Journal of Infectious Diseases
Volume 214 Issue 10 November 15, 2016
http://jid.oxfordjournals.org/content/current

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EDITORIAL COMMENTARIES
Challenges Remain for Influenza Vaccination of Children
J Infect Dis. (2016) 214 (10): 1470-1472 doi:10.1093/infdis/jiw384
Kathryn M. Edwards and Wendy A. Keitel
Extract
Over the past decades, multiple active surveillance and observational studies have demonstrated the major impact of influenza on children and underscored the need for effective vaccines [1–4]. Since 2009, annual influenza vaccination has been recommended for all children ≥6 months of age in the United States [5]. Extensive studies in children have been conducted over the years with both inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV). Influenza hemagglutination inhibition (HAI) antibody responses are considered to be the gold standard for assessing IIV immunogenicity and serve as the basis for their licensure. Although achievement of HAI antibody titers of ≥40 (putative protective titer) was associated with a 50% reduction in the occurrence of influenza [6, 7], others have proposed that the protective HAI titer is much higher [8]. Furthermore, there can be variability in HAI assay results among laboratories [9]. Cell-mediated immune (CMI) responses have been less well characterized, and no CMI correlate of protection (COP) has been proposed.’

In this issue of The Journal of Infectious Diseases, Reber et al report detailed humoral and CMI responses in 50 children ages 9–14 years after receipt of the 2010–2011 seasonal IIV [10]. In the previous year, 38% of the participants had received influenza vaccine (10% received LAIV and 28% received IIV), and 32% had been immunized with monovalent 2009 pandemic influenza A(H1N1) vaccine. Which vaccine(s) the children had received previously was not noted in the article, and their impact on subsequent immune responses was not assessed because of small sample size. HAI antibody responses were assayed against influenza virus antigens included in both the 2009–2010 and 2010–2011 vaccines, as well as the …

Journal of Medical Ethics
November 2016, Volume 42, Issue 11
http://jme.bmj.com/content/current

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Brief report
Ethical issues and best practice in clinically based genomic research: Exeter Stakeholders Meeting Report
D Carrieri, C Bewshea, G Walker, T Ahmad, W Bowen, A Hall, S Kelly, on behalf of the 7th of October 2015 Exeter Stakeholders Meeting
J Med Ethics 2016;42:695-697 Published Online First: 27 September 2016 doi:10.1136/medethics-2016-103530
Abstract
Current guidelines on consenting individuals to participate in genomic research are diverse. This creates problems for participants and also for researchers, particularly for clinicians who provide both clinical care and research to their patients. A group of 14 stakeholders met on 7 October 2015 in Exeter to discuss the ethical issues and the best practice arising in clinically based genomic research, with particular emphasis on the issue of returning results to study participants/patients in light of research findings affecting research and clinical practices. The group was deliberately multidisciplinary to ensure that a diversity of views was represented. This report outlines the main ethical issues, areas of best practice and principles underlying ethical clinically based genomic research discussed during the meeting. The main point emerging from the discussion is that ethical principles, rather than being formulaic, should guide researchers/clinicians to identify who the main stakeholders are to consult with for a specific project and to incorporate their voices/views strategically throughout the lifecycle of each project. We believe that the mix of principles and practical guidelines outlined in this report can contribute to current debates on how to conduct ethical clinically based genomic research.

The Lancet
Nov 05, 2016 Volume 388 Number 10057 p2209-2322 e12
http://www.thelancet.com/journals/lancet/issue/current

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Editorial
After Bolam: what’s the future for patient consent?
The Lancet
Published: 05 November 2016
“Patients are now widely regarded as persons holding rights, rather than as the passive recipients of the care of the medical profession”, declared the UK Supreme Court in the case of Montgomery vs Lanarkshire Health Board in 2015, affirming the patient as a subject and not simply the object of medical care. Before Montgomery, whether doctors reasonably communicated risks to patients about potential procedures was judged by reference to a responsible body of medical opinion (Bolam test), in line with the paternalistic model of medicine. Since Montgomery, what makes a risk material for a doctor to tell their patient about are the circumstances, views, and values of the individual patient, rather than the opinion of the medical profession.

In response to this renewed emphasis on patients’ rights to self-determination, the Royal College of Surgeons has released new guidance to help surgeons and other health-care professionals to obtain and document consent. Recognising that it is not enough to simply substitute expert opinion with an exhaustive list of potential risks and benefits, the guidance advocates for “supported decision-making”, with a focus on tailoring discussions to individual patients.

Considerable practical challenges loom large, not least of which is time. The guidance states that to determine the content of discussions around risk, doctors should take time to get to know their patients. These discussions need to take place long enough before planned interventions so patients have enough time to reflect, and in particularly complex or potentially life changing scenarios might need to take place over several sessions.

To deal with the new time pressures that this approach will involve, the guidance recommends surgeons raise the issue with their hospital management. But surely, to enable real patient-centred decision making to take root, we must do more than simply tell already time-pressed doctors to find yet more time. Such changes will require cultural and administrative reform at the institutional level. If we want to support patient choice and autonomy, then we must empower our medical professionals with the resources they need to make it happen.

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Series
Maternal Health
Drivers of maternity care in high-income countries: can health systems support woman-centred care?
Dorothy Shaw, Jeanne-Marie Guise, Neel Shah, Kristina Gemzell-Danielsson, KS Joseph, Barbara Levy, Fontayne Wong, Susannah Woodd, Elliott K Main

Maternal Health
Next generation maternal health: external shocks and health-system innovations
Margaret E Kruk, Stephanie Kujawski, Cheryl A Moyer, Richard M Adanu, Kaosar Afsana, Jessica Cohen, Amanda Glassman, Alain Labrique, K Srinath Reddy, Gavin Yamey

