Journal of Infectious Diseases
Volume 206 Issue 4 August 15, 2012
http://www.journals.uchicago.edu/toc/jid/current

Editorial Commentaries
Editor’s choice: Horizontal Transmission of Hepatitis B Virus—Why Discuss When We Can Vaccinate?
J Infect Dis. (2012) 206(4): 464-465 doi:10.1093/infdis/jis294
Ida Louise Heiberg and Birthe Hogh

Extract
Hepatitis B virus (HBV) infection remains an important global health problem despite the availability of a safe and effective vaccine; >350 million people worldwide are chronically infected [1]. Infection with HBV in adults most often results in self-limited, acute hepatitis that confers protective immunity and causes no further disease. In contrast, most children fail to clear the virus, resulting in chronic infection in 90% of children who are infected perinatally. Chronically infected children are generally asymptomatic but are at risk of developing liver cirrhosis and hepatocellular carcinoma [2, 3]. Since 1992, the World Health Organization has recommended global vaccination against HBV, and by the end of 2009, 177 countries had implemented a universal HBV immunization program for newborns, infants, and/or adolescents. Countries with a low level of HBV endemicity, such as Japan and many northern European countries, have adopted a strategy in which vaccination is offered to individuals at high risk of infection [4].

Spread of HBV occurs through contact with blood or other bodily fluids of an infected person. In countries with low endemicity, the spread of HBV is caused predominantly by sharing contaminated equipment during drug injections and through sexual contact.

In this issue of the Journal, Komatsu et al report their …

Journal of Infectious Diseases
Volume 206 Issue 4 August 15, 2012
http://www.journals.uchicago.edu/toc/jid/current

Measles Vaccine, HIV Infection, and Antiretroviral Therapy—A Window of Opportunity
J Infect Dis. (2012) 206(4): 466-468 doi:10.1093/infdis/jis392
Yvonne Maldonado

Extract
Measles virus infection, a systemic rash illness commonly acquired in infancy and early childhood, is one of the most contagious infectious diseases in humans [1]. Measles is also an important cause of global morbidity and mortality, primarily among infants and children living in resource-limited settings [2]. Since the development of measles vaccines in the 1960s, intensive vaccination efforts, especially in the 21st century, have led to substantial reductions in measles-related deaths on a global scale, resulting in a reduction in mortality from almost 750 000 childhood deaths worldwide in 2000 to 164 000 in 2008 [3]. Eradication of measles infection on a global scale can, in theory, be accomplished because measles virus has no nonhuman reservoirs, and vaccination strategies to prevent transmission are available and feasible [4]. However, because of the highly contagious nature of measles virus, at least 95% vaccination coverage with at least 1 dose (and preferably 2 doses) of measles vaccine must be achieved to suppress and eventually eradicate continued global measles transmission [5].

One important characteristic of measles infection is that it produces more serious illness and increased mortality among immunocompromised individuals, primarily those with defects in T-cell immunity [6]. Because >90% of human immunodeficiency virus (HIV)–infected children live in regions where measles is still endemic [7, 8], achieving high rates of measles vaccine coverage is especially important among these populations to suppress excess measles-associated morbidity and mortality. However, live virus vaccines may also result in disease and, in general, are not recommended for administration to severely immunocompromised individuals. Measles vaccines are also known to induce short-term immunosuppressive effects and, therefore, the risk of further adverse events among HIV-infected infants and children is of concern. Moreover, it is well known that …

Medical Decision Making (MDM)
July–August 2012; 32 (4)
http://mdm.sagepub.com/content/current
Theme: Patients’ Choices: Perceived Risk, Health State Values, and Decisions

Original Articles/Presenting Probabilities to Patients
The Influence of Graphic Display Format on the Interpretations of Quantitative Risk Information among Adults with Lower Education and Literacy: A Randomized Experimental Study
Kirsten J. McCaffery, Ann Dixon, Andrew Hayen, Jesse Jansen, Sian Smith, and Judy M. Simpson
Med Decis Making July–August 2012 32: 532-544, first published on November 10, 2011 doi:10.1177/0272989X11424926

Abstract
Objective To test optimal graphic risk communication formats for presenting small probabilities using graphics with a denominator of 1000 to adults with lower education and literacy.

Methods A randomized experimental study, which took place in adult basic education classes in Sydney, Australia. The participants were 120 adults with lower education and literacy. An experimental computer-based manipulation compared 1) pictographs in 2 forms, shaded “blocks” and unshaded “dots”; and 2) bar charts across different orientations (horizontal/vertical) and numerator size (small <100, medium 100–499, large 500–999). Accuracy (size of error) and ease of processing (reaction time) were assessed on a gist task (estimating the larger chance of survival) and a verbatim task (estimating the size of difference). Preferences for different graph types were also assessed.

Results Accuracy on the gist task was very high across all conditions (>95%) and not tested further. For the verbatim task, optimal graph type depended on the numerator size. For small numerators, pictographs resulted in fewer errors than bar charts (blocks: odds ratio [OR] = 0.047, 95% confidence interval [CI] = 0.023–0.098; dots: OR = 0.049, 95% CI = 0.024–0.099). For medium and large numerators, bar charts were more accurate (e.g., medium dots: OR = 4.29, 95% CI = 2.9–6.35). Pictographs were generally processed faster for small numerators (e.g., blocks: 14.9 seconds v. bars: 16.2 seconds) and bar charts for medium or large numerators (e.g., large blocks: 41.6 seconds v. 26.7 seconds). Vertical formats were processed slightly faster than horizontal graphs with no difference in accuracy. Most participants preferred bar charts (64%); however, there was no relationship with performance.

Conclusions For adults with low education and literacy, pictographs are likely to be the best format to use when displaying small numerators (<100/1000) and bar charts for larger numerators (>100/1000).

Medical Decision Making (MDM)
July–August 2012; 32 (4)
http://mdm.sagepub.com/content/current
Theme: Patients’ Choices: Perceived Risk, Health State Values, and Decisions

Valuing Health: A Brief Report on Subjective Well-Being versus Preferences
Paul Dolan and Robert Metcalfe
Med Decis Making July–August 2012 32: 578-582, first published on February 2, 2012 doi:10.1177/0272989X11435173

Extract
Health care can improve people’s quality of life, and it can help them live longer. The quality-adjusted-life-years (QALYs) approach has been developed to express these twin components of benefit (quality and quantity of life) in a single number. It expresses different health states on a scale between 0 for death and 1 for full health and then multiplies these values by how long the states last. One QALY is equivalent to 1 year of life in full health.1 By comparing how many QALYs different interventions are expected to generate with how much those interventions are expected to cost, it is possible to show the cost-effectiveness of different uses of resources.

In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends that “the value of changes in patients’ health related quality of life should be based on public preferences using a choice-based method . . . [and] the EQ-5D is the preferred measure of HRQL in adults.”2 The EQ-5D™ defines health in terms of 1 of 3 levels of severity (broadly, no problems, some problems, and extreme problems) associated with each of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each of the 243 (35) health states are represented by a 5-digit code, ranging from 11111 for full health to 33333 for extreme problems on all 5 dimensions. Values for these states have been elicited by asking members of the public for their time tradeoff (TTO) preferences, that is, to state how many years of life in 11111 they consider to be equivalent to a longer period of time in one of the remaining 242 “poor” health states.3,4

There is a long tradition of asking for people’s preferences over future, hypothetical prospects. 5,6 It is also not without its …

Medical Decision Making (MDM)
July–August 2012; 32 (4)
http://mdm.sagepub.com/content/current
Theme: Patients’ Choices: Perceived Risk, Health State Values, and Decisions

A Direct Method for Measuring Discounting and QALYs More Easily and Reliably
Arthur E. Attema, Han Bleichrodt, and Peter P. Wakker
Med Decis Making July–August 2012 32: 583-593, first published on June 15, 2012 doi:10.1177/0272989X12451654

Abstract
Time discounting and quality of life are two important factors in evaluations of medical interventions. The measurement of these two factors is complicated because they interact. Existing methods either simply assume one factor given, based on heuristic assumptions, or invoke complicating extraneous factors, such as risk, that generate extra biases. The authors introduce a method for measuring discounting (and then quality of life) that involves no extraneous factors and that avoids distorting interactions. Their method is considerably simpler and more realistic for subjects than existing methods. It is entirely choice based and thus can be founded on economic rationality requirements. An experiment demonstrates the feasibility of this method and its advantages over classical methods.

