iceberg—many mild cases are likely to have passed undetected.8 The upside of this is that the actual fatality rate among H7N9 cases is likely to be substantially lower than that observed among confirmed cases.9 The flipside is that the incidence of human infections, and therefore opportunities for H7N9 to adapt to humans or to re-assort through mixed influenza infections, could be much greater than for other bird flu viruses such as H5N1.

Although the number of H7N9 cases has fallen abruptly since April 2013, with no new cases reported for several weeks, we have been warned to expect a resurgence later in the year owing to seasonal effects on transmission.10 Thus, while the paper by Qi and colleagues2 might not suggest that H7N9 is any closer to delivering the next pandemic, it does provide a timely reminder of the need to remain extremely vigilant: the threat posed by H7N9 has by no means passed.

.
Research
Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation
BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f4752 (Published 6 August 2013)
Cite this as: BMJ 2013;347:f4752
http://www.bmj.com/content/347/bmj.f4752

Abstract
Objective  To determine whether the novel avian influenza H7N9 virus can transmit from person to person and its efficiency.
Design  Epidemiological investigations conducted after a family cluster of two patients with avian H7N9 in March 2013.
Setting  Wuxi, Eastern China.
Participants  Two patients, their close contacts, and relevant environments. Samples from the patients and environments were collected and tested by real time reverse transcriptase-polymerase chain reaction (rRT-PCR), viral culture, and haemagglutination inhibition assay. Any contacts who became ill had samples tested for avian H7N9 by rRT-PCR. Paired serum samples were obtained from contacts for serological testing by haemagglutination inhibition assays.
Main outcomes measures  Clinical data, history of exposure before the onset of illnesses, and results of laboratory testing of pathogens and further analysis of sequences and phylogenetic tree to isolated strains.
Results  The index patient became ill five to six days after his last exposure to poultry. The second patient, his daughter aged 32, who provided unprotected bedside care in the hospital, had no known exposure to poultry. She developed symptoms six days after her last contact with her father. Two strains were isolated successfully from the two patients. Genome sequence and analyses of phylogenetic trees showed that both viruses were almost genetically identical. Forty three close contacts of both patients were identified. One had mild illness but had negative results for avian H7N9 by rRT-PCR. All 43 close contacts tested negative for haemagglutination inhibition antibodies specific for avian H7N9.
Conclusions  The infection of the daughter probably resulted from contact with her father (the index patient) during unprotected exposure, suggesting that in this cluster the virus was able to transmit from person to person. The transmissibility was limited and non-sustainable

Cost Effectiveness and Resource Allocation
(Accessed 10 August 2013)
http://www.resource-allocation.com/

Methodology
Calculating disability-adjusted-life-years lost (DALYs) in discrete-time
Larson BA Cost Effectiveness and Resource Allocation 2013, 11:18 (8 August 2013)
Open Access
http://www.resource-allocation.com/content/11/1/18/abstract

Abstract (provisional)
Disability-adjusted-life-years lost (DALYs) is a common outcome metric for cost-effectiveness analyses, and the equations used for such calculations have been presented previously by Fox-Rushby and Hanson (see, e.g., “Health Policy and Planning 16:326–331, 2001”). While the equations are clear, the logic behind them is opaque at best for a large share of public health practitioners and students. The objective of this paper is to show how to calculate DALYs using a discrete time formulation that is easy to teach to students and public health practitioners, is easy to apply for those with basic discounting skills, and is consistent with the discounting methods typically included on the costing side of cost-effectiveness analysis. A continuous-time adjustment factor is derived that can be used to ensure exact consistency between the continuous and discrete time approaches, but this level of precision is typically unnecessary for cost-effectiveness analyses. To illustrate the approach, both a new, simple example and the same example presented in Fox-Rushby and Hanson are used throughout the paper.

Eurosurveillance
Volume 18, Issue 32, 08 August 2013
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

Research articles
Impact of universal two-dose vaccination on varicella epidemiology in Navarre, Spain, 2006 to 2012
by M García Cenoz, J Castilla, J Chamorro, I Martínez-Baz, V Martínez-Artola, F Irisarri, M Arriazu, C Ezpeleta, A Barricarte
[No abstract]

Eurosurveillance
Volume 18, Issue 32, 08 August 2013
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

Surveillance and outbreak reports
International infectious disease surveillance during the London Olympic and Paralympic Games 2012: process and outcomes
J Jones ¹, J Lawrence¹, L Payne Hallström², J Mantero², H Kirkbride³, A Walsh³, D Jermacane⁴, H Simons⁵, K M Hansford⁶, E Bennett⁶, M Catchpole⁷, on behalf of the international team⁸
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20554

Abstract
Surveillance for possible international infectious disease threats to the Olympic and Paralympic Games in London, United Kingdom, was conducted from 2 July to 12 September 2012 by a collaborative team comprising representatives from the Health Protection Agency (Public Health England since April 2013), the European Centre for Disease Prevention and Control and the National Travel Health Network and Centre. Team members enhanced their usual international surveillance activities and undertook joint risk assessments of incidents identified as relevant through an agreed set of criteria designed for the Games and using tools developed for this purpose. Although team members responded to a range of international disease incidents as part of their routine roles during this period, no incident was identified that represented a threat to the Games. Six incidents were highlighted by the team that were likely to attract media attention and hence could generate political and public concern. Responding to such concern is an important aspect of the overall public health management of mass gathering events. The lessons learned about the process and outcomes of the enhanced international surveillance will help inform planning by future hosts of similar events.

Journal of the Royal Society – Interface
October 6, 2013; 10 (87)
http://rsif.royalsocietypublishing.org/content/current

Perspective
Making wider use of the world’s most widely used vaccine: Bacille Calmette–Guérin revaccination reconsidered
Christopher Dye
J. R. Soc. Interface. 2013 10 20130365; doi:10.1098/rsif.2013.0365 (published 31 July 2013)
http://rsif.royalsocietypublishing.org/content/10/87/20130365.abstract

Abstract
Approximately 100 million newborn children receive Bacille Calmette–Guérin (BCG) annually, because vaccination is consistently protective against childhood tuberculous meningitis and miliary TB. By contrast, BCG efficacy against pulmonary TB in children and adults is highly variable, ranging from 0% to 80%, though it tends to be higher in individuals who have no detectable prior exposure to mycobacterial infections, as judged by the absence of delayed-type hypersensitivity response (a negative tuberculin skin test, TST). The duration of protection against pulmonary TB is also variable, but lasts about 10 years on average. These observations raise the possibility that BCG revaccination, following primary vaccination in infancy, could be efficacious among TST-negative adolescents as they move into adulthood, the period of highest risk for pulmonary disease. To inform continuing debate about revaccination, this paper assesses the effectiveness and cost-effectiveness of revaccinating adolescents in a setting with intense transmission—Cape Town, South Africa. For a cost of revaccination in the range US$1–10 per person, and vaccine efficacy between 10% and 80% with protection for 10 years, the incremental cost per year of healthy life recovered (disability-adjusted life years, DALY) in the vaccinated population lies between US$116 and US$9237. The intervention is about twice as cost-effective when allowing for the extra benefits of preventing transmission, with costs per DALY recovered in the range US$52–$4540. At 80% efficacy, revaccination averted 17% of cases. Under the scenarios investigated, BCG revaccination is cost-effective against international benchmarks, though not highly effective. Cost-effectiveness ratios would be more favourable if we also allow for TB cases averted by preventing transmission to HIV-positive people, for the protection of HIV-negative people who later acquire HIV infection, for the possible non-specific benefits of BCG, for the fact that some adolescents would receive BCG for the first time, and for cost sharing when BCG is integrated into an adolescent immunization programme. These findings suggest, subject to further evaluation, that BCG revaccination could be cost-effective in some settings.

Nature   
Volume 500 Number 7461 pp121-248  8 August 2013
http://www.nature.com/nature/current_issue.html

Nature | Editorial
Handle with care
The possibility that H7N9 avian influenza may evolve sufficiently to cause a pandemic has scientists turning again to controversial research —they must be careful how they justify the risks taken.
07 August 2013

The H7N9 avian flu virus first reported in China in March has so far infected at least 134 people, and killed 43 of them. Thankfully, there are no signs yet that it can easily be transmitted between people — instead it is sporadically being caught by humans through contact with chickens and other fowl.

Researchers now want to make genetically engineered versions of H7N9 that are more transmissible and pathogenic in mammals. In a Correspondence published jointly this week in Nature and Science (see page 150), 22 scientists, including Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, and Yoshihiro Kawaoka of the University of Wisconsin-Madison, argue that such research can help to assess the ‘pandemic potential’ of H7N9. The dilemma is that should such engineered strains be accidentally or deliberately released from a lab, they could spark a flu pandemic.

The announcement is likely to prompt some replay of last year’s debate over the creation by Fouchier and Kawaoka of lab strains of H5N1 that could transmit between ferrets. And it offers the first test of some of the review and oversight structures put in place for this ‘gain-of-function’ flu research. As this journal has said before, scientists who push for such research should be wary of over-selling the benefits to public health, at least in the short term, as a way to justify the risks taken.

A sense of perspective is crucial here. The long-term benefits of such work are clear — as long as it is done to the highest biosafety standards. It will shed light on, for example, the mechanisms of virus transmissibility and pathogenicity. But the immediate benefits to public health and our short-term ability to counter the threat of H7N9 are less clear-cut. Scientists cannot predict pandemics, so to assess the pandemic potential of viruses — and to decide which strains warrant the manufacture of trial vaccines — comes down to judgements of relative risk.

Tests of how flu viruses behave in animal models such as ferrets can certainly provide information on the risk of transmissibility and pathogenicity, although it can be difficult to extrapolate those results to humans. A rash of papers this year has shown that H7N9 does have limited airborne transmissibility in ferrets, although the virus is not transmitting between people in the current outbreak in China.

Another way to assess pandemic potential is to monitor wild-type viruses for mutations that allow the virus more ready access to human cells. H7N9 has already acquired some of these mutations, which is why it infects humans more easily than does H5N1. But as researchers pointed out in June, there is no scientific evidence that such mutations predict the risk of a pandemic (D. M. Morens et al. N. Engl. J. Med. 368, 2345–2348; 2013). Transmissibility is more complex than that.

In creating mammalian- transmissible versions of H7N9, scientists would go a step further and hope to identify combinations of mutations that could increase virus transmissibility in ferrets or other models. Such work could yield information on the biological principles affecting transmission. But nature could well come up with combinations for transmission that are different from those obtained in experiments.

Following the H5N1 controversy, the US Department of Health and Human Services has introduced an extra layer of review that will apply to anyone seeking funding for work to make mammalian-transmissible strains of H7N9 (see page 151). The risks and benefits of the work will be assessed by a panel of experts in public health, security, risk assessment, law and ethics, and, importantly, any extra steps needed to mitigate biosafety risks will be considered. The way the review handles H7N9 will be an important test of the effectiveness and transparency of this new approach.

http://www.nature.com/news/handle-with-care-1.13505

Pediatrics
August 2013, VOLUME 132 / ISSUE 2
http://pediatrics.aappublications.org/current.shtml

Article
Cost-Effectiveness of Using 2 vs 3 Primary Doses of 13-Valent Pneumococcal Conjugate Vaccine
Charles Stoecker, PhDa, Lee M. Hampton, MD, MSca,b, Ruth Link-Gelles, MPHa, Mark L. Messonnier, PhDa, Fangjun Zhou, PhDa, and Matthew R. Moore, MD, MPHa
+ Author Affiliations
aNational Center for Immunization and Respiratory Diseases, and
bEpidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia
http://pediatrics.aappublications.org/content/132/2/e324.abstract

Abstract
BACKGROUND AND OBJECTIVE: Although effective in preventing pneumococcal disease, 13-valent pneumococcal conjugate vaccine (PCV13) is the most expensive vaccine on the routinely recommended pediatric schedule in the United States. We examined the cost-effectiveness of switching from 4 total doses to 3 total doses by removing the third dose in the primary series in the United States.