Maternal Health
Quality maternity care for every woman, everywhere: a call to action
Marjorie Koblinsky, Cheryl A Moyer, Clara Calvert, James Campbell, Oona M R Campbell, Andrea B Feigl, Wendy J Graham, Laurel Hatt, Steve Hodgins, Zoe Matthews, Lori McDougall, Allisyn C Moran, Allyala K Nandakumar, Ana Langer
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Lancet Global Health
Nov 2016 Volume 4 Number 11 e761-e871
http://www.thelancet.com/journals/langlo/issue/current
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Articles
Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models
Rein M G J Houben, Nicolas A Menzies, Tom Sumner, Grace H Huynh, Nimalan Arinaminpathy, Jeremy D Goldhaber-Fiebert, Hsien-Ho Lin, Chieh-Yin Wu, Sandip Mandal, Surabhi Pandey, Sze-chuan Suen, Eran Bendavid, Andrew S Azman, David W Dowdy, Nicolas Bacaër, Allison S Rhines, Marcus W Feldman, Andreas Handel, Christopher C Whalen, Stewart T Chang, Bradley G Wagner, Philip A Eckhoff, James M Trauer, Justin T Denholm, Emma S McBryde, Ted Cohen, Joshua A Salomon, Carel Pretorius, Marek Lalli, Jeffrey W Eaton, Delia Boccia, Mehran Hosseini, Gabriela B Gomez, Suvanand Sahu, Colleen Daniels, Lucica Ditiu, Daniel P Chin, Lixia Wang, Vineet K Chadha, Kiran Rade, Puneet Dewan, Piotr Hippner, Salome Charalambous, Alison D Grant, Gavin Churchyard, Yogan Pillay, L David Mametja, Michael E Kimerling, Anna Vassall, Richard G White

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models
Nicolas A Menzies, Gabriela B Gomez, Fiammetta Bozzani, Susmita Chatterjee, Nicola Foster, Ines Garcia Baena, Yoko V Laurence, Sun Qiang, Andrew Siroka, Sedona Sweeney, Stéphane Verguet, Nimalan Arinaminpathy, Andrew S Azman, Eran Bendavid, Stewart T Chang, Ted Cohen, Justin T Denholm, David W Dowdy, Philip A Eckhoff, Jeremy D Goldhaber-Fiebert, Andreas Handel, Grace H Huynh, Marek Lalli, Hsien-Ho Lin, Sandip Mandal, Emma S McBryde, Surabhi Pandey, Joshua A Salomon, Sze-chuan Suen, Tom Sumner, James M Trauer, Bradley G Wagner, Christopher C Whalen, Chieh-Yin Wu, Delia Boccia, Vineet K Chadha, Salome Charalambous, Daniel P Chin, Gavin Churchyard, Colleen Daniels, Puneet Dewan, Lucica Ditiu, Jeffrey W Eaton, Alison D Grant, Piotr Hippner, Mehran Hosseini, David Mametja, Carel Pretorius, Yogan Pillay, Kiran Rade, Suvanand Sahu, Lixia Wang, Rein M G J Houben, Michael E Kimerling, Richard G White, Anna Vassall

Quality of basic maternal care functions in health facilities of five African countries: an analysis of national health system surveys
Margaret E Kruk, Hannah H Leslie, Stéphane Verguet, Godfrey M Mbaruku, Richard M K Adanu, Ana Langer

ancet Global Health
Nov 2016 Volume 4 Number 11 e761-e871
http://www.thelancet.com/journals/langlo/issue/current
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Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study
Andrew S Azman, Lucy A Parker, John Rumunu, Fisseha Tadesse, Francesco Grandesso, Lul L Deng, Richard Laku Lino, Bior K Bior, Michael Lasuba, Anne-Laure Page, Lameck Ontweka, Augusto E Llosa, Sandra Cohuet, Lorenzo Pezzoli, Dossou Vincent Sodjinou, Abdinasir Abubakar, Amanda K Debes, Allan M Mpairwe, Joseph F Wamala, Christine Jamet, Justin Lessler, David A Sack, Marie-Laure Quilici, Iza Ciglenecki, Francisco J Luquero
e856
Summary
Background
Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2–4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.
Methods
We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).
Findings
Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5–100·0) and after adjusting for potential confounders was 87·3% (70·2–100·0).
Interpretation
One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.
Funding
Médecins Sans Frontières.

Lancet Global Health
Nov 2016 Volume 4 Number 11 e761-e871
http://www.thelancet.com/journals/langlo/issue/current
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Comment
2016: the beginning of the end of rabies?
Bernadette Abela-Ridder, Lea Knopf, Stephen Martin, Louise Taylor, Gregorio Torres, Katinka De BaloghPublished: 27 September 2016
Open Access
DOI: http://dx.doi.org/10.1016/S2214-109X(16)30245-5
Sept 28 is the tenth annual World Rabies Day. It is a date that commemorates the anniversary of the 1895 death of Louis Pasteur, who developed the first human rabies vaccine. Modern effective vaccines, combined with other interventions, the necessary political will, and community awareness make the disease 100% preventable. Yet, an estimated 59 000 people still die from the disease every year.1 World Rabies Day is thus an uncomfortable reminder for the global health community of the ongoing neglect of this disease. The theme for 2016 is “Educate. Vaccinate. Eliminate”, a slogan that emphasises the pillars of rabies prevention and the vision to end human rabies deaths.

Rabies has no cure, and by the time of clinical onset it is invariably fatal. More than 95% of deaths occur in Africa and Asia, 80% of which are in people living in rural, underserved populations, most of whom are children.2 Community awareness about the power of preventing dog bites and of life-saving human post-exposure prophylaxis is key. 95–99% of human rabies cases are from dog bites, meaning that canine vaccination programmes are crucial if the transmission cycle is to be broken.3 Cross-sectoral solutions from stakeholders in both human and animal health systems are essential for the greatest benefits to be realised.

