New England Journal of Medicine
March 30, 2017  Vol. 376 No. 13
http://www.nejm.org/toc/nejm/medical-journal

Editorial
Ensuring Vaccine Safety in Pregnant Women
Kathryn M. Edwards, M.D.
N Engl J Med 2017; 376:1280-1282 March 30, 2017 DOI: 10.1056/NEJMe1701337
[Initial text]
In this issue of the Journal, investigators from Denmark present a comprehensive review of the adverse pregnancy outcomes encountered in women who received quadrivalent human papillomavirus (HPV) vaccine during pregnancy, as compared with those who did not.1 The investigators assembled data on all the pregnancies in Denmark that occurred within a 7-year period, and they used nationwide registries to identify the dates of pregnancy, pregnancy outcomes, and maternal characteristics, including receipt of HPV vaccine and dates of vaccine administration. Vaccinated women and unvaccinated women were propensity-score matched in a 1:4 ratio, and pregnancy outcomes were compared.

Pediatrics
April 2017, VOLUME 139 / ISSUE 4
http://pediatrics.aappublications.org/content/139/3?current-issue=y

Articles
Bacteremia in Children 3 to 36 Months Old After Introduction of Conjugated Pneumococcal Vaccines
Tara L. Greenhow, Yun-Yi Hung, Arnd Herz
Pediatrics Apr 2017, 139 (4) e20162098; DOI: 10.1542/peds.2016-2098

Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood
Monica Nayakwadi Singer, Claire Heath, Jackson Muinde, Virginia Gildengorin, Francis M. Mutuku, David Vu, Dunstan Mukoko, Christopher L. King, Indu J. Malhotra, Charles H. King, A. Desirée LaBeaud
Pediatrics Apr 2017, 139 (4) e20162781; DOI: 10.1542/peds.2016-2781

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
[Accessed 1 April 2017]

Research Article
Spatial Determinants of Ebola Virus Disease Risk for the West African Epidemic
March 31, 2017 ·
Introduction: Although many studies have investigated the probability of Ebola virus disease (EVD) outbreaks while other studies have simulated the size and speed of EVD outbreaks, few have investigated the environmental and population-level predictors of Ebola transmission once an outbreak is underway. Identifying strong predictors of transmission could help guide and target limited public health resources during an EVD outbreak. We examined several environmental and population-level demographic predictors of EVD risk from the West African epidemic. Methods: We obtained district-level estimates from the World Health Organization EVD case data, demographic indicators obtained from the Demographic and Health surveys, and satellite-derived temperature, rainfall, and land cover estimates. A Bayesian hierarchical Poisson model was used to estimate EVD risk and to evaluate the spatial variability explained by the selected predictors. Results: We found that districts had greater risk of EVD with increasing proportion of households not possessing a radio (RR 2.79, 0.90-8.78; RR 4.23, 1.16-15.93), increasing rainfall (RR 2.18; 0.66-7.20; 5.34, 1.20-23.90), and urban land cover (RR 4.87, 1.56-15.40; RR 5.74, 1.68-19.67). Discussion: The finding of radio ownership and reduced EVD transmission risk suggests that the use of radio messaging for control and prevention purposes may have been crucial in reducing the EVD transmission risk in certain districts, although this association requires further study. Future research should examine the etiologic relationships between the identified risk factors and human-to-human transmission of EVD with a focus on factors related to population mobility and healthcare accessibility, which are critical features of epidemic propagation and control.

PLoS One
http://www.plosone.org/
[Accessed 1 April 2017]

Research Article
The role of intervention mapping in designing disease prevention interventions: A systematic review of the literature
Rayyan M. Garba, Muktar A. Gadanya
Research Article | published 30 Mar 2017 PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0174438
Abstract
Objective
To assess the role of Intervention Mapping (IM) in designing disease prevention interventions worldwide.
Methods
Systematic search and review of the relevant literature—peer-reviewed and grey—was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.
Findings
Only five of the twenty two included studies reviewed were RCTs that compared intervention using IM protocol with placebo intervention, and provided the outcomes in terms of percentage increase in the uptake of disease-prevention programmes, and only one of the five studies provided an effect measure in the form of relative risk (RR=1.59, 95% CI=1.08–2.34, p=0.02). Of the five RCTs, three were rated as strong evidences, one as a medium evidence and one as a weak evidence, and they all reported statistically significant difference between the two study groups, with disease prevention interventions that have used the intervention mapping approach generally reported significant increases in the uptake of disease-prevention interventions, ranging from 9% to 28.5% (0.0001 ≤ p ≤ 0.02), On the other hand, all the 22 studies have successfully identified the determinants of the uptake of disease prevention interventions that is essential to the success of disease prevention programmes.
Conclusion
Intervention Mapping has been successfully used to plan, implement and evaluate interventions that showed significant increase in uptake of disease prevention programmes. This study has provided a good understanding of the role of intervention mapping in designing disease prevention interventions, and a good foundation upon which subsequent reviews can be guided.

PNAS – Proceedings of the National Academy of Sciences of the United States
of America
http://www.pnas.org/content/early/
[Accessed 1 April 2017]

Biological Sciences – Population Biology:
Comparing nonpharmaceutical interventions for containing emerging epidemics
Corey M. Peak, Lauren M. Childs, Yonatan H. Grad, and Caroline O. Buckee
PNAS 2017 ; published ahead of print March 28, 2017, doi:10.1073/pnas.1616438114
Significance
Quarantine and symptom monitoring of contacts with suspected exposure to an infectious disease are key interventions for the control of emerging epidemics; however, there does not yet exist a quantitative framework for comparing the control performance of each intervention. Here, we use a mathematical model of seven case-study diseases to show how the choice of intervention is influenced by the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. We use this information to identify the most important characteristics of the disease and setting that need to be considered for an emerging pathogen to make an informed decision between quarantine and symptom monitoring.
Abstract
Strategies for containing an emerging infectious disease outbreak must be nonpharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these nonpharmaceutical strategies will depend on not only the effectiveness of isolation measures but also the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen. Here, we compare the effectiveness of quarantine and symptom monitoring, implemented via contact tracing, in controlling epidemics using an agent-based branching model. We examine the relationship between epidemic containment and the disease dynamics of symptoms and infectiousness for seven case-study diseases with diverse natural histories, including Ebola, influenza A, and severe acute respiratory syndrome (SARS). We show that the comparative effectiveness of symptom monitoring and quarantine depends critically on the natural history of the infectious disease, its inherent transmissibility, and the intervention feasibility in the particular healthcare setting. The benefit of quarantine over symptom monitoring is generally maximized for fast-course diseases, but we show the conditions under which symptom monitoring alone can control certain outbreaks. This quantitative framework can guide policymakers on how best to use nonpharmaceutical interventions and prioritize research during an outbreak of an emerging pathogen.

PNAS – Proceedings of the National Academy of Sciences of the United States
of America
http://www.pnas.org/content/early/
[Accessed 1 April 2017]

Biological Sciences – Medical Sciences:
Meta-assessment of bias in science
Daniele Fanelli, Rodrigo Costas, and John P. A. Ioannidis
PNAS 2017 ; published ahead of print March 20, 2017, doi:10.1073/pnas.1618569114
Significance
Science is said to be suffering a reproducibility crisis caused by many biases. How common are these problems, across the wide diversity of research fields? We probed for multiple bias-related patterns in a large random sample of meta-analyses taken from all disciplines. The magnitude of these biases varied widely across fields and was on average relatively small. However, we consistently observed that small, early, highly cited studies published in peer-reviewed journals were likely to overestimate effects. We found little evidence that these biases were related to scientific productivity, and we found no difference between biases in male and female researchers. However, a scientist’s early-career status, isolation, and lack of scientific integrity might be significant risk factors for producing unreliable results.
Abstract
Numerous biases are believed to affect the scientific literature, but their actual prevalence across disciplines is unknown. To gain a comprehensive picture of the potential imprint of bias in science, we probed for the most commonly postulated bias-related patterns and risk factors, in a large random sample of meta-analyses taken from all disciplines. The magnitude of these biases varied widely across fields and was overall relatively small. However, we consistently observed a significant risk of small, early, and highly cited studies to overestimate effects and of studies not published in peer-reviewed journals to underestimate them. We also found at least partial confirmation of previous evidence suggesting that US studies and early studies might report more extreme effects, although these effects were smaller and more heterogeneously distributed across meta-analyses and disciplines. Authors publishing at high rates and receiving many citations were, overall, not at greater risk of bias. However, effect sizes were likely to be overestimated by early-career researchers, those working in small or long-distance collaborations, and those responsible for scientific misconduct, supporting hypotheses that connect bias to situational factors, lack of mutual control, and individual integrity. Some of these patterns and risk factors might have modestly increased in intensity over time, particularly in the social sciences. Our findings suggest that, besides one being routinely cautious that published small, highly-cited, and earlier studies may yield inflated results, the feasibility and costs of interventions to attenuate biases in the literature might need to be discussed on a discipline-specific and topic-specific basis.

Science Translational Medicine
29 March 2017 Vol 9, Issue 383
http://stm.sciencemag.org/

Research Articles
Using geospatial mapping to design HIV elimination strategies for sub-Saharan Africa
By Brian J. Coburn, Justin T. Okano, Sally Blower
Science Translational Medicine29 Mar 2017 Restricted Access
Mapping the geographic dispersion pattern of HIV-infected individuals in a sub-Saharan African country reveals the challenge to eliminating HIV.
Mapping a path to HIV elimination
About ~25 million individuals in sub-Saharan Africa are living with HIV. In new work, Coburn et al. design HIV elimination strategies for this region. The authors focused on Lesotho, where ~25% of the population is infected with HIV. They combined several large data sets and constructed a map that revealed the countrywide geographic dispersion pattern of HIV-infected individuals. They estimated that ~20% of the population lives in urban areas, and almost all rural communities have at least one HIV-infected individual. Their analyses showed that the spatial dispersion of Lesotho’s population hinders, and may even prevent, the elimination of HIV. This may hold true for other predominantly rural countries in sub-Saharan Africa.
Abstract
Treatment as prevention (TasP) has been proposed by the World Health Organization and the Joint United Nations Programme on HIV/AIDS (UNAIDS) as a global strategy for eliminating HIV. The rationale is that treating individuals reduces their infectivity. We present a geostatistical framework for designing TasP-based HIV elimination strategies in sub-Saharan Africa. We focused on Lesotho, where ~25% of the population is infected. We constructed a density of infection map by gridding high-resolution demographic data and spatially smoothing georeferenced HIV testing data. The map revealed the countrywide geographic dispersion pattern of HIV-infected individuals. We found that ~20% of the HIV-infected population lives in urban areas and that almost all rural communities have at least one HIV-infected individual. We used the map to design an optimal elimination strategy and identified which communities should use TasP. This strategy minimized the area that needed to be covered to find and treat HIV-infected individuals. We show that UNAIDS’s elimination strategy would not be feasible in Lesotho because it would require deploying treatment in areas where there are ~4 infected individuals/km2. Our results show that the spatial dispersion of Lesotho’s population hinders, and may even prevent, the elimination of HIV.

Science Translational Medicine
29 March 2017 Vol 9, Issue 383
http://stm.sciencemag.org/

Report
Estimation of polio infection prevalence from environmental surveillance data
By Yakir Berchenko, Yossi Manor, Laurence S. Freedman, Ehud Kaliner, Itamar Grotto, Ella Mendelson, Amit Huppert
Science Translational Medicine29 Mar 2017 Restricted Access
Close monitoring of virus shed into sewage systems allows quantitative surveillance of a polio outbreak
Keeping an eye on polio
As the eyes are a mirror of the soul, a city’s sewage is a reflection of its people’s health. Berchenko et al. take advantage of a natural experiment in southern Israel to quantify this relationship for polio. By measuring virus shed into sewage waste in cities in which a known number of people received a live polio vaccine, the authors created tools that can be used to monitor polio incidence in other cities. Thus, virus levels in sewage waste can give an early warning of the reappearance of viral disease or verify its absence.
Abstract
A major obstacle to eradicating polio is that poliovirus from endemic countries can be reintroduced to polio-free countries. Environmental surveillance (ES) can detect poliovirus from sewage or wastewaters samples, even in the absence of patients with paralysis. ES is underused, in part because its sensitivity is unknown. We used two unique data sets collected during a natural experiment provided by the 2013 polio outbreak in Israel: ES data from different locations and records of supplemental immunization with the live vaccine. Data from the intersecting population between the two data sets (covering more than 63,000 people) yielded a dose-dependent relationship between the number of poliovirus shedders and the amount of poliovirus in sewage. Using a mixed-effects linear regression analysis of these data, we developed several quantitative tools, such as (i) ascertainment of the number of infected individuals from ES data for application during future epidemics elsewhere, (ii) evaluation of the sensitivity of ES, and (iii) determination of the confidence level of the termination of poliovirus circulation after an outbreak. These results will be valuable in monitoring future outbreaks with ES, and this approach could be used to certify poliovirus elimination or to validate the need for more containment efforts.