METHODS: We used a probabilistic model following a single birth cohort of 4.3 million to calculate societal cost savings and increased disease burden from removing the 6-month dose of PCV13. Based on modified estimates of 7-valent pneumococcal conjugate vaccine from randomized trials and observational studies, we assumed that vaccine effectiveness under the 2 schedules is identical for the first 6 months of life and largely similar after administration of the 12- to 15-month booster dose.

RESULTS: Removing the third dose of PCV13 would annually save $500 million (in 2011$) but would also result in an estimated 2.5 additional deaths among inpatients with pneumonia or invasive pneumococcal disease. Such dose removal would also result in 261 000 estimated otitis media and 12 000 estimated pneumonia cases annually. These additional illnesses could be prevented through modest increases in coverage. Overall, societal savings per additional life-year lost would be ∼$6 million. When nonfatal outcomes are also considered, savings would range from $143 000 to $4 million per additional quality adjusted life-year lost, depending on the assumptions used for otitis media.

CONCLUSIONS: Sizable societal cost savings and a moderate pneumococcal disease increase could be expected from removing the PCV13 primary series’ third dose.

Pediatrics
August 2013, VOLUME 132 / ISSUE 2
http://pediatrics.aappublications.org/current.shtml

Article
Community-Centered Education Improves Vaccination Rates in Children From Low-Income Households
Manika Suryadevara, MD, Cynthia A. Bonville, MS, Frank Ferraioli, BS, and Joseph B. Domachowske, MD
+ Author Affiliations
Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, New York
http://pediatrics.aappublications.org/content/132/2/319.abstract

Abstract
OBJECTIVE: We partnered with the Salvation Army to educate resource-poor families regarding childhood immunizations in an effort to improve vaccine coverage rates.

METHODS: Eligibility for enrollment included children of families presenting at registration for our Salvation Army holiday gift program, available to families with an annual income <150% of federal poverty guidelines. Parents completed a questionnaire, were provided each child’s vaccination status as documented in the New York State Immunization Information System, and interacted with the study team to address immunization-related concerns. Missed vaccines were identified and parents were directed to their child’s medical home for necessary immunizations. Vaccine coverage was ascertained via the New York State Immunization Information System every 6 to 8 weeks with telephone follow-up for children who remained delayed. The McNemar test and standard 2-proportion comparison were used to determine confidence intervals when analyzing matched or independent data, respectively.

RESULTS: A total of 1531 children were enrolled; 416 (28%) of the 1477 children with accurate immunization records were vaccine complete. When we excluded influenza vaccine, 1034 (70%) of children had received all other recommended vaccines. Nine months later, vaccine completion rates increased from 28% to 45%, largely because of improvements in influenza vaccination rates, which increased by 17% (confidence interval [CI] 15.5–19.5), a significant improvement over county (8%, 95% CI 7.4–8.1) and statewide (5%, 95% CI 4.7–4.8) rates during the same period.

CONCLUSIONS: Immunization rates in poor children are suboptimal. Partnering with community-based organizations to address parental concerns, provide education, and perform follow-up was effective in improving immunization rates, particularly for influenza vaccine.

PLoS One
[Accessed 10 August 2013]
http://www.plosone.org/

Predictors of Three Dose On-Time Compliance with HPV4 Vaccination in a Disadvantaged, Underserved, Safety Net Population in the US Midwest
Inge Verdenius, Diane M. Harper, George D. Harris, R. Stephen Griffith, Jeffrey Wall, Laura K. Hempstead, Gerard J. Malnar, Ruud L. M. Bekkers
Research Article | published 08 Aug 2013 | PLOS ONE 10.1371/journal.pone.0071295

Abstract
Background
HPV4 is approved as a series of three timed doses expected to result in efficacy against specific HPV infections. Completion rates in the US are quite low at the same time the structure of health care delivery is changing. The aim of this study was to determine how the patient-, clinic- and systems-level characteristics facilitate or hinder the timely completion of three HPV4 doses in both adolescent and adult female populations in a high-risk safety net population.

Methods
This is a retrospective study in which patient-, clinic- and systems-level data are abstracted from the electronic medical record (EMR) for all females 10–26 years of age receiving at least one dose of HPV4 between July 1, 2006 and October 1, 2009.

Results
Adults were more likely to complete the three dose series if they had at least one health care visit in addition to their HPV4 visit, (aOR = 1.54 (95% CI:1.10, 2.15). Adults were less likely to complete the three dose series if they received their second HPV4 dose at an acute health care, preventive care or postpartum visits compared to an HPV4-only visit (aOR = 0.31 (95% CI: 0.13, 0.72), 0.12 (0.04, 0.35), 0.30 (0.14, 0.62), respectively). Hispanic adults were less likely than whites to complete the series (aOR = 0.24 (95% CI:0.10, 0.59). 39% of adolescents who completed two doses completed the series.

Conclusions
HPV4 is more likely to be effectively administered to adults in a safety net population if multiple health care needs can be met within the health care system.

PLoS Medicine
(Accessed 10 August 2013)
http://www.plosmedicine.org/

Public Engagement in Health Priority Setting in Low- and Middle-Income Countries: Current Trends and Considerations for Policy
Katartyna Bolsewicz Alderman, David Hipgrave, Eliana Jimenez-Soto
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001495

Summary Points
:: Many donors and low- and middle-income countries (LMICs) are now encouraging increased public participation in health sector priority setting (HPS).
:: Using country examples, we demonstrate that despite many attempts, affordable, appropriate, and effective engagement of the public in that context remains elusive.
:: Rather than mandating public participation in HPS, countries and donors should focus on building a policy environment that is conducive to grassroots initiatives and on strengthening the evidence for what works using small pilot studies.

Science        
9 August 2013 vol 341, issue 6146, pages 585-688
http://www.sciencemag.org/current.dtl
Science DOI: 10.1126/science.1241800

Research Article
Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine
Robert A. Seder1,*,†, Lee-Jah Chang1,*, Mary E. Enama1, Kathryn L. Zephir1, Uzma N. Sarwar1, Ingelise J. Gordon1, LaSonji A. Holman1, Eric R. James2, Peter F. Billingsley2,
Anusha Gunasekera2, Adam Richman2, Sumana Chakravarty2, Anita Manoj2, Soundarapandian Velmurugan2, MingLin Li3, Adam J. Ruben2, Tao Li2, Abraham G. Eappen2, Richard E. Stafford2,3, Sarah H. Plummer1, Cynthia S. Hendel1, Laura Novik1, Pamela J.M. Costner1,Floreliz H. Mendoza1, Jamie G. Saunders1, Martha C. Nason4, Jason H. Richardson5, Jittawadee Murphy5, Silas A. Davidson5, Thomas L. Richie6, Martha Sedegah6, Awalludin Sutamihardja6,Gary A. Fahle7, Kirsten E. Lyke8, Matthew B. Laurens8,9, Mario Roederer1, Kavita Tewari1, Judith E. Epstein6, B. Kim Lee Sim2,3, Julie E. Ledgerwood1, Barney S. Graham1,‡, Stephen L. Hoffman2,3,‡, the VRC 312 Study Team§
+ Author Affiliations
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
2Sanaria, Rockville, MD 20850, USA.
3Protein Potential LLC, Rockville, MD 20850, USA.
4Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
5Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
6U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
7Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, USA.
8Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
9Howard Hughes Medical Institute, Baltimore, MD 21201, USA.
↵†Corresponding author. E-mail: rseder@mail.nih.gov
↵* These authors contributed equally to this work.
↵‡ These authors contributed equally to this work.
http://www.sciencemag.org/content/early/2013/08/07/science.1241800.abstract

Abstract
Consistent high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ vaccine, composed of attenuated, aseptic, purified, cryopreserved PfSPZ, was safe and well-tolerated when administered 4 to 6 times intravenously (IV) to 40 adults. 0/6 subjects receiving 5 doses, 3/9 subjects receiving 4 doses of 1.35 x 105 PfSPZ vaccine, and 5/6 nonvaccinated controls developed malaria following controlled human malaria infection (P = 0.015 in the 5-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved by IV administration of a vaccine that is safe and meets regulatory standards.

Science        
9 August 2013 vol 341, issue 6146, pages 585-688
http://www.sciencemag.org/current.dtl

Letters
Gain-of-Function Experiments on H7N9
Science 9 August 2013:
Vol. 341 no. 6146 pp. 612-613
DOI: 10.1126/science.341.6146.612
http://www.sciencemag.org/content/341/6146/612.full

The A(H7N9) virus hemagglutinin protein has several motifs that are characteristic of mammalian-adapted and human influenza viruses, including mutations that confer human-type receptor-binding and enhanced virus replication in mammals. The pandemic risk rises exponentially should these viruses acquire the ability to transmit readily among humans.

Reports indicate that several A(H7N9) viruses from patients who were undergoing antiviral treatment acquired resistance to the primary medical countermeasure—neuraminidase inhibitors (such as oseltamivir, peramivir, and zanamivir). Acquisition of resistance to these inhibitors by A(H7N9) viruses could increase the risk of serious outcomes of A(H7N9) virus infections.

The hemagglutinin proteins of A(H7N9) viruses have a cleavage site consistent with a low-pathogenic phenotype in birds; in the past, highly pathogenic H7 variants (with basic amino acid insertions at the cleavage site that enable the spread of the virus to internal organs) have emerged from populations of low pathogenic strains circulating in domestic gallinaceous poultry.

Normally, epidemiological studies and characterization of viruses from field isolates are used to inform policy decisions regarding public health responses to a potential pandemic. However, classical epidemiological tracking does not give public health authorities the time they need to mount an effective response to mitigate the effects of a pandemic virus. To provide information that can assist surveillance activities—thus enabling appropriate public health preparations to be initiated before a pandemic—experiments that may result in GOF are critical.

Therefore, after review and approval, we propose to perform the following experiments that may result in GOF:
(i) Immunogenicity. To develop more effective vaccines and determine whether genetic changes that confer altered virulence, host range, or transmissibility also change antigenicity.
(ii) Adaptation. To assist with risk assessment of the pandemic potential of field strains and evaluate the potential of A(H7N9) viruses to become better adapted to mammals, including determining the ability of these viruses to reassort with other circulating influenza strains.
(iii) Drug resistance. To assess the potential for drug resistance to emerge in circulating viruses, evaluate the genetic stability of the mutations conferring drug resistance, evaluate the efficacy of combination therapy with antiviral therapeutics, determine whether the A(H7N9) viruses could become resistant to available antiviral drugs, and identify potential resistance mutations that should be monitored during antiviral treatment.
(iv) Transmission. To assess the pandemic potential of circulating strains and perform transmission studies to identify mutations and gene combinations that confer enhanced transmissibility in mammalian model systems (such as ferrets and/or guinea pigs).
(v) Pathogenicity. To aid risk assessment and identify mechanisms, including reassortment and changes to the hemagglutinin cleavage site, that would enable circulating A(H7N9) viruses to become more pathogenic.

All experiments proposed by influenza investigators are subject to review by institutional biosafety committees. The committees include experts in the fields of infectious disease, immunology, biosafety, molecular biology, and public health; also, members of the lay public represent views from outside the research community. Risk-mitigation plans for working with potentially dangerous influenza viruses, including 1918 virus and highly pathogenic avian H5N1 viruses, will be applied to conduct GOF experiments with A(H7N9) viruses (see supplementary text). Additional reviews may be required by the funding agencies for proposed studies of A(H7N9) viruses (see scim.ag/13BK5Hs).