In December, 2015, WHO, the World Organisation for Animal Health (OIE), the Food and Agriculture Organization (FAO), and the Global Alliance for Rabies Control (GARC) endorsed a global framework to eliminate human deaths from dog-mediated disease by 2030.4 The decision was reinforced by the OIE in May this year.5 A business plan by the key organisations to quantify the costs of reaching zero rabies deaths across the world is under development.
Under our One Health Initiative, WHO, OIE, FAO, and GARC are working on concurrent campaigns to eliminate canine rabies through the vaccination of dogs, the treatment of all potential human rabies exposures with wound washing and post-exposure prophylaxis, and the improvement of education about rabies prevention where it is needed most. By prioritising rabies, our partnership also intends to leverage the global political will needed to eliminate the disease. Reaching zero rabies deaths would contribute towards fulfilling the Sustainable Development Goals, particularly goal 3·3, which targets an end to epidemics of neglected tropical diseases. The goal is ambitious but possible, as evidenced by the progress made in rabies campaigns around the world.4, 6 Such examples of successful multisectoral approaches serve as both a reference and motivation for future campaigns.

Countries will need improved access to high quality and optimally priced dog and human vaccines, as well as to rabies immunoglobulins. Insufficient national forecasting at present means that vaccine requests from countries to manufacturers can be left unfulfilled because of long lead times in production. In such instances, countries are forced to turn to suppliers without quality-assured vaccine. Improvements in supply will help to overcome these difficulties. To match the OIE-led dog rabies vaccine bank,7 WHO is therefore creating a human rabies vaccine stockpile, planned to be operation by the end of next year.

The opportunity of a potential GAVI investment into human rabies vaccine in 2018 has rallied partners and countries to build the evidence base to help inform the investment decision process. Investment from GAVI would be a game changer and substantially increase awareness about this disease and stimulate the necessary political will. With dog vaccination campaigns increasing in reach, the possibility of interrupting rabies transmission will become more tangible. This goal is helped by the availability of online resources such as the Blueprint for Rabies Prevention and Control,8 which offers practical information, expert advice, and case studies to support countries that want to eliminate rabies. FAO and GARC are assisting countries with practical tools for developing their rabies control strategies.9

World Rabies Day increases the awareness about this neglected and horrific disease. It will also make people aware of the realistic ambition of interrupting transmission in dogs and, in turn, the reality of one day eliminating dog-mediated rabies in people. We have all the tools to end this neglected zoonotic disease—what is required is a coordinated effort from all stakeholders at local, national, regional, and global levels to realise the vision of zero human deaths from dog-mediated rabies by 2030.
We declare no competing interests.

Lancet Global Health
Nov 2016 Volume 4 Number 11 e761-e871
http://www.thelancet.com/journals/langlo/issue/current
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Comment
New strategies for cholera control
Louise C Ivers
Open Access
DOI: http://dx.doi.org/10.1016/S2214-109X(16)30257-1
Cholera remains a serious global public health problem, disproportionately affecting poor individuals, causing illness and death for thousands of people each year. Cholera cases are on the rise, with 47% more cases reported to WHO in 2014 than in 2013.1 Innovative approaches to control the disease are urgently needed, and the study by Andrew Azman and colleagues in The Lancet Global Health2 contributes to growing evidence of the important part that oral cholera vaccine strategies have to play in this regard.

Cholera can have devastating consequences, especially in epidemic settings. Azman and colleagues’ study assesses the effectiveness of a single dose of bivalent whole-cell oral cholera vaccine on epidemic cholera in Juba, South Sudan. Typically, this oral cholera vaccine is given in two doses 14 days apart, and studies have shown its efficacy and effectiveness with this dosing schedule.3, 4, 5 However, the use of one dose of vaccine for an outbreak response would reduce costs and double the number of people that could be served, which is especially important considering the global shortage of vaccine that is expected to last for the next few years. Faced with an emerging epidemic of cholera in South Sudan, limited vaccine supply, and some evidence that a single dose of vaccine might give sufficient protection to thwart an epidemic, local public health officials and the non-governmental organisation Médecins Sans Frontières decided to proceed with a single-dose public health oral cholera vaccine campaign in Juba. Public health activities and a research study took place hand in hand.

The study found that the adjusted single-dose vaccine effectiveness was 87·3% (70·2–100·0) for reducing medically attended cholera for up to 2 months. This adds to existing evidence including a randomised study of a single-dose regimen from Bangladesh that found 40% direct effectiveness for reducing all cholera, and 63% direct effectiveness for reducing severely dehydrating cholera at 6 months.6 By contrast, Azman and colleagues used a case-cohort study design in an effort to measure both the direct and indirect protection offered by the vaccine (ie, herd protection), and measured effectiveness in a shorter period. This design makes the study particularly interesting and pertinent to dilemmas in the approach to cholera outbreak control. Debate continues between water, sanitation, and hygiene (WASH) purists, who believe that investments in cholera vaccination campaigns are a distraction from the goal of universal access to water and sanitation, and a more progressive public health community that advocates for a combined approach to cholera control including vaccination and evidence-based WASH interventions. In this context, a study that helps us to measure the herd protection of an oral cholera vaccine strategy is key to understanding the population-level effect and therefore the public health usefulness of oral cholera vaccine (beyond individual protection).

This study is also an excellent example of research in action. Resolving, as the researchers did, to be scientific in the context of rapid decision making and the often chaotic environment of an epidemic response is not straightforward. The context of the study means that the results are particularly useful for understanding the intervention as it might happen in the real world, outside of a formal research setting. More studies like this are needed for us to understand the right approaches for use of cholera vaccine.

Armed with the results of this study, public health officials and implementing organisations in areas where cholera occurs with some frequency should consider the option of using a single-dose vaccination campaign as part of an emergency outbreak response. This should be coupled with good monitoring and evaluation activities to continue to add to our knowledge on the issue.

Importantly, the usefulness of single-dose oral cholera vaccine in cholera-naive populations cannot be presumed on the basis of this study, and the authors acknowledge this fact. The impetus now exists, though, to study the approach in cholera-naive populations. Further questions also emerge that remain to be answered. How long does the protective effect of a single dose of this oral cholera vaccine last in cholera-experienced populations such as Juba? Does a single-dose pre-emptive campaign prevent epidemic outbreaks in susceptible groups such as displaced people? How well protected are subgroups such as young children? What complementary emergency WASH activities at household or community level should be combined with the single-dose approach to ensure durable control of cholera? Would a booster dose sometime after the initial outbreak response contribute to longer-term cholera control? To answer these pragmatic questions, we require continued investment in the global stockpile of cholera vaccine, forward-thinking health officials, and continued assessment of the vaccine’s use.