Vaccine
Volume 35, Issue 17, Pages 2101-2278 (19 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/17
Building Next Generation Immunization Supply Chains
Edited by Bruce Y. Lee, Benjamin Schreiber and Raja Rao
Articles organized under thematic areas:
:: Making the Case: how immunization supply chains impact vaccine coverage
:: Challenges
:: Toward next generation supply chains: Successful pilots
:: Toward next generation supply chains: Promising ideas and innovations
:: Toward next generation supply chains: Upstream solutions

Vaccine
Volume 35, Issue 16, Pages 1985-2100 (11 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/16

Reviews
Facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination in the United States: Systematic review
Review Article
Pages 1987-1995
Gloria J. Kang, Rachel K. Culp, Kaja M. Abbas
Abstract
The study objective was to identify facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination in the United States. In 2009, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention expanded their recommendations for influenza vaccination to include school-aged children. We conducted a systematic review of studies focused on facilitators and barriers of parental attitudes toward school-located influenza vaccination in the United States from 1990 to 2016. We reviewed 11 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Facilitators were free/low cost vaccination; having belief in vaccine efficacy, influenza severity, and susceptibility; belief that vaccination is beneficial, important, and a social norm; perception of school setting advantages; trust; and parental presence. Barriers were cost; concerns regarding vaccine safety, efficacy, equipment sterility, and adverse effects; perception of school setting barriers; negative physician advice of contraindications; distrust in vaccines and school-located vaccination programs; and health information privacy concerns. We identified the facilitators and barriers of parental attitudes and beliefs toward school-located influenza vaccination to assist in the evidence-based design and implementation of influenza vaccination programs targeted for children in the United States and to improve influenza vaccination coverage for population-wide health benefits.

Vaccine
Volume 35, Issue 16, Pages 1985-2100 (11 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/16

Impact of meningococcal C conjugate vaccination four years after introduction of routine childhood immunization in Brazil
Original Research Article
Pages 2025-2033
Ana Lucia Andrade, Ruth Minamisava, Lisia Moura Tomich, Ana Paula Lemos, Maria Cecilia Gorla, Maria Cristina de Cunto Brandileone, Carla Madga S. Domingues, Camile de Moraes, Gabriela Policena, Ana Luiza Bierrenbach, Meningococcal Study Group
Abstract
Background
Routine infant immunization with meningococcal C conjugate (MCC) vaccination started in Brazil in November 2010, scheduled at three and five months plus a booster at 12–15 months of age. No catch-up was implemented. We assessed the impact of vaccination on meningococcal C disease (MenC) four years after vaccination start in the National Immunization Program.
Methods
We performed an ecological quasi-experimental design from 2008 to 2014 using a deterministic linkage between the National Notification and the National Reference Laboratory databases for meningitis. We conducted an interrupted time-series analysis considering Brazil except for Salvador municipality, because an epidemic of serogroup C disease occurred in this city, which prompted a mass vaccination campaign with catch-up for adolescents in 2010. Observed MenC rates in the post-vaccination period were compared to expected rates calculated from the pre-vaccination years. Results for Salvador were presented as descriptive data. An additional time-series analysis was performed for the state of São Paulo.
Results
A total of 18,136 MenC cases were analyzed. The highest incidence rates were observed for infants aged Conclusion
After four years of infants and toddlers vaccination start, MenC invasive disease reduced in the target population. This investigation provide a robust baseline to ascertain how much the upcoming catch-up dose in 12–13 years of age will accelerate the decrease in MenC incidence rates among youths in Brazil.

Vaccine
Volume 35, Issue 16, Pages 1985-2100 (11 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/16

Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial
Original Research Article
Pages 2084-2091
Thomas Nørrelykke Nissen, Nina Marie Birk, Gaby Smits, Dorthe Lisbeth Jeppesen, Lone Graff Stensballe, Mihai G. Netea, Fiona van der Klis, Christine Stabell Benn, Ole Pryds, The Calmette Study Group
Abstract
Introduction
BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants.
Methods
Within 7 days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12 months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4 weeks after the third vaccine dose.
Results
Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by ‘age at randomisation’ we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys.
Conclusions and relevance
Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed.

Vaccine
Volume 35, Issue 15, Pages 1817-1984 (4 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/15

Childhood pneumococcal disease in Africa – A systematic review and meta-analysis of incidence, serotype distribution, and antimicrobial susceptibility
Review Article
Pages 1817-1827
Pui-Ying Iroh Tam, Beth K. Thielen, Stephen K. Obaro, Ann M. Brearley, Alexander M. Kaizer, Haitao Chu, Edward N. Janoff
Abstract
Background
Determining the incidence, disease-associated serotypes and antimicrobial susceptibility of invasive pneumococcal disease (IPD) among children in Africa is essential in order to monitor the impact of these infections prior to widespread introduction of the pneumococcal conjugate vaccine (PCV).
Methods
To provide updated estimates of the incidence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae causing disease in Africa, we performed a systematic review of articles published from 2000 to 2015 using Ovid Medline and Embase. We included prospective and surveillance studies that applied predefined diagnostic criteria. Meta-analysis for all pooled analyses was based on random-effects models.
Results
We included 38 studies consisting of 386,880 participants in 21 countries over a total of 350,613 person-years. The pooled incidence of IPD was 62.6 (95% CI 16.9, 226.5) per 100,000 person-years, including meningitis which had a pooled incidence of 24.7 (95% CI 11.9, 51.6) per 100,000 person-years. The pooled prevalence of penicillin susceptibility was 78.1% (95% CI 61.9, 89.2). Cumulatively, PCV10 and PCV13 included 66.9% (95% CI 55.9, 76.7) and 80.6% (95% CI 66.3, 90.5) of IPD serotypes, respectively.
Conclusions
Our study provides an integrated and robust summary of incidence data, serotype distribution and antimicrobial susceptibility for S. pneumoniae in children ≤5 years of age in Africa prior to widespread introduction of PCV on the continent. The heterogeneity of studies and wide range of incidence rates across the continent indicate that surveillance efforts should be intensified in all regions of Africa to improve the integrity of epidemiologic data, vaccine impact and cost benefit. Although the incidence of IPD in young children in Africa is substantial, currently available conjugate vaccines are estimated to cover the majority of invasive disease-causing pneumococcal serotypes. These data provide a reliable baseline from which to monitor the impact of the broad introduction of PCV.

Vaccine
Volume 35, Issue 15, Pages 1817-1984 (4 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/15

Systematic review of the cost-effectiveness of influenza immunization programs
Review Article
Pages 1828-1843
Eon E.K. Ting, Beate Sander, Wendy J. Ungar
Abstract
Background
Seasonal influenza immunization programs vary widely across jurisdictions. In Canada, some provinces offer universal programs while others target specific population groups. However, whether targeted or universal programs provide more benefit and value-for-money is unclear. The cost-effectiveness of influenza immunization programs was systematically reviewed to inform policy.
Methods
Citation databases and the grey literature were searched for economic evaluations of influenza immunization programs. Eligible studies were appraised using the Scottish Intercollegiate Guidelines Network (SIGN) checklist with supplemental WHO vaccine-related questions. Data from high quality studies was extracted and the studies reviewed.
Results
A total of 41influenza immunization studies were identified. Of these, 31 were high quality. For pregnant and postpartum women, vaccinating all versus only high risk women study results ranged from dominance (less costly and more effective) to $9773 per QALY gained (societal) and from dominance to $58,000 per QALY gained (healthcare system). Studies of vaccinating all versus only high risk children found vaccination to be dominant to $47,000 per QALY gained (societal), and dominant to $18,000 per QALY gained (healthcare system). Vaccinating high risk adults was highly cost-effective and vaccinating health care workers resulted in $35,000 per QALY gained. Results for healthy working adults were mixed and sensitive to vaccine uptake, efficacy, and productivity loss.
Conclusions
From the societal perspective, vaccination was cost-effective for children, pregnant and postpartum women, high risk groups, and in some cases, healthy working age adults. Immunization programs using group administration are more cost-effective than programs using individual administration. The perspective, programmatic design, setting, and inclusion of herd immunity affects cost-effectiveness. In regions with targeted programs, re-evaluating “high risk” criteria and consideration of a universal program is warranted.

Vaccine
Volume 35, Issue 15, Pages 1817-1984 (4 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/15

The ADVANCE Code of Conduct for collaborative vaccine studies
Review Article
Pages 1844-1855
Xavier Kurz, Vincent Bauchau, Patrick Mahy, Steffen Glismann, Lieke Maria van der Aa, François Simondon, for the ADVANCE consortium
Abstract
Lessons learnt from the 2009 (H1N1) flu pandemic highlighted factors limiting the capacity to collect European data on vaccine exposure, safety and effectiveness, including lack of rapid access to available data sources or expertise, difficulties to establish efficient interactions between multiple parties, lack of confidence between private and public sectors, concerns about possible or actual conflicts of interest (or perceptions thereof) and inadequate funding mechanisms. The Innovative Medicines Initiative’s Accelerated Development of VAccine benefit-risk Collaboration in Europe (ADVANCE) consortium was established to create an efficient and sustainable infrastructure for rapid and integrated monitoring of post-approval benefit-risk of vaccines, including a code of conduct and governance principles for collaborative studies. The development of the code of conduct was guided by three core and common values (best science, strengthening public health, transparency) and a review of existing guidance and relevant published articles. The ADVANCE Code of Conduct includes 45 recommendations in 10 topics (Scientific integrity, Scientific independence, Transparency, Conflicts of interest, Study protocol, Study report, Publication, Subject privacy, Sharing of study data, Research contract). Each topic includes a definition, a set of recommendations and a list of additional reading. The concept of the study team is introduced as a key component of the ADVANCE Code of Conduct with a core set of roles and responsibilities. It is hoped that adoption of the ADVANCE Code of Conduct by all partners involved in a study will facilitate and speed-up its initiation, design, conduct and reporting. Adoption of the ADVANCE Code of Conduct should be stated in the study protocol, study report and publications and journal editors are encouraged to use it as an indication that good principles of public health, science and transparency were followed throughout the study.

Vaccine
Volume 35, Issue 15, Pages 1817-1984 (4 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/15

Assessing misclassification of vaccination status: Implications for studies of the safety of the childhood immunization schedule
Original Research Article
Pages 1873-1878
Matthew F. Daley, Jason M. Glanz, Sophia R. Newcomer, Michael L. Jackson, Holly C. Groom, Marlene M. Lugg, Huong Q. McLean, Nicola P. Klein, Eric S. Weintraub, Michael M. McNeil
Abstract
Background
To address public concern about the safety of the childhood immunization schedule, the Institute of Medicine recommended observational studies comparing adverse health outcomes of fully vaccinated children to children under-vaccinated due to parental choice. Misclassification of vaccination status could bias such studies.
Objective
To assess risk of misclassification of vaccination status within the Vaccine Safety Datalink (VSD).
Design/methods
A retrospective cohort study was conducted in three phases. In phase 1, electronic health record (EHR) data were used to identify patterns of under-vaccination during the first 24 months of life potentially due to parental choice. In phase 2, a random sample of records of under-vaccinated children was manually reviewed. In phase 3, a separate sample of parents were surveyed to assess whether EHR data accurately reflected their child’s vaccination status. Phases 1 and 2 were conducted at 6 VSD sites, phase 3 at 1 site.
Results
The study cohort included 361,901 children born 2004 through 2012. By 24 months of age, 198,249 (54.8%) were fully vaccinated with no delays, 84,698 (23.4%) experienced delays but were fully vaccinated by 24 months of age, 4865 (1.3%) received no vaccines, 3789 (1.0%) delayed starting vaccination until ≥4 months of age, 4781 (1.3%) had consistent vaccine-limiting (≤2 vaccines per visit), and the remaining 65,519 (18.1%) were missing vaccine series or doses. When a diagnosis code for vaccine refusal was present in EHR data, encounter notes confirmed vaccine refusal as the reason for under-vaccination for nearly 100% of sampled records. Parent surveys confirmed these findings. Parents of under-vaccinated children were more likely to report visiting an alternative medical provider than parents of fully vaccinated children.
Conclusions
Specific groups of children, under-vaccinated due to parental choice, can be identified with relatively low likelihood of misclassification of vaccination status using EHR-based vaccine data and diagnosis codes.