The recent H5N1 virus transmission controversy focused on the balance of risks and benefits of conducting research that proved the ability of the H5N1 virus to become transmissible in mammals (see http://www.sciencemag.org/special/h5n1). These findings demonstrated the pandemic potential of H5N1 viruses and reinforced the need for continued optimization of pandemic preparedness measures. Key mutations associated with adaptation to mammals, included in an annotated inventory for mutations in H5N1 viruses developed by the U.S. Centers for Disease Prevention and Control, were identified in human isolates of A(H7N9) viruses. Scientific evidence of the pandemic threat posed by A(H7N9) viruses, based on H5N1 GOF studies, factored into risk assessments by the public health officials in China, the United States, and other countries.

Since the H5N1 transmission papers were published, follow-up scientific studies have contributed to our understanding of host adaptation by influenza viruses, the development of vaccines and therapeutics, and improved surveillance.

Finally, a benefit of the H5N1 virus research controversy has been the increased dialogue regarding laboratory biosafety and dual-use research. The World Health Organization issued laboratory biosafety guidelines for conducting research on H5N1 transmission and, in the United States, additional oversight policies and risk-mitigation practices have been put in place or proposed. Some journals now encourage authors to include biosafety and biosecurity descriptions in their manuscripts, thereby raising the awareness of researchers intending to replicate experiments.

The risk of a pandemic caused by an avian influenza virus exists in nature. As members of the influenza research community, we believe that the avian A(H7N9) virus outbreak requires focused fundamental and applied research conducted by responsible investigators with appropriate facilities and risk-mitigation plans in place. To answer key questions important to public health, research that may result in GOF is necessary and should be done.

Ron A. M. Fouchier1,*,    Yoshihiro Kawaoka2,*,    Carol Cardona3,    Richard W. Compans4,    Adolfo García-Sastre5,    Elena A. Govorkova6,    Yi Guan7,    Sander Herfst1,    Walter A. Orenstein8, J. S. Malik Peiris9, Daniel R. Perez10, Juergen A. Richt11, Charles Russell6,  Stacey L. Schultz-Cherry6, Derek J. Smith12, John Steel4,  S. Mark Tompkins13, David J. Topham14,    John J. Treanor15, Ralph A. Tripp13,  Richard J. Webby6, Robert G. Webster6
1Department of Viroscience, Erasmus Medical Center, 3015GE, Rotterdam, Netherlands.
2Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
3Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA.
4Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
5Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
6Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
7State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong SAR.
8Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
9Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
10Department of Veterinary Medicine, University of Maryland, College Park, College Park, MD 20742, USA.
11College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.
12Department of Zoology, University of Cambridge, Cambridge, CB2 3EJ, UK.
13Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
14Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
15Infectious Diseases Division, University of Rochester Medical Center, Rochester, NY 14642, USA.
↵*Corresponding author. E-mail: r.fouchier@erasmusmc.nl (R.A.M.F.); kawaokay@svm.vetmed.wisc.edu (Y.K.)

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 38, Pages 4055-4216 (28 August 2013)

The impact of HPV vaccination delays in China: Lessons from HBV control programs
Pages 4057-4059
Danny V. Colombara, Shao-Ming Wang
[No abstract or summary]

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 38, Pages 4055-4216 (28 August 2013)

Unequal access to vaccines in the WHO European Region during the A(H1N1) influenza pandemic in 2009
Pages 4060-4062
Pernille Jorgensen, Annemarie Wasley, Jolita Mereckiene, Suzanne Cotter, J. Todd Weber, Caroline Sarah Brown

Abstract
In a severe pandemic, rapid production and deployment of vaccines will potentially be critical in mitigating the impact on populations and essential services. We compared access to vaccines and timing of delivery relative to identification of A(H1N1)pdm09 and the geographic progression of the pandemic in the WHO European Region in order to identify gaps in provision. Information on vaccine procurement and donations was collected through a web-based survey conducted in all 53 member states of the Region. Among the 51 countries responding to the survey, the majority (84%) implemented vaccination campaigns against A(H1N1)pdm09. However, time of vaccine receipt and number of doses varied substantially across the region, with delayed access in many countries especially in those in the lowest income range. Improving access to influenza vaccines in low resource countries and solving issues of product liability should help reduce inequalities and operational challenges arising during a future public health crisis.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 38, Pages 4055-4216 (28 August 2013)

The state-of-the-art of approved and under-development cholera vaccines
Review Article
Pages 4069-4078
M. Pastor, J.L. Pedraz, A. Esquisabel

Abstract
Cholera remains a huge public health problem. Although in 1894, the first cholera vaccination was reported, an ideal vaccine that meets all the requirements of the WHO has not yet been produced. Among the different approaches used for cholera vaccination, attenuated vaccines represent a major category; these vaccines are beneficial in being able to induce a strong protective response after a single administration. However, they have possible negative effects on immunocompromised patient populations. Both the licensed CVD103-HgR and other vaccine approaches under development are detailed in this article, such as the Vibrio cholerae 638 vaccine candidate, Peru-15 or CholeraGarde® and the VA1.3, VA1.4, IEM 108 VCUSM2 and CVD 112 vaccine candidates. In another strategy, killed V. cholerae vaccines have been developed, including Dukoral®, mORCAX® and Sanchol™. The killed vaccines are already sold, and they have successfully demonstrated their potential to protect populations in endemic areas or after natural disasters. However, these vaccines do not fulfill all the requirements of the WHO because they fail to confer long-term protection, are not suitable for children under two years, require more than a single dose and require a distribution chain with cold storage. Lastly, other vaccine strategies under development are summarized in this review. Among these strategies, vaccine candidates based on alternative drug delivery systems that have been reported lately in the literature are discussed, such as microparticles, proteoliposomes, LPS subunits, DNA vaccines and rice seeds containing toxin subunits. Preliminary results reported by many groups working on alternative delivery systems for cholera vaccines demonstrate the importance of new technologies in addressing old problems such as cholera. Although a fully ideal vaccine has not yet been designed, promising steps have been reported in the literature resulting in hope for the fight against cholera.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 38, Pages 4055-4216 (28 August 2013)

Trend of human rabies prophylaxis in developing countries: Toward optimal rabies immunization
Review Article
Pages 4079-4083
Nitipong Permpalung, Supakanya Wongrakpanich, Sira Korpaisarn, Pansakorn Tanratana, Jaruboot Angsanakul

Abstract
Rabies is a fatal infectious disease. Because prevention is the key management for rabies, many vaccination regimens have been developed and used worldwide. The aims for developing rabies vaccination regimens include decreasing the number and amount of dosages, decreasing the duration and the number of clinical visits, and reducing cost. Interestingly, some intradermal (ID) regimens have proved to be as effective as the standard intramuscular (IM) regimens, and have been increasingly used in developing countries because they are less expensive. In this article, we reviewed rabies vaccines based on results obtained from clinical trials and international treatment guidelines for post-exposure prophylaxis, pre-exposure prophylaxis for the high risk group, and booster vaccination.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 38, Pages 4055-4216 (28 August 2013)

How do anticipated worry and regret predict seasonal influenza vaccination uptake among Chinese adults?
Original Research Article
Pages 4084-4090
Q. Liao, W.S. Wong, R. Fielding

Abstract
Objectives
To test two hypothesized models of how anticipated affect, cognitive risk estimate and vaccination intention might influence vaccination uptake against seasonal influenza.

Methods
The study collected baseline and follow-up data during the main influenza seasons (January–March) of 2009 and 2010, respectively, among 507 university students and staff of a university in Hong Kong. Following logistic regression to determine eligible variables, two mediation models of cognitive risk estimate, anticipated affect, vaccination intention and vaccination uptake against seasonal influenza were tested using structural equation modeling.

Results
Mediation analyses found that anticipated worry if not vaccinated influenced seasonal influenza vaccination uptake through its effects on either perceived probability of influenza infection (β = 0.45) or intention (β = 0.45) while anticipated regret if not vaccinated influenced vaccination uptake through its effect on intention (β = 0.45) only; anticipated regret if vaccinated impeded vaccination uptake indirectly through its effect on vaccination intention (β = −0.26) or directly (β = −0.20); perceived probability of influenza infection influenced vaccination uptake through its effect on intention (β = 0.20) or directly (β = 0.22); and finally, intention influenced vaccination uptake directly (β = 0.58).

Conclusion
The results suggest that anticipated affect seems to drive risk estimates related to seasonal influenza vaccination rather than vice versa and intention remains an important mediator of the associations of anticipated affect and cognitive risk estimate with vaccination uptake against seasonal influenza.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 31, Issue 38, Pages 4055-4216 (28 August 2013)

Rotavirus-associated hospitalization and emergency department costs and rotavirus vaccine program impact
Original Research Article
Pages 4164-4171
April Kilgore, Stephanie Donauer, Kathryn M. Edwards, Geoffrey A. Weinberg, Daniel C. Payne, Peter G. Szilagyi, Marilyn Rice, Amy Cassedy, Ismael R. Ortega-Sanchez, Umesh D. Parashar, Mary Allen Staat

Abstract
Objectives
To determine the medical costs of laboratory-confirmed rotavirus hospitalizations and emergency department (ED) visits and estimate the economic impact of the rotavirus vaccine program.

Patients and methods
During 4 rotavirus seasons (2006–2009), children <3 years of age hospitalized or seen in the ED with laboratory-confirmed rotavirus were identified through active population-based rotavirus surveillance in three US counties. Medical costs were obtained from hospital and physician billing data, and factors associated with increased costs were examined. Annual national costs were estimated using rotavirus hospitalization and ED visit rates and medical costs for rotavirus hospitalizations and ED visits from our surveillance program for pre- (2006–2007) and post-vaccine (2008–2009) time periods.

Results
Pre-vaccine, for hospitalizations, the median medical cost per child was $3581, the rotavirus hospitalization rate was 22.1/10,000, with an estimated annual national cost of $91 million. Post-vaccine, the median medical cost was $4304, the hospitalization rate was 6.3/10,000 and the estimated annual national cost was $31 million. Increased costs were associated with study site, age <3 months, underlying medical conditions and an atypical acute gastroenteritis presentation. For ED visits, the pre-vaccine median medical cost per child was $574, the ED visit rate was 291/10,000 resulting in an estimated annual national cost of $192 million. Post-vaccine, the median medical cost was $794, the ED visit rate was 71/10,000 with an estimated annual national cost of $65 million.