When the right to universal access to safe water and sanitation is realised, the world will be a better, healthier place—this is not doubted. However, if Haiti is any example, the struggle to execute on water and sanitation ideals is real. Those challenges are related both to the availability of funding, and the ability to deliver WASH interventions in sufficient quantity and quality to interrupt transmission of cholera as a matter of urgency. While the 2016 rainy season brings a surge in cholera cases in Haiti, this study offers one potential vaccination strategy to consider in outbreak responses going forward. We can only wonder what might have happened in Haiti if Azman and colleagues’ research had pre-dated the Haitian cholera outbreak—the largest ongoing cholera outbreak in the world, with more than 10 000 deaths so far.7, 8 Perhaps officials, public health experts, and vaccine manufacturers would have done innovative work together in the early days, and helped to avert a disaster.
I declare no competing interests.

Lancet Global Health
Nov 2016 Volume 4 Number 11 e761-e871
http://www.thelancet.com/journals/langlo/issue/current
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Comment
Putting numbers on the End TB Strategy—an impossible dream?
Olivia Oxlade, Dick Menzies
In 2015, WHO announced a plan to end tuberculosis by 2035 (their End TB Strategy) and set ambitious intermediate targets to reduce tuberculosis incidence by 50% and mortality by 75% by 2025.1 In The Lancet Global Health, two related papers by Rein Houben2 and Nicolas Menzies3 and their colleagues describe the results of a unique international collaboration between 11 different tuberculosis modelling groups, and public health officials from national tuberculosis programmes. They assessed the feasibility, costs, and epidemiological outcomes of country-specific interventions in India, China, and South Africa, and determined that these 10-year targets could be achievable only in South Africa with a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care. In China and India, important reductions could be achieved, but they fell short of the WHO targets.2 All models that considered costs projected the need for massive and sustained increases in government health spending, to more than three times current levels, although most judged that these interventions could be considered cost-effective. Interestingly, all predicted that patients’ costs would be substantially reduced with most interventions.

This project showed the potential value of two innovative collaborations toward achieving global tuberculosis control. First, this investigation was accomplished simultaneously by several different modelling groups and investigators from a total of ten different countries—in itself a major achievement! The modelling groups worked independently, using their preferred modelling approaches, but with similar parameters and assumptions. Readers will usually want to know if the findings are unchanged when key assumptions are varied in sensitivity analyses, and if results are similar in studies published separately by different groups. We think readers should be sceptical, given the grand scale of assumptions made by the investigators of these two studies. In these Articles,2, 3 results from 11 models are presented together—a sort of uber-sensitivity analysis. The results are quite consistent and provide a coherent message, which we find reassuring. The second innovation was the partnership of these modelling teams with personnel from national tuberculosis programmes, who were responsible for the selection of interventions and helping to estimate their expected effects. This should make the results more applicable and realistic for the countries selected, while also enhancing knowledge translation.

For most health-care professionals, infectious-disease modelling is something of a black box. One can see the input assumptions (ie, what goes in) and the outputs (ie, what comes out), but what happens in between seems close to magic. Given their complexity, to understand any one of the models used in these studies is difficult; to understand the strengths and limitations of all 11 models might be beyond the capacity of most (if not all) readers. So, we must therefore accept a little magic, and rely on a careful review of what goes in, to decide if what comes out is credible. And the assumed inputs are a major limitation of these studies, for although the involvement of national tuberculosis programme officials in selecting interventions and targets was a strength, the actual population-level effect, and costs, of the interventions are unknown.
For example, active case finding through chest radiography was the cornerstone of tuberculosis control for decades in high-income countries,4 and interest in active case finding has been revived recently.5 However, scant published evidence of its effect on outcomes, transmission, or its cost-effectiveness is available,6 and therefore mass screening is not recommended by WHO.6 The true costs of these interventions, when applied at national scale, are also unknown.
Estimations of costs extrapolated from small projects might not be accurate for national-level interventions. For example, the finding that scaling up use of the Xpert RIF/MTB assay might simply reflect better information, since the actual costs for national expansion in South Africa have been carefully measured,7 by contrast with the estimated costs for the other interventions. Even feasibility is uncertain, particularly for population-level interventions such as mass chest radiography and isoniazid preventive therapy in South Africa, or partnerships with the rapidly evolving private sector in India.

Overall, however, we feel the investigators used all currently available information, and did a careful and thorough analysis of innovative approaches for global tuberculosis control. Although further research is required to better understand the epidemiological effects and the enormous health-system expenditures that will be needed to implement these interventions on a large scale, this requirement should not obscure two important messages from these studies. First, the consistent finding of substantial savings for patients is a reminder that reducing the tuberculosis burden is all about reducing the burden on patients. And second, that perhaps the goal of ending tuberculosis is not such an impossible dream.

We declare no competing interests.

Lancet Global Health
Nov 2016 Volume 4 Number 11 e761-e871
http://www.thelancet.com/journals/langlo/issue/current

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Editorial
Disease, conflict, and the challenge of elimination in the Americas
The Lancet Global Health
Good news from the Americas illuminated the global health scene in September. As the Ministers of Health from the western hemisphere gathered in Washington, DC, USA, for PAHO’s 55th Directing Council, a series of announcements confirmed the New World’s role as a pioneer of sorts in disease prevention and control. Repeating the pattern that began with smallpox in 1971, polio in 1994, and rubella in 2015, the region of the Americas was declared the first in the world to be free of endemic measles on Sept 27. This feat was achieved through 14 years of unrelenting efforts to reach the farthest pockets of unvaccinated populations and document the end of transmission of a virus that still caused over 110 000 deaths worldwide in 2014, mostly in children under 5 years of age. It is a laudable achievement and a testament to the success of yearly national immunisation campaigns and efforts to educate the populations of the region on the innocuity and efficacy of vaccines. The confidence in this essential global health tool in the countries of the Americas is highlighted in a recent article published in EBioMedicine, which shows that countries of the region reported low levels of scepticism on the dimensions surveyed, including the importance of vaccination and the safety and effectiveness of vaccines. The fact that other countries or regions do not show the same confidence, and the related impact on vaccination coverage, underscore the fragility of the elimination status and the importance of persistently promoting the value of vaccines at the global level.

Achievements such as these educate us on the feasibility of reaching elimination goals. They perhaps also provide additional thrust for efforts towards harder to reach, more uncertain milestones. The Ministers of Health concluded their gathering at PAHO with a set of agreements on the prevention, control, and elimination of diseases in the Americas, including a plan of action for malaria elimination with ambitious goals for the next 4 years. Elimination, if reached, would be a first step in a major global health quest: the eradication of malaria, a disease that currently threatens half of the world’s population, and in 2015 killed almost 500 000 people worldwide. Perhaps the Americas can show us once again how it is done.

While the region celebrated the elimination of one scourge, another—namely the devastating 52-year civil war in Colombia—was also on the brink of history. Over the years, and within the confines of Colombia’s borders, the conflict has touched on many issues that are now at the forefront of global health and development. Rapid urbanisation, fuelled in large part by the displacement of millions fleeing violence, led to the creation of slums and all their related health issues. Those who stayed in conflict zones, many of them of indigenous and African descent, were left in a health services vacuum and now suffer the consequences, on maternal and child health in particular, and in terms of inequalities. A historic peace agreement between the Colombian Government and the Revolutionary Armed Forces of Colombia (FARC) was signed in Cartagena on Sept 26. Yet on Oct 2, the Colombian people narrowly rejected this agreement in a national referendum, sending back to the negotiation table a document considered by some as too lenient towards the FARC.

So the promise of stronger social cohesion and human rights is not to be delivered just yet in Colombia, but the implications of the peace process and their potential impact on health must not be overlooked. Nobody denies the radical impact peace could have on these populations, and the now defunct agreement, negotiated with the active participation of women’s and minority groups in a process deemed by some as a model, had the consideration of health and inequalities threaded throughout its terms. So wherever the process goes in Colombia from this point forward, that experience and the point reached on the way to peace remain a much needed sign of hope in a world where violence is on the rise. War and violence, or the absence thereof, are now integral building blocks of the development agenda since their inclusion in SDG16. In Colombia and elsewhere, peace—just like health—is a delicate balancing act that requires constant work, but we must remain convinced that it is attainable.

The Lancet Infectious Diseases
Nov 2016 Volume 16 Number 11 p1203-1304 e241-e275
http://www.thelancet.com/journals/laninf/issue/current

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Articles
Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study
Isaac I Bogoch, Oliver J Brady, Moritz U G Kraemer, Matthew German, Maria I Creatore, Shannon Brent, Alexander G Watts, Simon I Hay, Manisha A Kulkarni, John S Brownstein, Kamran Khan

The number of privately treated tuberculosis cases in India: an estimation from drug sales data
Nimalan Arinaminpathy, Deepak Batra, Sunil Khaparde, Thongsuanmung Vualnam, Nilesh Maheshwari, Lokesh Sharma, Sreenivas A Nair, Puneet Dewan

Use of standardised patients to assess antibiotic dispensing for tuberculosis by pharmacies in urban India: a cross-sectional study
Srinath Satyanarayana, Ada Kwan, Benjamin Daniels, Ramnath Subbaraman, Andrew McDowell, Sofi Bergkvist, Ranendra K Das, Veena Das, Jishnu Das, Madhukar Pai
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The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis
Hannah Alsdurf, Philip C Hill, Alberto Matteelli, Haileyesus Getahun, Dick Menzies

Personal View
Affordable HIV drug-resistance testing for monitoring of antiretroviral therapy in sub-Saharan Africa
Seth C Inzaule, Pascale Ondoa, Trevor Peter, Peter N Mugyenyi, Wendy S Stevens, Tobias F Rinke de Wit, Raph L Hamers

Medical Decision Making (MDM)
November 2016; 36 (8)
http://mdm.sagepub.com/content/current

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Original Articles
Quantitative Framework for Retrospective Assessment of Interim Decisions in Clinical Trials
Roger Stanev
Med Decis Making November 2016 36: 999-1010, first published on June 27, 2016 doi:10.1177/0272989X16655346
Abstract
This article presents a quantitative way of modeling the interim decisions of clinical trials. While statistical approaches tend to focus on the epistemic aspects of statistical monitoring rules, often overlooking ethical considerations, ethical approaches tend to neglect the key epistemic dimension. The proposal is a second-order decision-analytic framework. The framework provides means for retrospective assessment of interim decisions based on a clear and consistent set of criteria that combines both ethical and epistemic considerations. The framework is broadly Bayesian and addresses a fundamental question behind many concerns about clinical trials: What does it take for an interim decision (e.g., whether to stop the trial or continue) to be a good decision? Simulations illustrating the modeling of interim decisions counterfactually are provided.

New England Journal of Medicine
November 3, 2016 Vol. 375 No. 18
http://www.nejm.org/toc/nejm/medical-journal

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Original Article
Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention
Mary G. Fowler, M.D., M.P.H., Min Qin, Ph.D., Susan A. Fiscus, Ph.D., Judith S. Currier, M.D., Patricia M. Flynn, M.D., Tsungai Chipato, M.B., Ch.B., M.C.E., James McIntyre, F.R.C.O.G., Devasena Gnanashanmugam, M.D., George K. Siberry, M.D., M.P.H., Anne S. Coletti, M.S., Taha E. Taha, M.D., Ph.D., Karin L. Klingman, M.D., Francis E. Martinson, M.B., Ch.B., Ph.D., Maxensia Owor, M.B., Ch.B., M.P.H., Avy Violari, M.D., Dhayendre Moodley, Ph.D., Gerhard B. Theron, M.D., Ramesh Bhosale, M.D., Raziya Bobat, M.B., Ch.B., M.D., Benjamin H. Chi, M.D., Renate Strehlau, M.B., Ch.B., Pendo Mlay, M.D., Amy J. Loftis, B.S., Renee Browning, R.N., M.S.N., Terence Fenton, Ed.D., Lynette Purdue, Pharm.D., Michael Basar, B.A., David E. Shapiro, Ph.D., and Lynne M. Mofenson, M.D., for the IMPAACT 1077BF/1077FF PROMISE Study Team*
N Engl J Med 2016; 375:1726-1737 November 3, 2016 DOI: 10.1056/NEJMoa1511691
Abstract
Background
Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.
Full Text of Background…
Methods
We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum “tail” of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety.
Full Text of Methods…
Results
The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, −1.3 percentage points; repeated confidence interval, −2.1 to −0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART.
Full Text of Results…
Conclusions
Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538.)