Vaccine
Volume 35, Issue 15, Pages 1817-1984 (4 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/15

Health professional feedback on HPV vaccination roll-out in a developing country
Original Research Article
Pages 1886-1891
Collette Venturas, Kanayo Umeh
Abstract
Background
Worldwide, Zambia has the highest cervical cancer incidence rates (58.4/100,000 per year) and mortality rates (36.2/100,000 per year). The human papilloma virus (HPV) vaccine is considered a vital preventative measure against cervical cancer, particularly in sub-Saharan countries, such as Zambia. Past research suggests health professionals’ experiences with HPV vaccination rollout can have practical implications for effective delivery.
Objective
To explore health professionals’ perspectives on the HPV vaccination programme in Zambia.
Methods
Researcher travelled to Zambia and conducted semi-structured interviews with fifteen health professionals working in private, government, and missionary clinics/hospitals. Observation was conducted for triangulation purposes. Thematic analysis was used to analyse the data.
Findings
Five main themes emerged; medical misconceptions about the HPV vaccination, particularly with regards to infertility; fear of the unknown, including possible side effects and inadequate empirical research; need for prior desensitisation to resolve cultural barriers prior to vaccination rollout; a rural-urban divide in health awareness, particularly in relation to cancer vaccines; and economic concerns associated with access to the HPV vaccination for most of the Zambian population.
Conclusion
Overall, the findings indicate that an essential avenue for facilitating HPV vaccination rollout in Zambia is by implementing a pre-rollout community effort that removes or softens cultural barriers, particularly in rural areas. It is also essential to correct erroneous HPV presumptions health professionals may have around infertility. Affordability remains a seemingly intractable hindrance that hampers HPV vaccination rollout in Zambia.

Vaccine
Volume 35, Issue 15, Pages 1817-1984 (4 April 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/15

Analysis of the effects of individual and community level factors on childhood immunization in Malawi
Original Research Article
Pages 1907-1917
Peter Austin Morton Ntenda, Kun-Yang Chuang, Fentanesh Nibret Tiruneh, Ying-Chih Chuang
Abstract
Background
Empirical evidence regarding the relationship between childhood immunization and individual- and community-level factors in low-income countries has received little attention. We compared the trends and the effects of a wide range of individual- and community-level socioeconomic factors on the likelihood of a child being immunized between 2004 and 2010 in Malawi.
Methods
We used data from the 2004 and 2010 Malawi Demographic and Health Survey and applied generalized estimating logistic regression equation to analyze data respectively on 2042 and 3496 children aged 12–23 months. We compared the relationship between individual- and community-level socioeconomic factors and a child’s vaccination status for four basic vaccines recommended by the World Health Organization: bacillus Calmette-Guérin (BCG) vaccine, diphtheria-tetanus-pertussis (DPT3) vaccine, oral polio vaccine (OPV3), and measles-containing vaccine 1 (MCV1).
Results
The trends of vaccination had a similar pattern in 2004 and 2010. The coverage of the four vaccinations was highest for BCG and lowest for OPV3 and complete immunization was higher in 2010. The multivariate analyses show that mother’s low education, having one or none antenatal visits, having no immunization card, having immunization card but not seen, residing in poor households, and living in central region were the most significant factors associated with decreased odds of achieving vaccination coverage and complete vaccination in both 2004 and 2010. However, maternal education was more likely to be associated with children’s immunization in 2010, while the geographical region was more likely to be associated with children’s immunization in 2004.
Conclusions
There were marked improvements in the national immunization coverage from 2004 to 2010. In order to achieve complete immunization, to further enhance the national immunization coverage as well as to lessen the gaps and disparities in childhood vaccination in Malawi, policy makers should design interventions based on the factors addressed in this study.

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

Cold Spring Harbor Perspectives in Biology
Published in Advance March 27, 2017, doi: 10.1101/cshperspect.a031583
What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models
RS Herati, EJ Wherry –
Abstract
Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans.

Journal of Community Health
First Online: 22 March 2017 DOI: 10.1007/s10900-017-0328-5
Practices and Attitudes of Missouri School Nurses Regarding Immunization Records and Select Immunizations of Graduating High School Seniors
Darson L. Rhodes, Michele Draper, Kendra Woolman, Carol Cox
Abstract
School nurses play a key role in maintaining a healthy student population, and one of their roles includes maintaining vaccination records. Further, they can play an important role in advocating for human papillomavirus (HPV) and meningococcal vaccination for students. All Missouri public high school nurses were sent an electronic survey addressing the knowledge, attitudes, and practices regarding immunization records and HPV and meningococcal vaccination of high school seniors. Approximately 75% of nurses reported their schools did not have or they did not know if the school had a written policy regarding the release of vaccination records. Approximately 1/2 and 1/3 of nurses do not communicate with parents/students about HPV or meningococcal vaccines, respectively. Although most favorable toward meningococcal, nurses had positive attitudes toward both vaccines. Recommendations include establishment of written policies regarding vaccination record release, and future research should focus on evaluating school nurses’ communication methods regarding HPV and meningococcal vaccination.

Media/Policy Watch
This watch section is intended to alert readers to substantive news, analysis and opinion from the general media and selected think tanks and similar organizations on vaccines, immunization, global public health and related themes. Media Watch is not intended to be exhaustive, but indicative of themes and issues CVEP is actively tracking. This section will grow from an initial base of newspapers, magazines and blog sources, and is segregated from Journal Watch above which scans the peer-reviewed journal ecology.

We acknowledge the Western/Northern bias in this initial selection of titles and invite suggestions for expanded coverage. We are conservative in our outlook in adding news sources which largely report on primary content we are already covering above. Many electronic media sources have tiered, fee-based subscription models for access. We will provide full-text where content is published without restriction, but most publications require registration and some subscription level.

The Economist
http://www.economist.com/
Accessed 1 April 2017

Taking stock – Managing supplies of vaccines is a huge problem
New research asks how often vaccines are exposed to temperatures below the lower limit
Mar 30th 2017

New York Times
http://www.nytimes.com/
Accessed 1 April 2017

Meningitis C Kills 282 in Nigeria Amid Shortage of Vaccines
March 30, 2017 –

UN Sends 3.5M Emergency Yellow Fever Vaccines to Brazil
March 30, 2017

As Cholera Spreads, Somalia Begins Vaccination Campaign
March 27, 2017

Think Tanks et al

Brookings
http://www.brookings.edu/
Accessed 1 April 2017
TechTank
Brookings report assesses health governance capacity in low- and middle-income countries
Jake Schneider, John Villasenor, and Darrell M. West
Wednesday, March 29, 2017
[See Research above for more detail]

Milestones :: Perspectives :: Featured Journal Content

From coast to coast: Africa unites to tackle threat of polio
116 million children to be immunized from coast to coast across the continent, as regional emergency outbreak response intensifies
GENEVA/BRAZZAVILLE/NEW YORK/DAKAR, 24 March 2017 –  More than 190,000 polio vaccinators in 13 countries across west and central Africa will immunize more than 116 million children over the next week, to tackle the last remaining stronghold of polio on the continent.

The synchronized vaccination campaign, one of the largest of its kind ever implemented in Africa, is part of urgent measures to permanently stop polio on the continent. All children under five years of age in the 13 countries – Benin, Cameroon, Central African Republic, Chad, Côte d’Ivoire, Democratic Republic of Congo, Guinea, Liberia, Mali, Mauritania, Niger, Nigeria and Sierra Leone – will be simultaneously immunized in a coordinated effort to raise childhood immunity to polio across the continent. In August 2016, four children were paralysed by the disease in security-compromised areas in Borno state, north-eastern Nigeria, widely considered to be the only place on the continent where the virus maintains its grip.

“Twenty years ago, Nelson Mandela launched the pan-African ‘Kick Polio Out of Africa’ campaign,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “At that time, every single country on the continent was endemic to polio, and every year, more than 75,000 children were paralysed for life by this terrible disease. Thanks to the dedication of governments, communities, parents and health workers, this disease is now beaten back to this final reservoir.”

Dr Moeti cautioned, however, that progress was fragile, given the epidemic-prone nature of the virus. Although confined to a comparatively small region of the continent, experts warned that the virus could easily spread to under-protected areas of neighbouring countries. That is why regional public health ministers from five Lake Chad Basin countries – Cameroon, Central African Republic, Chad, Niger, and Nigeria – declared the outbreak a regional public health emergency and have committed to multiple synchronized immunization campaigns…

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New England Journal of Medicine
March 23, 2017  Vol. 376 No. 12
http://www.nejm.org/toc/nejm/medical-journal
Editorial
Rotavirus Vaccines — A New Hope
Mathuram Santosham, M.D., M.P.H., and Duncan Steele, Ph.D.
N Engl J Med 2017; 376:1170-1172 March 23, 2017 DOI: 10.1056/NEJMe1701347

Rotavirus gastroenteritis is the leading cause of diarrhea-associated hospitalization and death in children younger than 5 years of age,1 with more than 85% of the approximately 200,000 annual rotavirus deaths occurring in Africa and Asia.2 Since improvements in water, sanitation, and hygiene do not prevent rotavirus transmission, as they do with the spread of bacterial enteropathogens, the implementation of a rotavirus vaccine is essential to prevent death and complications from childhood diarrhea.

Two rotavirus vaccines — Rotarix (an attenuated G1P8 rotavirus manufactured by GlaxoSmithKline) and RotaTeq (containing five human–bovine reassortant rotaviruses, manufactured by Merck), attained prequalification by the World Health Organization (WHO) in 2008, which paved the way for UNICEF vaccine procurement through the financing mechanisms of the Gavi Alliance. These vaccines, which have been introduced in 42 Gavi-eligible countries and in 6 countries that have been designated as low-income and middle-income, have had a major effect on rotavirus deaths and hospitalizations in all settings.3

However, the uptake of rotavirus vaccines has slowed for various reasons, including supply constraints, high cost, and programmatic concerns for national immunization programs, particularly cold-chain capacity.4 Gavi countries have predominantly selected the attenuated G1P8 rotavirus vaccine,5 which has a smaller vaccine vial size and comes with a vaccine vial monitor for temperature monitoring. The two approved rotavirus vaccines have a liquid ready-to-use formulation. However, issues of cost of the vaccine and vaccine supply remain.
With Gavi support, low-income countries can procure rotavirus vaccines with a minimal copayment of 40 cents (in U.S. currency) per course, and Gavi cofinances the remainder of the UNICEF price (which ranges from $4.50 to $10.50). Low-income and middle-income countries, which are not Gavi-eligible, pay substantially higher costs for rotavirus vaccines.5 Gavi’s principles for vaccine-supply security emphasize the need for multiple manufacturers in the market to drive down prices while establishing sufficient vaccine supply. This protocol will become more critical as countries transition from Gavi support owing to socioeconomic development.

Fortunately, the situation is improving. In 2013, an indigenously developed rotavirus vaccine (ROTAVAC, Bharat Biotech International) was licensed in India and has been introduced in the routine childhood immunization program in four Indian states, with expanded rollout expected this year. This vaccine is under consideration for WHO prequalification, which would make it eligible for UNICEF procurement and Gavi subsidy. Bharat Biotech has committed to a cost of approximately $3.00 per course for global public markets.

In this issue of the Journal, Isanaka and colleagues6 document the safety and efficacy of an oral bovine rotavirus pentavalent vaccine (BRV-PV) developed by Serum Institute of India. The vaccine, which the investigators evaluated in an impoverished setting in Niger, had a reported efficacy of 66.7%,6 which is similar to that of other licensed rotavirus vaccines in similar settings. Efficacy data from an Indian study are pending. Despite this modest efficacy, the absolute public health benefits of vaccination are large, given the tremendous disease burden.