Conclusions
After implementation of rotavirus immunization, the total annual medical costs decreased from $283 million to $96 million, an annual reduction of $187 million.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Editorial
Hib vaccine in India: A case for universal immunization
Pages 3763-3765
Ajay Kumar, Meenu Singh, Kiran Kumar Thumburu, Nishant Jaiswal, Harpreet Kaur, Shruti Sharma, Amit Agarwal
[No abstract or summary]

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Report on the first WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Hong Kong SAR, China, 24–26 January 2013
Pages 3766-3771
Marc P. Girard, John S. Tam, Yuri Pervikov, Jacqueline M. Katz

Abstract
On January 24–26, 2013, the World Health Organization convened the first integrated meeting on “The development and clinical trials of vaccines that induce broadly protective and long-lasting immune responses” to review the current status of development and clinical evaluation of novel influenza vaccines as well as strategies to produce and deliver vaccines in novel ways. Special attention was given to the development of possible universal influenza vaccines. Other topics that were addressed included an update on clinical trials of pandemic and seasonal influenza vaccines in high-risk groups and vaccine safety, as well as regulatory issue.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Enhancing access to immunization services and exploiting the benefits of recent innovations in the African region
Pages 3772-3776
J.C. Okeibunor, B.D. Akanmori, G.M. Balcha, R. Mihigo, R.M. Vaz, D. Nshimirimana

Abstract
The African Regional Office of the World Health Organization (WHO AFRO) organized the annual regional conference on immunization (ARCI) from 10 to 12 December 2012 in Dar es Salaam, Tanzania, under the theme, “Innovations, access and the right of all to vaccines”. The meeting reviewed the status of immunization in the region and identified all innovations, strategies and technologies available and how these could be fully utilized to enhance the access and the rights of all to vaccines. Over 50 oral presentations were made in plenary and parallel sessions of the conference which was attended by over 200 participants drawn from national immunization programs, academia, public health experts and immunization partners. In addition there were 40 poster presentations. This manuscript summarizes of the meeting, highlighting the innovations in immunization being piloted or scaled-up, their impact and suggesting ways to further improve immunization service delivery for the eradication, elimination and control of vaccine-preventable diseases in the region.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: A systematic review
Review Article
Pages 3786-3804
Michaela Fesenfeld, Raymond Hutubessy, Mark Jit

Abstract
The World Health Organization recommends establishing that human papillomavirus vaccination is cost-effective before vaccine introduction. We searched Pubmed, Embase and the Cochrane Library to 1 April 2012 for economic evaluations of human papillomavirus vaccination in low and middle income countries. We found 25 articles, but almost all low income countries and many middle income countries lacked country-specific studies. Methods, assumptions and consequently results varied widely, even for studies conducted for the same country. Despite the heterogeneity, most studies conclude that vaccination is likely to be cost-effective and possibly even cost saving, particularly in settings without organized cervical screening programmes. However, study uncertainty could be reduced by clarity about vaccine prices and vaccine delivery costs. The review supports extending vaccination to low income settings where vaccine prices are competitive, donor funding is available, cervical cancer burden is high and screening options are limited.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Human papillomavirus (HPV) vaccine implementation in low and middle-income countries (LMICs): Health system experiences and prospects
Review Article
Pages 3811-3817
Jannah Wigle, Ernestina Coast, Deborah Watson-Jones

Abstract
Prophylactic vaccines for human papillomavirus (HPV) are being introduced in many countries for the prevention of cervical cancer, the second most important cause of cancer-related death in women globally. This is likely to have a significant impact on the future burden of cervical cancer, particularly where screening is non-existent or limited in scale. Previous research on the challenges of vaccinating girls with the HPV vaccine has focused on evidence from developed countries. We conducted a systematic search of the literature in order to describe the barriers and challenges to implementation of HPV vaccine in low- and middle-income countries. We identified literature published post-2006 to September 2012 from five major databases. We validated the findings of the literature review with evidence from qualitative key informant interviews. Three key barriers to HPV vaccine implementation were identified: sociocultural, health systems and political. A linked theme, the sustainability of HPV vaccines programmes in low- and middle-income countries, cuts across these three barriers. Delivering HPV vaccine successfully will require multiple barriers to be addressed. Earlier research in developed countries emphasised sociocultural issues as the most significant barriers for vaccine roll-out. Our evidence suggests that the range of challenges for poorer countries is significantly greater, not least the challenge of reaching girls for three doses in settings where school attendance is low and/or irregular. Financial and political barriers to HPV vaccine roll-out continue to be significant for many poorer countries. Several demonstration and pilot projects have achieved high rates of acceptability and coverage and lessons learned should be documented and shared.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Strengthening vaccination policies in Latin America: An evidence-based approach
Review Article
Pages 3826-3833
Roberto Tapia-Conyer, Miguel Betancourt-Cravioto, Rodrigo Saucedo-Martínez, Lourdes Motta-Murguía, Héctor Gallardo-Rincón

Abstract
Despite many successes in the region, Latin American vaccination policies have significant shortcomings, and further work is needed to maintain progress and prepare for the introduction of newly available vaccines. In order to address the challenges facing Latin America, the Commission for the Future of Vaccines in Latin America (COFVAL) has made recommendations for strengthening evidence-based policy-making and reducing regional inequalities in immunisation. We have conducted a comprehensive literature review to assess the feasibility of these recommendations. Standardisation of performance indicators for disease burden, vaccine coverage, epidemiological surveillance and national health resourcing can ensure comparability of the data used to assess vaccination programmes, allowing deeper analysis of how best to provide services. Regional vaccination reference schemes, as used in Europe, can be used to develop best practice models for vaccine introduction and scheduling. Successful models exist for the continuous training of vaccination providers and decision-makers, with a new Latin American diploma aiming to contribute to the successful implementation of vaccination programmes. Permanent, independent vaccine advisory committees, based on the US Advisory Committee on Immunization Practices (ACIP), could facilitate the uptake of new vaccines and support evidence-based decision-making in the administration of national immunisation programmes. Innovative financing mechanisms for the purchase of new vaccines, such as advance market commitments and cost front-loading, have shown potential for improving vaccine coverage. A common regulatory framework for vaccine approval is needed to accelerate delivery and pool human, technological and scientific resources in the region. Finally, public–private partnerships between industry, government, academia and non-profit sectors could provide new investment to stimulate vaccine development in the region, reducing prices in the long term. These reforms are now crucial, particularly as vaccines for previously neglected, developing-world diseases become available. In summary, a regionally-coordinated health policy will reduce vaccination inequality in Latin America.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Single-dose varicella vaccine effectiveness in school settings in China
Original Research Article
Pages 3834-3838
Zhe Wang, Huili Yang, Keli Li, Aihua Zhang, Zijian Feng, Jane F. Seward, Stephanie R. Bialek, Chengbin Wang

Abstract
Background
Varicella vaccine has been available in the private sector in China for a decade as a single-dose regimen, but varicella vaccine effectiveness (VE) has not been fully examined in school settings yet.

Methods
A matched case–control study was carried out in elementary schools and daycares in Tai’an prefecture, Shandong province, China. Clinical diagnosis of varicella and breakthrough disease was used for this study. Four controls were randomly selected from classmates; two from classmates of the case and two from another class of the same grade without cases. Vaccination status, date of vaccination, and vaccine product received if vaccinated were collected from home and clinic immunization records. Vaccination status of all students in schools/daycares with varicella cases from home immunization records or parental recall was used to calculate vaccination coverage.

Results
The overall varicella VE was 83.4% (95% confidence interval 71.4–90.3%). Receipt of varicella vaccine five years or more years before the outbreak was significantly associated with breakthrough varicella (odds ratio = 4.7, P < 0.001), while age at vaccination (<15 vs. ≥15 months) was not (odds ratio = 1.5, P = 0.62). Varicella vaccination coverage was 41% with substantial variation across schools (range of 0–93.8%).

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Comparative cost-effectiveness of the quadrivalent and bivalent human papillomavirus vaccines: A transmission-dynamic modeling study
Original Research Article
Pages 3863-3871
Marc Brisson, Jean-François Laprise, Mélanie Drolet, Nicolas Van de Velde, Eduardo L. Franco, Erich V. Kliewer, Gina Ogilvie, Shelley L. Deeks, Marie-Claude Boily

Abstract
Background
The quadrivalent and bivalent human papillomavirus (HPV) vaccines are now licensed in several countries. We compared the cost-effectiveness of the HPV vaccines to provide evidence for policy decisions.

Methods
We developed HPV-ADVISE, a multi-type individual-based transmission-dynamic model of HPV infection and disease (anogenital warts, and cervical, anogenital and oropharyngeal cancers). We calibrated the model to sexual behavior and epidemiologic data from Canada, and estimated quality-adjusted life-years (QALYs) lost and costs ($CAN 2010) from the literature. Vaccine-type efficacy was based on a systematic literature review. The analysis was performed from the healthcare provider perspective, and costs and benefits were discounted at 3%. Predictions are presented using the median [10th;90th percentiles] of simulations.

Results
Under base-case assumptions (vaccinating 10-year-old girls, 80% coverage, $95/dose), using the quadrivalent and bivalent vaccines is estimated to cost $15,528 [12,056;19,140] and $20,182 [15,531;25,240] per QALY-gained, respectively. At equal price, the quadrivalent vaccine is more cost-effective than bivalent under all scenarios investigated, except when assuming longer duration of protection for the bivalent and minimal anogenital warts burden. Under base-case assumptions, the maximum additional cost per dose for the quadrivalent vaccine to remain more cost-effective than the bivalent is $32 [17;46] (using a $40,000/QALY-gained threshold). Results were most sensitive to discounting, time-horizon, differences in durations of protection and anogenital warts burden.

Conclusions
Vaccinating pre-adolescent girls against HPV is predicted to be highly cost-effective. If equally priced, the quadrivalent is the most economically desirable vaccine. However, ultimately, the most cost-effective HPV vaccine will be determined by their relative price.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Potential influence of seasonal influenza vaccination requirement versus traditional vaccine promotion strategies on unvaccinated healthcare personnel
Original Research Article
Pages 3915-3921
Mark G. Thompson, Anne F. McIntyre, Allison L. Naleway, Carla Black, Erin D. Kennedy, Sarah Ball, Deborah Klein Walker, Emily M. Henkle, Manjusha J. Gaglani

Abstract
In a prospective cohort study of 1670 healthcare personnel (HCP) providing direct patient care at Scott & White Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington, we examined the potential impact of twelve vaccine promotion strategies on the likelihood of being vaccinated. Internet-based surveys were conducted at enrollment (Fall, 2010) and at post-season (Spring, 2011), which asked HCP whether twelve vaccination promotion strategies would make them “much less” to “much more” likely to be vaccinated next season (on a 5-point Likert scale). Overall, 366 of 1670 HCP (22%) were unvaccinated. Half (50%) of unvaccinated HCP self-reported that a vaccination requirement would make them more likely to be vaccinated and most (62%) identified at least one strategy other than a vaccination requirement that would make them more likely to be vaccinated. In sub-groups of unvaccinated HCPs with specific barriers to vaccination, about one in three (range = 27–35%) indicated that interventions targeting specific vaccination barrier would increase the likelihood they would be vaccinated. However, in all cases, significantly more unvaccinated HCP reported that a vaccination requirement would increase the likelihood of vaccination than reported a targeted intervention would have this effect (range in difference scores = +11–23%).

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Cost–effectiveness of the prophylactic HPV vaccine: An application to the Netherlands taking non-cervical cancers and cross-protection into account
Original Research Article
Pages 3922-3927
J. Luttjeboer, T.A. Westra, J.C. Wilschut, H.W. Nijman, T. Daemen, M.J. Postm

Abstract
Despite an effective screening programme, 600–700 women are still diagnosed with cervical cancer in the Netherlands each year. In 2009 a prophylactic vaccine against HPV-type 16 and 18 was implemented in the national immunisation programme to decrease the incidence of cervical cancer. There is evidence that infections with several oncogenic HPV types other than the vaccine types 16 and 18 are also prevented by vaccination, also known as cross-protection. Besides cervical cancer, HPV can also cause cancers at other sites such as the oropharynx, vulva, vagina and the anus/anal area. In this study we estimated the maximum health and economic benefits of vaccinating 12-year old girls against infection with HPV, taking cross-protection and non-cervical cancers into account. In the base-case, we found an incremental cost ratio (ICER) of €5815 per quality adjusted life year (QALY). Robustness of this result was examined in sensitivity analysis. The ICER proved to be most sensitive to vaccine price, discounting rates, costs of cervical cancer and to variation in the disutility of cervical cancer.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Cost-effectiveness of pneumococcal conjugate vaccination in immunocompromised adults
Original Research Article
Pages 3950-3956
Kenneth J. Smith, Mary Patricia Nowalk, Mahlon Raymund, Richard K. Zimmerman

Abstract
Objective
Pneumococcal disease is a significant problem in immunocompromised persons, particularly in HIV-infected individuals. The CDC recently updated pneumococcal vaccination recommendations for immunocompromised adults, adding the 13-valent pneumococcal conjugate vaccine (PCV13) to the previously recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23). This analysis estimates the cost-effectiveness of pneumococcal vaccination strategies in HIV-infected individuals and in the broader immunocompromised adult group.