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Editorial
First-in-Human Clinical Trials — What We Can Learn from Tragic Failures
Sergio Bonini, M.D., and Guido Rasi, M.D.
N Engl J Med 2016; 375:1788-1789 November 3, 2016 DOI: 10.1056/NEJMe1609006
This article has no abstract; the first 100 words appear below.
On January 10, 2016, a healthy volunteer who had received 50 mg per day of a fatty acid amide hydrolase (FAAH) inhibitor for 5 days as part of a first-in-human phase 1 clinical trial was admitted to Rennes University Hospital with neurologic and gait disturbances. After a dramatic worsening of neurologic symptoms, the participant died on January 17. Another 5 participants who received the same drug dose for 6 days were subsequently admitted to the hospital, 4 of them with similar neurologic symptoms. In this issue of the Journal, Kerbrat et al.1 report the clinical and imaging findings of the…

Pediatrics
November 2016, VOLUME 138 / ISSUE
http://pediatrics.aappublications.org/content/138/5?current-issue=y
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Articles
Complementary and Alternative Medicine and Influenza Vaccine Uptake in US Children
William K. Bleser, Bilikisu Reni Elewonibi, Patricia Y. Miranda, Rhonda BeLue
Pediatrics Nov 2016, 138 (5) e20154664; DOI: 10.1542/peds.2015-4664
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Quality Reports
Achieving High Adolescent HPV Vaccination Coverage
Anna-Lisa M. Farmar, Kathryn Love-Osborne, Katherine Chichester, Kristin Breslin, Kristi Bronkan, Simon J. Hambidge
Pediatrics Nov 2016, 138 (5) e20152653; DOI: 10.1542/peds.2015-2653
Abstract
BACKGROUND AND OBJECTIVE: Despite national recommendations for adolescent human papillomavirus (HPV) vaccination, rates have lagged behind those of other adolescent vaccines. We implemented interventions and examined rates of vaccination coverage in a large, urban, safety net health care system to understand whether our tactics for achieving high rates of adolescent vaccination were successful.
METHODS: Denver Health is an integrated urban safety net health system serving >17 000 adolescents annually. The process for achieving high vaccination rates in our health system includes “bundling” of vaccines, offering vaccines at every visit, and standard orders. Data from vaccine registry and utilization statistics were used to determine vaccination rates in adolescents aged 13 to 17 years from 2004 to 2014, and these findings were compared with state and national rates for 2013. Regression analysis was used to identify characteristics associated with vaccination.
RESULTS: In 2013 (N=11,463), HPV coverage of ≥1 dose was 89.8% (female subjects) and 89.3% (male subjects), compared with national rates of 57.3% and 34.6%. Rates of HPV coverage (≥3 doses) were 66.0% for female subjects and 52.5% for male subjects, versus 37.6% and 13.9% nationally. For both sexes, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed, vaccine coverage was 95.9% (86.0% nationally), and meningococcal conjugate vaccine coverage was 93.5% (77.8% nationally). Female subjects, Hispanic subjects, non-English speakers, and teenagers <200% below the federal poverty level were more likely to have received 3 doses of HPV.
CONCLUSIONS: Through low-cost, system-wide standard procedures, Denver Health achieved adolescent vaccination rates well above national coverage rates. Avoiding missed opportunities for vaccination and normalizing the HPV vaccine were key procedures that contributed to high coverage rates.

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
[Accessed 5 November 2016]

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The Ebola Crisis and the Corresponding Public Behavior: A System Dynamics Approach
November 3, 2016 · Research Article
Background: The interaction of several sociocultural and environmental factors during an epidemic crisis leads to behavioral responses that consequently make the crisis control a complex problem.
Methods: The system dynamics approach has been adopted to study the relationships between spread of disease, public attention, situational awareness, and community’s response to the Ebola epidemic.
Results: In developing different simulation models to capture the trend of death and incidence data from the World Health Organization for the Ebola outbreak, the final model has the best fit to the historical trends. Results demonstrate that the increase of quarantining rate over time due to increase in situational awareness and performing safe burials had a significant impact on the control of epidemic. However, public attention did not play a significant role.
Conclusion: The best fit to historical data are achieved when behavioral factors specific to West Africa like studying the Situational Awareness and Public Attention are included in the model. However, by ignoring the sociocultural factors, the model is not able to represent the reality; therefore, in the case of any epidemics, it is necessary that all the parties and community members find the most significant behavioral factors that can curb the epidemic.

PLoS Medicine
http://www.plosmedicine.org/
(Accessed 5 November 2016)

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Research Article
Risk Factors for Childhood Stunting in 137 Developing Countries: A Comparative Risk Assessment Analysis at Global, Regional, and Country Levels
Goodarz Danaei, Kathryn G. Andrews, Christopher R. Sudfeld, Günther Fink, Dana Charles McCoy, Evan Peet, Ayesha Sania, Mary C. Smith Fawzi, Majid Ezzati, Wafaie W. Fawzi
Research Article | published 01 Nov 2016 PLOS Medicine
http://dx.doi.org/10.1371/journal.pmed.1002164
Abstract
Background
Stunting affects one-third of children under 5 y old in developing countries, and 14% of childhood deaths are attributable to it. A large number of risk factors for stunting have been identified in epidemiological studies. However, the relative contribution of these risk factors to stunting has not been examined across countries. We estimated the number of stunting cases among children aged 24–35 mo (i.e., at the end of the 1,000 days’ period of vulnerability) that are attributable to 18 risk factors in 137 developing countries.
Methods and Findings
We classified risk factors into five clusters: maternal nutrition and infection, teenage motherhood and short birth intervals, fetal growth restriction (FGR) and preterm birth, child nutrition and infection, and environmental factors. We combined published estimates and individual-level data from population-based surveys to derive risk factor prevalence in each country in 2010 and identified the most recent meta-analysis or conducted de novo reviews to derive effect sizes. We estimated the prevalence of stunting and the number of stunting cases that were attributable to each risk factor and cluster of risk factors by country and region.
The leading risk worldwide was FGR, defined as being term and small for gestational age, and 10.8 million cases (95% CI 9.1 million–12.6 million) of stunting (out of 44.1 million) were attributable to it, followed by unimproved sanitation, with 7.2 million (95% CI 6.3 million–8.2 million), and diarrhea with 5.8 million (95% CI 2.4 million–9.2 million). FGR and preterm birth was the leading risk factor cluster in all regions. Environmental risks had the second largest estimated impact on stunting globally and in the South Asia, sub-Saharan Africa, and East Asia and Pacific regions, whereas child nutrition and infection was the second leading cluster of risk factors in other regions.
Although extensive, our analysis is limited to risk factors for which effect sizes and country-level exposure data were available. The global nature of the study required approximations (e.g., using exposures estimated among women of reproductive age as a proxy for maternal exposures, or estimating the impact of risk factors on stunting through a mediator rather than directly on stunting). Finally, as is standard in global risk factor analyses, we used the effect size of risk factors on stunting from meta-analyses of epidemiological studies and assumed that proportional effects were fairly similar across countries.
Conclusions
FGR and unimproved sanitation are the leading risk factors for stunting in developing countries. Reducing the burden of stunting requires a paradigm shift from interventions focusing solely on children and infants to those that reach mothers and families and improve their living environment and nutrition.

PLoS Neglected Tropical Diseases
http://www.plosntds.org/

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Research Article
Containing Ebola at the Source with Ring Vaccination
Stefano Merler, Marco Ajelli, Laura Fumanelli, Stefano Parlamento, Ana Pastore y Piontti, Natalie E. Dean, Giovanni Putoto, Dante Carraro, Ira M. Longini Jr., M. Elizabeth Halloran, Alessandro Vespignani
| published 02 Nov 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0005093
Abstract
Interim results from the Guinea Ebola ring vaccination trial suggest high efficacy of the rVSV-ZEBOV vaccine. These findings open the door to the use of ring vaccination strategies in which the contacts and contacts of contacts of each index case are promptly vaccinated to contain future Ebola virus disease outbreaks. To provide a numerical estimate of the effectiveness of ring vaccination strategies we introduce a spatially explicit agent-based model to simulate Ebola outbreaks in the Pujehun district, Sierra Leone, structurally similar to previous modelling approaches. We find that ring vaccination can successfully contain an outbreak for values of the effective reproduction number up to 1.6. Through an extensive sensitivity analysis of parameters characterising the readiness and capacity of the health care system, we identify interventions that, alongside ring vaccination, could increase the likelihood of containment. In particular, shortening the time from symptoms onset to hospitalisation to 2–3 days on average through improved contact tracing procedures, adding a 2km spatial component to the vaccination ring, and decreasing human mobility by quarantining affected areas might contribute increase our ability to contain outbreaks with effective reproduction number up to 2.6. These results have implications for future control of Ebola and other emerging infectious disease threats.
Author Summary
When the 2014–15 Ebola outbreak in West Africa began, no licensed vaccines for the disease were available. The rVSV-ZEBOV vaccine was developed during the course of the epidemic and underwent a clinical trial demonstrating 100% efficacy when vaccinating contacts and contacts of contacts of confirmed Ebola cases (an approach called ring vaccination). However, the trial did not provide any understanding on whether this vaccination strategy can be effective in containing future Ebola virus disease outbreaks. Through a modelling study on a region of Sierra Leone, we provide numerical estimates for the effectiveness of ring vaccination: we show that outbreaks with moderate transmission potential, with no more than 1.6 secondary cases generated by an index case on average, can be successfully contained; more extensive vaccination(e.g., including spatial rings around index cases) and reinforcement of the healthcare system would increase the likelihood of containment even if the virus were more transmissible than in the past. Our results provide implications for control plans of possible future Ebola outbreaks.
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Symposium
The Art of Writing and Implementing Standard Operating Procedures (SOPs) for Laboratories in Low-Resource Settings: Review of Guidelines and Best Practices
Barbara Barbé, Kristien Verdonck, Deby Mukendi, Veerle Lejon, Jean-Roger Lilo Kalo, Emilie Alirol, Philippe Gillet, Ninon Horié, Raffaella Ravinetto, Emmanuel Bottieau, Cedric Yansouni, Andrea S. Winkler, Harry van Loen, Marleen Boelaert, Pascal Lutumba, Jan Jacobs
| published 03 Nov 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0005053
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Editorial
Clinical Research on Neglected Tropical Diseases: Challenges and Solutions
Marleen Boelaert, The NIDIAG Consortium
| published 03 Nov 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0004853
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Viewpoints
The Challenges of Conducting Clinical Research on Neglected Tropical Diseases in Remote Endemic Areas in Sudan
Sayda El-Safi, François Chappuis, Marleen Boelaert
| published 03 Nov 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0004736
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Viewpoints
Rapid Diagnostic Tests for Neglected Infectious Diseases: Case Study Highlights Need for Customer Awareness and Postmarket Surveillance
Barbara Barbé, Kristien Verdonck, Sayda El-Safi, Basudha Khanal, Syna Teav, Jean-Roger Lilo Kalo, Raffaella Ravinetto, François Chappuis, Marleen Boelaert, Jan Jacobs
Viewpoints | published 03 Nov 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0004655

Viewpoints
Clinical Research in Neglected Tropical Diseases: The Challenge of Implementing Good Clinical (Laboratory) Practices
Raffaella Ravinetto, Emilie Alirol, Yodi Mahendradhata, Suman Rijal, Pascal Lutumba, Moussa Sacko, Sayda El-Safi, Kruy Lim, Harry van Loen, Jan Jacobs, Rosanna W. Peeling, Francois Chappuis, Marleen Boelaert
Viewpoints | published 03 Nov 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0004654