Estimates suggest that rotavirus vaccines have the potential to prevent 2.46 million childhood deaths and 83 million disability-adjusted life-years during the period from 2011 through 2030.7
The authors describe a rotavirus vaccine that is thermostable for 24 months at 37°C and for 6 months at 40°C, which may provide advantages for vaccine delivery in remote areas where cold-chain capacity is limited. However, this vaccine is freeze-dried, and practitioners in many countries may prefer other rotavirus vaccines that have liquid all-in-one formulations to simplify programmatic considerations. The projected cost of this heat-stable vaccine falls between the Gavi prices for the two currently used vaccines. The availability of vaccines from several manufacturers will increase global supply.

During the past three decades, remarkable progress has been made in reducing mortality from diarrheal disease, but the goal of ending such deaths cannot be achieved without aggressive implementation of a comprehensive approach to diarrhea prevention and treatment, including providing access of rotavirus vaccines to every child regardless of economic status. Increased availability of low-cost, programmatically suitable vaccines in abundant supply will be key to achieving this goal.

Original Article
Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger
Sheila Isanaka, Sc.D., Ousmane Guindo, M.D., Celine Langendorf, Pharm.D., M.P.H., Amadou Matar Seck, M.D., Brian D. Plikaytis, M.Sc., Nathan Sayinzoga-Makombe, M.P.H., Monica M. McNeal, M.Sc., Nicole Meyer, M.Sc., Eric Adehossi, M.D., Ali Djibo, M.D., Bruno Jochum, M.S., and Rebecca F. Grais, Ph.D.
N Engl J Med 2017; 376:1121-1130 March 23, 2017 DOI: 10.1056/NEJMoa1609462
Abstract
Background
Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa.
Methods
We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3.
Results
Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception.
Conclusions
Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000.)

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Editor’s Note:
Please note World TB Day announcements across this edition.

Emergencies

WHO Grade 3 Emergencies  [to 25 March 2017]
Iraq  –
WHO scales up disease surveillance reporting in East Mosul and Hamdaniya districts, Iraq
19 March 2017, Erbil, Iraq – The World Health Organization (WHO) and the United Nations Office for the Coordination of Humanitarian Affairs (UNOCHA) are scaling up disease surveillance activities in newly accessible areas of Ninewa governorate, Iraq, to reduce the risk of disease outbreaks. As a result of acute shortages of safe water, sanitation services, food, and electricity in East Mosul and Hamdaniya districts, current humanitarian conditions pose a high risk of communicable diseases among displaced persons, returnees, and host communities.

Nigeria – No new announcements identified
South Sudan  – No new announcements identified
The Syrian Arab Republic  – No new announcements identified
Yemen – No new announcements identified

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WHO Grade 2 Emergencies  [to 25 March 2017]
Cameroon  – No new announcements identified.
Central African Republic  – No new announcements identified.
Democratic Republic of the Congo – No new announcements identified.
Ethiopia – No new announcements identified.
Libya – No new announcements identified.
Myanmar – No new announcements identified.
Niger  – No new announcements identified.
Ukraine  – No new announcements identified.

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 UN OCHA – L3 Emergencies
The UN and its humanitarian partners are currently responding to three ‘L3’ emergencies. This is the global humanitarian system’s classification for the response to the most severe, large-scale humanitarian crises. 

Iraq
:: UN Expresses Profound Concern about Terrible Loss of Life in Western Mosul
Published on 24 Mar 2017
The United Nations is profoundly concerned by reports yesterday of a high number of civilian casualties in Al Aghawat Al Jadidah, a densely populated neighborhood in Mosul. Initial reports indicate hundreds of causalities.

“We are stunned by this terrible loss of life and wish to express our deepest condolences to the many families who have reportedly been impacted by this tragedy,” said Ms. Lise Grande, the Humanitarian Coordinator for Iraq.

“Nothing in this conflict is more important than protecting civilians,” said Ms. Grande.    “International humanitarian law is clear. Parties to the conflict — all parties – are obliged to do everything possible to protect civilians. This means that combatants cannot use people as human shields and cannot imperil lives through indiscriminate use of fire-power.”

As the fighting to retake Mosul intensifies, civilians are being put at extreme risk. “We fear for the families who are caught in the conflict,” said Ms. Grande. “Everything must be done to avoid civilian casualties.

:: Iraq: Humanitarian Bulletin, February 2017 | Issued on 23 March
:: Iraq: Mosul Humanitarian Response Situation Report No. 25 (13-19 March 2017)

Syria  
:: 24 Mar 2017   Emergency Telecommunications Cluster (ETC) Syria Operation, March 2017

Yemen –
:: 19 Mar 2017  Yemen Humanitarian Bulletin Issue 21 | As of 18 March 2017
HIGHLIGHTS
…Two years of conflict puts future of coming generations at great risk
..First UN cross-line medical aid delivery to Taizz city in months
…117,107 people migrate to Yemen from the Horn of Africa in 2016
…Cholera response gives promising results

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POLIO [to 25 March 2017]
Public Health Emergency of International Concern (PHEIC)

Polio this week as of 22 March 2017
:: From 25 to 28 March, synchronised polio campaigns will take place across 13 counties in west and central Africa including Nigeria, Chad, Cameroon, Guinea, Mali and Niger. Over 190 000 vaccinators will immunize more than 116 million children over the course of the campaigns..

Country Updates [Selected Excerpts]
New cases or environmental samples reported across the monitored country/region settings: Afghanistan, Pakistan, Nigeria, Lake Chad Basin, Guinea and West Africa, Lao People’s Democratic Republic.
:: No new case activity reported

 [See report on story on polio immunization across Africa in Milestones above]

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Editor’s Note:
We will cluster these recent emergencies as below and continue to monitor the WHO webpages for updates and key developments.

 Yellow Fever  [to 25 March 2017]
http://www.who.int/emergencies/yellow-fever/en/
Disease outbreak news
20 March 2017
Updates on yellow fever vaccination recommendations for international travellers related to the current situation in Brazil

As of 16 March 2017, yellow fever virus transmission continues to expand towards the Atlantic coast of Brazil in areas not deemed to be at risk for yellow fever transmission prior to the revised risk assessment, supported by the scientific and technical advisory group on geographical yellow fever risk mapping (GRYF), and published by WHO in the Disease Outbreak News of 27 January 2017 and 6 March 2017; as well as on the WHO International Travel and Health website on 31 January 2017,14 February 2017, and 6 March 2017.

As of 16 March 2017, confirmed cases of yellow fever virus infection in humans were reported in Rio de Janeiro State, and epizootics and human cases are under investigation for yellow fever virus infection in São Paulo State. These reports are consistent with the increased yellow fever activity observed in other States (Espírito Santo and Minas Gerais) that share the same ecosystem — tropical and sub-tropical broad leaved forests. As of 16 March 2017, there is no evidence of human cases of yellow fever virus infection transmitted by Aedes aegypti, the vector that could sustain urban transmission of yellow fever.

The WHO Secretariat has determined that the State of Rio de Janeiro, with the exception of the urban areas of Rio de Janeiro City and Niterói, and the State of São Paulo, with the exception of the urban areas of São Paulo City and Campinas, should also be considered at risk for yellow fever transmission.

Consequently, vaccination against yellow fever is recommended for international travellers visiting those areas in the States of Rio de Janeiro and São Paulo. The typology of activities that international travellers anticipate to undertake while visiting areas determined to be at risk for yellow fever transmission should be weighted in the risk-benefit analysis informing the individual decision to be immunized against yellow fever.

There are no other additional changes with respect to other areas of Brazil determined to be at risk for yellow fever transmission in 2013, as published by WHO in the Disease Outbreak News on 31 January 2017 and 6 March 2017…

 EBOLA/EVD  [to 25 March 2017]
http://www.who.int/ebola/en/
No new digest content identified for this edition.

 MERS-CoV [to 25 March 2017]
http://www.who.int/emergencies/mers-cov/en/
No new digest content identified for this edition.

 Zika virus  [to 25 March 2017]
http://www.who.int/emergencies/zika-virus/en/
No new digest content identified for this edition.

WHO & Regional Offices [to 25 March 2017]

Highlights

10th meeting of the Strategic and Technical Advisory Group for Neglected Tropical Diseases
March 2017 – The meeting, taking place on 29–30 March 2017, will cover issues on Global Vector Control Response, examination of dossiers requesting the potential inclusion of diseases as NTDs, gaps in disease elimination, eradication of dracunculiasis, integrated data management, and the 2nd WHO NTD Global Partners’ Meeting.

Global Health Sector Strategy on Viral Hepatitis
March 2017 – Worldwide, approximately 240 million people have chronic hepatitis B infection and 80 million people have chronic hepatitis C infection. A dedicated portal has been developed for the first ever Global Health Sector Strategy on Viral Hepatitis 2016–2021.

Ad-hoc Interagency Coordination Group on antimicrobial resistance
March 2017 – At the UN General Assembly’s high-level meeting on antimicrobial resistance in September 2016, Member States requested the Secretary-General to establish, in consultation with WHO, the Food and Agriculture Organization, and the World Organisation for Animal Health, an ad-hoc interagency coordination group on antimicrobial resistance.

Weekly Epidemiological Record, 24 March 2017, vol. 92, 12 (pp. 129–144)
Zoonotic influenza viruses: antigenic and genetic characteristics and development of candidate vaccine viruses for pandemic preparedness

Disease outbreak news

:: Meningococcal disease – Nigeria  24 March 2017
:: Human infection with avian influenza A(H7N9) virus – China  23 March 2017
:: Yellow fever – Brazil  20 March 2017  [See Yellow Fever above]

:: WHO Regional Offices
Selected Press Releases, Announcements

WHO African Region AFRO
:: From coast to coast: Africa unites to tackle threat of polio – 23 March 2017
:: Dr Matshidiso Moeti on an official visit to Republic of Niger – 21 March 2017

WHO Region of the Americas PAHO
:: PAHO/WHO: “Let’s unite to end TB, leaving no one behind” (03/23/2017)

WHO South-East Asia Region SEARO
No new digest content identified.

WHO European Region EURO
:: World TB Day: leave no one behind 23-03-2017
:: France becomes one of the first countries in Region to recommend colour-coded nutrition labelling system 22-03-2017
:: World Water Day: good health and managing wastewater go hand-in-hand 22-03-2017
:: TB/HIV co-infections up 40% across Europe over the last five years 20-03-2017

WHO Eastern Mediterranean Region EMRO
:: World TB Day: Unite to End TB and alleviate the suffering of millions  22 March 2017
:: WHO reinforces monitoring of health facilities, services and resources in Syria  22 March 2017
:: WHO scales up disease surveillance reporting in East Mosul and Hamdaniya districts, Iraq
19 March 2017

WHO Western Pacific Region
:: Unite to End TB, by properly financing care MANILA, 24 March 2017

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CDC/ACIP [to 25 March 2017]
http://www.cdc.gov/media/index.html

MMWR Weekly March 24, 2017 / No. 11
[Excerpts]
:: World TB Day — March 24, 2017
:: Tuberculosis — United States, 2016
:: Tuberculosis Among Foreign-Born Persons Diagnosed ≥10 Years After Arrival in the United States, 2010–2015
:: Establishing a Timeline to Discontinue Routine Testing of Asymptomatic Pregnant Women for Zika Virus Infection — American Samoa, 2016–2017
:: Notes from the Field: Obstetric Tetanus in an Unvaccinated Woman After a Home Birth Delivery — Kentucky, 2016

Announcements

Gavi [to 25 March 2017]
http://www.gavi.org/library/news/press-releases/
21 March 2017
Gavi ‘effective and fit for purpose’
Network of 19 donor countries assesses Gavi, the Vaccine Alliance’s performance

Gavi is an effective, ‘fit for purpose’ organisation, scoring top ratings in a number key performance areas, according to the Multilateral Organisation Performance Assessment Network (MOPAN).

In its second institutional review of the organisation, MOPAN commends Gavi as being both “strategic and nimble in meeting new vaccine challenges and countries’ evolving needs, while keeping a clear focus on its mission goals.” Gavi is also recognised as being a “strong model for sustainability”.