Design
Markov model-based cost-effectiveness analysis.

Methods
The model considered immunocompromised persons aged 19–64 years and accounted for childhood PCV13 herd immunity; in a separate analysis, an HIV-infected subgroup was considered. PCV13 effectiveness was estimated by an expert panel; PPSV23 protection was modeled relative to PCV13 effectiveness. We assumed that both vaccines prevented invasive pneumococcal disease, but only PCV13 prevented nonbacteremic pneumonia.

Results
In all immunocompromised individuals, a single PCV13 cost $70,937 per quality adjusted life year (QALY) gained compared to no vaccination; current recommendations cost $136,724/QALY. In HIV patients, with a longer life expectancy (22.5 years), current recommendations cost $89,391/QALY compared to a single PCV13. Results were sensitive to variation of life expectancy and vaccine effectiveness. The prior recommendation was not favored in any scenario.

Conclusions
One dose of PCV13 is more cost-effective for immunocompromised individuals than previous vaccination recommendations and may be more economically reasonable than current recommendations, depending on life expectancy and vaccine effectiveness in the immunocompromised.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Dengue dynamics and vaccine cost-effectiveness in Brazil
Original Research Article
Pages 3957-3961
David P. Durham, Martial L. Ndeffo Mbah, Jan Medlock, Paula M. Luz, Lauren A. Meyers, A. David Paltiel, Alison P. Galvani

Abstract
Recent Phase 2b dengue vaccine trials have demonstrated the safety of the vaccine and estimated the vaccine efficacy with further trials underway. In anticipation of vaccine roll-out, cost-effectiveness analysis of potential vaccination policies that quantify the dynamics of disease transmission are fundamental to the optimal allocation of available doses.

We developed a dengue transmission and vaccination model and calculated, for a range of vaccination costs and willingness-to-pay thresholds, the level of vaccination coverage necessary to sustain herd-immunity, the price at which vaccination is cost-effective and is cost-saving, and the sensitivity of our results to parameter uncertainty. We compared two vaccine efficacy scenarios, one a more optimistic scenario and another based on the recent lower-than-expected efficacy from the latest clinical trials.

We found that herd-immunity may be achieved by vaccinating 82% (95% CI 58–100%) of the population at a vaccine efficacy of 70%. At this efficacy, vaccination may be cost-effective for vaccination costs up to US$ 534 (95% CI $369–1008) per vaccinated individual and cost-saving up to $204 (95% CI $39–678). At the latest clinical trial estimates of an average of 30% vaccine efficacy, vaccination may be cost-effective and cost-saving at costs of up to $237 (95% CI $159–512) and $93 (95% CI $15–368), respectively.

Our model provides an assessment of the cost-effectiveness of dengue vaccination in Brazil and incorporates the effect of herd immunity into dengue vaccination cost-effectiveness. Our results demonstrate that at the relatively low vaccine efficacy from the recent Phase 2b dengue vaccine trials, age-targeted vaccination may still be cost-effective provided the total vaccination cost is sufficiently low.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Incremental cost-effectiveness evaluation of vaccinating girls against cervical cancer pre- and post-sexual debut in Belgium
Original Research Article
Pages 3962-3971
Nadia Demarteau, Georges Van Kriekinge, Philippe Simon

Abstract
Background
Vaccination against human papillomavirus (HPV) to prevent cervical cancer (CC) primarily targets young girls before sexual debut and is cost-effective. We assessed whether vaccination with the HPV-16/18 AS04-adjuvanted vaccine added to screening remains cost-effective in females after sexual debut compared to screening alone in Belgium. The role of protection against non-HPV-16/18 was also investigated.

Methods
A published Markov cohort model was adapted to Belgium. The model replicated the natural history of HPV infection, the effects of screening, and vaccination. Vaccine efficacy (VE) included non-HPV-16/18 protection based on the PATRICIA clinical trial data. Pre- and post-HPV exposure VE were differentiated. Lifetime vaccine protection was assumed. Input data were obtained from literature review, national databases and a Delphi panel. Costing was from a healthcare payer perspective. Costs were discounted at 3% and effects at 1.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the number of lesions prevented with vaccination from age 12 to 40 was evaluated. The specific effect of non-HPV-16/18 protection was investigated. Univariate sensitivity analysis was performed on key variables.

Results
The model estimated that vaccinating a cohort of 100,000 girls at age 12 would prevent 646 CC cases over a lifetime (102 non-HPV-16/18) with an ICER of €9171/QALY. Vaccinating at age 26 would prevent 340 CC cases (40 non-HPV-16/18) with an ICER of €17,348/QALY and vaccinating at age 40 would prevent 146 CC cases (17 non-HPV-16/18) with an ICER of €42,847/QALY. The ICER remained under the highly cost-effective threshold (1×GDP/capita) until age 33 years and under the cost-effective threshold (3×GDP/capita) beyond age 40.

Conclusion
Extending HPV vaccination to females post-sexual debut could lead to a substantial reduction in CC-related burden and would be cost-effective in Belgium.

Vaccine
Volume 31, Issue 37, Pages 3763-4054 (20 August 2013)
http://www.sciencedirect.com/science/journal/0264410X/31/37

Pregnant women’s intention to take up a post-partum pertussis vaccine, and their willingness to take up the vaccine while pregnant: A cross sectional survey
Original Research Article
Pages 3972-3978
K.E. Wiley, P.D. Massey, S.C. Cooper, N. Wood, H.E. Quinn, J. Leask

Abstract
Introduction
Post-partum vaccination of new mothers is currently recommended in Australia to reduce pertussis infection in infants. Internationally, vaccination recommendations now include pregnant women in some countries. Understanding the awareness of pertussis vaccination recommendations among pregnant women, and their willingness to have the vaccine while pregnant is important for informing vaccine program implementation.

Objective
To determine awareness and intentions toward current recommendations for post-partum pertussis vaccination among Australian pregnant women, and their willingness to accept pertussis vaccine during pregnancy, should it be recommended in Australia in the future.

Design
Quantitative self-administered survey, using a non-random stratified sampling plan based on representative proportions by age, parity and region of residence.

Participants and setting
Pregnant women receiving antenatal care through three large, demographically diverse referral hospitals in metropolitan, urban and rural New South Wales, Australia.

Results
The response rate was 815/939 (87%). Most women (80%) reported willingness to have the pertussis vaccine during pregnancy, should it be recommended. Thirty four per cent of women intended to receive a pertussis vaccine post-partum, 17% had received it previously, while 45% had never heard of pertussis vaccine, had not thought about it, or were undecided about having it. Compared with those who had not received a recommendation to have the vaccine post-partum, women who had received a recommendation were 7 times more likely (95% CI 4–14) to report intention to have the vaccine.

Conclusions
Health care provider recommendation is paramount to raising awareness of pertussis vaccination recommendations among pregnant women. Women’s willingness to have the vaccine while pregnant is encouraging, and indicates the potential for high pertussis vaccine coverage among pregnant women, should it be recommended in Australia.

From Google Scholar & other sources: Selected Journal Articles, Newsletters, Dissertations, Theses, Commentary

Prevention and control of influenza and dengue through vaccine development.
DP Greenberg, CA Robertson, DM Gordon – Pediatric annals, 2013
CME EDUCATIONAL OBJECTIVES 1. Review the impact of influenza infection in the pediatric population. 2. Discuss the importance of influenza B as a key cause of morbidity
and review the progress on development and deployment of quadrivalent influenza …

P5. 106 Charting the Path For Human Papillomavirus (HPV) Vaccine Introduction in Kenya: Assessing HPV Vaccine Acceptability Among Caregivers and Opinion …
AL Friedman, E Dunne, K Onyango, M Habel, J Ford… – Sexually Transmitted …, 2013
Background Cervical cancer is the second most common cancer diagnosed, and the leading cause of cancer-related mortality among women in Kenya. Kenya’s Ministry of Health has outlined new prevention strategies, including support for vaccination. Formative research …

P3. 369 Acceptability of HPV Tetravalent Vaccine Among Males Attending the STD Clinic of Milan-The Importance of the Costs For Patients
M Cusini, S Ramoni – Sexually Transmitted Infections, 2013
Background HPV infection is usually transmitted by sexual contact and represent the most prevalent sexually transmitted infection all over the world. The clinical spectrum of HPV
infection varies from the asymptomatic status to benign genital lesions to the development …

1 5 Chronic Non-Communicable
KMV NARAYAN, D YACH – Social Injustice and Public Health, 2013
… In recent years, new private foundations have appropriately invested billions of dollars for HIV/AIDS, malaria, tuberculosis, and immunizable diseases. And international donor organizations have increased support for tobacco control. …

The Hepatitis B Vaccine Protects Re-Exposed Healthcare Workers, but Does Not Provide Sterilizing Immunity
JM Werner, A Abdalla, N Gara, MG Ghany… – Gastroenterology, 2013
Background & Aims: Infection with hepatitis B virus (HBV) can be prevented by vaccination with HBV surface (HBs) antigen, which induces HBs-specific antibodies and T cells.
However, the duration of vaccine-induced protective immunity is poorly defined for …

Interview: An insight into cutting-edge tuberculosis vaccine research
EM Agger – Immunotherapy, 2013
Else Marie Agger speaks to Katie Lockwood, Assistant Commissioning Editor Else Marie Agger was appointed Director of the Department of Infectious Disease Immunology, Statens Serum Institut in Denmark in 2011. Prior to this, she had been heading two different …

Forbes
http://www.forbes.com/
Accessed 10 August 2013
Entrepreneurs
8/06/2013

Delivering Vaccines To Where They’re Needed Most
Editor’s Note: In advance of the many health-related discussions to take place in September at the Clinton Global Initiative, the Social Good Summit, UN week and other such events, the Skoll World Forum asked some of the world’s leading voices in global health to paint a comprehensive picture of key trends, challenges and opportunities to realizing healthcare access and treatment around the world. A new piece will be posted everyday through Friday, and you can view the entire series here.
   Kevin Reilly is a senior business executive with more than 30 years’ experience in the pharmaceutical and vaccine industries. During his 20 years with Wyeth Pharmaceuticals, he served in several positions covering responsibilities in Canada, Asia, and the Pacific region. From 1999 until his retirement in 2003, he was president of Wyeth’s $2 billion Vaccine and Nutrition Division.

Rahim Kanani: You bring a unique perspective to global health work, coming from a long career in the pharmaceutical and vaccine industries. What are some of the lessons you’ve learned or “aha” moments you’ve experienced in your work on broader global health and development issues?
Kevin Reilly: Personally, I’ve developed a deeper appreciation for the complexity involved in running successful immunization programs. From the point of view of the vaccine manufacturer, you focus on the specific activities needed to move a vaccine successfully through the stages of development, but the many challenges involved in delivering and distributing that vaccine in developing countries may be less obvious. Getting a vaccine successfully from the factory door to the arms of millions of children in low-resource settings—that’s an enormously complicated task. Increasingly, I see pharmaceutical and vaccine manufacturers engaging in the dialogue about strengthening immunization and distribution systems to ensure vaccines get to where they are needed. Vaccine manufacturers were among the key partners involved in the early conversations that led to the formation of the GAVI Alliance, for example. They could see that global immunization rates were stagnating and that something needed to be done.

Similarly, I see growing awareness among global health organizations about the difficult, multiyear process required to develop vaccines and how that process influences the price. Where some organizations may once have advocated for a flat price of, say, less than $1 per dose for developing countries, now I think there is greater appreciation for the fact that new vaccines are extremely complex and expensive to develop. There are more efforts now to create a productive dialogue between manufacturers and global health organizations and to think creatively about funding structures and other mechanisms that may expand access to vaccines while also recognizing the need of manufacturers to ensure the financial health and well-being of their own corporations.