PNAS – Proceedings of the National Academy of Sciences of the United States of America
http://www.pnas.org/content/early/
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Sackler Colloquium on Coupled Human and Environmental Systems – Social Sciences – Environmental Sciences – Biological Sciences – Sustainability Science:
Whales, science, and scientific whaling in the International Court of Justice
Marc Mangel
PNAS 2016 ; published ahead of print October 31, 2016, doi:10.1073/pnas.1604988113
Abstract
I provide a brief review of the origins of the International Convention on the Regulation of Whaling and the failure to successfully regulate whaling that led to the commercial moratorium in 1986. I then describe the Japanese Whale Research Programs Under Special Permit in the Antarctica (JARPA I, JARPA II) and the origins of the case Whaling in the Antarctic (Australia v. Japan: New Zealand Intervening) in the International Court of Justice. I explain that the International Court of Justice chose to conduct an objective review of JARPA II, the standard that it used for the review, and the pathway that it took to adjudicate the case without providing a definition of science to be used in international law. I conclude with a brief discussion of the implications of the Judgment for the International Convention on the Regulation of Whaling, and the International Whaling Commission in particular, for other international treaties, and for the interaction of science and law more generally.

PNAS – Proceedings of the National Academy of Sciences of the United States of America
http://www.pnas.org/content/early/
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Biological Sciences – Population Biology:
Vaccination strategies against respiratory syncytial virus
Dan Yamin, Forrest K. Jones, John P. DeVincenzo, Shai Gertler, Oren Kobiler, Jeffrey P. ownsend, and Alison P. Galvani
PNAS 2016 ; published ahead of print October 31, 2016, doi:10.1073/pnas.1522597113
Significance
The WHO estimates that respiratory syncytial virus (RSV) vaccination will be available in the next 5–10 y. To evaluate the population effectiveness of an RSV vaccination program in the United States, we developed a transmission model that integrates data on daily infectious viral load and behavior changes while symptomatic. Our model simulations demonstrate that vaccinating children younger than 5 y of age will be the most efficient and effective way to prevent RSV infection in both children and older adults, a result that is robust across the US states considered. Accordingly, the population burden of RSV would be most effectively reduced if current vaccine candidates were to focus on children.
Abstract
Respiratory syncytial virus (RSV) is the most common cause of US infant hospitalization. Additionally, RSV is responsible for 10,000 deaths annually among the elderly across the United States, and accounts for nearly as many hospitalizations as influenza. Currently, several RSV vaccine candidates are under development to target different age groups. To evaluate the potential effectiveness of age-specific vaccination strategies in averting RSV incidence, we developed a transmission model that integrates data on daily infectious viral load and changes of behavior associated with RSV symptoms. Calibrating to RSV weekly incidence rates in Texas, California, Colorado, and Pennsylvania, we show that in all states considered, an infected child under 5 y of age is more than twice as likely as a person over 50 y of age to transmit the virus. Geographic variability in the effectiveness of a vaccination program across states arises from interplay between seasonality patterns, population demography, vaccination uptake, and vaccine mechanism of action. Regardless of these variabilities, our analysis showed that allocating vaccine to children under 5 y of age would be the most efficient strategy per dose to avert RSV in both children and adults. Furthermore, due to substantial indirect protection, the targeting of children is even predicted to reduce RSV in the elderly more than directly vaccinating the elderly themselves. Our results can help inform ongoing clinical trials and future recommendations on RSV vaccination.

Qualitative Health Research
December 2016; 26 (14)
http://qhr.sagepub.com/content/current
Special Issue: General

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General Articles
Reframing Narratives of Aboriginal Health Inequity: Exploring Cree Elder Resilience and Well-Being in Contexts of Historical Trauma
Andrew R. Hatala, Michel Desjardins, and Amy Bombay
Qual Health Res December 2016 26: 1911-1927, first published on October 21, 2015 doi:10.1177/1049732315609569
Abstract
A large body of literature explores historical trauma or intergenerational trauma among Aboriginal communities around the globe. This literature connects contemporary forms of social suffering and health inequity to broader historical processes of colonization and the residential school systems in Canada. There are tendencies within this literature, however, to focus on individual pathology and victimization while minimizing notions of resilience or well-being. Through a social constructionist lens, this research examined how interpersonal responses to historical traumas can be intertwined with moments of and strategies for resilience. Detailed narrative interviews occurred with four Aboriginal Cree elders living in central Saskatchewan, Canada, who all experienced historical trauma to some extent. From this analysis, we argue that health research among Aboriginal populations must be sensitive to the complex individual and social realities that necessarily involve both processes of historical and contemporary traumas as well as resilience, strength, and well-being.

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General Articles
Toward an Understanding of the Poor Health Status of Indigenous Australian Men
David Mellor, Marita McCabe, Lina Ricciardelli, Alex Mussap, and Matthew Tyler
Qual Health Res December 2016 26: 1949-1960, first published on October 18, 2015 doi:10.1177/1049732315609898

Science
04 November 2016 Vol 354, Issue 6312
http://www.sciencemag.org/current.dtl

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In Depth
Controversial HIV vaccine strategy gets a second chance
By Jon Cohen
Science04 Nov 2016 : 535 Restricted Access
Modest success in Thailand inspires South Africa trial
Summary
A two-pronged HIV vaccine strategy that delivered lackluster results in a trial in Thailand 7 years ago will get another chance in South Africa. Last week, researchers injected the first of what they hope will be 5400 participants in the $130 million study, which should show once and for all whether the combination actually works. But some researchers say the trial amounts to a waste of money. In the Thai study, the vaccine combination reduced the risk of HIV infection by only 31.2%, and the study failed to show a mechanism that explained this modest benefit, critics say. Backers of the new trial counter that there’s enough evidence to give it another try and argue that even a modestly efficacious vaccine would help South Africa, which has more than 6 million HIV-infected people.