MOPAN is a network of 19 donor countries, representing 95% of Overseas Development Assistance (ODA), which assesses the effectiveness of the multilateral organisations that receive development and humanitarian funding.

“Gavi has a clear long-term vision based on a distinct business and partnership model” states the report. “It plays a catalytic role in expanding immunisation coverage and shaping the global vaccine market.”

The review, covering the period from 2014 to mid-2016, notes that Gavi demonstrates transparency and accountability in its operations, with strong compliance with fiduciary and social requirements and safeguards. It has recently strengthened its internal audit and risk management functions to meet its increased organisational ambition, complexity and size.
As a performance and results orientated organisation, “Gavi has a clear framework of indicators, targets and metrics at the country level. Results-based management is integral to its planning and grant allocation.”…

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NIH [to 25 March 2017]
http://www.nih.gov/news-events/news-releases
March 24, 2017
NIH Statement on World Tuberculosis Day
— Statement of Christine F. Sizemore, PhD., Richard Hafner, M.D., and Anthony S. Fauci, M.D. National Institute of Allergy and Infectious Diseases.
Tuberculosis (TB) is one of the world’s most devastating infectious diseases. March 24th marks the day in 1882 when German microbiologist Robert Koch announced he had discovered Mycobacterium tuberculosis, the bacterium that causes this ancient scourge. Today, in recognition of World TB Day, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), reasserts its commitment to improving our understanding of TB and how to prevent, diagnose and treat it. Around the globe, researchers and the public health community are united in working toward these goals.

TB is the world’s leading cause of death from an infectious disease, especially among women and children. The World Health Organization estimates that more than 1.8 million people worldwide died of TB in 2015. The symptoms of the disease, which is transmitted through the air and primarily affects the lungs, often begin with coughing, shortness of breath or swollen lymph nodes — but can end in death if left untreated. People with HIV are especially vulnerable: of deaths among people co-infected with HIV and TB, about one quarter are due to TB. In addition, the World Health Organization estimates that about one-third of the world’s population is infected with “latent” TB, in which people carry the bacterium while exhibiting no symptoms.  Five to 10 percent of these latent TB carriers risk developing active TB at some point in their lifetimes. For latent TB carriers who are infected with HIV, this risk is approximately 10 percent per year. Finally, it is important to note that smoking substantially increases TB disease occurrence and risk of death due to TB worldwide.

A safe and highly effective vaccine against TB will be a critical tool in ultimately controlling the infection. Currently, the only available vaccine against TB is bacille Calmette-Guerin (BCG), developed in 1921. While this vaccine offers protection against disseminated disease and death in children, it is much less effective against the transmissible pulmonary form of the disease in adults. NIAID supports research across the spectrum of basic, preclinical and clinical development to arrive at innovative new approaches toward the development of vaccines to prevent this disease…

.

NIH achieves milestone to accelerate multisite clinical studies
March 23, 2017 — CTSA Program paves way for nationwide single IRB mode
Developing new treatments for diseases often requires large numbers of clinical research participants enrolled in the same study at numerous geographical sites. These multisite clinical trials are well-positioned to discover whether a promising therapeutic is safe and effective, and may provide medical professionals with the information needed for treating their patients. However, the initiation of such studies may be delayed because each site typically relies on its own Institutional Review Boards (IRBs) to provide ethics reviews of the risks and benefits of the proposed research.

The National Institutes of Health is leading policy and programmatic initiatives to streamline this overly cumbersome process. NIH’s National Center for Advancing Translational Sciences (NCATS) announced today that all Clinical and Translational Science Awards (CTSA) Program sites have signed on to the NCATS Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB authorization agreement. This agreement — which now includes a total of more than 150 top medical research institutions — will enable all participating study sites to rely on the ethics review of one IRB for each study, making it possible to initiate multisite studies within weeks instead of months. For patients waiting to enroll in a study, this could make a life-saving difference.

The SMART IRB authorization agreement serves as a model to help investigators adhere to the NIH’s policy on single IRB use for multisite studies. This policy was designed to improve IRB efficiencies while ensuring the protection of research participants so that research can proceed expeditiously.

The authorization agreement effort was led by Harvard Catalyst, University of Wisconsin-Madison Institute for Clinical and Translational Research, and Dartmouth Synergy. Through these institutions, a team of NCATS-supported SMART IRB ambassadors facilitated and provided critical guidance and support to assist institutions in joining and implementing the SMART IRB authorization agreement.

“This milestone is a giant step toward a nationwide model for greater efficiency in IRB review, which is critical to getting more treatments to more patients more quickly,” said NCATS Director Christopher P. Austin, M.D. “It was made possible by the teamwork of hundreds of experts across the country who worked together to achieve what was thought to be impossible even a few years ago.”…

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Global Fund [to 25 March 2017]
http://www.theglobalfund.org/en/news/?topic=&type=NEWS;&country=
News
Global Fund and Inter-Parliamentary Union Sign MOU
23 March 2017
The Global Fund and the Inter-Parliamentary Union (IPU) have signed a memorandum of understanding to promote mutual advocacy, engage in joint technical work and raise awareness in the fight against AIDS, TB and malaria and building resilient and sustainable systems for health.

News
Senegal and the Global Fund Extend Their Partnership
21 March 2017
The Honorable Macky Sall, President of the Republic of Senegal, today welcomed a delegation from the Global Fund to Fight AIDS, Tuberculosis and Malaria led by Dr. Mark Dybul, Executive Director. The meeting marked the official signing of the Agreement on the Privileges and Immunities of the Global Fund, a symbolic step in strengthening the partnership between the Global Fund and Senegal that has been in place for 15 years. Senegal is now the 15th country to sign the agreement; Côte d’Ivoire, Togo, Burkina Faso, Rwanda as well as some ten European and African states have already done so.

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PATH [to 25 March 2017]
http://www.path.org/news/index.php
Announcement | March 23, 2017
PATH welcomes new promising study results for rotavirus vaccine candidate
A new article published today in the New England Journal of Medicine provides the results of a recent Phase 3 clinical trial conducted in Niger with a rotavirus vaccine candidate from India. The study, conducted by Médecins Sans Frontières (MSF) and Epicentre, evaluated the efficacy and safety of the pentavalent bovine-human reassortant rotavirus vaccine (BRV-PV) manufactured by Serum Institute of India Pvt. Ltd. in infants in Niger. Data from the trial revealed the BRV-PV to be highly efficacious for the prevention of severe rotavirus gastroenteritis and to have an excellent safety profile. In addition, the vaccine was transported and stored at ambient temperature, thus bypassing the typically challenging cold-chain requirements that apply to most other vaccines…

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UNAIDS [to 25 March 2017]
http://www.unaids.org/
Press release
UNAIDS warns that countries will miss the 2020 target of reducing HIV-associated TB deaths by 75% unless urgent action is taken
GENEVA, 24 March 2017—On World Tuberculosis Day, 24 March, UNAIDS is urging countries to do much more to reduce the number of tuberculosis (TB) deaths among people living with HIV. TB is the most common cause of hospital admission and death among people living with HIV. In 2015, 1.1 million people died from an AIDS-related illness—around 400 000 of whom died from TB, including 40 000 children.
“It is unacceptable that so many people living with HIV die from tuberculosis, and that most are undiagnosed or untreated,” said Michel Sidibé, Executive Director of UNAIDS. “Only by stepping up collaboration between HIV and tuberculosis programmes to accelerate joint action can the world reach its critical HIV and tuberculosis targets.”
Eight countries—the Democratic Republic of the Congo, India, Indonesia, Mozambique, Nigeria, South Africa, the United Republic of Tanzania and Zambia—account for around 70% of all TB deaths among people living with HIV. Scaling up action in these eight countries would put the world on track to reach the ambitious target in the 2016 United Nations Political Declaration on Ending AIDS of reducing TB-related deaths among people living with HIV by 75% by 2020…

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Wellcome Trust [to 25 March 2017]
https://wellcome.ac.uk/news
Published: 24 March 2017
Breakthrough in battle against resistant TB
A cutting-edge technique developed by Wellcome-funded researchers in Oxford means that tuberculosis (TB) can now be diagnosed much faster and more accurately.
The researchers’ method uses whole genome sequencing to quickly assess which strains of TB a patient is infected with. Patients will receive their diagnosis in just over a week, rather than waiting up to a month.
This will improve treatments and help reduce the spread of drug-resistant infections.
It will also be possible to improve identification and treatment of other resistant pathogens.
The news comes as World TB Day marks global efforts to eliminate a disease that infects 10 million people and kills 1.5 million each year. The spread of resistant strains of TB are of particular concern. In 2015, an estimated 480,000 people worldwide developed multidrug-resistant TB…

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EDCTP [to 25 March 2017]
http://www.edctp.org/
The European & Developing Countries Clinical Trials Partnership (EDCTP) aims to accelerate the development of new or improved drugs, vaccines, microbicides and diagnostics against HIV/AIDS, tuberculosis and malaria as well as other poverty-related and neglected infectious diseases in sub-Saharan Africa, with a focus on phase II and III clinical trials
24 March 2017
World TB day 2017: closing the gaps to end tuberculosis
Ending the tuberculosis (TB) epidemic by 2030 is one of the health targets of the Sustainable Development Goals. Although TB incidence has fallen by an average of 1.5% per year since 2000, TB is still one of the top 10 causes of death worldwide. Over 95% of TB deaths occur in low- and middle-income countries. In 2015, an estimated 480,000 people globally developed multidrug-resistant TB (MDR-TB). This ambitious aim to end the TB epidemic by 2030 can only be achieved by uniting efforts to close the research gaps…

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Industry Watch [to 25 March 2017]
:: Pfizer Receives Positive CHMP Opinion for TRUMENBA® for Prevention of Meningococcal Group B Disease
TRUMENBA Has Been Studied in a Global Clinical Development Program Evaluating the Vaccine in Adolescents and Adults1
The Majority of Meningococcal Disease Cases in Europe are Caused by Meningococcal Group B (MenB), with Adolescents and Young Adults at Increased Risk2
March 24, 2017
NEW YORK–(BUSINESS WIRE)–Pfizer Inc. (NYSE:PFE) today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending that TRUMENBA® (Meningococcal Group B Vaccine) be granted marketing authorization in the European Union (EU) for active immunization of individuals 10 years and older to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB).3 The CHMP’s opinion will now be sent to the European Commission (EC) for final decision.
“This positive opinion by the CHMP to recommend marketing authorization of TRUMENBA in the EU is an additional step toward the fight to help protect individuals over 10 years of age from meningococcal disease caused by serogroup B, an uncommon yet devastating and life-threatening disease,” said Kathrin Jansen, Ph.D., senior vice president and head of Vaccine Research and Development for Pfizer Inc. “This decision further affirms the effectiveness and robust safety profile of TRUMENBA.”…

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AERAS [to 25 March 2017]
http://www.aeras.org/pressreleases
No new digest content identified.

BIO [to 25 March 2017]
http://www.bio.org/insights
No new digest content identified.

BMGF – Gates Foundation [to 25 March 2017]
http://www.gatesfoundation.org/Media-Center/Press-Releases
No new digest content identified.

CEPI – Coalition for Epidemic Preparedness Innovations [to 25 March 2017]
http://cepi.net/
No new digest content identified.

DCVMN [to 25 March 2017]
http://www.dcvmn.org/
No new digest content identified.

European Vaccine Initiative [to 25 March 2017]
http://www.euvaccine.eu/news-events
No new digest content identified.

FDA [to 25 March 2017]
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/default.htm
No new digest content identified.

Fondation Merieux [to 25 March 2017]
http://www.fondation-merieux.org/news
Mission: Contribute to global health by strengthening local capacities of developing countries to reduce the impact of infectious diseases on vulnerable populations.
No new digest content identified.

GHIT Fund [to 25 March 2017]
https://www.ghitfund.org/
GHIT was set up in 2012 with the aim of developing new tools to tackle infectious diseases that devastate the world’s poorest people. Other funders include six Japanese pharmaceutical companies, the Japanese Government and the Bill & Melinda Gates Foundation.
No new digest content identified.

Hilleman Laboratories [to 25 March 2017]
http://www.hillemanlabs.org/
No new digest content identified.