Pharmacoeconomics
August 1, 2012 – Volume 30 – Issue 8  pp: 633-747,e1-e15
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Commentary
Valuing Children’s Health: Whose Quality of Life Matters?
Wittenberg, Eve
Pharmacoeconomics. 30(8):633-635, August 1, 2012.
doi: 10.2165/11632490-000000000-00000

[No abstract]

Pharmacoeconomics
August 1, 2012 – Volume 30 – Issue 8  pp: 633-747,e1-e15
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Current Opinion
Comparative Effectiveness and Child Health
Prosser, Lisa A.
Pharmacoeconomics. 30(8):637-645, August 1, 2012.
doi: 10.2165/11633830-000000000-00000

Abstract
Comparative effectiveness research is expected to play an important role in future clinical and policy decision making in the US; however, the application of comparative effectiveness methodologies to child health requires special attention to aspects of health and healthcare that are specific to children. These special considerations include the role of parent/caregiver as joint decision maker and co-participant in many types of interventions, how the effectiveness of an intervention varies by age and developmental stage, and the difficulties in translating short-term data from childhood into projected effectiveness over the lifespan. Each aspect of comparative effectiveness, such as conducting new studies, synthesizing existing evidence, emphasizing real-world settings, considering multiple decision makers, and measuring patient-relevant outcomes, will require expanded definitions when considered in the context of child health.

This paper discusses how comparative effectiveness methods and concepts will differ when applied to child health and suggests a potential role for decision analysis as a method to synthesize data and project long-term outcomes. The initiation of comparative effectiveness studies for children represents an exciting opportunity to provide evidence that can guide clinical and policy decisions for child health.

Pharmacoeconomics
August 1, 2012 – Volume 30 – Issue 8  pp: 633-747,e1-e15
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Review Article
Economic Evaluations of Childhood Influenza Vaccination: A Critical Review
Newall, Anthony T.; Jit, Mark; Beutels, Philippe
Pharmacoeconomics. 30(8):647-660, August 1, 2012.
doi: 10.2165/11599130-000000000-00000

Abstract:
The potential benefits of influenza vaccination programmes targeted at children have gained increasing attention in recent years.

We conducted a literature search of economic evaluations of influenza vaccination in those aged ≤18 years. The search revealed 20 relevant articles, which were reviewed.    The studies differed widely in terms of the costs and benefits that were included. The conclusions were generally favourable for vaccination, but often applied a wider perspective (i.e. including productivity losses) than the reference case for economic evaluations used in many countries. Several evaluations estimated outcomes from a single-year epidemiological study, which may limit their validity given the year-to-year variation in influenza transmissibility, virulence, vaccine match and prior immunity. Only one study used a dynamic transmission model able to fully incorporate the indirect herd protection to the wider community.

The use of dynamic models offers great scope to capture the population-wide implications of seasonal vaccination efforts, particularly those targeted at children.

Pharmacoeconomics
August 1, 2012 – Volume 30 – Issue 8  pp: 633-747,e1-e15
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

The Impact of Rotavirus Vaccination on Discounted Net Tax Revenue in Egypt: A Government Perspective Analysis
Connolly, Mark P.; Topachevskyi, Oleksandr; Standaert, Baudouin; Ortega, Omayra; Postma, Maarten
Pharmacoeconomics. 30(8):681-695, August 1, 2012.
doi: 10.2165/11597750-000000000-00000

Abstract
Background: We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of children consuming government resource, and an increased number of future tax payers.

Objective: Our objective was to evaluate the difference in lifetime discounted net tax revenue generated by RV vaccinated and unvaccinated cohorts from the Egyptian government perspective.

Methods: The model framework adopts the Egyptian government perspective for RV immunization costs (year 2009 values) and all government transfers (e.g. education costs, health costs, pensions). To reflect the government tax revenue, we applied a fixed income tax burden to earnings over the lifetime of vaccinated and unvaccinated cohorts. At each year of the model, we derive net taxes (gross taxes less transfers) discounted to the immunization year to reflect the present value of RV vaccination investment costs.

Results: Projected incremental net present values of the vaccinated cohort versus the unvaccinated cohort are $US6.1 million, $US58.1 million and $US55.7 million at 25-, 50- and 72-year time horizons, respectively. The internal rate of return for the government based on RV vaccination at years 25, 50 and 72 was 10.8%, 15.1% and 14.9, respectively. Within the first 5 years of vaccination, 76% of vaccine acquisition costs were offset due to direct and indirect cost savings attributed to a reduction in RV-related disease burden. Investments in RV vaccination in a single year are entirely offset when the vaccinated cohort of newborns reach 22 years of age.

Conclusion: The government perspective is useful for evaluating investments in RV vaccination because of ongoing government transfers and tax receipts attributed to changes in RV-attributed morbidity and mortality. The analysis described here illustrates that investing in RV offers tangible long-term fiscal benefits for government over many generations that would not ordinarily be captured in economic evaluations typically applied to healthcare interventions.

PLoS One
[Accessed 21 July 2012]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Effect of Serotype on Focus and Mortality of Invasive Pneumococcal Disease: Coverage of Different Vaccines and Insight into Non-Vaccine Serotypes
Albert Jan van Hoek, Nick Andrews, Pauline A. Waight, Robert George, Elizabeth Miller PLoS ONE: Research Article, published 16 Jul 2012 10.1371/journal.pone.0039150

Abstract 
Background
Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13).

Method
Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients’ diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5–64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines.

Results
The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines’ coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals.

Conclusion
Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss.

PNAS – Proceedings of the National Academy of Sciences of the United States
of America
(Accessed 21 July 2012)
http://www.pnas.org/content/early/recent

Biological Sciences – Microbiology:
Sibao Wang, Anil K. Ghosh, Nicholas Bongio, Kevin A. Stebbings, David J. Lampe, and Marcelo Jacobs-Lorena
Fighting malaria with engineered symbiotic bacteria from vector mosquitoes
PNAS 2012 ; published ahead of print July 16, 2012, doi:10.1073/pnas.1204158109

Abstract
The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)4, four copies of Plasmodium enolase–plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria.

Science Translational Medicine
18 July 2012 vol 4, issue 143
http://stm.sciencemag.org/content/current

Commentary: Policy
Reporting Actionable Research Results: Shared Secrets Can Save Lives
Lawrence E. Hunter, Christian Hopfer, Sharon F. Terry, and Marilyn E. Coors
18 July 2012: 143cm8

Abstract
In this Commentary, we describe a cryptographic method for returning research results to individuals who participate in clinical studies. Controlled use of this method, which relaxes the typical anonymization guarantee, can ensure that clinically actionable results reach participants while also addressing most privacy concerns.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 36 pp. 5299-5448 (3 August 2012)

Regular Papers
Feasibility of a randomized controlled trial to evaluate Text Reminders for Immunization Compliance in Kids (TRICKs)
Original Research Article
Pages 5305-5309
Carolyn R. Ahlers-Schmidt, Amy K. Chesser, Tuan Nguyen, Jennifer Brannon, Traci A. Hart, Katherine S. Williams, Robert R. Wittler

Abstract
Objective
To pilot test the Text Reminders for Immunization Compliance in Kids (TRICKs) program to evaluate its feasibility and potential to increase immunization coverage.

Design
Randomized controlled trial (RCT).

Setting
Pediatric clinic.

Participants
Parents of newborns being discharged from a local hospital who intended to seek child health care at the University-sponsored pediatric resident and faculty clinic.

Intervention
Text message immunization reminders prior to immunization due dates.

Main Outcome Measures
Receipt and timeliness of immunizations at 2, 4 and 6 months of age.

Results
Participants (N = 90) were English (83%) or Spanish (17%) speaking. The majority were female (83%), on public insurance (59%), and had adequate health literacy (96%). Parents were married or a member of an unmarried couple (62%). Over 66% had a high school diploma or less. Greater numbers of intervention children received immunizations and were “on time” using per protocol analysis; though not statistically significance. Limitations include sample size, problematic text messaging software, and loss of phone service at 7 months for 40% of intervention parents. However, post-intervention interviews (N = 18) indicated strong support for TRICKs; 83% found the text message reminders very helpful and 17% somewhat helpful.