Rahim Kanani: What makes public-private partnerships between business, government, and civil society an effective way to tackle global health challenges? And what are some examples of big pharmaceutical companies partnering with other sectors?
Kevin Reilly: Vaccine manufacturers have a long history of providing vaccines at heavily discounted prices for use in the developing world, a practice that stretches back over half a century. For example, early in my career, I was involved in helping to provide polio vaccine to UNICEF for 2 cents per dose. While the prices have gone up for various reasons, this practice is still active today and is a critical factor in many vaccines reaching millions of children in the developing world.

From the standpoint of business, one of the keys to success for public-private partnerships is recognition that vaccine and pharmaceutical manufacturers have an important contribution to make but also have corporate interests that they must protect as well. So companies are striving to find that balance between using their discoveries to maximize the good they can do for people around the world and achieving a reasonable return on their investment.

I was also involved in helping bring Prevnar, the first pneumococcal conjugate vaccine, to market as president of Wyeth Pharmaceuticals’ Vaccine and Nutrition Division. Wyeth and GAVI entered into a discussion early on about how the vaccine could help meet the needs of developing countries, where pneumonia is the leading cause of death in young children. Through those conversations and GAVI’s innovative financing mechanism, Wyeth was able to make special arrangements for the supply of the vaccine, thus accelerating the availability of a new, complex vaccine in low-income countries.

Rahim Kanani: Is developing a vaccine the hardest part, or is it the delivery and distribution of that vaccine to the developing world?
Kevin Reilly: Both are essential for successful health outcomes—and both are immensely challenging. Developing a vaccine involves a relatively narrow set of activities driven by scientific and clinical research work. Since 2000, barely a handful of new vaccines have been developed. That’s because this is complicated work dotted with setbacks and failures along the way. You try things in the lab that fail, or things don’t work out clinically the way you predicted they would based on results in the lab. Prevnar was 17 years in development and went through ownership by three different corporate entities on its way to market.

On the other hand, vaccine delivery is a broad-based, multidimensional, and cross-sector activity involving many different systems and stakeholders. Ideally, you aim to bridge the two sides of this process, to develop a vaccine that is safe and effective while also being suited for efficient distribution and delivery. Sometimes, the complex biological and scientific factors involved in vaccine development limit your ability to optimize design for the distribution and delivery of the vaccine —for example, it may have special cold chain requirements that make it difficult to reach remote areas.

PATH’s work on the MenAfriVac® vaccine is a good example of how vaccine development, distribution, and delivery are inextricably linked. PATH and the World Health Organization worked with dozens of global collaborators over a decade to develop the vaccine against deadly meningitis A. Simultaneously, they worked with countries across Africa’s “meningitis belt” to build their capacity to integrate the vaccine into their health programs by strengthening disease surveillance, enhancing lab capacity, and reaching out to policymakers, health workers, and journalists with information and training. Recently, the vaccine became the first in Africa approved for transport and storage outside the traditional cold chain. To date, more than 100 million Africans across ten countries have received this new vaccine.

Rahim Kanani: It’s clear that businesses do a tremendous amount of work in researching and developing new drugs and vaccines to fight disease and illness. What role should governments and educational institutions play in terms of investment and research, and how can they complement each other?
Kevin Reilly: Businesses primarily focus on developing products directed at specific disease targets. In many cases, they are building on the broad base of knowledge created by academic and government research facilities. A lot of this early, upstream research may not be highly visible, but it provides a crucial foundation for the specific products coming out of pharmaceutical and biotech companies. This base of knowledge is a critical asset for the progress of health and medicine, and because this approach has been most successfully applied in the US, I believe it also gives the US a significant competitive advantage. This allows business to focus on the specific development work needed to deliver a product—work that usually involves large investments and significant risk-taking associated with the success or failure of the project. I think that matching of risk capital with high-risk activity seems appropriate.

Increasingly, we are seeing drug and vaccine manufacturers coming together with global health organizations to reduce the lag time between product launches in the developed world and the developing world. This is a relatively new trend, and a welcome one. With Prevnar, for example, Wyeth was in dialogue with GAVI soon after the vaccine launched in 2000 in the US and Europe about how to accelerate the launch of the vaccine in developing countries.

Rahim Kanani: Finally, as someone with more than 30 years of experience in this space, what are some of the leadership lessons you’ve learned along the way when it comes to advancing global health?
Kevin Reilly: Patience and persistence. These are essential elements of success in improving health around the world. The development of drugs and vaccines is an extremely long and high-risk process. Maintaining momentum requires an unwavering faith in the final objective and an unrelenting focus on doing what it takes to get there. The same is true in other kinds of global health initiatives. Some of these programs take decades to reach fruition. Polio eradication, for example, has been a global health priority for more than 50 years. In the case of polio, it’s not a matter of developing a vaccine. We’ve had the vaccine since the 1950s. It’s overcoming the challenges of delivering the vaccine to every child in every village in every country around the world. The global health community has been pushing on this for years, knowing what a powerful payoff there will be if we are successful.

– Vaccines: The Week in Review is a weekly digest — summarizing news, events, announcements, peer-reviewed articles and research in the global vaccine ethics and policy space. Content is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage. You are viewing the blog version of our weekly digest, typically comprised of between 30 and 40 posts below all dated “29 June 2013″
.
– Email Summary: Vaccines: The Week in Review is published as a single email summary, scheduled for release each Saturday eveningbefore midnight (EDT in the U.S.). If you would like to receive the email version, please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.
.
– pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_3 August 2013
.
– Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.
.
– Links: We endeavor to test each link as we incorporate it into any post, but recognize that some links may become “stale” as publications and websites reorganize content over time. We apologize in advance for any links that may not be operative. We believe the contextual information in a given post should allow retrieval, but please contact us as above for assistance if necessary.
.
– Support: If you would like to join the growing list of individuals who support this service and its contribution to their roles in public health, clinical practice, government, IGOs/NGOs, research, industry and academia, please visit this page at The Wistar Institute, our co-founder and fiduciary. Thank you…
.
David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy
a program of the
– Division of Medical Ethics, NYU Medical School
– The Wistar Institute Vaccine Center
– Children’s Hospital of Philadelphia Vaccine Education Center
Associate Faculty, Division of Medical Ethics, NYU Medical School

GAVI said that the price it pays pneumococcal vaccines will be reduced under new agreements among GAVI, UNICEF, The World Bank, GlaxoSmithKline and Pfizer. GAVI said that under previous agreements both manufacturers offered pneumococcal vaccine at US$3.50 per dose, but that under new pricing arrangements Pfizer will provide the vaccine at $3.40 per dose with a further reduction to $3.30 per dose from 2014 onwards. The new prices will apply to all doses to be purchased from Pfizer under current contracts, including those awarded under two previous agreements. GSK will lower its price to $3.40 per dose for this new contract covering the period 2014-2024. GAVI purchases pneumococcal vaccines through UNICEF as part of an Advance Market Commitment (AMC) which “aims to accelerate the development of new products, bring forward supply availability and increase the introduction of appropriate and affordable vaccines to tackle pneumococcal disease.” The AMC involved is supported by the governments of Italy, the United Kingdom, Canada, the Russian Federation and Norway, and the Bill & Melinda Gates Foundation, which have committed a total of US$1.5 billion to the initiative. The AMC was launched in 2009 and is being implemented by GAVI, The World Bank and UNICEF.

http://www.gavialliance.org/library/news/statements/2013/price-reduced-for-vaccine-against-pneumococcal-disease/

GAVI said it approved US$21 million “to help improve vaccine supply chains in Nigeria as part of a partnership aimed at scaling up routine immunisation.” The funds will be used by Nigeria’s National Primary Health Care Development Agency “to procure vital equipment for storing vaccines and to improve data collection, both of which have been identified as key pillars in protecting children’s lives as enshrined in the government’s Saving One Million Lives Initiative.” As part of this initiative, Nigeria has set a target to increase routine immunisation coverage to 87% through 2015. The GAVI support “…comes as part of a broader partnership on health system strengthening including vaccine supply chain improvement, that is expected to be complemented with support from other partners including the European Union, UNICEF, the Bill & Melinda Gates Foundation, the Clinton Health Access Initiative, the Japan International Cooperation Agency, the UK’s Department of International Development and the Canadian International Development Agency.”

http://www.gavialliance.org/library/news/press-releases/2013/gavi-aims-to-improve-access-to-vaccines-in-nigeria-through-supply-chains-project/

PATH announced a five-year, US$19.5 million grant from the Bill & Melinda Gates Foundation to “help countries strengthen their immunization management systems” through the Better Immunization Data (BID) Initiative. The BID Initiative is described as “one of the first and largest data management projects of its kind, bringing together on-the-ground knowledge of immunization programs with a focus on eHealth and data quality and use issues. It recognizes that to improve immunization management, information technology is only part of the solution—and that it may not always be the right solution for all levels of the health system. The BID Initiative will invest in supporting existing and new national health information systems and help address the operational challenges health workers face in delivering immunization services.”  PATH noted that it will work with John Snow, Inc. and partner with countries and global stakeholders “to solve these data collection, quality, and use issues. While the initial focus will be on ensuring that the most accurate information is made available for the best decision-making around immunization programs, the BID Initiative inherently recognizes that point-of-care service delivery collects information beyond immunizations.”

PATH said that as a first step in the initiative, the Bill & Melinda Gates Foundation will invite a number of African countries to a country consultation meeting to outline the concept, collect feedback, and identify partners interested in working with the BID Initiative. The BID Initiative will partner with lead countries to “develop and deploy scalable solution components involving products, practices, people, and packaging these components into a replicable solution that can be easily and cost-effectively adopted by other countries interested in using the solution to improve their immunization management.”

http://www.path.org/news/press-room/639/

The Chinese Center for Disease Control and Prevention and Aeras said they signed a memorandum of understanding “to advance research and development of new tuberculosis vaccines.” The new collaboration “will accelerate research efforts for new vaccines by supporting studies that determine the incidence of TB infection, and will aim to strengthen the capacity within China to conduct future vaccine clinical trials.” The announcement noted that “while China has achieved significant reductions in TB illness and death over the past 30 years, TB remains a major public threat, with over one million new cases in China each year. A study published in the New England Journal of Medicine last year found that one in 10 cases of TB in China are resistant to the most commonly-used drugs. Based on the World Health Organization’s estimates of global multidrug-resistant TB (MDR-TB), China has the highest annual number of cases of MDR-TB in the world—a quarter of the cases worldwide.” Dr. Wang Yu, China CDC Director General, said, ”…we have embraced innovation in our TB control efforts in China. We have adopted the latest technologies to diagnose TB. We have advanced innovative approaches to address TB and drug-resistant TB, and to promote the research that is necessary to urgently develop needed new tools to prevent, diagnose and treat it. We have made TB a high priority on our public health agenda, and will continue to seek out new and better ways to prevent and treat TB in communities across our country. But we know that this will not be enough. We will not defeat TB in our country or in the world without new, more effective vaccines. There is a coordinated, global effort underway to develop these urgently needed vaccines, and China must be a partner in this endeavor. With that goal in mind, we are excited to announce a new collaboration with Aeras to advance the research and development of new, more effective vaccines.”…

http://www.aeras.org/newscenter/news-detail.php?id=1370

Novartis said that the US Food and Drug Administration (FDA) approved its Menveo for use in infants and toddlers from 2 months of age. Menveo (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM₁₉₇ Conjugate Vaccine) helps prevent meningococcal disease caused by four strains of the bacterium Neisseria meningitidis (N. meningitidis). Novartis said that with this expanded indication, “pediatricians in the US can now offer a single vaccine to help protect infants, children and adolescents against four of the five most common serogroups that cause meningococcal disease.” This FDA approval was based on data from three randomized multicenter studies involving more than 8,700 infants, conducted in Australia, Canada, Latin America, Taiwan and the US. The studies demonstrated that Menveo “generated a robust protective immune response and a demonstrated safety profile when co-administered with routine pediatric vaccines¹.”