Human Vaccines Project [to 25 March 2017]
http://www.humanvaccinesproject.org/media/press-releases/
No new digest content identified.

IAVI – International AIDS Vaccine Initiative [to 25 March 2017]
http://www.iavi.org/
No new digest content identified.

IFPMA [to 25 March 2017]
http://www.ifpma.org/resources/news-releases/
No new digest content identified.

IVI [to 25 March 2017]
http://www.ivi.int/
No new digest content identified.

PhRMA [to 25 March 2017]
http://www.phrma.org/press-room
No new digest content identified.

Sabin Vaccine Institute [to 25 March 2017]
http://www.sabin.org/updates/pressreleases
No new digest content identified.

Reports/Research/Analysis/Commentary/Conferences/Meetings/Book Watch/Tenders
Vaccines and Global Health: The Week in Review has expanded its coverage of new reports, books, research and analysis published independent of the journal channel covered in Journal Watch below. Our interests span immunization and vaccines, as well as global public health, health governance, and associated themes. If you would like to suggest content to be included in this service, please contact David Curry at: david.r.curry@centerforvaccineethicsandpolicy.org

WHO issues ethics guidance to protect rights of TB patients
World TB Day 2017 – Unite efforts to leave no one behind
News release
22 March 2017 | GENEVA – New tuberculosis (TB) ethics guidance, launched today by the World Health Organization (WHO), aims to help ensure that countries implementing the End TB Strategy adhere to sound ethical standards to protect the rights of all those affected.

TB, the world’s top infectious disease killer, claims 5 000 lives each day. The heaviest burden is carried by communities which already face socio-economic challenges: migrants, refugees, prisoners, ethnic minorities, miners and others working and living in risk-prone settings, and marginalized women, children and older people.

“TB strikes some of the world’s poorest people hardest,” said Dr Margaret Chan, WHO Director-General. “WHO is determined to overcome the stigma, discrimination, and other barriers that prevent so many of these people from obtaining the services they so badly need.”

Poverty, malnutrition, poor housing and sanitation, compounded by other risk factors such as HIV, tobacco, alcohol use and diabetes, can put people at heightened risk of TB and make it harder for them to access care. More than a third (4.3 million) of people with TB go undiagnosed or unreported, some receive no care at all and others access care of questionable quality.

The new WHO ethics guidance addresses contentious issues such as, the isolation of contagious patients, the rights of TB patients in prison, discriminatory policies against migrants affected by TB, among others. It emphasizes five key ethical obligations for governments, health workers, care providers, nongovernmental organizations, researchers and other stakeholders to:
:: provide patients with the social support they need to fulfil their responsibilities
:: refrain from isolating TB patients before exhausting all options to enable treatment adherence and only under very specific conditions
:: enable “key populations” to access same standard of care offered to other citizens
ensure all health workers operate in a safe environment
:: rapidly share evidence from research to inform national and global TB policy updates…

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Journal of Global Oncology
DOI: http://dx.doi.org/10.1200/JGO.2016.008151
Special Article
Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline
Silvina Arrossi, Instituto Nacional del Cancer, Buenos Aires, Argentina; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Suzanne Garland, University of Melbourne, Melbourne, Victoria, Australia; Linda O’Neal Eckert, University of Washington; Vivien Tsu, PATH, Seattle, WA; Neerja Bhatla, All India Institute of Medical Sciences, New Delhi, India; Xavier Castellsagué and Silvia de Sanjosé, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain; Sharifa Ezat Alkaff, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; Tamika Felder, Cervivor, Upper Marlboro, MD; Doudja Hammouda, Institut National de Santé Publique, Algiers, Algeria; Ryo Konno, Jichi Medical University, Saitama Medical Center, Saitama, Japan; Gilberto Lopes, Sylvester Comprehensive Cancer Center, Miami, FL; Emmanuel Mugisha, PATH, Kampala, Uganda; Rául Murillo, International Agency for Research on Cancer, Lyon, France; Isabel C. Scarinci, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Margaret Stanley, University of Cambridge, Cambridge, United Kingdom; Cosette M. Wheeler, University of New Mexico, Albuquerque, NM; and Isaac Folorunso Adewole, Ministry of Health, Abuja, Nigeria
Abstract
Purpose
To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally.
Methods
The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/ biostatistics, health economics, behavioral/ implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings.
Results E
xisting sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of >= 75%.
Recommendations
In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age >= 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if >= 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus–related cancers and diseases. Basic settings: vaccinating boys is not recommended.

It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Journal Watch
Vaccines and Global Health: The Week in Review continues its weekly scanning of key peer-reviewed journals to identify and cite articles, commentary and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is not intended to be exhaustive, but indicative of themes and issues the Center is actively tracking. We selectively provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to some of the links provided may require subscription or other access arrangement unique to the publisher.

If you would like to suggest other journal titles to include in this service, please contact David Curry at: david.r.curry@centerforvaccineethicsandpolicy.org

BMC Infectious Diseases

(Accessed 25 March 2017)

Research article
Multidrug resistant tuberculosis in Ethiopian settings and its association with previous history of anti-tuberculosis treatment: a systematic review and meta-analysis
Efforts to control the global burden of tuberculosis (TB) have been jeopardized by the rapid evolution of multi-drug resistant Mycobacterium tuberculosis (MTB), which is resistant to at least isoniazid and rifamp…
Setegn Eshetie, Mucheye Gizachew, Mulat Dagnew, Gemechu Kumera, Haile Woldie, Fekadu Ambaw, Belay Tessema and Feleke Moges
BMC Infectious Diseases 2017 17:219
Published on: 20 March 2017

BMC Medical Ethics
http://www.biomedcentral.com/bmcmedethics/content
(Accessed 25 March 2017)

Research article
A qualitative study of participants’ views on re-consent in a longitudinal biobank
Biomedical research increasingly relies on long-term studies involving use and re-use of biological samples and data stored in large repositories or “biobanks” over lengthy periods, often raising questions about whether and when a re-consenting process should be activated. We sought to investigate the views on re-consent of participants in a longitudinal biobank.
Mary Dixon-Woods, David Kocman, Liz Brewster, Janet Willars, Graeme Laurie and Carolyn Tarrant
BMC Medical Ethics 2017 18:22
Published on: 23 March 2017

Epidemiology and Infection
Volume 145 – Issue 5 – April 2017
http://www.cambridge.org/core/journals/epidemiology-and-infection/latest-issue

Research Article
Long-term effectiveness of plasma-derived hepatitis B vaccine 22–28 years after immunization in a hepatitis B virus endemic rural area: is an adult booster dose needed?
Published online: 09 January 2017, pp. 887-894
H. LI, G. J. LI, Q. Y. CHEN, Z. L. FANG, X. Y. WANG, C. TAN, Q. L. YANG, F. Z. WANG, F. WANG, S. ZHANG, S. L. BI, L. P. SHEN
DOI: https://doi.org/10.1017/S0950268816003046

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Research Article
Maximizing the benefits of ART and PrEP in resource-limited settings
Published online: 29 December 2016, pp. 942-956
G. AKUDIBILLAH, A. PANDEY, J. MEDLOCK
DOI: https://doi.org/10.1017/S0950268816002958
Abstract
Antiretroviral therapy (ART) is increasingly being used as an HIV-prevention tool, administered to uninfected people with ongoing HIV exposure as pre-exposure prophylaxis (PrEP) and to infected people to reduce their infectiousness. We used a modelling approach to determine the optimal population-level combination of ART and PrEP allocations required in South Africa to maximize programme effectiveness for four outcome measures: new infections, infection-years, death and cost. We considered two different strategies for allocating treatment, one that selectively allocates drugs to sex workers and one that does not. We found that for low treatment availability, prevention through PrEP to the general population or PrEP and ART to sex workers is key to maximizing effectiveness, while for higher drug availability, ART to the general population is optimal. At South Africa’s current level of treatment availability, using prevention is most effective at reducing new infections, infection-years, and cost, while using the treatment as ART to the general population best reduces deaths. At treatment levels that meet the UNAIDS’s ambitious new 90–90–90 target, using all or almost all treatment as ART to the general population best reduces all four outcome measures considered.

Globalization and Health
http://www.globalizationandhealth.com/
[Accessed 25 March 2017]

Debate
Obstacles and opportunities in Chinese pharmaceutical innovation
Global healthcare innovation networks nowadays have expanded beyond developed countries with many developing countries joining the force and becoming important players. China, in particular, has seen a significant increase in the number of innovative firms and research organizations stepping up to the global network in recent years. Nevertheless, the intense Research and Development input has not brought about the expectable output. While China is ascending at a great speed to a leading position worldwide in terms of Research and Development investment, scientific publications and patents, the innovation capabilities in the pharmaceutical sector remain weak.
Jingyun Ni, Junrui Zhao, Carolina Oi Lam Ung, Yuanjia Hu, Hao Hu and Yitao Wang
Globalization and Health 2017 13:21
Published on: 24 March 2017

Globalization and Health
http://www.globalizationandhealth.com/
[Accessed 25 March 2017]

Research
Operational and implementation research within Global Fund to Fight AIDS, Tuberculosis and Malaria grants: a situation analysis in six countries
Sabine Kiefer, Astrid M. Knoblauch, Peter Steinmann, Tanja Barth-Jaeggi, Mahnaz Vahedi, Dermot Maher, Jürg Utzinger and Kaspar Wyss
Globalization and Health 2017 13:22
Published on: 24 March 2017
Abstract
Background
Operational/implementation research (OR/IR) is a key activity to improve disease control programme performance. We assessed the extent to which malaria and tuberculosis (TB) grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria (“Global Fund”) include support for OR/IR, and discuss the implications of the current Global Fund operating mechanisms for OR/IR support.
Methods
The situation analysis focussed on malaria and TB, while HIV was excluded. Stakeholder interviews were conducted at the Global Fund secretariat and in six purposefully selected high disease burden countries, namely the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Myanmar and Zimbabwe. Interviewed in-country stakeholders included the relevant disease control programme managers, project implementation partners, representatives from international organisations with a stake in global health, academic and governmental research institutions, and other relevant individuals such as members of the country coordination mechanism. Additionally, documentation of grants and OR/IR obtained from the Global Fund was reviewed.
Results
The Global Fund provides substantial resources for malaria and TB surveys, and supports OR/IR if such support is requested and the application is well justified. We observed considerable variations from one country to another and between programmes with regards to need, demand, absorption capacity and funding for OR/IR related to malaria and TB. Important determinants for the extent of such funding are the involvement of national research coordination bodies, established research agendas and priorities, human and technical research capacity, and involvement of relevant stakeholders in concept note development. Efforts to disseminate OR/IR findings were generally weak, and the Global Fund does not maintain a central OR/IR database. When faced with a need to choose between procurement of commodities for disease control and supporting research, countries tend to seek research funding from other donors. The Global Fund is expected to issue more specific guidance on the conditions under which it supports OR/IR, and to adapt administrative procedures to facilitate research.
Conclusions
The importance of OR/IR for optimising disease control programmes is generally accepted but countries vary in their capacity to demand and implement studies. Countries expect guidance on OR/IR from the Global Fund. Administrative procedures specifically related to the budget planning should be modified to facilitate ad-hoc OR/IR funding. More generally, several countries expressed a need to strengthen capacity for planning, negotiating and implementing research

Health Policy and Planning
Volume 32 Issue 3 April 2017
http://heapol.oxfordjournals.org/content/current

Editorial
Privilege and inclusivity in shaping Global Health agendas
Health Policy Plan (2017) 32 (3): 303-304.
Kabir Sheikh, Sara C Bennett, Fadi el Jardali, George Gotsadze
DOI: https://doi.org/10.1093/heapol/czw146
Published: 24 October 2016
Initial text
Northern voices dominate Global Health discussions. Of recent Lancet Commissions, excluding representatives from international organizations, 70% of commissioners on the Women and Health commission came from the global North, and likewise, 71% of the Health and Climate Change commission, 72% of the Global Surgery commission and 73% of the Global Health commission (Lancet 2016). Only two out of the 16-member Board of Directors of the Consortium of Universities of Global Health come from the global South (CUGH 2016). No current or past president and only one current member of the World Health Summit’s scientific committee is from the global South (WHS 2016). Only one of the 17 advisory board members of the journal Global Health Governance is based in a low/middle income…

Health Policy and Planning
Volume 32 Issue 3 April 2017
http://heapol.oxfordjournals.org/content/current

Public health expenditure and health system responsiveness for low-income individuals: results from 63 countries
Chetna Malhotra; Young Kyung Do
Abstract
Improvement in overall responsiveness to people’s expectations is an important goal for any health system; socioeconomic equity in responsiveness is equally important. However, it is not known if socioeconomic disparities in responsiveness can be reduced through greater public health expenditures. This article assesses the relationship of the proportion of public health expenditure over total health expenditure (PPHE) with responsiveness for poorest individuals and the difference in responsiveness between the richest and poorest individuals. We used data from six responsiveness dimensions (prompt attention, dignity, choice, clarity of information, confidentiality and quality of basic amenities) of outpatient services from World Health Survey data from 63 countries. Hierarchical Ordered Probit (HOPIT) models assessed the probability of ‘very good’ responsiveness in each domain among the poorest and richest individuals for each country, correcting for reporting heterogeneity through vignettes. Linear regression models were then used to assess the association between predicted probabilities from HOPIT models and PPHE, adjusting for (log) Gross Domestic Product per capita. The study findings showed that higher PPHE was associated with a higher probability of ‘very good’ responsiveness for each domain among the poorest individuals, and with smaller pro-rich disparities in responsiveness between the richest and poorest individuals. In conclusion, increasing PPHE may improve the responsiveness of health services for the poorest individuals and reduce disparities in responsiveness between the richest and poorest individuals.