Discussion
Pilot testing allowed us to assess processes, including recruitment, retention, and software, which will increase the success of an RCT. Software with built-in backup systems is needed for follow-up when mobile service is interrupted. However, in spite of limitations, immunization rates were higher in the text message reminder group, though not statistically significant. Parent support and interest was high. A fully powered RCT is needed with follow-up over the full 4-3-1-3-3-1 series. Based on our results, for 80% power where we expected 90% compliance in the intervention group and 80% in the control group we need 219 per group, plus increases to address drop out and loss of follow-up.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 36 pp. 5299-5448 (3 August 2012)

Knowledge about human papillomavirus (HPV), and health beliefs and intention to recommend HPV vaccination for girls and boys among Korean health teachers
Original Research Article
Pages 5327-5334
Hae Won Kim

Abstract
The human papillomavirus (HPV) vaccination rate in Korea is very low because a school-based HPV vaccination program has not yet been introduced. This study was designed to assess HPV knowledge, compare the health beliefs toward HPV vaccination and intention to recommend HPV vaccination for girls and boys, and identify the factors influencing the intention to recommend HPV vaccination for girls and boys among Korean health teachers. A descriptive cross-sectional study design was employed, in which 757 health teachers who worked at elementary, middle, high, and special schools in Korea participated via an online survey. A self-administered, structured questionnaire was applied, which included items on sociodemographics, HPV awareness, HPV knowledge, perceived benefits, susceptibility, severity, and barriers toward HPV vaccination for girls and boys, and intention to recommend HPV vaccination for girls and boys. The rate of correct HPV knowledge items ranged from 5.2% to 89.2%; 23.4% of the health teachers answered that they had ever taught about HPV, 97% answered that both boys and girls should receive HPV vaccination, and 47.6% answered that the best time for HPV vaccination is when students are at middle school. There were differences regarding the perceived benefits (Z = −7.69, p < 0.001), perceived susceptibility (Z = −3.37, p = 0.001), perceived severity (Z = −4.13, p < 0.001), and perceived barriers (Z = −4.90, p < 0.001) toward HPV vaccination, and regarding intention to recommend HPV vaccination (Z = −15.21, p < 0.001) for girls and boys. Factors associated with the intention to recommend HPV vaccination for girls were the HPV vaccination status of the health teachers’ children [odds ratio (OR) = 4.24, 95% confidence interval (95% CI) = 1.14–15.72], and the teachers’ Pap-test experience (OR = 2.50, 95% CI = 1.05–5.91), perceived benefits (OR = 3.30, 95% CI = 1.26–7.40), perceived susceptibility (OR = 3.25, 95% CI = 1.58–6.68), and perceived barriers (OR = 0.51, 95% CI = 0.30–0.99); these factors for boys were the health teachers’ career duration (OR = 1.61, 95% CI = 1.12–2.32), HPV knowledge (OR = 1.45, 95% CI = 1.01–2.09), perceived benefits (OR = 3.46, 95% CI = 2.27–5.26), perceived susceptibility (OR = 1.55, 95% CI = 1.04–2.29), and perceived severity (OR = 1.71, 95% CI = 1.15–2.56). General awareness of HPV should be increased and more specific information about HPV—including that related to vaccination of boys and men—should be provided for health teachers. Although a school-based HPV vaccine program has yet to be introduced in Korea, health teachers should possess general knowledge about HPV and HPV vaccination, and differences in attitudes and intentions related to HPV vaccination between girls and boys should be reduced.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 36 pp. 5299-5448 (3 August 2012)

Human papillomavirus vaccine knowledge and hypothetical acceptance among women in Appalachia Ohio
Original Research Article
Pages 5349-5357
Mack T. Ruffin IV, Erinn M. Hade, Melissa R. Gorsline, Cecilia R. DeGraffinreid, Mira L. Katz, Sarah C. Kobrin, Electra D. Paske

Abstract
Objective
To assess hypothetical acceptance of the human papillomavirus (HPV) vaccine for themselves and a daughter age 9–12 years among Appalachia Ohio women.

Methods
Women with an abnormal Pap smear and randomly selected women with a normal Pap smear from 17 clinics completed an interview in 2006–2008.

Results
From 1131 original study participants, 807 (71%) completed a survey about the HPV vaccine for their daughters and themselves. Nearly half, 380 (47%), of the participants had heard of a vaccine to prevent cancer, and 362 (95%) of respondents had heard of HPV. The participants were then told that the FDA had approved a vaccine to prevent HPV. Only 379 (38%) participants identified girls ages 9–12 years as a group who should get the vaccine. After being given the official HPV vaccine recommendation statement, 252 (31%) wanted the vaccine; 198 (25%) were “not sure”; and 353 (44%) did not want the vaccine for themselves. With respect to giving the HPV vaccine to a daughter ages 9–12 years, participants responded “yes” 445 (55%); “not sure” 163 (20%); or “no” 185 (23%). Numerous reasons were provided supporting and opposing vaccine acceptance for themselves and for a daughter. Their physician’s recommendation for the HPV vaccine increased vaccine acceptance to 86% for themselves and 90% for a daughter.

Conclusion
Knowledge, acceptance, and barriers about the HPV vaccine vary among women living in Appalachia Ohio. Physician recommendation is a key facilitator for vaccine diffusion in this region.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 36 pp. 5299-5448 (3 August 2012)

A qualitative study of HPV vaccine acceptability among health workers, teachers, parents, female pupils, and religious leaders in northwest Tanzania
Original Research Article
Pages 5363-5367
Pieter Remes, Veronica Selestine, John Changalucha, David A. Ross, Daniel Wight, Silvia de Sanjosé, Saidi Kapiga, Richard J. Hayes, Deborah Watson-Jone

Abstract
Background
As human papillomavirus (HPV) vaccines become available in developing countries, acceptability studies can help to better understand potential barriers and facilitators of HPV vaccination and guide immunisation programs.

Methods
Prior to a cluster-randomised phase IV trial of HPV vaccination delivery strategies in Mwanza Region, Tanzania, qualitative research was conducted to assess attitudes and knowledge about cervical cancer and HPV, and acceptability of and potential barriers to HPV vaccination of Tanzanian primary schoolgirls. Semi-structured interviews (n = 31) and group discussions (n = 12) were conducted with a total of 169 respondents (parents, female pupils, teachers, health workers and religious leaders).

Results
While participants had heard of cancer in general, most respondents had no knowledge of cervical cancer, HPV, or HPV vaccines. Only health workers had heard of cervical cancer but very few knew its cause or had any awareness about HPV vaccines. After participants were provided with information about cervical cancer and HPV vaccination, the majority stated that they would support HPV vaccination of their daughter to protect them against cervical cancer. Opt-out consent for vaccination was considered acceptable. Most preferred age-based vaccination, saying this would target more girls before sexual debut than class-based vaccination. Potential side effects and infertility concerns were raised by 5/14 of participating male teachers.

Discussion
Reported acceptability of HPV vaccination amongst parents, teachers and other community members was high in this population. Respondents stressed the need to provide adequate information about the vaccine to parents, that also addresses side effects and infertility concerns.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 36 pp. 5299-5448 (3 August 2012)
Public health and economic impact of 13-valent pneumococcal conjugate vaccine in US adults aged ≥50 years
Original Research Article
Pages 5437-5444
Derek Weycker, Reiko Sato, David Strutton, John Edelsberg, Mark Atwood, Lisa A. Jackson

Abstract
Background
A 13-valent pneumococcal conjugate vaccine (PCV13) was recently developed for use in older adults, and may be effective not only against invasive pneumococcal disease (IPD) but also nonbacteremic pneumococcal pneumonia. The potential public health and economic impact of PCV13 in this population is unknown.

Methods
A microsimulation model depicting risk and costs of IPD and all-cause nonbacteremic pneumonia (NBP) in US adults aged ≥50 years (n = 96.1 million), as well as expected impact of vaccination, was developed. Effectiveness of PPSV23 was based on published literature, and for all-cause NBP, was zero; effectiveness of PCV13 was based on PCV7 data in children, and for all-cause NBP, was varied across a reasonable range. Lifetime outcomes and costs were projected assuming: (1) use of PCV13 in all subjects at model entry, with and without periodic revaccination; and (2) use of PPSV23 per current ACIP recommendations.

Results
Use of PCV13 in all subjects at model entry without revaccination – in lieu of PPSV23 use per recommendations – reduced cases of IPD by 15,000 (95% CI 9000–21,000); cases of NBP by 1.2 million (0.9–1.5); total healthcare costs by $3.5 billion (1.9–5.2); and total societal costs by $7.4 billion (5.3–9.8). Use of PCV13 with revaccination every 5–10 years resulted in fewest cases of disease and lowest total costs. Findings were largely unchanged in sensitivity analyses.

Conclusions
Assuming that the effectiveness of PCV13 in adults is comparable to that observed for PCV7 in children and under reasonable assumptions regarding the underlying risks and costs of IPD and NBP, model projections suggest that routine use of PCV13 – in lieu of PPSV23 – would result in a greater reduction in the overall burden of pneumococcal disease in older US adults.