http://www.multivu.com/mnr/62664-fda-expands-age-indication-for-menveo-quadrivalent-meningococcal-vaccine

CDC/MMWR Watch [to 3 August 2013]
MMWR August 2, 2013 / Vol. 62 / No. 30
Vaccination Coverage Among Children in Kindergarten — United States, 2012–13 School Year
Weekly
August 2, 2013 / 62(30);607-612
Excerpt – Editor’s Text Bolding
State and local school vaccination requirements are implemented to maintain high vaccination coverage and minimize the risk from vaccine preventable diseases (1). To assess school vaccination coverage and exemptions, CDC annually analyzes school vaccination coverage data from federally funded immunization programs. These awardees include 50 states and the District of Columbia (DC), five cities, and eight U.S.-affiliated jurisdictions.* This report summarizes vaccination coverage from 48 states and DC and exemption rates from 49 states and DC for children entering kindergarten for the 2012–13 school year. Forty-eight states and DC reported vaccination coverage, with medians of 94.5% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.1% for local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccination; and 93.8% for 2 doses of varicella vaccine among awardees with a 2-dose requirement. Forty-nine states and DC reported exemption rates, with the median total of 1.8%. Although school entry coverage for most awardees was at or near national Healthy People 2020 targets of maintaining 95% vaccination coverage levels for 2 doses of MMR vaccine, 4 doses of DTaP† vaccine, and 2 doses of varicella vaccine (2), low vaccination and high exemption levels can cluster within communities, increasing the risk for disease. Reports to CDC are aggregated at the state level; however, local reporting of school vaccination coverage might be accessible by awardees. These local-level data can be used to create evidence-based health communication strategies to help parents understand the risks for vaccine-preventable diseases and the benefits of vaccinations to the health of their children and other kindergarteners.

Vaccination coverage among children entering kindergarten is assessed annually by awardees. Each school year, the health department, school nurse, or other school personnel assess the vaccination and exemption status of a census or sample of kindergarteners enrolled in public and private schools to determine vaccination coverage, as defined by state and local school requirements established to protect children from vaccine-preventable diseases. Among the 50 states and DC, 43 awardees used an immunization information system (IIS) as at least one source of data for some of their school assessment. To collect data, 33 awardees used a census of kindergarteners; 11 a sample of schools, kindergarteners, or both; two a voluntary response of schools; and five a mix of methods. Results of the school-level assessments are reported to the health department. Aggregated data are reported to CDC for public and private schools. Data for homeschooled students were not reported to CDC. All estimates of coverage and exemption were weighted based on each awardee’s response rates and sampling methodology, unless otherwise noted. Of the 50 states and DC, 12 awardees met CDC standards for school assessment methods in 2012–13.

Kindergarteners were considered up-to-date for each vaccination if they had received all of the doses required for school entry in their jurisdiction. School entry requirements varied by awardee: all reporting awardees required 2 doses of MMR vaccine; for DTaP vaccine, two awardees required 3 doses, 35 required 4 doses, and 20 required 5 doses; and for varicella vaccine, 13 required 1 dose, 41 required 2 doses, and three did not require varicella vaccination.

   The types of exemptions allowed varied by awardee. All reporting awardees allowed medical exemptions, 46 allowed religious exemptions, 18 allowed philosophic exemptions, and two (Mississippi and West Virginia) did not allow exemptions for religious or philosophic reasons. Medical, religious, and philosophic exemptions were reported as the percentage of kindergarteners with each type of exemption. Total exemptions were reported as the percentage of kindergarteners with any exemption.

Overall, among the 48 states and DC that reported 2012–13 school vaccination coverage, median 2-dose MMR vaccination coverage was 94.5% (range: 85.7% in Colorado to ≥99.9% in Mississippi); 20 reported coverage ≥95% (Table 1). Median DTaP vaccination coverage was 95.1% (range: 82.9% in Colorado and Arkansas to ≥99.9% in Mississippi); 25 reported coverage ≥95%. Median 2-dose varicella vaccination coverage among the 36 states and DC requiring and reporting 2 doses was 93.8% (range: 84.6% in Colorado to ≥99.9% in Mississippi); 14 reported coverage ≥95%.

    An estimated 91,453 exemptions were reported among a total estimated population of 4,242,558 kindergarteners. Overall, among the 49 states and DC that reported 2012–13 school vaccination exemptions, the percentage of kindergarteners with an exemption was <1% for nine awardees and >4% for 11 awardees (range: <0.1% in Mississippi to 6.5% in Oregon), with a median of 1.8% (Figure; Table 2). The largest increases in total exemptions between 2011–12 and 2012–13 were reported by Georgia and West Virginia, each with an increase of 1.0 percentage point; four states reported decreases of >1.0 percentage points (range: -1.3 in Colorado to -1.6 in New Mexico). Where reported separately, the median medical exemption level was 0.3% (range: <0.1% in five states [Arkansas, Minnesota, Mississippi, North Dakota, and Virginia] to 1.6% in Alaska). Where allowed and reported separately, the median nonmedical exemption level was 1.5% (range: 0.2% in New Mexico to 6.4% in Oregon).

Reported by

Ranee Seither, MPH, Lauren Shaw, MS, Cynthia L. Knighton, Stacie M. Greby, DVM, Shannon Stokley, MPH, Immunization Svcs Div, National Center for Immunization and Respiratory Diseases, CDC. Corresponding contributor: Ranee Seither, rseither@cdc.gov, 404-639-8693.

WHO: Global Alert and Response (GAR) – Disease Outbreak News
http://www.who.int/csr/don/2013_03_12/en/index.html

Middle East respiratory syndrome coronavirus (MERS-CoV) – update 1 August 2013
Excerpt
1 August 2013 – WHO has been informed of an additional three laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Saudi Arabia.
The first patient is a 67-year-old woman from Riyadh with underlying medical conditions. She became ill on 25 July 2013. She has no known exposure to animals or to a case confirmed with MERS-CoV infection. She is currently hospitalized.

The other two patients are health care workers, both women, from Assir and Riyadh regions . Both of them have mild symptoms and were exposed to patients who were laboratory-confirmed cases.

Globally, from September 2012 to date, WHO has been informed of a total of 94 laboratory-confirmed cases of infection with MERS-CoV, including 46 deaths.

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns.

Health care providers are advised to maintain vigilance. Recent travellers returning from the Middle East who develop SARI should be tested for MERS-CoV as advised in the current surveillance recommendations…

Update: Polio this week – As of 24 July 2013
Global Polio Eradication Initiative
http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx

[Editor’s extract and bolded text]
:: In Nigeria, the Presidential Task Force has reviewed the latest epidemiology of poliovirus transmission and strategies to overcome remaining challenges. A new risk-classification system of low-performing areas aims to focus resources where they are most needed. See ‘Nigeria’ section for more.
:: In Pakistan, the outbreak in Federally Administered Tribal Areas (FATA) is continuing, with a new case reported from Khyber Agency. The current outbreak is threatening progress achieved elsewhere in the country, as well as efforts in neighbouring Afghanistan. See ‘Pakistan’ section

Nigeria
:: Five new WPV cases were reported in the past week (four WPV1s from Kano state and one WPV1 from Yobe state), bringing the total number of WPV1 cases for 2013 to 40. The most recent WPV1 case had onset of paralysis on 9 July (WPV1 from Kano)…
:: The latest epidemiology and strategies were discussed at last week’s Presidential Task Force meeting on 23 July in Abuja. The meeting underscored that more than half of this year’s cases are from two states: Borno and Yobe.
:: Performance during Immunization Plus Days (IPDs) continues to improve in all high-risk states. However, vaccination coverage gaps persist in low-performing Local Government Areas (LGAs), particularly in Kano, Borno and Yobe.
:: Although Borno and Yobe are affected by insecurity, polio eradication activities are continuing in most LGAs of Borno and all LGAs of Yobe. Special strategies are being evaluated for these areas, including conducting ‘wall fencing’ immunizations around insecure areas, use of permanent health teams and increased use of Short Interval Additional Dose (SIADs) campaigns, as and when opportunities arise. Social mobilization activities are being targeted, to increase community demand for polio vaccination.
:: Efforts must continue to improve micro planning, reaching ‘absent’ children, and further engaging communities and traditional leaders to address non-compliance.
:: At the same time, more needs to be done to foster subnational political engagement – the involvement of LGA Chairpersons remains inconsistent across high-risk states. Engagement at state-level is also inconsistent, as measured by the Abuja Commitments.
:: A new risk classification system will improve the delivery of resources to areas where they are most needed. Across the high-risk states, 129 LGAs have now been classified as ‘very very high risk’, ‘very high risk’, or ‘special situation’ (security-affected LGAs in Borno and Yobe).
:: The next subnational IPD in northern states is planned for early September using bivalent OPV. Measles vaccine will also be offered during this round.

Pakistan
:: One new WPV1 case was reported in the past week (WPV1 from Khyber Agency, Federally Administered Tribal Area – FATA), bringing the total number of WPV1 cases for 2013 to 22. It is the most recent WPV1 case in the country and had onset of paralysis on 3 July…
:: Federally Administered Tribal Areas (FATA) is the major WPV1 reservoir in Pakistan at the moment, accounting for 13 of this year’s 22 cases in the country. Khyber Agency is particularly affected, with nine cases, and in particular Bara tehsil of Khyber. This outbreak is threatening progress achieved elsewhere in the country and in neighbouring Afghanistan. In 2011 and 2012, Bara was the epicentre of a major outbreak which also spread to other areas.

Horn of Africa
:: 24 new WPV1 cases were reported in the past week (23 from Somalia and one from Kenya), bringing the total number of WPV1 cases in the region to 105 (95 from Somalia and ten from Kenya). The most recent case in the region had onset of paralysis on 10 July (from Somalia).
:: Eleven of the newly-reported cases are from Banadir, which remains the epicentre of the outbreak, accounting for more than half of all cases associated with this outbreak.
:: Four of the newly-reported cases are from Lower Shabelle, areas of which are inaccessible due to insecurity. Special strategies continue to be implemented for these areas, including increased local-level access negotiations, immunizing older age groups and setting up vaccination posts at entry/exit points of inaccessible areas.
:: In Somalia, nationwide campaigns were conducted last week, targeting children under the age of five years. In Kenya, SIAs are currently ongoing (27-30 July), aiming to reach host communities around the Dadaab camps…

The Weekly Epidemiological Record (WER) for 2 August 2013, vol. 88, 31 (pp. 321–336) includes:
:: Cholera, 2012
:: Monthly report on dracunculiasis cases, January–May 2013

http://www.who.int/entity/wer/2013/wer8831.pdf

Report: A rapid survey of Global Vaccine Action Plan implementation
25 July 2013
Sabin Vaccine Institute
Mariya Savchuk*, Senior Program Officer; Mike McQuestion, Director, Sustainable Immunization Financing Program

Summary (excerpt)
An online survey of the global immunization community was carried out to measure knowledge and practices relating to the Global Vaccine Action Plan (GVAP). Of 62 respondents, 58% live in a GVAP target country and 29% are government or elected officials. Respondents were knowledgeable about GVAP goals and strategic objectives. Two-thirds reported they were working to make immunization a national priority and/or to strengthen immunization as an integral part of health systems. Respondents most often associated country ownership with self reliance, government prioritizing immunization or government control…

…Discussion
A sample of immunization practitioners and supporters from all six WHO Regions responded to the survey. At just 4%, the response rate was low. Results are thus not generalizable to the entire global immunization community.