Health Policy and Planning
Volume 32 Issue 3 April 2017
http://heapol.oxfordjournals.org/content/current

Editor’s Choice
Government stewardship of the for-profit private health sector in Afghanistan
Harry E. Cross; Omarzaman Sayedi; Laili Irani; Lauren C. Archer; Kathleen Sears …
Abstract
Background: Since 2003, Afghanistan’s largely unregulated for-profit private health sector has grown at a rapid pace. In 2008, the Ministry of Public Health (MoPH) launched a long-term stewardship initiative to oversee and regulate private providers and align the sector with national health goals.
Aim: We examine the progress the MoPH has made towards more effective stewardship, consider the challenges and assess the early impacts on for-profit performance.
Methods: We reviewed publicly available documents, publications and the grey literature to analyse the development, adoption and implementation of strategies, policies and regulations. We carried out a series of key informant/participant interviews, organizational capacity assessments and analyses of hospital standards checklists. Using a literature review of health systems strengthening, we proposed an Afghan-specific definition of six key stewardship functions to assess progress towards MoPH stewardship objectives.
Results: The MoPH and its partners have achieved positive results in strengthening its private sector stewardship functions especially in generating actionable intelligence and establishing strategic policy directions, administrative structures and a legal and regulatory framework. Progress has also been made on improving accountability and transparency, building partnerships and applying minimum required standards to private hospitals. Procedural and operational issues still need resolution and the MoPH is establishing mechanisms for resolving them.
Conclusions: The MoPH stewardship initiative is notable for its achievements to date under challenging circumstances. Its success is due to the focus on developing a solid policy framework and building institutions and systems aimed at ensuring higher quality private services, and a rational long-term and sustainable role for the private sector. Although the MoPH stewardship initiative is still at an early stage, the evidence suggests that enhanced stewardship functions in the MoPH are leading to a more efficient and effective for-profit private sector. These successful early efforts offer high-leverage potential to rapidly scale up going forward.

Health Policy and Planning
Volume 32 Issue 3 April 2017
http://heapol.oxfordjournals.org/content/current

The impact of health insurance on maternal health care utilization: evidence from Ghana, Indonesia and Rwanda
Wenjuan Wang; Gheda Temsah; Lindsay Mallick
Abstract
While research has assessed the impact of health insurance on health care utilization, few studies have focused on the effects of health insurance on use of maternal health care. Analyzing nationally representative data from the Demographic and Health Surveys (DHS), this study estimates the impact of health insurance status on the use of maternal health services in three countries with relatively high levels of health insurance coverage—Ghana, Indonesia and Rwanda. The analysis uses propensity score matching to adjust for selection bias in health insurance uptake and to assess the effect of health insurance on four measurements of maternal health care utilization: making at least one antenatal care visit; making four or more antenatal care visits; initiating antenatal care within the first trimester and giving birth in a health facility. Although health insurance schemes in these three countries are mostly designed to focus on the poor, coverage has been highly skewed toward the rich, especially in Ghana and Rwanda. Indonesia shows less variation in coverage by wealth status. The analysis found significant positive effects of health insurance coverage on at least two of the four measures of maternal health care utilization in each of the three countries. Indonesia stands out for the most systematic effect of health insurance across all four measures. The positive impact of health insurance appears more consistent on use of facility-based delivery than use of antenatal care. The analysis suggests that broadening health insurance to include income-sensitive premiums or exemptions for the poor and low or no copayments can increase use of maternal health care.

Health Policy and Planning
Volume 32 Issue 3 April 2017
http://heapol.oxfordjournals.org/content/current

Review
Support and performance improvement for primary health care workers in low- and middle-income countries: a scoping review of intervention design and methods
Ashwin Vasan; David C. Mabey; Simran Chaudhri; Helen-Ann Brown Epstein; Stephen D. Lawn
Abstract
Primary health care workers (HCWs) in low- and middle-income settings (LMIC) often work in challenging conditions in remote, rural areas, in isolation from the rest of the health system and particularly specialist care. Much attention has been given to implementation of interventions to support quality and performance improvement for workers in such settings. However, little is known about the design of such initiatives and which approaches predominate, let alone those that are most effective. We aimed for a broad understanding of what distinguishes different approaches to primary HCW support and performance improvement and to clarify the existing evidence as well as gaps in evidence in order to inform decision-making and design of programs intended to support and improve the performance of health workers in these settings. We systematically searched the literature for articles addressing this topic, and undertook a comparative review to document the principal approaches to performance and quality improvement for primary HCWs in LMIC settings. We identified 40 eligible papers reporting on interventions that we categorized into five different approaches: (1) supervision and supportive supervision; (2) mentoring; (3) tools and aids; (4) quality improvement methods, and (5) coaching. The variety of study designs and quality/performance indicators precluded a formal quantitative data synthesis. The most extensive literature was on supervision, but there was little clarity on what defines the most effective approach to the supervision activities themselves, let alone the design and implementation of supervision programs. The mentoring literature was limited, and largely focused on clinical skills building and educational strategies. Further research on how best to incorporate mentorship into pre-service clinical training, while maintaining its function within the routine health system, is needed. There is insufficient evidence to draw conclusions about coaching in this setting, however a review of the corporate and the business school literature is warranted to identify transferrable approaches. A substantial literature exists on tools, but significant variation in approaches makes comparison challenging. We found examples of effective individual projects and designs in specific settings, but there was a lack of comparative research on tools across approaches or across settings, and no systematic analysis within specific approaches to provide evidence with clear generalizability. Future research should prioritize comparative intervention trials to establish clear global standards for performance and quality improvement initiatives. Such standards will be critical to creating and sustaining a well-functioning health workforce and for global initiatives such as universal health coverage.

Health Research Policy and Systems
http://www.health-policy-systems.com/content
[Accessed 25 March 2017]

Research
International consultation on long-term global health research priorities, research capacity and research uptake in developing countries
David Mc Conalogue, Sue Kinn, Jo-Ann Mulligan and Malcolm McNeil
Health Research Policy and Systems 2017 15:24
Published on: 21 March 2017
Abstract
Background
In recognition of the need for long-term planning for global health research, and to inform future global health research priorities, the United Kingdom Department for International Development (DfID) carried out a public consultation between May and June 2015. The consultation aimed to elicit views on the (1) the long-term future global health research priorities; (2) areas likely to be less important over time; (3) how to improve research uptake in low-income countries; and (4) how to build research capacity in low-income countries.
Methods
An online consultation was used to survey a wide range of participants on global health research priorities. The qualitative data was analysed using a thematic analysis, with frequency of codes in responses tabulated to approximate relative importance of themes and sub-themes.
Results
The public consultation yielded 421 responses. The survey responses confirmed the growing importance of non-communicable disease as a global health research priority, being placed above infectious diseases. Participants felt that the key area for reducing funding prioritisation was infectious diseases. The involvement of policymakers and other key stakeholders was seen as critical to drive research uptake, as was collaboration and partnership. Several methods to build research capacity in low-income countries were described, including capacity building educational programmes, mentorship programmes and research institution collaboration and partnership.
Conclusions
The outcomes from this consultation survey provide valuable insights into how DfID stakeholders prioritise research. The outcomes from this survey were reviewed alongside other elements of a wider DfID consultation process to help inform long-term research prioritisation of global health research. There are limitations in this approach; the opportunistic nature of the survey’s dissemination means the findings presented may not be representative of the full range of stakeholders or views.

International Health
Volume 9, Issue 2 March 2017
http://inthealth.oxfordjournals.org/content/current

Editor’s Choice
Strategies for halting the rise of multidrug resistant TB epidemics: assessing the effect of early case detection and isolation
Aquino L. Espindola; Marie Varughese; Marek Laskowski; Affan Shoukat; Jane M. Heffernan …
Abstract
Background
The increasing rates of multidrug resistant TB (MDR-TB) have posed the question of whether control programs under enhanced directly observed treatment, short-course (DOTS-Plus) are sufficient or implemented optimally. Despite enhanced efforts on early case detection and improved treatment regimens, direct transmission of MDR-TB remains a major hurdle for global TB control.
Methods
We developed an agent-based simulation model of TB dynamics to evaluate the effect of transmission reduction measures on the incidence of MDR-TB. We implemented a 15-day isolation period following the start of treatment in active TB cases. The model was parameterized with the latest estimates derived from the published literature.
Results
We found that if high rates (over 90%) of TB case identification are achieved within 4 weeks of developing active TB, then a 15-day patient isolation strategy with 50% effectiveness in interrupting disease transmission leads to 10% reduction in the incidence of MDR-TB over 10 years. If transmission is fully prevented, the rise of MDR-TB can be halted within 10 years, but the temporal reduction of MDR-TB incidence remains below 20% in this period.
Conclusions
The impact of transmission reduction measures on the TB incidence depends critically on the rates and timelines of case identification. The high costs and adverse effects associated with MDR-TB treatment warrant increased efforts and investments on measures that can interrupt direct transmission through early case detection.

International Health
Volume 9, Issue 2 March 2017
http://inthealth.oxfordjournals.org/content/current

The yield and feasibility of integrated screening for TB, diabetes and HIV in four public hospitals in Ethiopia
Degu Jerene; Nebiyu Hiruy; Ilili Jemal; Wondimu Gebrekiros; Tadesse Anteneh …
Abstract
Background
Our objective was to demonstrate the feasibility of integrated care for TB, HIV and diabetes mellitus (DM) in a pilot project in Ethiopia.
Methods
Healthcare workers in four hospitals screened patients with TB for HIV and DM; patients with HIV for DM and TB; and patients with DM for TB. Fasting and random plasma glucose (RPG) tests were used to confirm the diagnosis of DM. We used screening checklists for TB and DM, and additional risk scoring criteria to identify patients at risk of DM.
Results
Of 3439 study participants, 888 were patients with DM, 439 patients with TB and 2112 from HIV clinics. Six of the patients with DM had TB of whom five were already on treatment; and 141 (32.4%) patients with TB had DM, of whom only five were previously diagnosed with DM. Symptomatic patients and those with a risk score of 5 or more were about three times more likely to have abnormal blood glucose level. Of 2075 HIV patients with RPG determined, only 31 (1.5%) had abnormal RPG.
Conclusions
Tri-directional screening was feasible for detecting and managing previously undiagnosed TB and DM. More work is needed to better understand the interaction between HIV and DM.

Journal of the Pediatric Infectious Diseases Society (JPIDS)
Volume 6 Issue 1, March 2017
http://jpids.oxfordjournals.org/content/current

ORIGINAL ARTICLES
Reflections of a Vaccinologist: Lessons Learned About What We Can Do to Improve Trust in Vaccines and Vaccine Programs
Neal A. Halsey
Abstract
Public trust can be improved by learning from past mistakes, by establishing a standing forum for review of new concerns as they arise, and by maintaining a robust vaccine safety system. Developing standard guidelines for reporting causality assessment in case reports would help educate physicians and prevent future unnecessary concerns based on false assumptions of causal relationships.