Vaccine
Volume 30, Issue 35 pp. 5179-5298 (27 July 2012)

Reviews
Acellular pertussis vaccine use in risk groups (adolescents, pregnant women, newborns and health care workers): A review of evidences and recommendations
Review Article
Pages 5179-5190
Angela Bechini, Emilia Tiscione, Sara Boccalini, Miriam Levi, Paolo Bonanni

Abstract
Objective
Our review aims at describing the current knowledge on the impact of acellular pertussis vaccination in adolescents and adults, with particular focus on specific risk groups: adolescents, pregnant women and their newborns, and health care workers (HCWs), and secondly at suggesting possible immunization strategies.

Methods
Data were retrieved by searches of Pubmed, references, from relevant articles and open-access websites.

Results
In countries where an adolescent booster dose was adopted, a certain decrease of incidence rates was observed. No serologic correlate of protection after immunization exists, but subjects with high antibody levels against pertussis antigens are less likely to develop the disease. Tdap vaccine was demonstrated to induce antibodies to pertussis antigens exceeding those associated with efficacy in infants, in both adolescents and adults. Tdap use in pregnant women seems to be safe and might represent a useful tool in order to prevent pertussis cases in the first months of life. Neonatal immunization with monovalent acellular pertussis vaccine can efficiently prime T and B cells and act as a basis for future immune responses. Cocooning strategies involving all those surrounding newborns have started to be implemented. Their impact on infant pertussis cases will be evaluated in the coming years. Coverage in HCWs should be increased, given their important role in pertussis transmission in health care settings.

Conclusions
Despite the more recent position paper of WHO gives priority to infant and childhood vaccination against pertussis and leaves adolescent, adult and risk group immunization as an option for the future, data are quickly accumulating to support the need to consider pertussis vaccination as a crucial preventative intervention even in adolescents and special risk groups.

Vaccine
Volume 30, Issue 35 pp. 5179-5298 (27 July 2012)

Reviews
Malaria vaccines: Focus on adenovirus based vectors
Review Article
Pages 5191-5198
Nathaniel J. Schuldt, Andrea Amalfitano

Abstract
Protection against malaria through vaccination is known to be achievable, as first demonstrated over 30 years ago. Vaccination via repeated bites with Plasmodium falciparum infected and irradiated mosquitoes provided short lived protection from malaria infection to these vaccinees. Though this method still remains the most protective malaria vaccine to date, it is likely impractical for widespread use. However, recent developments in sub-unit malaria vaccine platforms are bridging the gap between high levels of protection and feasibility. The current leading sub-unit vaccine, RTS,S (which consists of a fusion of a portion of the P. falciparum derived circumsporozoite protein to the Hepatitis B surface antigen), has demonstrated the ability to induce protection from malaria infection in up 56% of RTS,S vaccinees. Though encouraging, these results may fall short of protection levels generally considered to be required to achieve eradication of malaria. Therefore, the use of viral vectored vaccine platforms has recently been pursued to further improve the efficacy of malaria targeted vaccines. Adenovirus based vaccine platforms have demonstrated potent anti-malaria immune responses when used alone, as well when utilized in heterologous prime boost regimens. This review will provide an update as to the current advancements in malaria vaccine development, with a focus on the use of adenovirus vectored malaria vaccines.

Vaccine
Volume 30, Issue 35 pp. 5179-5298 (27 July 2012)

Regular Papers
Variation in adult vaccination policies across Europe: An overview from VENICE network on vaccine recommendations, funding and coverage
Original Research Article
Pages 5222-5228
Elisabeth E. Kanitz, Lauren A. Wu, Cristina Giambi, Raymond A. Strikas, Daniel Levy-Bruhl, Pawel Stefanoff, Jolita Mereckiene, Eva Appelgren, Fortunato D’Ancona, VENICE (Vaccine European New Integrated Collaboration Effort) National Gatekeepers, Contact Points

Abstract
Background
In 2010–2011, in the framework of the VENICE project, we surveyed European Union (EU) and Economic Area (EEA) countries to fill the gap of information regarding vaccination policies in adults. This project was carried out in collaboration with the United States National Vaccine Program Office, who conducted a similar survey in all developed countries.

Methods
VENICE representatives of all 29 EU/EEA-countries received an online questionnaire including vaccination schedule, recommendations, funding and coverage in adults for 17 vaccine-preventable diseases.

Results
The response rate was 100%. The definition of age threshold for adulthood for the purpose of vaccination ranged from 15 to 19 years (median = 18 years). EU/EEA-countries recommend between 4 and 16 vaccines for adults (median = 11 vaccines). Tetanus and diphtheria vaccines are recommended to all adults in 22 and 21 countries respectively. The other vaccines are mostly recommended to specific risk groups; recommendations for seasonal influenza and hepatitis B exist in all surveyed countries. Six countries have a comprehensive summary document or schedule describing all vaccines which are recommended for adults. None of the surveyed countries was able to provide coverage estimates for all the recommended adult vaccines.

Conclusions
Vaccination policies for adults are not consistent across Europe, including the meaning of “recommended vaccine” which is not comparable among countries. Coverage data for adults should be collected routinely like for children vaccination.

Vaccine
Volume 30, Issue 34  pp. 5059-5178 (20 July 2012)
Regular Papers
Perceptions of mumps and MMR vaccination among university students in England: An online survey

Original Research Article
Pages 5081-5085
Diane Bolton-Maggs, David Conrad, Alex Keenan, Ken Lamden, Sam Ghebrehewet, Roberto Vivancos

Abstract
Mumps is easily preventable through vaccination. Investigation of a number of recent mumps outbreaks in universities in the North West of England, however, found that affected students were either not vaccinated or only partially vaccinated. An online survey of students (n = 2456) attending five universities in the region was undertaken during 2010 to establish MMR vaccination status, knowledge of mumps and willingness to take up vaccination if offered. Regression analysis was undertaken to identify characteristics of unimmunized students to ascertain likely target groups for future vaccination campaigns. Students least likely to be fully vaccinated with MMR included males; those not registered with a GP; first year students; mature students; and those with poor knowledge of mumps. A high proportion of students were willing to accept MMR vaccination if offered at university. Those least likely to take up vaccination included students not registered with a GP; mature students; and those who did not consider mumps to be a serious disease. The survey also highlighted that misconceptions remain about both the MMR vaccine safety and perceptions of risk/benefit of the vaccine. Encouraging registration with a GP and awareness raising should be a key part of campaigns to improve vaccination uptake among university students.

Vaccine
Volume 30, Issue 34  pp. 5059-5178 (20 July 2012)
Regular Papers

Immunization coverage and timeliness of vaccination in Italian children with chronic diseases
Original Research Article
Pages 5172-5178
E. Pandolfi, E. Carloni, M.G. Marino, M.L. Ciofi degli Atti, F. Gesualdo, M. Romano, A. Giannattasio, A. Guarino, R. Carloni, P. Borgia, E. Volpe, F. Perrelli, R. Pizzuti, A.E. Tozz

Abstract
Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months–18 years were included in the study. Coverage for diphtheria–tetanus–pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles–mumps–rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.

Twitter Watch [accessed 21 July 2012 – 18:23]
Items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and is by no means intended to be exhaustive.
Editor’s Note: Despite expanding the number of institutions and individuals we follow on twitter – all broadly active in the global pubic health space – we are finding fewer and fewer tweets of substance…. We will likely step away from TwitterWatch soon unless we see a change in this assessment…

joinRED ‏@joinRED
We’re excited: With the #HIV travel ban lifted the Int’l AIDS Conference is happening in the US for 1st time in over two decades. #AIDS2012
Retweeted by Gates Foundation
1:02 PM – 20 Jul 12

UNICEF ‏@UNICEF
#WHO and #UNICEF thoughts are with family and friends of community #polio worker Muhammad Ishaq, shot and killed in Karachi on Friday pm.
1:42 PM – 21 Jul 12

IAVI ‏@AIDSvaccine
IAVI 2011 interactive Annual Progress Report is out, highlighting several of our great partners worldwide: http://bit.ly/LAk4E6 #AIDS2012
1:19 PM – 19 Jul 12

The Guardian
http://www.guardiannews.com/
Accessed 21 July 2012

Comment
To deny schoolgirls a cervical cancer jab on religious grounds is scandalous
It’s absurd for schools to opt out because of ‘Christian values’. Policing girls’ bodies to satisfy outdated ideals puts lives at risk
Reni Eddo-Lodge
Thursday 19 July 2012 05.19 EDT

Extract
There’s something unique about women’s health initiatives that seems to incite moral panic. Last week’s 2012 London Summit on Family Planning discussed in detail the perceived and continued controversy around access to contraceptives for women in developing countries. But with issues such as reproductive rights and reproductive health, it’s always worth analysing affairs closer to home. Just yesterday it was revealed that a number of religious schools in the UK chose to opt out of providing female pupils the HPV vaccine – an immunisation that the World Health Organisation recommends young women receive to prevent cervical cancers…

Editor’s Notes:

– Email Summary: Vaccines: The Week in Review is available as a weekly email summary: 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_14 July 2012

– Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.