The sample results showed GVAP exposure and knowledge to be relatively high. GVAP information appears to have reached English speakers sooner than the French speakers.

Respondents are working across the range of GVAP strategic objectives. All are devoting the most effort to high-level immunization advocacy (SO1). French speakers appear to be more mindful of sustainability issues (SO5).

An open-ended question about the meaning of country ownership ownership- a guiding GVAP principle- elicited varied responses. Respondents most frequently associated country ownership with the ability of a country to fully finance its immunization program.

These results must be interpreted with caution. The sample is small, nonrandom and self-selected. A random, population-based sample would likely be less engaged in immunization and less familiar with GVAP. What can be said is that GVAP messages have effectively reached the subgroups most engaged in global immunization. Further research will reveal more about variations in how countries are pursuing the GVAP objectives.

http://www.e-activist.com/ea-campaign/broadcast.response.do?ea.url.id=159333&ea.campaigner.email=qd2%2F6877ruYwARKtvejUesVX6qTqRyvRW%2BqAhU7rob9LBuYQ8fF2Yx0Yhx5yCmZXGG3JSTkQz%2F0=&ea_broadcast_target_id=0

IOM: International Regulatory Harmonization Amid Globalization of Drug Development – Workshop Summary
Released: August 1, 2013
http://iom.edu/Reports/2013/International-Regulatory-Harmonization-Amid-Globalization-of-Drug-Development.aspx

The past several decades have been a time of rapid globalization in the development, manufacture, marketing, and distribution of medical products and technologies. Increasingly, research on the safety and effectiveness of new drugs is being conducted in countries with little experience in regulation of medical product development. Demand has been increasing for globally harmonized, science-based standards for the development and evaluation of the safety, quality, and efficacy of medical products. Consistency of such standards could improve the efficiency and clarity of the drug development and evaluation process and, ultimately, promote and enhance product quality and the public health.

To explore the need and prospects for greater international regulatory harmonization for drug development, the IOM Forum on Drug Discovery, Development, and Translation hosted a workshop on February 13-14, 2013. Discussions at the workshop helped identify principles, potential approaches, and strategies to advance the development or evolution of more harmonized regulatory standards. This document summarizes the workshop.

American Journal of Infection Control
Vol 41 | No. 8 | August 2013 | Pages 667-758
http://www.ajicjournal.org/current

Evaluating influenza vaccination campaigns beyond coverage: A before-after study among health care workers
Anna Llupià, Guillermo Mena, Victòria Olivé, Sebastiana Quesada, et al.
http://www.ajicjournal.org/article/S0196-6553%2813%2900847-X/abstract

Abstract
Background
Influenza vaccination campaigns based on educational interventions do not seem to increase coverage in the hospital setting, and their impact on educational goals is not usually evaluated. This study describes the campaign implemented in a university hospital and assesses the achievement of the strategic objectives, which were to increase health care workers (HCW) perceptions of the risk of influenza and of their role as promoters of influenza vaccination among their colleagues and to increase knowledge about influenza.

Methods
A before-after study was conducted using a self-administered survey in a randomized sample of HCW during the 2010-2011 influenza vaccination campaign. The Wilcoxon paired measures test was used to assess attainment of the strategic objectives.

Results
The campaign had a positive impact on the strategic objectives (Wilcoxon test, P value <.05 in all cases). The reach of the campaign was high (91.9%), and HCW rated it as positive (7.19 [standard deviation, 2.3] out of 10) but did not achieve increased coverage (34%; 95% confidence interval: 33.8-36.4).

Conclusion
Evaluation of the campaign shows that its effect responded to the strategic objectives. However, it seems that increasing the information provided to HCW and heightening their risk perception do not necessarily lead to greater acceptance of influenza vaccination.

.

Predicting influenza vaccination uptake among health care workers: What are the key motivators?
Kimberly Corace, Chatura Prematunge, Anne McCarthy, Rama C. Nair, et al.
http://www.ajicjournal.org/article/S0196-6553%2813%2900114-4/abstract
Abstract
Background
Health care worker (HCW) vaccination was critical to protecting HCW during the H1N1 pandemic. However, vaccine uptake rates fell below recommended targets. This study examined motivators and barriers influencing HCW pH1N1 vaccination to identify modifiable factors that can improve influenza vaccine uptake.

Methods
A cross-sectional survey was conducted at a large Canadian tertiary care hospital. HCW (N = 3,275) completed measures of demographics, vaccination history, influenza risk factors, and attitudes toward pH1N1 vaccination. Self-reported vaccination was verified with staff vaccination records. Of the total sample, 2,862 (87.4%) HCW received the pH1N1 vaccine. Multiple logistic regression analyses were used to predict HCW vaccination.

Results
HCW attitudes toward vaccination significantly predicted vaccination, even after adjusting for demographics, vaccine history, and influenza risk factors. This model correctly predicted 95% (confidence interval [CI]: 0.93-0.96) of HCW vaccination. Key modifiable factors driving HCW vaccination include (1) desire to protect family members and patients, (2) belief that vaccination is important even if one is healthy, (3) confidence in vaccine safety, and (4) supervisor and physician encouragement.

Conclusion
This research identified fundamental reasons why HCW get vaccinated and provides direction for future influenza vaccination programs. To enhance vaccine uptake, it is important to target HCW attitudes in influenza vaccine campaigns and create a culture of vaccine promotion in the workplace, including strong messaging from supervisors and physicians

.

Health care worker influenza immunization rates: The missing pieces of the puzzle
Susan Quach, Jennifer A. Pereira, Christine L. Heidebrecht, Jeffrey C. Kwong, et al.
http://www.ajicjournal.org/article/S0196-6553%2812%2901302-8/abstract
Abstract
Background
Immunization rates are used to assess the level of protection against influenza, but limited data exist on how such rates are measured in health care organizations. We conducted key informant interviews with campaign planners to learn about processes for collecting immunization data, including barriers and facilitating factors for measuring and reporting rates.

Methods
We conducted telephone interviews with 23 influenza immunization program planners across Canada working in 7 acute care hospitals, 6 continuing care facilities, and 8 public health organizations in 2012. We used content analysis to examine the interview data.

Results
The methods used to collect immunization data varied by the size and type of health care organization. Immunization data from different personnel groups were included in immunization rate calculations depending on the local public health reporting requirements and the organization’s size. Challenges associated with collecting immunization data and calculating rates included lack of resources for identifying personnel immunized off-site, tracking personnel who declined immunization, identifying non-payroll staff, and interpreting unclear public health reporting requirements.

Conclusion
Support from other vaccine providers, public health, employers, and professional and external bodies is needed to provide the necessary information and resources to calculate accurate and complete rates. Further work is needed to refine and standardize the collection of HCW influenza immunization data so that it may be used for surveillance and quality assessment purposes.

.

Using a validated health promotion tool to improve patient safety and increase health care personnel influenza vaccination rates
Kevin Real, Sujin Kim, Joseph Conigliaro
http://www.ajicjournal.org/article/S0196-6553%2812%2901338-7/abstract
Abstract
Background
This study employed the risk perception attitude (RPA) framework to determine whether health care personnel (HCP) influenza-related risk perceptions and efficacy beliefs could be used to segment individuals into meaningful groups related to vaccination uptake, absenteeism, and patient safety beliefs.
Methods
After pilot interviews, a questionnaire was administered to 318 hospital-based HCP (80%) and nonclinical support staff (20%) in Lexington, KY, in 2011. Follow-up interviews were conducted with 29 respondents.
Results
Cluster analysis was used to create 4 groups that correspond to the RPA framework: responsive (high risk, strong efficacy), avoidance (high risk, weak efficacy), proactive (low risk, strong efficacy), and indifference (low risk, weak efficacy). A significant association was found between membership in 1 or more of the 4 RPA groups and the 3 study variables of interest: influenza vaccination uptake (F7,299 = 2.51, P < .05), influenza-related absenteeism (F7,269=3.6, P<.001), and perceptions of patient safety climate (F7,304=6.21, P<.001). A subset of respondents indicated the principal reasons for not getting vaccinated were “had one before and got sick anyway,” “concerned about vaccine safety,” and “no convenient time.” In follow-up interviews, HCP indicated that employee vaccinations were altruistic, increased herd immunity, and important for patient safety.
Conclusion
The RPA framework is a valid health promotion tool for improving patient safety, targeting specific groups for interventions, and improving HCP influenza vaccination rates.

.

Impact of hospital policies on health care workers’ influenza vaccination rates
Mary Patricia Nowalk, Chyongchiou Jeng Lin, Mahlon Raymund, Jamie Bialor, et al.
http://www.ajicjournal.org/article/S0196-6553%2813%2900025-4/abstract
Abstract
Background
Overall annual influenza vaccination rate has slowly increased among health care workers but still remains below the national goal of 90%.
Methods
To compare hospitals that mandate annual health care worker (HCW) influenza vaccination with and without consequences for noncompliance, a 34-item survey was mailed to an infection control professional in 964 hospitals across the United States in 4 waves. Respondents were grouped by presence of a hospital policy that required annual influenza vaccination of HCWs with and without consequences for noncompliance. Combined with hospital characteristics from the American Hospital Association, data were analyzed using χ2 or Fisher exact tests for categorical variables and t tests for continuous variables.
Results
One hundred fifty hospitals required influenza vaccination, 84 with consequences (wear a mask, termination, education, restriction from patient care duties, unpaid leave) and 66 without consequences for noncompliance. Hospitals whose mandates have consequences for noncompliance included a broader range of personnel, were less likely to allow personal belief exemptions, or to require formal declination. The change in vaccination rates in hospitals with mandates with consequences (19.5%) was nearly double that of the hospitals with mandates without consequences (11%; P=.002). Presence of a state law regulating HCW influenza vaccination was associated with an increase in rates for mandates with consequences nearly 3 times the increase for mandates without consequences.
Conclusion
Hospital mandates for HCW influenza vaccination with consequences for noncompliance are associated with larger increases in HCW influenza vaccination rates than mandates without such consequences.

.

Influenza vaccination knowledge and perceptions among Veterans Affairs nurses
Andrea R. Jennings, Christopher J. Burant
http://www.ajicjournal.org/article/S0196-6553%2813%2900104-1/abstract
Abstract
Flu vaccination among nurses in the Veterans Health Administration system is crucial in the prevention of influenza. Nurses working at a Veterans Administration Medical Center completed the Influenza Vaccination Knowledge and Perceptions Survey. The findings from this survey suggest the need for additional education for nurses as it relates to flu vaccination.

.

A mandatory campaign to vaccinate health care workers against pertussis
Lisa M. Esolen, Kimberly L. Kilheeney
http://www.ajicjournal.org/article/S0196-6553%2812%2901341-7/abstract
Abstract
Pertussis is a highly contagious respiratory infection that has dramatically increased in recent decades and has caused outbreaks in health care facilities. Because of these trends, we implemented a mandatory pertussis (Tdap) employee vaccination program. Final vaccination compliance was 97.8% across all clinical campuses.

.

Influenza immunization coverage of residents and employees of long-term care facilities in New York State, 2000-2010
Cara J. Person, Jessica A. Nadeau, Joshua K. Schaffzin, Lynn Pollock, et al.
http://www.ajicjournal.org/article/S0196-6553%2812%2901335-1/abstract
Abstract
We describe influenza immunization coverage trends from the New York State (NYS) Department of Health long-term care facility (LTCF) reports. Overall median immunization coverage levels for NYS LTCF residents and employees were 84.0% (range: 81.6%-86.0%) and 37.7% (range: 32.7%-50.0%), respectively. LTCF resident immunization coverage levels in NYS have neared the Healthy People 2020 target of 90% but have not achieved high LTCF employee coverage, suggesting a need for more regulatory interventions