The Lancet
Mar 25, 2017 Volume 389 Number 10075 p1165-1272 e4
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Trauma for migrant children stranded in Greece
The Lancet
A Save the Children report released on March 16 raises alarm about the dire consequences of the deal made between the European Union (EU) and Turkey that limits the number of migrants and refugees entering Europe via Greece. 1 year after the agreement, thousands of people, many escaping Syria or Iraq, are now stranded on Greek islands. They are living in limbo waiting for asylum or passage, prohibited from leaving, and effectively imprisoned. Conditions are said to be appalling with limited infrastructure and facilities. Of the 13 200 migrants and refugees stranded in the Aegean islands, more than 5000 are children, some of whom are unaccompanied or separated from their families. The report calls for the EU and Greece to immediately end the illegal detention of children and to better protect them. But given the extent of the health consequences documented by Save the Children, the medical community also needs to act urgently.

The charity says that children trapped on the Greek islands are showing signs of depression, anxiety, and distress. Bedwetting, nightmares, and aggressive behaviour are increasing. Some children have witnessed deaths, fires, protests, and police violence in the camps. Basic needs for food, water, and sanitation are barely being met, says the report. Shockingly, children as young as 9 years have attempted suicide or self-harm.

Affected children are clearly traumatised. Many will have already fled war, poverty, or persecution. Along the way they may have lost parents or siblings or been separated from them. But instead of treating that trauma, our collective failure has led to their re-traumatisation. At such a crucial time of a child’s development, the physical and mental health effects of this unacceptable detention are devastating. The long-term consequences will be worse. The medical community should act immediately: we must insist on the removal of these children from the camps with their families into safe and humane shelter. We must provide the health care and treatment these children need to recover from their trauma. And we must support all efforts to help them regain their resilience and hope for free and full lives.

The Lancet
Mar 25, 2017 Volume 389 Number 10075 p1165-1272 e4
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Preparing for future global health emergencies
The Lancet
On March 13–14, Chatham House and the Graduate Institute Geneva-Global Health Centre hosted a roundtable meeting on preparedness for global health crises. Representatives from WHO and the UN, including member states, global health and development agencies, foundations, academia, and non-profit initiatives shared their work and experiences on monitoring preparedness for outbreaks and other public health emergencies.

Several themes emerged. Global preparedness for outbreaks is improving in some regions, and changes to the global response architecture are underway. A broad range of sectors must be involved, from animal and livestock to human health and trade. Current monitoring and tracking of preparedness use indicators from the International Health Regulations (IHR) and a joint external evaluation process for IHR requirements has begun. Tracking for Sustainable Development Goals and the Sendai framework for disaster risk reduction is being considered. Reporting on progress is voluntary, non-existent, or overlapping, and tracking of global commitments and responsibilities is largely absent.

Views differed on how to monitor contributions to global, national, and regional preparedness and mutual accountability, but there was consensus that country-level preparedness, financing, and sharing of information, research, and health technologies are vital. Independent accountability is needed to ensure all stakeholders are acting on their commitments to help raise the profile of preparedness politically. This effort will require an ecosystem of multiple stakeholders, a range of expertise, and diverse data sources.

Chatham House and the Graduate Institute will contribute to this ecosystem through a new Monitoring and Accountability for Preparedness initiative (MAP-Global Health Crises). Harvard University and the US National Academy of Sciences have convened a meeting to advance these discussions on April 18, and meetings are planned by others. The Geneva meeting is a good first step towards identifying the stakeholder ecosystem required to ensure that countries and the global community continue to strengthen their collective preparedness for the health crises that will inevitably arise.

The Lancet
Mar 25, 2017 Volume 389 Number 10075 p1165-1272 e4
http://www.thelancet.com/journals/lancet/issue/current

Articles
Socioeconomic status and the 25 × 25 risk factors as determinants of premature mortality: a multicohort study and meta-analysis of 1·7 million men and women
Silvia Stringhini, Cristian Carmeli, Markus Jokela, Mauricio Avendaño, Peter Muennig, Florence Guida, Fulvio Ricceri, Angelo d’Errico, Henrique Barros, Murielle Bochud, Marc Chadeau-Hyam, Françoise Clavel-Chapelon, Giuseppe Costa, Cyrille Delpierre, Silvia Fraga, Marcel Goldberg, Graham G Giles, Vittorio Krogh, Michelle Kelly-Irving, Richard Layte, Aurélie M Lasserre, Michael G Marmot, Martin Preisig, Martin J Shipley, Peter Vollenweider, Marie Zins, Ichiro Kawachi, Andrew Steptoe, Johan P Mackenbach, Paolo Vineis, Mika Kivimäki for the LIFEPATH consortium
1229
Open Access
Abstract
Background
In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors.
Methods
We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1,751,479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors.
Findings
During 26.6 million person-years at risk (mean follow-up 13.3 years [SD 6.4 years]), 310,277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1.04 (95% CI 0.98–1.11) for obesity in men and 2.17 (2·06–2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1.42, 95% CI 1.38–1.45 for men; 1.34, 1.28–1.39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1.26, 1·21–1.32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2.1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0.5 years for high alcohol intake, 0.7 years for obesity, 3.9 years for diabetes, 1.6 years for hypertension, 2.4 years for physical inactivity, and 4.8 years for current smoking.
Interpretation
Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality.
Funding
European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.

Lancet Respiratory Medicine
Apr 2017 Volume 5 Number 4 p235-360
http://www.thelancet.com/journals/lanres/issue/current
The Lancet Respiratory Medicine Commission

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh Jr, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
291
Summary
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem.

In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms—including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions—are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.

Nature
Volume 543 Number 7646 pp463-582 23 March 2017
http://www.nature.com/nature/current_issue.html

Editorial
Trump faces backlash on health-agency cuts
Crippling the US National Institutes of Health might increase resistance to other attacks on science.

Editorial
The FDA chief must not be a proxy for industry
Trump’s pick for the US regulatory agency will bring experience and a clear vision — as well as ties to industry.

New England Journal of Medicine
March 23, 2017  Vol. 376 No. 12
http://www.nejm.org/toc/nejm/medical-journal

Perspective
Chilling Effect? Post-Election Health Care Use by Undocumented and Mixed-Status Families
K.R. Page and S. Polk
Excerpt
…Today, the ACA’s fate is unclear, with implications for millions of Americans.5 We cannot predict how health care access will be reshaped, yet it’s all but certain that undocumented immigrants who were never eligible for ACA benefits will not have better access to care. Access may be significantly reduced if financial penalties are applied to states or cities that refuse to cooperate with ICE. Overt restrictions on basic public services, such as schools or public health clinics, are unlikely, given that such measures were ruled unconstitutional in the 1990s (California Proposition 187), but access could be restricted by requiring government-issued identification cards or Social Security numbers at federally qualified health centers or health department clinics. In addition, as our pregnant patient showed us, a climate of deportation may dampen the use of existing resources, even among eligible people.5

To reduce barriers to care for immigrant families, the medical and public health community can engage in local and national politics and promote a welcoming, inclusive environment in our practices. Clinicians have access to powerful stories of human suffering and strength. The current climate presents a renewed opportunity to partner with advocacy groups and media to share stories of human experience that counter the Trump administration’s negative narrative about immigrants. The sharing of personal stories about the impact of the temporary immigrant ban through social and mainstream media has energized millions of people to express opposition to the ban. Portraits of scientists and doctors affected by the ban highlighted its unintended consequences for science and health care. Telling human stories is an effective rapid-response tool that we can use to advocate for our patients.

Clinicians and public health practitioners can also join forces to harness the power of data. We can monitor and measure health care utilization and health outcomes. Clinicians can pay attention to patterns in health care utilization among their immigrant patients and communicate worrisome trends to public health professionals. Some markers of child well-being — such as Medicaid enrollment rates among eligible children of foreign-born parents, teen pregnancy rates, uptake of supplemental nutrition assistance programs, school attendance, and bullying reports — are already monitored, allowing comparison of the pre- and post-election periods.

The election’s implications for undocumented adults may be more complicated to evaluate, since these adults are often invisible in conventional databases because of barriers to care and insufficient collection of relevant sociodemographic data (i.e., ethnic background, country of origin, and language preference). It’s important to develop inclusive methods that account for the unique needs of hidden populations. Some existing measures, however, can provide indications of a chilling effect, including utilization of safety-net clinics for sexual and reproductive health care, timeliness of prenatal care, domestic violence reports, and hate crimes (especially assaults resulting in emergency department visits)…

There are many reasons to support equitable access to care for all, regardless of nationality. Objective and scientifically rigorous data analysis will be essential in elucidating the interconnection between immigrants’ health and the public health and health care costs of the United States.

.

Editorial
Rotavirus Vaccines — A New Hope
Mathuram Santosham, M.D., M.P.H., and Duncan Steele, Ph.D.
N Engl J Med 2017; 376:1170-1172 March 23, 2017 DOI: 10.1056/NEJMe1701347
[See full text in Milestones section above]

.

Original Article
Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger
Sheila Isanaka, Sc.D., Ousmane Guindo, M.D., Celine Langendorf, Pharm.D., M.P.H., Amadou Matar Seck, M.D., Brian D. Plikaytis, M.Sc., Nathan Sayinzoga-Makombe, M.P.H., Monica M. McNeal, M.Sc., Nicole Meyer, M.Sc., Eric Adehossi, M.D., Ali Djibo, M.D., Bruno Jochum, M.S., and Rebecca F. Grais, Ph.D.
N Engl J Med 2017; 376:1121-1130 March 23, 2017 DOI: 10.1056/NEJMoa1609462
Abstract
[See full abstract in Milestones section above]

PLOS Currents: Disasters
http://currents.plos.org/disasters/
[Accessed 25 March 2017]

Brief Report
The Development of a Veterans Health Administration Emergency Management Research Agenda
March 23, 2017 ·
Introduction: The Veterans Health Administration (VHA), the largest integrated healthcare delivery system in the United States, is charged with ensuring timely access to high-quality care for veterans during disasters, and supporting national, state, local, and tribal emergency management and homeland security efforts. In 2008, the VHA Office of Public Health (OPH) sponsored the first VHA Emergency Management Research Agenda-setting conference to develop research priorities that address the needs of veterans and to position VHA as a national leader in emergency management by having VHA serve as a “laboratory” for the development of evidence-based emergency management practices.
Methods: We focused on four steps: #1: Appraising the emergency management research portfolio of VHA-based researchers; #2: Obtaining systematic information on VHA’s role in emergency management and the healthcare needs of veterans during disasters; #3: Based upon gaps between the current research portfolio and the existing evidence base, identifying strategic priorities using a research agenda-setting conference; and #4: Laying the groundwork to foster the conduct of emergency management research within VHA.
Results: Identified research priorities included how to prevent and treat behavioral health problems related to a disaster, the efficacy of training programs, crisis communication strategies, workforce resilience, and evacuating veterans from health care facilities.
Conclusion: VHA is uniquely situated to answer research questions that cannot be readily addressed in other settings. VHA should partner with other governmental and private entities to build on existing work and establish shared research priorities.

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 25 March 2017)

Editorial
Will a new 2017 global leadership commit to NTDs?
Peter J. Hotez, Serap Aksoy
| published 23 Mar 2017 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0005309
Initial text
[In] 2017 we will experience a nearly wholesale shift in global governance as it relates to the world’s neglected tropical diseases (NTDs). A new United Nations (UN) Secretary General, Antonio Guterres from Portugal, was just appointed and we’ll soon have in place a new World Health Organization (WHO) Director General. In addition, the United States Government has so far been the largest financier of NTD mass drug administration (MDA), as well as research and development (R&D) for NTDs. A new US President, President Donald Trump, is now in the White House, while Prime Minister Theresa May has been appointed as the new British Prime Minister. The United Kingdom is probably the second largest global supporter of NTDs.
How shall we advocate? What does our community of NTD scientists, public health experts, and health care providers want this new global leadership to know about our diseases? What should they prioritize? Clearly, consensus on this front is problematic, but based on your submissions, emails, and letters, here are some early thoughts…