– 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…

[Editor’s Note: Last week we provided the full text of a GAR update: Undiagnosed illness in Cambodia – update 6 July 2012  http://www.who.int/csr/don/2012_07_06a/en/index.html
The following announcement concludes the joint investigation undertaken:

Severe complications of hand, foot and mouth disease (HFMD) caused by EV-71 in Cambodia – conclusion of the joint investigation
Extract from announcement
13 July 2012 – The investigation into the illnesses and deaths in Cambodia, which mainly affected very young children, concluded that a severe form of hand, foot and mouth disease (HFMD) was the cause in the majority of cases reported to the Ministry of Health.
Samples from a total of 31 patients were obtained and tested for a number of pathogens by Institut Pasteur du Cambodge. Most of these samples tested positive for enterovirus 71 (EV-71) which causes HFMD. A small proportion of samples also tested positive for other pathogens including Haemophilus Influenzae type B and Streptococcus suis. It was not possible to test all the patients as some of them died before appropriate samples could be taken.

The investigation included:
– a thorough review of the hospital records of the patients from Kantha Bhopa hospital as well as from other hospitals;
– laboratory tests;
– active follow-up with the affected families by the local Rapid Response Teams (RRT); and
– evaluation of the data from the national surveillance system…
http://www.who.int/csr/don/2012_07_13/en/index.html

The Democratic People’s Republic of Korea launched the pentavalent vaccine at a ceremony at the People Palace of Culture in Pyongyang on 12 July 2012. This vaccine introduction “will mean that now around 350,000 children under one will be vaccinated every year against Hib” in addition to other diseases. The DPR Korea “will continue to co-finance the cost of GAVI vaccines at US$834,000 from 2012 to 2015.” GAVI said that, working closely with WHO and UNICEF which have staff in the country, it has supported DPR Korea since 2001 and “has helped the country strengthen its immunisation systems, including a major upgrade of the cold chain system to ensure sufficient space for introduction of pentavalent and potentially other new vaccines such as rotavirus and pneumococcal…” The announcement noted that “DPR Korea is one of the few countries in the WHO South-East Asia Region to achieve consistently high coverage for vaccines. There have been no reported cases of poliomyelitis since 1996 and no measles since the mass vaccination campaign in April 2007.” http://www.gavialliance.org/library/news/gavi-features/2012/dpr-korea-introduces-pentavalent-vaccine/

   The World Bank’s Board approved an International Development Association (IDA) credit of US$95 million for the Nigeria Polio Eradication Support Project, which will “help the country to achieve and sustain at least 80% polio immunization across all states, supporting the eventual eradication of the disease from Nigeria.” The project will finance roughly 655 million doses of oral polio vaccine for children under age five across Nigeria, with a special focus on the northern states where polio is more prevalent. The World Bank has worked with Nigeria’s National Primary Health Care Agency since 2003 to ensure timely vaccine supply. The project continues a “buy-down” arrangement by which the Gates Foundation, the US Centers for Diseases Control and Prevention, and Rotary International (via the UN Foundation), will repay the loan’s present value when pre-agreed results are met. Of the World Bank’s lending commitments to Nigeria for polio from 2003 to 2012—a total of $195 million—Nigeria has already qualified for a 70 percent buy-down.

http://web.worldbank.org/WBSITE/EXTERNAL/NEWS/0,,contentMDK:23240730~pagePK:34370~piPK:34424~theSitePK:4607,00.html

    NIH said it awarded US$31 million in first-year funding to Duke University and Scripps Research Institute to lead a new consortium: the Centers for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI-ID). The funding is from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The initiative is projected to receive up to US$186 million or more over the next six years with a goal “to accelerate HIV vaccine development by supporting multidisciplinary research into immune responses that prevent or contain HIV infection and generating model vaccine components that can induce these protective immune responses.” CHAVI-ID is described as a consortium of researchers at universities and academic medical centers which will build on advances made in several laboratories, including the Center for HIV/AIDS Vaccine Immunology (CHAVI) based at Duke. CHAVI’s seven-year funding award from NIAID ended in June. NIAID Director Anthony S. Fauci, M.D. commented, “In recent years, considerable progress has been made in identifying antibodies that can prevent a broad range of HIV strains from infecting human cells. CHAVI-ID will attempt to understand how those antibodies and other immune responses work to protect against HIV infection, providing scientists with a rational foundation for designing what we hope will be an effective HIV vaccine.”

More at: http://www.nih.gov/news/health/jul2012/niaid-13.htm

Conference: The International AIDS Conference
22-27 July 2012; Washington DC

Overview
“The International AIDS Conference is the premier gathering for those working in the field of HIV, as well as policy makers, persons living with HIV and other individuals committed to ending the pandemic. It is a chance to assess where we are, evaluate recent scientific developments and lessons learnt, and collectively chart a course forward.
“The AIDS 2012 programme will present new scientific knowledge and offer many opportunities for structured dialogue on the major issues facing the global response to HIV. A variety of session types – from abstract-driven presentations to symposia, bridging and plenary sessions – will meet the needs of various participants. Other related activities, including the Global Village, satellite meetings, exhibitions and affiliated independent events, will contribute to an exceptional opportunity for professional development and networking.”
http://www.aids2012.org/Default.aspx?pageId=305

The Global Fund released an analysis of audits and investigations by its Office of the Inspector General which showed “that 3.0 percent of funding audited or investigated between 2005 and 2012 had been misspent, fraudulently misappropriated or inadequately accounted for.” Cees Klumper, Chief Risk Officer at the Global Fund who conducted the analysis, said, “We do not tolerate any misuse of funds, no matter how minor. Although some of these funds were misspent, and are just ineligible expenses, a small percentage of funds are misappropriated through fraud. We actively pursue and expose all such cases.” The Office of the Inspector General is “fully independent and reports directly to the Board” and, since it was established in 2005, has compiled 28 reports on audits and investigations that it has carried out in 27 countries, where a total of $3.8 billion has been disbursed, approximately 23 percent of all disbursements that the Global Fund has made to date.

The analysis showed that, cumulatively, the 3 percent of the funding that not spent in compliance with the grant agreements included:

– Ineligible expenses – or activities not covered by the grant agreements – 1.1 percent

– Inadequately substantiated due to poor or missing documentation – 1.1 percent

– Fraud – 0.5 percent

– Failed to report funds as required – 0.3 percent

The Global Fund noted that the analysis “…did not represent a comprehensive accounting of all misspent funds. Instead, the analysis is a factual rendering of the percentages of funding that had been determined by Global Fund audits and investigations to be ineligible, fraudulently misappropriated or inadequately accounted for.” Further, the release “cautioned that audits and investigations conducted…tend to focus on high-risk areas and on grants where specific risks have been identified, and that it was “…not possible to extrapolate to say that this reflects an accurate picture of misused funds…Our audits and investigations are not a representative sampling of all Global Fund grants.”

http://www.theglobalfund.org/en/mediacenter/newsreleases/2012-07-10_Global_Fund_Releases_an_Analysis_of_Audits_and_Investigations_2012/

The London Summit on Family Planning, co-hosted by the UK Government’s Department for International Development and the Bill & Melinda Gates Foundation, was held in London last week, resulting in a “new set of commitments…by more than 150 leaders from donor and developing countries, international agencies, civil society, foundations and the private sector…(to extend” voluntary family planning services to reach an additional 120 million women and girls in the world’s poorest countries by 2020.”

http://www.gatesfoundation.org/press-releases/Pages/summit-women-global-health-120711.aspx

WHO: Questions and answers on new facts and figures on vaccines and the global mercury treaty

[Initial question from document]
Q. Are there new data on the human health impact of thiomersal in vaccines?
A. Yes, an independent scientific advisory body convened by WHO, the Global Advisory Committee on Vaccine Safety (GACVS), reviewed the latest data on 7 June 2012. The report of the meeting will be published in the WHO Weekly Epidemiological Record on 20 July 2012 (http://www.who.int/wer/2012/en/ ). The Committee concluded that numerous well–‐designed Epidemiological studies conducted in many countries have failed to find a causal relationship Between prenatal, neonatal, or postnatal exposures to thiomersal in vaccines and a host of Neuropsychological outcomes, including autism.

The small number of studies which had suggested an association had significant flaws in their design and underlying assumptions, thus invalidating their conclusions. Other studies conducted Since 2008, including analysis of mercury in blood and hair, provided confirmation that the half –‐ life of thiomersal (ethyl mercury) was much shorter than that of methyl mercury.
Document pdf: http://www.who.int/entity/immunization/newsroom/QAs_new_facts_figures_thiomersal_June_2012.pdf

Guidelines on regulatory expectations related to the elimination, reduction or replace of thiomersal in vaccines (2004)
http://www.who.int/entity/biologicals/publications/trs/areas/vaccines/thiomersal/Annex%204%20(95-102)TRS926thiomersal.pdf

 
INC4: The fourth session of the Intergovernmental Negotiating Committee to prepare a global legally binding instrument on Mercury (INC4) was held in Punta del Este, Uruguay, from 27 June to 2 July 2012.
http://www.unep.org/hazardoussubstances/Mercury/Negotiations/INC4/tabid/3470/Default.aspx

WHO Fact Sheet: Vaccine success story: congenital rubella syndrome
13 July 2012 — A newly released WHO fact sheet explains how vaccination has drastically reduced congenital rubella syndrome and describes the global strategy to achieve elimination. An estimated 110 000 babies are born with congenital rubella syndrome every year. While the illness is generally mild in children, it has serious consequences in pregnant women causing fetal death or congenital defects.

Read the rubella fact sheet

Read the Global Measles and Rubella Strategic Plan

WHO: GIN – Global Immunization News   30 June 2012
http://www.who.int/entity/immunization/GIN_June_2012.pdf

This issue includes:
SUMMARY TABLES OF WHO ROUTINE IMMUNIZATION RECOMMENDATIONS
The Summary Tables of WHO Routine Immunization Recommendations have been updated as of May 31, 2012 to reflect:
– The new WHO Vaccine Position Paper on Pneumococcal vaccines (published in the WHO Weekly epidemiological record (WER) 6 April 2012); and
– The lifting of the age restrictions for Rotavirus vaccines recommended by SAGE at their April 2012 Meeting (See SAGE Meeting Report in WER 25 May 2012)
– The revised version of the Summary Tables can be downloaded from the WHO website and are also available in French (Note: French version of Table 3 will be available soon).
The Summary Tables are intended for use by national immunization managers and key decision-makers, chairs and members of national advisory committees on immunization, and partner organizations, including industry.
http://www.who.int/immunization/policy/immunization_tables/en/index.html

GLOBAL VACCINE SAFETY BLUEPRINT (WHO/IVB/12.07)
This IVB document is now online. The Global Vaccine Safety Blueprint is a WHO strategic document that proposes new approaches to a consortium for strengthening vaccine pharmacovigilance systems in low-and middle-income countries.
http://extranet.who.int/iris/restricted/bitstream/10665/70919/1/WHO_IVB_12.07_eng.pdf

The Weekly Epidemiological Record (WER) for 13 July 2012, vol. 87, 28/29 (pp 261–276) includes: WHO position paper on hepatitis A vaccines – June 2012
http://www.who.int/entity/wer/2012/wer8728_29.pdf

WHO: Hepatitis A vaccination should be part of a comprehensive plan for prevention and control of viral hepatitis
Media Release Extract
13 July 2012 – In an updated position paper, published in the Weekly Epidemiological Record today, WHO recommends that hepatitis A vaccination be integrated into national immunization schedule for children over the age of one, if indicated on the basis of acute hepatitis A incidence and consideration of cost-effectiveness.

Vaccination should particularly be considered in countries with improving socioeconomic status when there is a change from high to intermediate endemicity and when the age of infection shifts to older age group thus increasing the risk of more severe disease and mortality. In these situations vaccination is likely to be cost-effective.    In highly endemic countries where hepatitis A virus is widespread, almost all persons are infected with hepatitis A virus in early childhood, when the infection is asymptomatic or results in very mild disease. In these countries, large-scale vaccination programmes are not recommended.

Vaccination against hepatitis A should be part of a comprehensive plan for the prevention and control of viral hepatitis, including measures to improve hygiene and sanitation and measures for outbreak control. Targeted vaccination of high-risk groups should be considered in low and very low endemicity settings to provide individual health benefits. Groups at increased risk of hepatitis A include travellers to areas of intermediate or high endemicity, those requiring life-long treatment with blood products, men who have sex with men, workers in contact with non-human primates, and injection drug users. In addition, patients with chronic liver disease are at increased risk for fulminant hepatitis A and should be vaccinated…

More at: http://www.who.int/immunization/newsroom/newsstory_hepa_vaccine_control_viral_hepatitis/en/index.html

Twitter Watch [accessed 14 July 2012 – 13:42]
Items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and is by no means intended to be exhaustive.

GAVI Alliance ‏@GAVIAlliance
There is still plenty of time to give feedback on @GAVIAlliance country by country approach. Share your thoughts! http://ht.ly/ceIJq
6:49 AM – 14 Jul 12

World Bank ‏@WorldBank
News: World Bank to support Nigeria’s final push to eradicate #polio http://bit.ly/NhTnEI
4:51 PM – 13 Jul 12

IVAC at JHSPH ‏@IVACtweets
Did you know scientists discovered Streptococcus pneumoniae bacterium 131 years ago? Find out what’s happened since: http://bit.ly/NeFEwl
Retweeted by History of Vaccines
2:37 PM – 12 Jul 12

IVAC at JHSPH @IVACtweets
New! @HuffingtonPost blog from @OrinLevine. 4 ways that investment bankers can help developing countries http://huff.to/PPU21h #FPSummit
4:50 PM – 12 Jul 12

CDC Global Health ‏@CDCGlobal
With CDC help, Burkina Faso has vaccinated 17M kids for #polio, 2.4M kids for #measles & >12M ppl for #meningitis. http://go.usa.gov/w8X
Retweeted by M&R Initiative
1:54 PM – 11 Jul 12

IAVI @AIDSvaccine
IAVI congratulates @ScrippsResearch @Duke_Medicine on award of @NIAIDnews grants to support #HIV #vaccine R&D http://bit.ly/Mj870D #AIDS2012
2:58 PM – 11 Jul 12

Amanda Glassman @glassmanamanda
HHA declaration on value for money, accountability and sustainability in health in Africa – music to my ears… http://www.hha-online.org/hso/system/files/tunis_declaration_english_july6.pdf
10:52 AM – 10 Jul 12

NIH Research: Vaccine and antibiotics stabilized so refrigeration is not needed

Extract from media release
Researchers funded by the National Institutes of Health have developed a new silk-based stabilizer that, in the laboratory, kept some vaccines and antibiotics stable up to temperatures of 140 degrees Fahrenheit. This provides a new avenue toward eliminating the need to keep some vaccines and antibiotics refrigerated, which could save billions of dollars every year and increase accessibility to third world populations.

Vaccines and antibiotics often need to be refrigerated to prevent alteration of their chemical structures; such alteration can result in less potent or ineffective medications. By immobilizing their bioactive molecules using silk protein matrices, researchers were able to protect and stabilize both live vaccines and antibiotics when stored at higher than recommended temperatures for periods far longer than recommended.

The research was led by grantees of NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), David Kaplan, Ph.D., and Jeney Zhang, Ph.D. candidate, at Tufts University School of Engineering in Medford, Mass. The National Eye Institute and the National Institute of Dental and Craniofacial Research at NIH also contributed to this research. The researchers reported on their findings in the online issue of Proceedings of the National Academy of Sciences on July 9, 2012.

“This truly exciting development is the culmination of years of creative exploration and research focused on a major problem in the delivery of health care. Dr. Kaplan and his team have done a masterful job at both understanding the key properties of silk, and applying these insights to a global medical challenge,” said NIBIB Director Roderic I. Pettigrew, Ph.D., M.D. “This is also a wonderful validation of the type of team science we see in our Biotechnology Resource and Development Centers and their ability to combine cutting edge science in a number of fields to a variety of health needs.”

Pettigrew also points out that the next step is to test it in the field.

http://www.nih.gov/news/health/jul2012/nibib-09.htm

[See PNAS citation in Journal Watch below]

Report: HIV and the Law: Risks, Rights & Health
Global Commission on HIV and the Law (UNDP)
09 July 2012
“The final report presents a coherent and compelling evidence base on human rights and legal issues relating to HIV.”
http://www.undp.org/content/undp/en/home/librarypage/hiv-aids/hiv-and-the-law–risks–rights—health.html

Report pdf:
http://www.undp.org/content/dam/undp/library/HIV-AIDS/Governance%20of%20HIV%20Responses/FinalReport-Risks,Rights&Health-EN.pdf

Report: Horizon 2025: creative destruction in the aid industry
Homi Kharas and Andrew Rogerson
ODI (Overseas Development Institute)
July 2012

This paper aims to stimulate debate on the future of the international development architecture and explores how far some of today’s major development agencies are likely to be exposed to the resulting pressures to change course, emulate the disruptors or face irrelevance.

Summary [full text]
The global economic landscape has evolved dramatically since 2000: developing and emerging economies have been driving global growth, new sources of development finance have mushroomed and the diversification of actors, instruments and delivery mechanisms has continued. Transformations in the poverty map and new forces on the supply side of development finance are challenging the international development architecture. This paper aims to stimulate debate on the future of this architecture.
The authors project that, by 2025, the locus of global poverty will overwhelmingly be in fragile, mainly low-income and African, states, contrary to current policy preoccupations with the transitory phenomenon of poverty concentration in middle-income countries. Moreover, a smaller share of industrialised country income than ever before will potentially close the remaining global poverty gap, although direct income transfers are not yet feasible in many fragile country contexts.
Against this backdrop, new institutions, business models and practices are challenging long-established ‘aid industry’ actors. Agencies providing development finance for improved social welfare, for mutual self-interest in growth and trade and for the provision of global public goods will find that, in each area, disruptors to their programmes may force a change in positioning.
The paper focuses on one such disruptor for each of these three complementary rationales for development cooperation. The key disruptor we discuss in the first area is high-impact philanthropy and non-governmental giving channels; in the second, South–South cooperation combining trade and finance, and blended public–private funding in general; and in the third, the power of climate change finance, particularly its quite different country and project allocation logic.
From this analysis, this paper explores how far some of today’s major development agencies are likely to be exposed to the resulting pressures to change course, emulate the disruptors or face irrelevance.
The authors construct an index of vulnerability, presented in a traffic-light ranking, based on recent shares of each agency’s operations going to, first, middle-income and low poverty gap countries and, second, purposes linked respectively to social welfare, growth and global public goods, with appropriate weights.
These assessments are offered not as predictions but as possible stress test tools for further, context-specific analysis. The paper ends with questions for further research.

British Medical Journal
14 July 2012 (Vol 345, Issue 7865)
http://www.bmj.com/content/345/7865

Analysis
Problems of stopping trials early
BMJ 2012; 344 doi: 10.1136/bmj.e3863 (Published 15 June 2012
Gordon H Guyatt, Matthias Briel, Paul Glasziou, Dirk Bassler, Victor M Montori,

Extract
When interim analyses of randomised trials suggest large beneficial treatment effects, investigators sometimes terminate trials earlier than planned. Gordon H Guyatt and colleagues show how this practice can have far reaching and harmful consequences

In a seminal simulation study published in 1989, Pocock and Hughes showed that randomised control trials stopped early for benefit will, on average, overestimate treatment effects.1 Since then, the warning implicit in this simulation study has been largely ignored.

Fifteen years later, we reported a systematic survey which showed that trials stopped early for benefit—which we will refer to as truncated trials—yield treatment effects that are often not credible (relative risk reductions over 47% in half, over 70% in a quarter), and that the apparent overestimates were larger in smaller trials.2 We subsequently compared effect estimates from all the truncated trials we could identify that had been included in systematic reviews and meta-analyses with the results of non-truncated trials in those same meta-analyses. We found, on average, substantially larger effects in the truncated trials (ratio of relative risks in truncated versus non-truncated of 0.71). Again, we showed an association with the size of the truncated trial: large overestimates were common when the total number of events was less than 200; smaller but important overestimates occurred with 200 to 500 events; and trials with over 500 events showed small overestimates.3

The results of simulation studies and systematic surveys of truncated trials therefore show that when true underlying treatment effects are modest—as is usually the case—small trials that are stopped early with few events will result in large overestimates. Larger trials will still, on average, overestimate effects, and these overestimates may also lead to important spurious inferences. Uncritical belief in truncated trials will often, therefore, be misleading—and sometimes very misleading.

The tendency for truncated trials …

Globalization and Health
[Accessed 14 July 2012]
http://www.globalizationandhealth.com/

Debate
Models for financing the regulation of pharmaceutical promotion
Joel Lexchin

Abstract (provisional)
Pharmaceutical companies spend huge sums promoting their products whereas regulation of promotional activities is typically underfinanced. Any option for financing the monitoring and regulation of promotion should adhere to three basic principles: stability, predictability and lack of (perverse) ties between the level of financing and performance. This paper explores the strengths and weaknesses of six different models. All these six models considered here have positive and negative features and none may necessarily be ideal in any particular country. Different countries may choose to utilize a combination of two or more of these models in order to raise sufficient revenue. Financing of regulation of drug promotion should more than pay for itself through the prevention of extra unnecessary drug costs and the avoidance of adverse health effects due to inappropriate prescribing. However, it involves an initial outlay of money that is currently not being spent and many national governments, in both rich and poor countries, are unwilling to incur extra costs.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Health Affairs
July 2012; Volume 31, Issue 7
http://content.healthaffairs.org/content/current

Theme: Assessing The President’s Emergency Plan For AIDS Relief
–  From Emergency to Sustainability

–  How Bush Dramatically Expanded US Response

–  Toward An AIDS-Free Generation

–  Building on the Scientific Progress

–  Applying PEPFAR’s Lessons to the US

–  The Global Health Strategy of HHS

–  PEPFAR’s Public and Private Partnerships

– Antiretroviral Drugs: Treatment As Prevention

– Eliminating Mother-to-Child HIV Transmission

–  The “Third Wave” of HIV Prevention

–  A Clinician’s Experience In Nigeria

–  Collaborating With the Global Fund

– View Table of Contents

Health Affairs
July 2012; Volume 31, Issue 7
http://content.healthaffairs.org/content/current
Theme: Assessing The President’s Emergency Plan For AIDS Relief

Given Financial Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention
Ruth Macklin and Ethan Cowan

Abstract
Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies—preexposure prophylaxis and treatment as prevention—use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention.

Health Economics, Policy and Law 
Volume 7 – Issue 03 – July 2012
http://journals.cambridge.org/action/displayIssue?jid=HEP&tab=currentissue

Articles
Incentives, health promotion and equality
Kristin Voigt
Department of Politics, Philosophy & Religion, Lancaster University, Lancaster, UK

Abstract
The use of incentives to encourage individuals to adopt ‘healthier’ behaviours is an increasingly popular instrument in health policy. Much of the literature has been critical of ‘negative’ incentives, often due to concerns about equality; ‘positive’ incentives, however, have largely been welcomed as an instrument for the improvement of population health and possibly the reduction of health inequalities. The aim of this paper is to provide a more systematic assessment of the use of incentives from the perspective of equality. The paper begins with an overview of existing and proposed incentive schemes. I then suggest that the distinction between ‘positive’ and ‘negative’ incentives – or ‘carrots’ and ‘sticks’ – is of limited use in distinguishing those incentive schemes that raise concerns of equality from those that do not. The paper assesses incentive schemes with respect to two important considerations of equality: equality of access and equality of outcomes. While our assessment of incentive schemes will, ultimately, depend on various empirical facts, the paper aims to advance the debate by identifying some of the empirical questions we need to ask. The paper concludes by considering a number of trade-offs and caveats relevant to the assessment of incentive schemes.

JAMA   
July 11, 2012, Vol 308, No. 2
http://jama.ama-assn.org/current.dtl

Viewpoint
The Moral Duty to Buy Health Insurance
Tina Rulli, PhD; Ezekiel J. Emanuel, MD, PhD; David Wendler, PhD

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The 2010 Patient Protection and Affordable Care Act (ACA) was designed to increase health insurance coverage in the United States. Its most controversial feature is the requirement that US residents purchase health insurance or pay a financial penalty.    Although debate focuses on the constitutionality of this individual mandate, the central concern is a moral matter—is it morally appropriate to require individuals to purchase health insurance?

Proponents argue that a mandate could lower insurance premiums for everyone by pooling individuals with varying health risks. Opponents respond that requiring people to contribute to the collective good is inconsistent with respect for individual liberty. Appeal to the collective good could justify requiring individuals to buy gym memberships or eat broccoli.1

Rather than appeal to the collective good, this Viewpoint argues for a duty to buy health insurance based on the moral duty individuals have to reduce certain burdens they pose on others. Because physicians and hospitals have a duty to rescue the uninsured by providing acute and emergency care, individuals have a corresponding duty to purchase insurance to cover the costs of this care. Requiring individuals to meet this obligation is consistent with respect for individual liberty and does not imply that they must buy gym memberships or eat broccoli….

JAMA   
July 11, 2012, Vol 308, No. 2
http://jama.ama-assn.org/current.dtl

Viewpoint | July 11, 2012 ONLINE FIRST
Ending Preventable Child Death in a Generation
Roger I. Glass, MD, PhD; Alan E. Guttmacher, MD; Robert E. Black, MD

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During the past 20 years, there has been a substantial decline in mortality among children younger than 5 years from 12.0 million deaths in 1990 to 7.6 million in 2010.1 In these decades alone, global health and development efforts have saved the lives of more than 50 million children, half of them by preventing deaths due to pneumonia, diarrhea, and measles.2 This improvement in child survival was catalyzed in part by setting aspirational global targets such as the Millennium Development Goals (MDGs).3

As 2015 approaches, and with it a final assessment of progress toward MDG 4 on reducing child mortality, it is appropriate to consider a post-2015 vision for child health.    A new common vision for a global commitment to end all preventable child deaths is needed. Such a vision will not be compelling unless it can be tied to concrete and measurable benchmarks at the global and country levels that are both ambitious and plausible. In this Viewpoint, a new benchmark is detailed: that all countries achieve a national under-5 mortality rate (U5MR) of no more than 20 deaths per 1000 live births by 2035 and that the global average U5MR should decline to 15 deaths per 1000 in 2035. Of 195 countries, 98 already have U5MRs of 20 per 1000 or fewer; 43 countries would be expected to reach this goal by 2035 at current annual rates of reduction (ARRs), and 54 countries would have to accelerate progress above the 2000-2010 ARRs.4

JAMA   
July 11, 2012, Vol 308, No. 2
http://jama.ama-assn.org/current.dtl

Original Contribution | July 11, 2012
Risk of Guillain-Barré Syndrome Following H1N1 Influenza Vaccination in Quebec
Philippe De Wals, PhD; Geneviève Deceuninck, MD; Eveline Toth, MSc; Nicole Boulianne, MSc; Denis Brunet, MD; Renée-Myriam Boucher, MD; Monique Landry, MD; Gaston De Serres, PhD

Abstract
Context  In fall 2009 in Quebec, Canada, an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain, mostly using an AS03 adjuvant vaccine. By the end of the year, 57% of the 7.8 million residents had been vaccinated.

Objective  To assess the risk of Guillain-Barré syndrome (GBS) following pandemic influenza vaccine administration.

Design  Population-based cohort study with follow-up over the 6-month period October 2009 through March 2010. The investigation was ordered by the chief medical officer of health in accordance with the Quebec Public Health Act.

Setting  All acute care hospitals and neurology clinics in Quebec.

Population  Suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Medical records were reviewed and cases classified according to Brighton Collaboration definitions (categorized as level 1, 2, or 3, corresponding to criteria of decreasing certainty in diagnosis). Immunization status was verified and denominators were estimated from the provincial immunization registry (4.4 million vaccinated) and census data (total target population aged ≥6 months, 7.8 million), with a total of 3 623 046 person-years of observation.

Main Outcome Measures  Relative and attributable risks were calculated using a Poisson model and the self-controlled case-series method.

Results  Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

Conclusions  In Quebec, the 2009 influenza A(H1N1) vaccine was associated with a small but significant risk of GBS. It is likely that the benefits of immunization outweigh the risks.

Guillain-Barré syndrome (GBS) is a peripheral neuropathy with acute onset and is characterized, in its typical presentation, by rapidly developing motor weakness and areflexia.1 – 2 The disease is thought to be autoimmune and triggered by a stimulus of external origin.1 – 2 In 1976-1977, an unusually high rate of GBS was identified in the United States following the administration of inactivated “swine” influenza A(H1N1) vaccines.3 In 2003, the Institute of Medicine (IOM) concluded that the evidence favored acceptance of a causal relationship between the 1976 swine influenza vaccines and GBS in adults.4 Studies of seasonal influenza vaccines administered in subsequent years have found small or no increased risk.5 In mice, different influenza vaccines can induce antiganglioside antibodies that are associated with the development of GBS in humans.6 Extrapolation of results of animal studies to humans, however, is difficult. In a more recent assessment of epidemiologic studies on seasonal influenza vaccines, experimental studies in animals, and case reports in humans, the IOM Committee to Review Adverse Effects of Vaccines concluded that the evidence was inadequate to accept or reject a causal relationship.7

In the province of Quebec, Canada, a mass immunization campaign was launched in the fall of 2009 to control a pandemic caused by a new influenza A(H1N1) virus.8 – 9 Herein we report results of a population-based epidemiologic investigation ordered by the chief medical officer of health, based on GBS cases notified to public health authorities and others found in the MEDECHO provincial hospitalization database.

JAMA   
July 11, 2012, Vol 308, No. 2
http://jama.ama-assn.org/current.dtl

Editorial | July 11, 2012
Influenza Pandemics—Pregnancy, Pathogenesis, and Perinatal Outcomes
Mark C. Steinhoff, MD; Noni E. MacDonald, MD, MSc, FRCPC

Extract [Free full text]
Since the 1918 influenza pandemic, it has been clear that pandemic influenza is associated with increased morbidity and mortality in pregnancy, and more recent studies have shown that nonpandemic seasonal influenza strains also lead to morbidity for pregnant women and their infants.1 In the 2009 worldwide pandemic of influenza A(H1N1)pdm09, pregnant women were at high risk for severe complications, including death and intensive care unit admission.2

The adverse effects of antenatal influenza infection on pregnant women and their infants suggest a biological effect of influenza infection in the mother that compromises the fetus. These effects are rarely associated with direct infection of the fetus with influenza virus, although fetal infection has been reported infrequently during epidemics, pandemics,3 – 4 and with the H5N1 influenza strain.5 Instead, it appears that the normal pregnancy-associated immunologic changes may inhibit the inflammatory response to influenza virus infection in pregnancy,6 leading to increased risks to mother and infant. Because of these observations, pregnant women have been listed among high-risk groups for seasonal influenza vaccine in the United States since 1997, and safety data suggest these vaccines are safe in pregnancy.7 – 8 Pregnant women were prioritized for immunization during the 2009 influenza A(H1N1)pdm09 pandemic, despite limited data on the safety of pandemic influenza vaccines in pregnancy.

In this issue of JAMA, Pasternak and colleagues9 report the results of an observational cohort study on the safety in pregnancy of the monovalent inactivated ASO3-adjuvanted split virion influenza A(H1N1)pdm09 vaccine…

JAMA   
July 11, 2012, Vol 308, No. 2
http://jama.ama-assn.org/current.dtl

Original Contribution | July 11, 2012
Risk of Adverse Fetal Outcomes Following Administration of a Pandemic Influenza A(H1N1) Vaccine During Pregnancy
Björn Pasternak, MD, PhD; Henrik Svanström, MSc; Ditte Mølgaard-Nielsen, MSc; Tyra G. Krause, MD, PhD; Hanne-Dorthe Emborg, DVM; Mads Melbye, MD, DrMedSci; Anders Hviid, MSc, DrMedSci

Abstract
Context  Assessment of the fetal safety of vaccination against influenza A(H1N1)pdm09 in pregnancy has been limited.

Objective  To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes.

Design, Setting, and Participants  Registry-based cohort study based on all liveborn singleton infants in Denmark, delivered between November 2, 2009, and September 30, 2010. In propensity score–matched analyses, we estimated prevalence odds ratios (PORs) of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy.

Main Outcome Measures  Major birth defects, preterm birth, and small size for gestational age.

Results  From a cohort of 53,432 infants (6989 [13.1%] exposed to the influenza A[H1N1]pdm09 vaccine during pregnancy [345 in the first trimester and 6644 in the second or third trimester]), 660 (330 exposed) were included in propensity score–matched analyses of adverse fetal outcomes associated with first-trimester exposure. For analysis of small size for gestational age after second- or third-trimester exposure, 13 284 (6642 exposed) were included; for analyses of preterm birth, 12,909 (6543 exposed) were included. A major birth defect was diagnosed in 18 of 330 infants (5.5%) exposed to the vaccine in the first trimester, compared with 15 of 330 unexposed infants (4.5%) (POR, 1.21; 95% CI, 0.60-2.45). Preterm birth occurred in 31 of 330 infants (9.4%) exposed in the first trimester, compared with 24 of 330 unexposed infants (7.3%) (POR, 1.32; 95% CI, 0.76-2.31), and in 302 of 6543 infants (4.6%) with second- or third-trimester exposure, compared with 295 of 6366 unexposed infants (4.6%) (POR, 1.00; 95% CI, 0.84-1.17). Small size for gestational age was observed in 25 of 330 infants (7.6%) with first-trimester exposure compared with 31 of 330 unexposed infants (9.4%) (POR, 0.79; 95% CI, 0.46-1.37), and in 641 of 6642 infants (9.7%) with second- or third-trimester exposure, compared with 657 of 6642 unexposed infants (9.9%) (POR, 0.97; 95% CI, 0.87-1.09).

Conclusions  In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction.