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

Lancet 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
School-Located Influenza Vaccinations: A Randomized Trial
Peter G. Szilagyi, Stanley Schaffer, Cynthia M. Rand, Phyllis Vincelli, Ashley Eagan, Nicolas P.N. Goldstein, A. Dirk Hightower, Mary Younge, Aaron Blumkin, Christina S. Albertin, Byung-Kwang Yoo, Sharon G. Humiston
Pediatrics Nov 2016, 138 (5) e20161746; DOI: 10.1542/peds.2016-1746
Abstract
OBJECTIVE: Assess impact of offering school-located influenza vaccination (SLIV) clinics using both Web-based and paper consent upon overall influenza vaccination rates among elementary school children.
METHODS: We conducted a cluster-randomized trial (stratified by suburban/urban districts) in upstate New York in 2014–2015. We randomized 44 elementary schools, selected similar pairs of schools within districts, and allocated schools to SLIV versus usual care (control). Parents of children at SLIV schools were sent information and vaccination consent forms via e-mail, backpack fliers, or both (depending on school preferences) regarding school vaccine clinics. Health department nurses conducted vaccine clinics and billed insurers. For all children registered at SLIV/control schools, we compared receipt of influenza vaccination anywhere (primary outcome).
RESULTS: The 44 schools served 19 776 eligible children in 2014–2015. Children in SLIV schools had higher influenza vaccination rates than children in control schools county-wide (54.1% vs 47.4%, P < .001) and in suburban (61.9% vs 53.6%, P < .001) and urban schools (43.9% vs 39.2%; P < .001). Multivariate analyses (controlling for age, grade, vaccination in previous season) confirmed bivariate findings. Among parents who consented for SLIV, nearly half of those notified by backpack fliers and four-fifths of those notified by e-mail consented online. In suburban districts, SLIV did not substitute for primary care influenza vaccination. In urban schools, some substitution occurred. CONCLUSIONS: SLIV raised seasonal influenza vaccination rates county-wide and in both suburban and urban settings. SLIV did not substitute for primary care vaccinations in suburban settings where pediatricians often preorder influenza vaccine but did substitute somewhat in urban settings. 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 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.
.
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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Perspective
Improving the Pipeline for Developing and Testing Pharmacological Treatments in Pregnancy
Lucy C. Chappell, Anna L. David
Perspective | published 01 Nov 2016 PLOS Medicine
http://dx.doi.org/10.1371/journal.pmed.1002161

Research Article
Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review
Gali Pariente, Tom Leibson, Alexandra Carls, Thomasin Adams-Webber, Shinya Ito, Gideon Koren
published 01 Nov 2016 PLOS Medicine
http://dx.doi.org/10.1371/journal.pmed.1002160

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.

PLoS One
http://www.plosone.org/
[Accessed 5 November 2016]

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Research Article
Cost-Effectiveness Analysis of Hepatitis B Vaccination Strategies to Prevent Perinatal Transmission in North Korea: Selective Vaccination vs. Universal Vaccination
Donghoon Lee, Sang Min Park
Research Article | published 01 Nov 2016 PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0165879
Abstract
Background
To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered.
Methods
To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country’s current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer’s perspectives and evaluated by Disability Adjusted Life Year (DALY).
Results
The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer’s perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer’s perspective.
Conclusion
Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination.

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.

PNAS – Proceedings of the National Academy of Sciences of the United States of America
http://www.pnas.org/content/early/

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Commentary:
Timing and periodicity of influenza epidemics
Ottar N. Bjørnstad and Cecile Viboud
PNAS 2016 ; published ahead of print November 3, 2016, doi:10.1073/pnas.1616052113
[Extract]
Although the annual cycle of summers and winters is a long-resolved mystery of astronomy, the annual antipodal waxing and waning of influenza epidemics is still an unresolved question in epidemiology. In 1981, R. E. Hope-Simpson, an astute British physician who maintained and analyzed detailed records of his patients and their diseases for more than three decades, observed that “Influenza outbreaks are globally ubiquitous and epidemics move smoothly to and fro across the surface of the earth almost every year in a sinuous curve that runs parallel with the ‘midsummer’ curve of vertical solar radiation…” (1). In PNAS Deyle et al. (2) combine convergent cross-mapping with empirical dynamic modeling to elucidate the nonlinear roles of absolute humidity and temperature in explaining influenza’s “sinuous curve that runs parallel with the ‘midsummer’” across the globe (1).

Understanding interepidemic intervals and timing of outbreaks has been a focus of mathematical epidemiologists for more than 50 y (3, 4). Acute immunizing infections have internal cyclic clockworks determined by the overcompensatory predator/prey-like interaction that results from slow susceptible recruitment, through births and loss of immunity, and rapid susceptible depletion from transmission during epidemics. The internal clock depends on traits of both the pathogen and the host and determines the frequency of oscillations we expect to see in the presence of random perturbations to the disease dynamics (3). The “flu” is a recurrent menace—and sometime scourge—caused by cocirculating strains of influenza A and B viruses, which at the strain-aggregate level can be modeled using the “susceptible-infected-recovered-(re)suceptible” compartmental model (5). For influenza, the internal interepidemic period is usually in the 10- to 16-mo range depending on the infectious period and transmissibility (the basic reproductive ratio, R0) of each strain (Fig. 1A). The prediction is that, in the absence of extrinsic forcing, the flu peak would …

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.

Tropical Medicine & International Health
November 2016 Volume 21, Issue 11 Pages 1347–1488, E1–E1
http://onlinelibrary.wiley.com/doi/10.1111/tmi.2016.21.issue-11/issuetoc

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Original Research Papers
Rotavirus vaccines contribute towards universal health coverage in a mixed public–private healthcare system (pages 1458–1467)
Tharani Loganathan, Mark Jit, Raymond Hutubessy, Chiu-Wan Ng, Way-Seah Lee and Stéphane Verguet
Version of Record online: 24 AUG 2016 | DOI: 10.1111/tmi.12766
Abstract
Objectives
To evaluate rotavirus vaccination in Malaysia from the household’s perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies the broader value of universal vaccination starting with non-health benefits such as financial risk protection and equity. These dimensions better enable decision-makers to evaluate policy on the public finance of health programmes.
Methods
The incidence, health service utilisation and household expenditure related to rotavirus gastroenteritis according to national income quintiles were obtained from local data sources. Multiple birth cohorts were distributed into income quintiles and followed from birth over the first five years of life in a multicohort, static model.
Results
We found that the rich pay more out of pocket (OOP) than the poor, as the rich use more expensive private care. OOP payments among the poorest although small are high as a proportion of household income. Rotavirus vaccination results in substantial reduction in rotavirus episodes and expenditure and provides financial risk protection to all income groups. Poverty reduction benefits are concentrated amongst the poorest two income quintiles.
Conclusion
We propose that universal vaccination complements health financing reforms in strengthening Universal Health Coverage (UHC). ECEA provides an important tool to understand the implications of vaccination for UHC, beyond traditional considerations of economic efficiency.

Travel Medicine and Infectious Diseases
September-October, 2016 Volume 14, Issue 5
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Editorials
Hajj 2016: Required vaccinations, crowd control, novel wearable tech and the Zika threat
Qanta A. Ahmed, Ziad A. Memish
Vol. 14, Issue 5, p429–432
Published online: September 20, 2016
Article Outline [initial text]
Today 1,323,520 Muslims arrived in Saudi Arabia joining millions more Muslims from around the world to perform Hajj. As physician experts in Hajj medicine who have also performed the Hajj pilgrimage and attended pilgrim-patients both during Hajj at the Hajj sites we welcome the arrival of novel wearable technology introduced by Saudi Arabia to safeguard the Hajj pilgrim during what is one of the world’s largest mass gatherings [1].

Like all mass gatherings, physical hazards are a risk and among them one of the most dangerous is stampede that unfortunately impacted Hajj 2015 on a causeway on route to the Three Pillars in the Mina area of the Holy Sites [2]. Looking at the modern history of the Hajj, stampedes have indeed occurred sporadically though the 2015 events marked the end of years free of mass stampedes following significant reengineering of crowd management. Certainly this calamity is at the forefront of Hajj planners’ priorities with some interesting solutions already being piloted, but as every year basic precautions -cough etiquette, facemask use, hand hygiene and careful food hygiene remain paramount [[3], [4]].

Routine vaccination is not only recommended but is required- Hajj visa applications being accepted contingent upon on full sets of immunizations as is standard. Like every year, the three key vaccine requirements for visa issuing include yellow fever vaccination for all travellers arriving from countries or areas at risk of yellow fever given at least 10 days prior to arrival, quadrivalent (ACYW135) meningococcal vaccine; both polysaccharide and conjugated vaccines are valid with attention to differing duration of protection [5] issued no more than 3 years and no less than 10 days before arrival in Saudi Arabia and proof of receipt of a dose of oral polio vaccine (OPV) or inactivated poliovirus vaccine (IPV), within the previous 12 months and at least 6 weeks prior to departure for travellers arriving from polio-endemic countries which have never interrupted indigenous virus transmission. In addition, the Ministry of Health of Saudi Arabia continues to recommend that international pilgrims be vaccinated against seasonal influenza with most recently available vaccines particularly those at increased risk of severe influenza diseases including pregnant women, children aged over 5 years, the elderly, and individuals with pre-existing health conditions such as asthma, chronic heart or lung diseases and HIV/AIDS infection [[5], [6], [7]]…

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Original Research Article
Manufacturing costs of HPV vaccines for developing countries
Pages 5984-5989
Chaevia Clendinen, Yapei Zhang, Rebecca N. Warburton, Donald W. Light
Abstract
Background
Nearly all of the 500,000 new cases of cervical cancer and 270,000 deaths occur in middle or lower income countries. Yet the two most prevalent HPV vaccines are unaffordable to most. Even prices to Gavi, the Vaccine Alliance, are unaffordable to graduating countries, once they lose Gavi subsidies. Merck and Glaxosmithkline (GSK) claim their prices to Gavi equal their manufacturing costs; but these costs remain undisclosed. We undertook this investigation to estimate those costs.
Methods
Searches in published and commercial literature for information about the manufacturing of these vaccines. Interviews with experts in vaccine manufacturing.
Findings
This detailed sensitivity analysis, based on the best available evidence, finds that after a first set of batches for affluent markets, manufacturing costs of Gardasil for developing countries range between $0.48 and $0.59 a dose, a fraction of its alleged costs of $4.50. Because volume of Cervarix is low, its per unit costs are much higher, though at comparable volumes, its costs would be similar.
Interpretation
Given the recovery of fixed and annual costs from sales in affluent markets, Merck’s break-even price to Gavi could be $0.50–$0.60, not $4.50. These savings could support Gavi programs to strengthen delivery and increase coverage. Outside Gavi, prices to lower- and middle-income countries, with profit, could also be lowered and made available to millions more adolescents at risk. These estimates and their policy implications deserve further discussion.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Original Research Article
Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans
Original Research Article
Pages 5959-5967
Karen L. Mansfield, Nick Andrews, Hooman Goharriz, Trudy Goddard, Lorraine M. McElhinney, Kevin E. Brown, Anthony R. Fooks
Abstract
Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed. In particular, the antibody response to primary vaccinations and boosters, and the waning of antibody post primary vaccination and post booster were investigated. The significance of gender, age at vaccination, vaccine manufacturer and vaccination intervals were also evaluated. These data confirm that rabies vaccination can elicit a neutralising antibody response that can remain at detectable levels for a number of years, without additional booster vaccinations. The antibody response following both primary vaccination and booster was significantly influenced by the gender of the subject (p = 0.002 and 0.03 respectively), with supportive data that suggests an effect by the make of vaccine administered following primary vaccination, with significantly higher VNA titres observed for one vaccine manufactured prior to 2006 (p < 0.001) in a small subset of recipients (n = 5). Additionally, the decay rate was demonstrated through the overall decline in antibody titre for all individuals, which was a 37% and 27% reduction per 2-fold change in time following primary and booster vaccination respectively. Individuals within older age groups demonstrated a significantly faster decline in antibody titre following the primary vaccination course (p = 0.012). Rate of decline in antibody titre was also significantly influenced by the vaccine make following primary course (p < 0.001). The assessment of neutralising antibody titre decline has also provided an insight into the most appropriate timing for booster administration, and enabled the prediction of long term titres from post-vaccination antibody titres.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Original Research Article
Measuring polio immunity to plan immunization activities
Pages 5946-5952
Arend Voorman, Hil M. Lyons
Abstract
The Global Polio Eradication Initiative is closer than ever to achieving a polio-free world. Immunization activities must still be carried out in non-endemic countries to maintain population immunity at levels which will stop poliovirus from spreading if it is re-introduced from still-infected areas. In areas where there is no active transmission of poliovirus, programs must rely on surrogate indicators of population immunity to determine the appropriate immunization activities, typically caregiver-reported vaccination history obtained from non-polio acute flaccid paralysis patients identified through polio surveillance. We used regression models to examine the relationship between polio vaccination campaigns and caregiver-reported polio vaccination history. We find that in many countries, vaccination campaigns have a surprisingly weak impact on these commonly used indicators. We conclude that alternative criteria and data, such as routine immunization indicators from vaccination records or household surveys, should be considered for planning polio vaccination campaigns, and that validation of such surrogate indicators is necessary if they are to be used as the basis for program planning and risk assessment. We recommend that the GPEI and similar organizations consider or continue devoting additional resources to rigorously study population immunity and campaign effectiveness in at-risk countries.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Original Research Article
Rotavirus, vaccine failure or diagnostic error?
Pages 5912-5915
Monica Lopez-Lacort, Susana Collado, Ana Díez-Gandía, Javier Díez-Domingo
Abstract
Immunochromatography (ICG) is highly used in clinical settings for rotavirus (RV) diagnosis. The specificity of the tests differs by brand type and is not 100%, therefore its use when the prevalence of the disease is low (i.e. in vaccinated children) may result in a proportion of false positive diagnoses.
In some areas, vaccine effectiveness studies or surveillance is done using ICG. Our objective was to estimate the validity of ICG test in vaccinated children, and estimate the number of false positive results in the Valencian Region of Spain, where all RV infections are diagnosed using ICG and are not confirmed by PCR.
Population based registries were used to identify all results from the RV antigen tests performed between January 2008 and June 2012 in children under 37 months. Hospitalization and vaccination status of the patients were obtained by linking different databases through a unique identification number. The Positive Predictive Value of the ICG test depending on the vaccination status of the child, hospitalization and the rotavirus season was estimated by a Bayesian model of latent classes.
Of the 48,833 tests with valid results, 9429 were done in vaccinated children, and of those 3963 (42%) during the rotavirus season. The prevalence of positive results in vaccinated varied from 2.9 to 21.4% of the tests depending on the hospitalization and seasonality. The estimated PPV also varied from 27.1 to 84.6% when stratified by these two parameters. Globally it is calculated that approximately 267 out of the 520 (51.3%) positives in vaccinated children were false positive tests.
The large percentage of false positives, due to an excessive number of tests in vaccinated and out of the RV season, if interpreted as vaccine failures, can cause a loss of confidence in the vaccine and lower the estimates of vaccine effectiveness.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Original Research Article
Knowledge, attitudes, and practices of healthcare providers in the country of Georgia regarding influenza vaccinations for pregnant women
Pages 5907-5911
Mariam Dvalishvili, Darejan Mesxishvili, Maia Butsashvili, George Kamkamidze, Deborah McFarland, Robert A. Bednarczyk
Abstract
Objective
To document knowledge, attitudes, and practices of Georgian obstetrician-gynecologists concerning influenza infection and vaccination during pregnancy.
Methods
We conducted a cross-sectional study of obstetrician-gynecologists in 8 cities in the country of Georgian, from June to July, 2015, using an anonymous, self-administered, written survey. Collected data included demographics; knowledge, attitudes, and practices related to influenza vaccination during pregnancy; perceptions of influenza infection in pregnancy; perceived barriers to influenza vaccination during pregnancy; and willingness to receive education about influenza infection and vaccination during pregnancy.
Results
A total of 278 obstetrician-gynecologists completed surveys. Most physicians perceived influenza to be a serious infectious disease (88%) and that pregnant women are more susceptible to it than the general population. Only 43% of physicians reported recommending influenza vaccination during pregnancy; 18% reported vaccinating any pregnant patients during the last influenza season. Most (75%) physicians reported a perception that there is insufficient evidence supporting influenza vaccination during pregnancy. Most (93%) were receptive to receiving additional education on maternal vaccination.
Conclusions
Georgian physicians are hesitant to vaccinate pregnant women, but are receptive to education about maternal vaccination. Future educational outreach to Georgian physicians could reduce concerns about maternal vaccination, potentially increasing influenza vaccination among pregnant Georgian women.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Review Article
Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative
Pages 5855-5862
Ray Borrow, Jin-Soo Lee, Julio A. Vázquez, Godwin Enwere, Muhamed-Kheir Taha, Hajime Kamiya, Hwang Min Kim, Dae Sun Jo, the Global Meningococcal Initiative
Abstract
The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014. The GMI reviewed the epidemiology of MD, surveillance, and prevention strategies, and outbreak control practices from participating countries in the Asia-Pacific region. Although, in general, MD is underreported in this region, serogroup A disease is most prominent in low-income countries such as India and the Philippines, while Taiwan, Japan, and Korea reported disease from serogroups C, W, and Y. China has a mixed epidemiology of serogroups A, B, C, and W.
Perspectives from countries outside of the region were also provided to provide insight into lessons learnt. Based on the available data and meeting discussions, a number of challenges and data gaps were identified and, as a consequence, several recommendations were formulated: strengthen surveillance; improve diagnosis, typing and case reporting; standardize case definitions; develop guidelines for outbreak management; and promote awareness of MD among healthcare professionals, public health officials, and the general public.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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Brief report
Parental experiences with vaccine information statements: Implications for timing, delivery, and parent-provider immunization communication
Pages 5840-5844
Paula M. Frew, Yunmi Chung, Allison Kennedy Fisher, Jay Schamel, Michelle M. Basket
Abstract
Objective
We examined Vaccine Information Statements (VIS) dissemination practices and parental use and perceptions.
Methods
We conducted a national online panel survey of 2603 US parents of children aged Results
Most parents received a VIS (77.2%; [95% CI: 74.5–79.7%]), 59.7% [56.6–62.7%] before vaccination but 14.5% [12.5–16.8%] reported receiving it after their child’s immunization; 15.1% [13.0–17.6%] were unsure of receipt status or timing; another 10.7% [9.0–12.6%] reported non-receipt of a VIS. Less than half who received a VIS before vaccination completed it before vaccination (46.2% [42.4, 50.0%]), but most who read at least some found the information useful (95.7% [93.8–97.0%]). Parents who delayed or refused at least one recommended non-influenza vaccine reported fewer opportunities to ask providers VIS questions.
Conclusions
Most parents report receiving VIS before vaccination as per federal guidelines. Continued effort is needed to enhance VIS distribution practice and parent-provider VIS content communication.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48
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WHO Report
Investing in life saving vaccines to guarantee life of future generations in Africa
Pages 5827-5832
R.M. Mihigo, J.C. Okeibunor, H. O’Malley, B. Masresha, P. Mkanda, F. Zawaira
Abstract
The World Health Organization’s Regional Offices for Africa and for the Eastern Mediterranean in conjunction with the African Union and the Government of Ethiopia hosted a ministerial conference on immunization in Africa from 24 to 25 February 2016 in Addis Ababa, Ethiopia under the theme “towards universal immunization coverage as a cornerstone for health and development in Africa”. The conference brought together African leaders – including health and finance ministers, and parliamentarians thus creating a powerful platform for governments to demonstrate their commitment to advancing universal access to immunization on the continent in line with the Global Vaccine Action Plan. The event also brought together advocates, technical experts, policymakers, partner agencies, donors and journalists to examine how best to drive forward immunization across Africa, ensuring every child has access to the vaccines they need. Key points highlighted throughout conference were: universal access to immunization is at the forefront of enabling Africa to reach its full potential – by improving health, driving economic growth and empowering future generations; it is one of the most cost-effective solutions in global health, with clear benefits for health and development; and immunization brings economic benefits too, reducing health care costs and increasing productivity. At the close of the conference, 46 African countries signed a historic ministerial declaration on “Universal Access to Immunization as a Cornerstone for Health and Development in Africa” signaling fierce determination among African leaders to secure the health and prosperity of their societies through immunization.

Vaccine
Volume 34, Issue 48, Pages 5819-5990 (21 November 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/48

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Conference report
Pertussis: Biology, epidemiology and prevention
Pages 5819-5826
Mitra Saadatian-Elahi, Stanley Plotkin, Kingston H.G. Mills, Scott A. Halperin, Peter B. McIntyre, Valentina Picot, Jacques Louis, David R. Johnson
Abstract
Despite long-standing vaccination programs, substantial increases in reported cases of pertussis have been described in several countries during the last 5 years. Cases among very young infants who are at greatest risk of pertussis-related hospitalizations and mortality are the most alarming. Multiple hypotheses including but not limited to the availability of more sensitive diagnostic tests, greater awareness, and waning vaccine-induced immunity over time have been posited for the current challenges with pertussis. The conference “Pertussis: biology, epidemiology and prevention” held in Annecy-France (November 11–13, 2015) brought together experts and interested individuals to examine these issues and to formulate recommendations for optimal use of current vaccines, with a particular focus on strategies to minimize severe morbidity and mortality among infants during the first months of life. The expert panel concluded that improving vaccination strategies with current vaccines and development of new highly immunogenic and efficacious pertussis vaccines that have acceptable adverse event profiles are currently the two main areas of investigation for the control of pertussis. Some possible pathways forward to address these main challenges are discussed in this report.

Vaccines — Open Access Journal
http://www.mdpi.com/journal/vaccines
(Accessed 5 November 2016)

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Targeting Immune Regulatory Networks to Counteract Immune Suppression in Cancer
Vaccines 2016, 4(4), 38; doi:10.3390/vaccines4040038 (registering DOI) – 4 November 2016
by Chiara Camisaschi, Viviana Vallacchi, Elisabetta Vergani, Marcella Tazzari, Simona Ferro, Alessandra Tuccitto, Olga Kuchuk, Eriomina Shahaj, Roberta Sulsenti, Chiara Castelli, Monica Rodolfo, Licia Rivoltini and Veronica Huber
Abstract
The onset of cancer is unavoidably accompanied by suppression of antitumor immunity. This occurs through mechanisms ranging from the progressive accumulation of regulatory immune cells associated with chronic immune stimulation and inflammation, to the expression of immunosuppressive molecules. Some of them are being successfully exploited as therapeutic targets, with impressive clinical results achieved in patients, as in the case of immune checkpoint inhibitors. To limit immune attack, tumor cells exploit specific pathways to render the tumor microenvironment hostile for antitumor effector cells. Local acidification might, in fact, anergize activated T cells and facilitate the accumulation of immune suppressive cells. Moreover, the release of extracellular vesicles by tumor cells can condition distant immune sites contributing to the onset of systemic immune suppression. Understanding which mechanisms may be prevalent in specific cancers or disease stages, and identifying possible strategies to counterbalance would majorly contribute to improving clinical efficacy of cancer immunotherapy. Here, we intend to highlight these mechanisms, how they could be targeted and the tools that might be available in the near future to achieve this goal.

Journal of Preventive Medicine and Hygiene
Vol 57, No 3 (2016)
http://www.jpmh.org/index.php/jpmh/issue/view/2016573
Article
History and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines
Ilaria Barberis, Puja Myles, Steven Ault, Nicola Luigi Bragazzi, Mariano Martini
Abstract
Influenza is a highly infectious airborne disease with an important epidemiological and societal burden; annual epidemics and pandemics have occurred since ancient times, causing tens of millions of deaths. A hundred years after this virus was first isolated, influenza vaccines now ensure effective protection, and the preparations used display good safety and tolerability profiles.
Innovative tools, such as recombinant technologies and intra-dermal devices, are currently being investigated in order to elicit good immunity even in the event of unforeseen changes in the virus due to drift and antigenic shift or the co-circulation different viral strains.
The recurring mutations of influenza strains has prompted the recent introduction of a quadrivalent inactivated vaccine. In the near future, scientific research will strive to produce a long-lasting universal vaccine containing an antigen that is not subject to genetic modifications, and surveillance systems will be implemented in order to exactly predict circulating strains.

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.

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BBC
http://www.bbc.co.uk/
Accessed 5 November 2016
UK forms global infection response team
1 November 2016
The UK has created a specialist team of health experts who can be deployed anywhere around the world within 48 hours if a disease outbreak strikes.

The aim is to stamp out infections like Ebola before they spread far and wide.
The scientists, academics and clinicians will be funded by £20m from the government over five years.

When not responding to an immediate emergency, the rapid response team will assess future disease threats and train colleagues from home and abroad.

Public Health Minister Nicola Blackwood said the Ebola crisis highlighted the need for such a team.
“Ebola shook the world and brave experts from the UK led the global response in Sierra Leone. The ability to deploy emergency support to investigate and respond to disease outbreaks within 48 hours will save lives, prevent further outbreaks and cement the UK’s position as a leader in global health security.”

Public Health England will run the project with the London School of Hygiene and Tropical Medicine…

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Forbes
http://www.forbes.com/
Accessed 5 November 2016

Is It Fair To Reward Medicaid Patients For Receiving Flu Shots?
Peter Ubel, Contributor

Big Pharma Has Broken Its Social Contract: How To Restore Fairness In Drug Pricing
Kenneth L. Davis, Contributor
The pharmaceutical industry must restore the social contract governing its business practices and lower drug prices so Americans can better afford medication.

Why The Approach To Drug Pricing Has To Change Now
1 November 2016
By Joseph Jimenez, CEO of Novartis
As CEO of one of the world’s largest pharmaceutical companies, I believe that we need a new perspective on drug pricing: As an industry, we must shift to a model that focuses on value and outcomes delivered, both to patients and to health systems.

New Measles Study Shows Why Anti-Vaccination Thinking Is Deadly
30 October 2016
New research on fatal measles complications shows how the failure to vaccinate not only endangers the patient, but also everyone else susceptible to the disease. Subacute sclerosing panencephalitis (SSPE) is a neurological disorder that can develop years after someone has measles, and it is fatal 100% of the time. Previously it was thought rare at about one in 100,000 post-measles cases. But recent research in Germany shows that it occurs in one in 1,700 children infected with measles before they turned five, and a new study finds the incidence can be as many as one in 600 for infants who contract measles before they’re vaccinated. The findings were presented at IDWeek 2016, the annual meeting of the Infectious Diseases Society of America…

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Fortune
http://fortune.com/
Accessed 5 November 2016
Here’s What We Could Be Doing to Stop Pandemics Like Zika and Ebola
1 November 2016
…A boiling pot of global conditions, like ubiquitous travel and the growing populations of developing cities, have led to an outbreak of pandemics like Ebola, Zika, SARs, and even the flu over the past decade.

But while the global health industry and national governments and regulators have made a lot of progress, there’s still much more that these groups can do together to better plan, fund, and organize the battle against emerging pandemics, said a group of experts at Fortune’s Brainstorm Health conference in San Diego, Calif. on Tuesday night.
Once an outbreak occurs, the response is all about speed, said Bruce Gellin, director of the U.S. National Vaccine Program Office.

GSK’s CEO Explains How Big Pharma Can Help the Poor and Still Make Money
2 November 2016
Capitalism and doing good don’t have to be mutually exclusive.
Big pharma has been a persistent villain in the public’s consciousness over the past year in the wake of exorbitant drug price hikes, including on ancient medications. But drug makers don’t necessarily have to conform to some Monopoly man caricature to be successful, according to the chief executive of pharma giant

Outgoing GSK chief Sir Andrew Witty laid out a straightforward manifesto to drug pricing, especially when it comes to vaccines, at Fortune’s Brainstorm Health conference on Wednesday. His message: Pharma can do good while still turning a profit.

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New York Times
http://www.nytimes.com/
Accessed 5 November 2016
Colombia is Hit Hard by Zika, but Not by Microcephaly
By DONALD G. McNEIL Jr. and JULIA SYMMES COBB OCT. 31, 2016
BARRANQUILLA, Colombia — This tropical city on the Caribbean coast may hold the answer to one of the deeper mysteries of the Zika epidemic: Why has the world’s second-largest outbreak, after Brazil’s, produced so few birth defects?

In Brazil, more than 2,000 babies have been born with microcephaly, abnormally small heads and brain damage caused by the Zika virus. In Colombia, officials had predicted there might be as many as 700 such babies by the end of this year. There have been merely 47.
The gap has been seen all over the Americas. According to the World Health Organization, the United States has 28 cases — almost all linked to women infected elsewhere. Guatemala has 15, and Martinique has 12.

Had the rest of the Americas been as affected as northeastern Brazil, a tidal wave of microcephaly would be washing over the region. Most experts say that will not happen, but they are at a loss as to why…

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Washington Post
http://www.washingtonpost.com/
Accessed 5 November 2016
Washington state polio-like cases linked to rare syndrome
Eight of nine children hospitalized in Washington state for a polio-like illness have a rare syndrome that causes varying degrees of limb weakness, state health officials confirmed on Friday.
Lisa Baumann | AP | National | Nov 4, 2016

Think Tanks et al

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Council on Foreign Relations
http://www.cfr.org/
Accessed 5 November 2016
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Health and U.S. Foreign Policy in the Age of Miracles
3 November 2016
Thomas J. Bollyky, Senior Fellow for Global Health, Economics, and Development, and Eric Goosby, UN Special Envoy on Tuberculosis and Former U.S. Global AIDS Coordinator

…Global deaths from malaria and tuberculosis (TB) declined 48 percent and 47 percent, respectively, over this period. Maternal mortality dropped 43 percent. Deaths for children under five have halved, which means nineteen thousand fewer of these children die each day. More than ten million people with HIV/AIDS in sub-Saharan Africa are on lifesaving antiretroviral treatment, up from just one hundred thousand in 2003.

U.S. leadership and investment helped spur this progress. The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) program, created in 2003, remains the largest financial commitment of any country to global health or the treatment of a specific disease. The United States is the biggest funder of GAVI, the global vaccine alliance, as well as the Global Fund to Fight AIDS, Tuberculosis, and Malaria, which immunize and treat millions of people each year. The United States also provides the most aid to fight neglected tropical diseases and poor maternal and child health. These investments have been consistently bipartisan, and their returns are, quite literally, measured in reduced human suffering and longer lives around the globe.

Can this age of miracles endure? Yes, but only with continued U.S. leadership and investment amid some challenging headwinds. The next president should build on the recent efforts to harness the positive synergies between global health and U.S. foreign policy…

Vaccines and Global Health: The Week in Review is a weekly digest  summarizing news, events, announcements, peer-reviewed articles and research in the global vaccine ethics and policy space. Content is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage. You are viewing the blog version of our weekly digest, typically comprised of between 30 and 40 posts below all dated with the current issue date

.– Request an Email Summary: Vaccines and Global Health : The Week in Review is published as a single email summary, scheduled for release each Saturday evening before midnight (EDT in the U.S.). If you would like to receive the email version, please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.

– pdf version:  A pdf of the current issue is available here: vaccines-and-global-health_the-week-in-review_29-october-2016-docx

– blog edition: comprised of the approx. 35+ entries posted below.

– Twitter:  Readers can also follow developments on twitter: @vaxethicspolicy.
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– Links:  We endeavor to test each link as we incorporate it into any post, but recognize that some links may become “stale” as publications and websites reorganize content over time. We apologize in advance for any links that may not be operative. We believe the contextual information in a given post should allow retrieval, but please contact us as above for assistance if necessary.

Support this knowledge-sharing service: Your financial support helps us cover our costs and to address a current shortfall in our annual operating budget. Click here to donate and thank you in advance for your contribution.

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David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy

Milestones

Editor’s Note:
We provide the full text of the preliminary report of the WHO SAGE meeting just concluded. The full meeting report will be published in the WHO Weekly Epidemiological Record on 2 December 2016. The meeting documents — including presentations and background readings — can be found at http://www.who.int/immunization/sage/meetings/2016/October/en/

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Summary of the October 2016 meeting of the Strategic Advisory Group of Experts on immunization (SAGE)
The Strategic Advisory Group of Experts (SAGE) on immunization1 met on 18-20 October 2016 in Geneva, Switzerland.
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Global Vaccine Action Plan: 2016 mid-term review of progress and recommendations
At the mid-term of the Decade of Vaccines (DoV), SAGE reviewed the progress made towards the achievement of the Global Vaccine Action Plan (GVAP) goals. SAGE assessment was based on the report prepared by the DoV secretariat on progress against each of the GVAP indicators2; including a section on “Sustainable financing and supply for immunization” to detail the activities initiated in response to the WHA resolution on access to affordable vaccines3 adopted in 2014, progress reports from the regions4 and from priority countries5.

At the midpoint of the GVAP, SAGE remains very concerned that progress toward the goals to eradicate polio, eliminate measles and rubella, eliminate maternal and neonatal tetanus, and increase equitable access to lifesaving vaccines is too slow.

Global immunization coverage has increased by only 1% since 2010. In 2015, 68 countries fell short of the target to achieve at least 90% national coverage with the third dose of diphtheria-tetanus-pertussis vaccine. Twenty-six of these countries reported no change and 25 reported a net decrease in coverage since 2010.

However, SAGE sees many reasons for hope. Sixteen countries, including some of the countries with the highest numbers of un- or under-vaccinated children, have made measurable progress since 2010. Research and development efforts are accelerating the discovery and testing of an expanded portfolio of vaccine candidates and platform delivery technologies.

SAGE reaffirmed that immunization is one of the world’s most effective and cost-effective tools against both the threat of emerging diseases and anti-microbial resistance and has a powerful impact on social and economic development. Finally, SAGE made several important recommendations to countries, immunization partners and the DoV secretariat.

Among those recommendations, SAGE recommends that countries demonstrate stronger leadership and governance of national immunization systems by: 2

a) Ensuring ministers at all levels are strong immunization advocates within their countries and regions, conveying the high return on investment, the urgency and the value of investing more in immunization programmes as an integral part of government-supported Universal Health Coverage packages.
b) Governments are encouraged to enact laws that guarantee access to immunization, establish National Immunization Technical Advisory Groups or equivalent groups, ensure that sufficient budgets are allocated to immunization each year and create mechanisms to monitor and efficiently manage funds at all levels (including those from the private sector).
c) National leaders must take courageous decisions to initiate necessary upgrades to systems, protocols, and policies that will ensure high immunization coverage that is sustained. Such upgrades might require redesigning supply chains, information systems and procurement policies, and reassessing roles and responsibilities in case the government decides to implement the decentralization of the health system.
d) National immunization programme managers should report each year to their National Immunization Technical Advisory Group or equivalent groups on progress made, lessons learnt and remaining challenges toward implementing National Immunization Plans and show how these plans are aligned to Regional and Global Vaccine Action Plan goals.

SAGE recommends that countries secure necessary investments to sustain immunization during polio and Gavi transitions.
a) All countries should mitigate any risk to sustaining effective immunization programmes when polio funding decreases. All Member States with substantial numbers of staff and resources issued from the Global Polio Eradication Initiative are requested to describe, in their polio transition plan, how they propose to maintain and fund critical immunization, laboratory and surveillance activities that are currently supported with polio funding and staff.
b) In all countries transitioning from Gavi support, all national and global immunization partners must advocate strongly and persistently for increased domestic financing to sustain immunization gains over time.

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Yellow fever
Recent outbreaks of yellow fever in Central Africa highlighted the need to revisit and expand the control strategy as well as the vaccine supply, and the need for vaccine supply surge capacity. Therefore, WHO has initiated the development of a new global strategy to Eliminate Yellow Fever Epidemics (EYE strategy) globally by 2026. There are 3 strategic objectives: protect at risk populations, prevent international spread, and rapidly contain outbreaks. The Strategy outlines four key activities: continued access to affordable vaccines through a sustainable vaccine market; political commitment at global, regional and country levels; robust governance and strong partnerships; and research to support better tools and practices. New aspects of the strategy from previous efforts include the revised country risk category, the aim to protect specific risk populations, the need to address the urban risk, and the establishment of a revolving emergency vaccine stockpile. Following establishment of the EYE strategy, WHO and partners will develop an implementation plan.

SAGE confirmed the need for new strategic thinking and supported the general approach of the EYE strategy. SAGE emphasized the importance to link the EYE strategy to existing programmes/initiatives, e.g. measles-rubella strategy, integrated disease surveillance, and also vector control. It was noted that EYE can serve as a driver to raise awareness and preparedness in urban settings for other outbreak prone diseases.
Considering the global spread of Aedes mosquitos, rapid urbanization, and increased international travel, it is critical to have surge capacity in the event of an outbreak. SAGE previously reviewed the evidence for the minimum effective dose (also called fractional dose) in June 2016 in the context of the outbreak in Central Africa and supported its use in this type of situation. The minimum effective dose, administered as a fraction of the volume of the normal dose, should induce a protective immune response equivalent to a full dose. SAGE was updated on the evidence for minimum effective dose, for which most evidence is limited to one of the yellow fever vaccine products. Available studies suggest that a reduced volume dose was equivalent to the standard dose with respect to all measured immunological and virological parameters as long as the dose contained at least 3000 International Units.

SAGE was also updated on the experience of the minimum effective dose campaign in Kinshasa in August 2016. Logistically and operationally, the use of a minimum effective dose was shown to be feasible and a promising approach to protect at-risk populations that would otherwise be left unprotected.

Based on the available evidence, SAGE reaffirmed that a minimum effective dose can be used as part of an exceptional response in a time when there is a large outbreak and a shortage of vaccine.

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Measles and rubella elimination
SAGE reviewed the findings and the recommendations outlined in the mid-term review of the Measles and Rubella Strategic Plan 2012-2022. SAGE commended the MTR team on their work and endorsed the report and its recommendations.

SAGE stressed the critical role of high quality measles and rubella case-based surveillance for achieving the goals of the measles and rubella strategic plans and that countries should move towards weekly reporting to regions. SAGE stressed the importance of achieving and maintaining high population immunity in order to achieve the regional and global measles and rubella goals.

SAGE recommended that a routine second dose of measles containing vaccine (MCV) should be added to national immunization schedules in all countries regardless of MCV1 coverage. In countries meeting the criteria for rubella containing vaccine introduction into national immunization programmes6 , measles and rubella containing vaccines (MRCV) should be used in place of single-antigen MCV.

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Maternal and neonatal tetanus elimination (MNTE) and broader tetanus prevention
SAGE noted that while there was progress with MNTE, the goal to achieve global elimination by 2015 was missed once again. The failure to achieve this goal is a reminder of the persisting health inequities and the inability of some countries to provide basic health services to the most marginalized and vulnerable populations.

Countries yet to achieve MNTE should establish/update and implement their operational plans to achieve the required action within the timelines stated in the report from the Working Group on MNTE and broader tetanus prevention. Achievement of MNTE by 2020 is feasible with timely availability of financial resources and compact single-dose pre-filled auto-disable injection devices (CPAD) to reach the most marginalized populations.

UNICEF, UNFPA (United Nations Populations Fund) and WHO should work with countries to generate and sustain political interest in the continuing elimination of MNT to guard against complacency once a country has been declared to have eliminated the disease.

All immunization programmes should review and adjust their routine immunization schedules to ensure tetanus protection over the life course (3 priming doses in infancy and 3 booster doses in childhood/adolescence). All countries should also scale up and sustain the coverage of clean delivery and improve clean cord care practices. The 3 booster doses schedule intended to achieve protection throughout adulthood (reproductive age for women), and probably providing lifelong protection should preferably be given during the second year of life, between 4-7 years of age, and between 9-15 years of age.

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Hepatitis B vaccination
SAGE reemphasized the importance of introduction of the birth dose and urged all countries to introduce universal birth dose without further delays.

All infants should receive their first dose of hepatitis B vaccine as soon as possible after birth, preferably within 24 hours. However, if this is not feasible the birth dose will still be beneficial in preventing perinatal transmission if given within 7 days, although somewhat less than if given within 24 hours. After 7 days, a late birth dose is effective in preventing horizontal transmission and therefore remains beneficial. Therefore, SAGE recommends that all infants receive the birth dose during the first contact with health facilities any time up to the time of the first primary dose.

Schedules and strategies for human papillomavirus immunization
Noting the high effectiveness and safety of the human papillomavirus (HPV) vaccine, SAGE recommends that it is promptly introduced for adolescent girls as part of a coordinated and comprehensive strategy to prevent cervical cancer and other diseases caused by HPV. The 5

immunization of multiple cohorts of girls aged 9–14 years is recommended when the vaccine is first introduced. If resources are available, the age range could be expanded up to 18 years.
SAGE also discussed polio eradication. It was updated on the tOPV to bOPV switch and the progress with polio eradication and started an initial discussion on post eradication.

The full meeting report will be published in the WHO Weekly Epidemiological Record on 2 December 2016. The meeting documents — including presentations and background readings — can be found at http://www.who.int/immunization/sage/meetings/2016/October/en/

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References
1 http://www.who.int/imunization/sage/en/index.html
2 http://www.who.int/entity/immunization/global_vaccine_action_plan/gvap_secretariat_report_2016.pdf?ua=1
3 http://apps.who.int/gb/ebwha/pdf_files/WHA68-REC1/A68_R1_REC1-en.pdf
4 http://www.who.int/entity/immunization/global_vaccine_action_plan/2_Regional_reports_annex_GVAP_secretariat_report_2016.pdf?ua=1
5
http://www.who.int/entity/immunization/global_vaccine_action_plan/3_Country_reports_annex_GVAP_secretariat_report_2016.pdf?ua=1
6 Rubella Vaccines: WHO Position Paper. WER No. 29, 2011, 86, Pp. 301–316.

ZikaPLAN: 25 Research Organizations Unite to Fight Zika Virus and Build Long-term Outbreak Response Capacity in Latin America
RECIFE, Brazil, October 25, 2016 /PRNewswire/ — 25 leading research and public health organizations from Latin America, North America, Africa, Asia, and Europe gathered in Recife for the launch of ZikaPLAN (Zika Preparedness Latin American Network). This global initiative, created in response to a Horizon 2020 funding call by the European Commission’s Directorate-General Research and Innovation, has been formed to address the Zika virus outbreak and the many research and public health challenges it poses. The initiative takes a comprehensive approach to tackle the Zika threat by:
:: addressing the knowledge gaps and needs in the current Zika outbreak to better understand the disease, prevent its spread and educate the affected populations,
:: building a sustainable response capacity in Latin America for Zika and other emerging infectious diseases (EID).

The impact of the Zika outbreak took scientists and public health authorities by surprise and hit the most vulnerable populations the hardest. The severity of the outbreak and mutation of the virus have generated numerous research questions. To take effective measures, health authorities need to know the severity of the disease and its impact on public health, what interventions will work to prevent and stop its spread, and how best to manage and treat those who have been infected. This unprecedented Zika outbreak has also highlighted the need to build local capacities: in some of the regions where the virus struck there was not the necessary research infrastructure to understand the threat and take action quickly.

To bridge these gaps, research organizations in the ZikaPLAN consortium will look at Zika’s connection with congenital syndromes and neurological complications, and the pathogenesis of severe cases, through a series of clinical studies. They will explore non-vector and vector transmission and risk factors for geographic spread, measure the burden of disease and investigate how the virus has evolved, comparing current and historic strains. ZikaPLAN will look at novel personal preventive measures, innovation in diagnostics and modelling of vector control and vaccine strategies to inform policy decisions. The social sciences will also play a role in ZikaPLAN, which aims to determine the best communication strategies to keep the affected communities informed.

ZikaPLAN will work closely with two other European Union-funded consortia, ZIKAction and ZikAlliance, to establish a Latin American and Caribbean network. This network will address the broader issue of building local capacity in Latin America to prepare for and rapidly launch a large-scale research response to emerging infectious disease threats. ZikaPLAN will contribute to developing an inter-epidemic research plan, policy recommendations, training, research networks and dissemination strategies that are designed to permanently strengthen local capacities, beyond the four years of the project. The three consortia will set up common bodies for the global management of scientific programs, communication, and ethical, regulatory and legal issues.

ZikaPLAN is receiving a €11.5 million grant from the European Union’s Horizon 2020 research and innovation program, under grant agreement number 734584.

Emergencies

WHO Grade 3 Emergencies [to 29 October 2016]
Iraq
:: WHO and partners gear up to safeguard lives of displaced persons fleeing Mosul
26 October 2016 — The World Health Organization, together with national health authorities and health cluster partners, have accelerated preparedness and response measures for internally displaced persons from Mosul by prepositioning 46 mobile medical clinics, 45 mobile health teams and 26 ambulances in a number of prioritized areas around the country. Life-saving medicines and supplies for more than 350 000 beneficiaries have also been prepositioned, including chronic disease medicines, diarrhoeal disease medicines, and trauma and surgical supplies. Additional essential medicines are being delivered from WHO’s logistics hub in Dubai, and are also being procured locally.

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 29 October 2016]
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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Editor’s Note:
While the WHO Emergency webpages above do not capture the announcements below, we add them here for continuity in understanding emergency contexts.
WHO Eastern Mediterranean Region EMRO
:: WHO releases emergency funds to support cholera response in Yemen
27 October 2016 – WHO has released approximately US$ 1 million from its internal emergency funds to support the ongoing response to the cholera outbreak in Yemen. Since the outbreak was announced by the Ministry of Public Health and Population on 6 October, a total of 1184 suspected cases of cholera, including 6 deaths, have been reported. More than 7.6 million people are currently living in areas affected by the outbreak, and more than 3 million internally displaced persons are especially vulnerable.

: WHO expands the system for detection, alert, and containment of potential epidemics in light of Mosul humanitarian response – 26 October 2016
Baghdad, 26 October 2016 – In coordination with the Iraqi Federal Ministry of Health and Ministry of Health of Kurdistan Regional Government, WHO conducted 3 consecutive training sessions from 28 September to 6 October 2016 in Erbil and Suleimaniyah in the Kurdistan region.
The training focused on the early warning alert and response network system (EWARNS) and was targeted at staff from the new health facilities established to respond to the health needs of newly displaced populations in formal and emergency settlements, and hosting communities.
“We have to monitor communicable diseases trends, patterns and vigilance,” said Altaf Musani, WHO Representative to Iraq. “EWARNS will be the tool to measure these trends and help to detect early epidemics in displaced population areas to support the federal and regional ministries of health and health cluster partners with effective epidemic-prone disease prevention and control measures,” he added.
This series of trainings marked the entry of new 43 health facilities to the network in Iraq to scale up the number of reporting sites to over 180. 24 health staff from Ninewa Directorate of Health received comprehensive training on EWARNS reporting and are ready for deployment to the new health facilities to resume related EWARNS functions…

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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 –
:: Iraq: Mosul Humanitarian Response Situation Report #3 (23-25 October 2016)
Highlights
…Over 10,500 people are currently displaced and in need of humanitarian assistance. Partners are providing emergency assistance in camps and host communities. The majority of displaced people are sheltering in host communities.
…Population movements are fluctuating as the front lines move, including people returning to their homes following improved security conditions in the immediate area.
…Assessments have recorded a significant number of female-headed households, raising concerns around the detention or capture of men and boys.
…Almost 14,500 people have received emergency assistance within 24 hours of areas newly-retaken from ISIL becoming accessible to humanitarian partners since the start of military operations.

Syria
:: 28 Oct 2016 Turkey | Syria: Flash Update – Developments in Eastern Aleppo (as of 27 October 2016) [EN/AR]
:: 26 October 2016 Under-Secretary-General for Humanitarian Affairs and Emergency Relief Coordinator Stephen O’Brien Statement to the Security Council on Syria, 26 October 2016

Yemen
– No new announcements identified.

Haiti’s Ministry of Health organizing a vaccination campaign against cholera in areas affected by Hurricane Matthew, supported by PAHO-WHO, UNICEF and other partners
Port-au-Prince, Haiti, 27 Oct. 2016– The Haitian Ministry of Health (MSPP) is setting up a vaccination campaign against cholera in areas ravaged by Hurricane Matthew, with support from the Pan American Health Organization / World Health Organization (PAHO / WHO).

The decision of WHO and other member of the Global Task Force for Cholera Control to approve the request of the MSPP to bring 1 million doses of oral vaccine against cholera is based on the goal of reducing the burden of cholera cases on health care facilities, and of reducing deaths in the departments of the Sud and Grand’Anse, the areas most affected by Hurricane Matthew.

The target population is estimated at over 820,000 people over one year of age. The vaccination campaign will begin November 8, 2016. Activities will focus on the municipalities most vulnerable to cholera outbreaks in the two southern departments of Grand’Anse and Sud, where there has been significant destruction of water and sanitation supply systems.

Haiti’s Minister of Public Health, Dr. Daphne Benoit, said that the emergency vaccination campaign was taking place in tragic circumstances that have affected the populations of the south. “The vaccine is an additional intervention which will help us to save lives, but does not replace the efforts that the government supports in the field of water and sanitation,” she emphasized.

PAHO-WHO Representative Dr. Jean-Luc Poncelet stressed the importance of the leadership of MSPP in this vaccination campaign, which “will contribute to limit the suffering of individuals and families affected by Hurricane Matthew.” Some municipalities in the south west peninsula have reported outbreaks of cholera since the hurricane hit on October 4, “so it is important to work together and with partners to build local capacity for clinical management of cases in the cholera treatment centers,” he said.

Poncelet noted that PAHO-WHO will support the Ministry of Health in activities including development of tools and technical support as well as reception, storage and transport of the vaccines and supplies in departments, municipalities and institutions. PAHO/WHO will also support training of vaccination staff supervisors and operators, and the coordination, collection and analysis of information, monitoring and evaluation.

Since Hurricane Matthew struck Haiti on October 4, significant increases in suspected cases of cholera and deaths have been reported from several places in the departments of Sud and Grand’Anse.

Numerous partners that work in Haiti are supporting the cholera vaccination campaign, including UNICEF, GHESKIO, Partners in Health, US Centers for Disease Control and Prevention (CDC), International Medical Corps and others.

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UNOG – REGULAR PRESS BRIEFING BY THE INFORMATION SERVICE
25 October 2016
Haiti
Tarik Jasarevic, for the World Health Organization (WHO), said that 500,0000 cholera vaccines had arrived on 22 October and another 500,000 had arrived on 24 October in Port-au-Prince. The one million vaccines had been sent to Haiti following a decision of the Global Taskforce on Cholera Control, taken on 10 October. Vaccination was expected to start early in the week of 31 October, or even on 30 October, in affected departments of Haiti, Sud and Grand Anse. The objective of the campaign was to reduce the burden of cholera cases on health care facilities and reduce deaths in departments affected by the hurricane, preventing cholera’s further spread to neighboring departments, including to the capital Port-au-Prince. WHO was in the process of preparing the campaign and would keep the press informed.

In response to a question, Mr. Jasarevic said that as of 17 October there were 465 suspected cholera cases in Grand Anse and 684 in Sud. There was a decrease and stabilization of admissions in cholera treatment centres operating in the two departments, but the peak of cases followed by a rapid decline was to be expected. A second peak could not be excluded given the current situation with water and sanitation. That is why it was important to proceed with the emergency vaccination campaign, and why the Global Taskforce had decided to send the vaccines.

In response to other questions, he said that there would be a single-dose strategy, allowing to cover twice as many people as if the classical two-dose strategy was to be applied. The protection would be lesser, 60 to 70 per cent for severe cases, and shorter in duration, but the objective was to vaccinate as many people as possible in affected areas and to try to reduce the burden. The target population was all persons over one year of age. The protection with a single dose would be less than a year. Out of the one million doses, 700,000 would be moved to the two departments in question as the target population was 655,000 people so far. Some prioritization would be done to vaccinate in communes where people could be rapidly accessed and where the impact would be the biggest, in urban centres where there was more density and an increased risk of transmission. Some 300,000 vaccines would remain in the capital for the time being…

Zika virus [to 29 October 2016]
Public Health Emergency of International Concern (PHEIC)
http://www.who.int/emergencies/zika-virus/en/

[See ZikaPLan announcement in Milestones section above]

Zika situation report – 20 October 2016
Full report: http://apps.who.int/iris/bitstream/10665/250590/1/zikasitrep20Oct16-eng.pdf?ua=1
Key Updates
:: Countries and territories reporting mosquito-borne Zika virus infections for the first time in the past week:
… None
:: Countries and territories reporting microcephaly and other central nervous system (CNS) malformations potentially associated with Zika virus infection for the first time in the past week:
… None
:: Countries and territories reporting Guillain-Barré syndrome (GBS) cases associated with Zika virus infection for the first time in the past week:
… None
:: The Ministry of Health of Viet Nam has reported a case of microcephaly, for which testing is underway to determine the cause.
:: The WHO Zika Virus Research Agenda has been published. The goal of the Agenda is to support the gathering of evidence to strengthen essential public health guidance to prevent and limit the impact of Zika virus and its complications. The Research Agenda identifies critical areas of research for which WHO is uniquely placed to implement and coordinate global action. [see below]
:: The quarterly update of the Zika Strategic Response Plan has been published. This update provides key information on the epidemiological situation, response, and updated funding information for WHO and partners.

Analysis
:: Overall, the global risk assessment has not changed.

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WHO Zika virus research agenda
October 2016 :: 19 pages
Languages: English
WHO reference number: WHO/ZIKV/PHR/16.1
PDF: http://apps.who.int/iris/bitstream/10665/250615/1/WHO-ZIKV-PHR-16.1-eng.pdf?ua=1
Overview
The goal of the WHO Zika Virus Research Agenda is to support the generation of evidence needed to strengthen essential public health guidance and actions to prevent and limit the impact of Zika virus and its complications.

The Research Agenda identifies critical areas of research where WHO is uniquely placed to implement or coordinate global activities. Research and evidence are the foundation for sound health policies.

A document summarizes the ongoing efforts of the World Health Organization and Pan American Health Organization, Institut Pasteur and the networks of Fiocruz, CONSISE and ISARIC to generate standardized clinical and epidemiological research protocols and questionnaires to address key public health questions. Specifically, data collected using the standardized protocols will be used to refine and update recommendations for prevention of Zika virus spread, surveillance and case definitions for microcephaly, to help understand the spread, severity, spectrum and impact on the community of ZIKV and to guide public health measures, particularly for pregnant women and couples planning a pregnancy.
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Zika Open [to 29 October 2016]
[Bulletin of the World Health Organization]
:: All papers available here
No new papers identified.

EBOLA/EVD [to 29 October 2016]
http://www.who.int/ebola/en/
“Threat to international peace and security” (UN Security Council)

Editor’s Note:
We note that the Ebola tab – which had been listed along with Zika, Yellow Fever, MERS CoV and other emergencies – has been removed from the WHO “home page”. We deduce that WHO has suspended issuance of new Situation Reports after resuming them for several weekly cycles. The most recent report posted is EBOLA VIRUS DISEASE – Situation Report – 10 JUNE 2016. We have not encountered any UN Security Council action changing its 2014 designation of Ebola as a “threat to international peace and security.” We will continue to highlight key articles and other developments around Ebola in this space.

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NIH [to 29 October 2016]
http://www.nih.gov/news-events/news-releases
October 26, 2016
Ebola-affected countries receive NIH support to strengthen research capacity
The recent Ebola epidemic in West Africa highlighted the need for better global preparedness and response to disease outbreaks. To help address that need in Guinea, Liberia and Sierra Leone — the countries most affected by the epidemic — the National Institutes of Health has established a new program to strengthen the research capacity to study Ebola, Lassa fever, yellow fever and other emerging viral diseases. In the initiative’s first funding round, NIH’s Fogarty International Center is awarding grants to four U.S. institutions that will partner with West African academic centers to design training programs for their scientists and health researchers.

The collaborations aim to develop research training proposals that would strengthen the skills required to evaluate vaccines, develop new diagnostic tests and treatments, and identify the most effective intervention strategies for disease outbreaks. These planning grants, totaling $200,000, are intended to help institutions prepare to compete for larger, longer-term Fogarty grants to implement research training programs.

“We hope these awards will catalyze efforts to identify existing resources and plan to address development of sustainable research capacity in the countries that suffered so horribly from Ebola,” said Fogarty Director Roger I. Glass, M.D., Ph.D. “By training local researchers in epidemiology and lab skills, and helping them form networks with U.S. scientists, we believe future disease outbreaks can be better contained.”…

POLIO [to 29 October 2016]
Public Health Emergency of International Concern (PHEIC)

Polio this week as of 25 October 2016
:: 24 October marked World Polio Day, providing an opportunity to celebrate progress towards a polio-free world and the tireless efforts of many towards this goal. Rotarians and other partners across the world celebrated the day, by raising critical awareness of the need to complete the job. Click the following links for a selection of global awareness raising events marking World Polio Day: Rotary’s annual World Polio Day event; Getting to zero cases by Philanthropy Age; and Spotlight World Polio Day 2016.

: The Strategic Advisory Group of Experts on immunization (SAGE) met last week in Geneva, Switzerland. On polio eradication, the group expressed serious concern at the global supply situation of inactivated polio vaccine (IPV), and strongly recommended that countries consider adopting fractional intradermal use of IPV in both routine and supplementary immunization activities, to reduce the volume of IPV needed to cover a population.

:: News from around the polio world:
Afghanistan National Emergency Action Plan 2016-2017; Recognizing Health Care Workers; and, the Fight to End Polio in Afghanistan

:: News from around the polio world:
Polio Programme Supports Anti-Fistula Efforts in Ethiopia
Containment: Shutting the Proverbial Door on Polioviruses

Country Updates [Selected Excerpts]
Pakistan
:: Three new WPV1 positive environmental samples were reported in the past week, all from Balochistan (Quetta, Pishin and Killa Abdullah), with collection dates in mid-September. Continued detection of environmental positives throughout 2016 confirms that virus transmission remains geographically widespread across the country, despite strong improvements being achieved.
:: Efforts continue to further strengthen immunization and surveillance activities in all provinces of the country.

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Major campaign launched to immunize 5.8 million Iraqi children against polio
Baghdad, Iraq, 25 October 2016 – On World Polio Day the Ministry of Health with support from UNICEF and the World Health Organization (WHO) launched a weeklong nationwide campaign to immunize Iraq’s children against polio.

Under the slogan “two drops can change a life,” the 5-day campaign aims to reach an estimated 5.8 million children under the age of 5 in Iraq, regardless of previous vaccination status.

Polio is a highly infectious viral disease that attacks the nervous system. Children under 5 years of age are the most vulnerable to the disease, but timely immunization can prevent infection.
“The Government of Iraq is committed to polio eradication, and conducted 16 campaigns to that end in 2014 and 2015 as part of the Middle East polio outbreak response,” said UNICEF Representative in Iraq Peter Hawkins.

Since April 2014, no new polio cases have been reported in Iraq, thanks to the Government’s strong commitment and the hard work of frontline workers. In May 2015, Iraq was removed from the list of infected countries.

However, the risks of a resurgence persist due to possible surveillance and immunization coverage gaps among Iraq’s displaced populations as well as those living in inaccessible areas and informal settlements.

“There is still a risk of polio returning to Iraq,” said WHO Representative to Iraq, Altaf Musani. “Polio transmission is ongoing in Pakistan and Afghanistan and new cases of polio have also been confirmed in Nigeria,” he said. ”Until transmission is stopped globally, we need to maintain high levels of vaccination coverage and keep surveillance systems strong, to be on the alert for the virus,” he added.

The Iraq Polio partnership conducted 2 national immunization rounds in February and April this year, reaching over 91% of the targeted population.

This month’s vaccination campaign will be conducted by the Iraqi Ministry of Health (with support from WHO and UNICEF, with special attention to the most vulnerable children in internally displaced persons (IDPs) and Syrian refugee camps, informal settlements, host affected communities and newly retaken areas. More than 25 000 vaccinators will go from house to house during the campaign, visiting families.

WHO will cover the operational cost, intra and post campaign monitoring, while UNICEF will provide support for focused social mobilization services. In coordination with the Federal Ministry of Health, the Kurdistan Regional Government Ministry of Health, Zain and Korek Telecommunications Company will contribute into social mobilization and communications campaign with a focus on IDPs.

Yellow Fever [to 29 October 2016]
http://www.who.int/emergencies/yellow-fever/en/

[See Yellow Fever discussion in SAGE meeting summary in Milestones section above]

Yellow fever situation report
28 October 2016
Read the full situation report
Key updates
Angola epidemiological update (as of 22 September):
:: The last confirmed case had symptom onset on 23 June.
:: Two new probable cases without a history of yellow fever vaccination were reported from Kwanza Sul province in the last week.
:: Phase II of the vaccination campaign is ongoing targeting more than 2 million people in 10 provinces.

Democratic Republic of the Congo epidemiological update (as of 18 September):
:: The last confirmed non-sylvatic case had symptom onset on 12 July.
:: A new confirmed, sylvatic case was reported from Bominenge Health Zone in Sud Ubangui province.
:: 14 probable cases are under investigation
:: The reactive campaign in Mushenge Health Zone in Kasai province, which began on 20 October, is ongoing.

Analysis
:: The majority of the probable cases in Angola have been ruled out as yellow fever cases by the Institut Pasteur of Dakar. They will remain classified as probable cases until a full battery of tests has been run to determine other possible causes of illness. Once the final results are received the cases will be reclassified. Coincidentally, a previously scheduled pre-emptive vaccination campaign is ongoing in Kwanza Sul province where 2 new probable cases were reported.

WHO & Regional Offices [to 29 October 2016]

WHO financing dialogue
28 October 2016 – The financing dialogue is a key element of WHO’s reform process to better address the increasingly complex challenges of health in the 21st century. From persisting problems to new and emerging health threats, WHO needs the capability and flexibility to respond to this evolving environment. WHO is making some fundamental changes to enable it to respond faster and more effectively to emergencies, as well as to anticipate future health challenges and to minimize their impact

Over 1 million treated with highly effective hepatitis C medicines
27 October 2016 – Over one million people in low- and middle-income countries have been treated with a revolutionary new cure for hepatitis C since its introduction two years ago. The new medicines have a cure rate of over 95%, fewer side effects than previously available therapies, and can completely cure the disease within three months.

Highlights
Trachoma: WHO-led alliance awarded for saving the sight of millions
October 2016 – The WHO Alliance for the Global Elimination of Trachoma by the year 2020 (GET2020) has been awarded the Global Partnership Award by the International Agency for the Prevention of Blindness. The award is in recognition of the remarkable work accomplished by the Alliance in implementing the WHO-recommended SAFE strategy.

New web portal on health law and universal health coverage
October 2016 – With countries working towards universal health coverage and the Sustainable Development Goals, WHO has developed a new portal to help strengthen health laws and regulatory systems. The portal provides guidelines, case studies, research, lessons learned, and other resources on health law topics

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Weekly Epidemiological Record, 28 October 2016, vol. 91, 43 (pp. 501–516)
Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification of elimination of transmission in Guatemala
Progress report on the elimination of human onchocerciasis, 2015–2016
10 facts on rabies

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:: WHO Regional Offices
Selected Press Releases, Announcements
WHO African Region AFRO
No new content identified.

WHO Region of the Americas PAHO
:: Haiti’s Ministry of Health organizing a vaccination campaign against cholera in areas affected by Hurricane Matthew, supported by PAHO-WHO, UNICEF and other partners (10/27/2016)

WHO South-East Asia Region SEARO
:: Prevent brain stroke – 29 October 2016

WHO European Region EURO
:: Europe strengthens its role in international outbreak response and calls for GOARN 2.0 27-10-2016
:: Italian Government provides funding to improve health services in eastern Ukraine 26-10-2016
:: Lead Poisoning Prevention Week: ban lead paint 26-10-2016

WHO Eastern Mediterranean Region EMRO
:: WHO releases emergency funds to support cholera response in Yemen
27 October 2016 – WHO has released approximately US$ 1 million from its internal emergency funds to support the ongoing response to the cholera outbreak in Yemen. Since the outbreak was announced by the Ministry of Public Health and Population on 6 October, a total of 1184 suspected cases of cholera, including 6 deaths, have been reported. More than 7.6 million people are currently living in areas affected by the outbreak, and more than 3 million internally displaced persons are especially vulnerable.
:: New neonatal intensive care unit at Heevi Paediatric Hospital in Iraq gives newborns a fighting chance – 26 October 2016
: WHO expands the system for detection, alert, and containment of potential epidemics in light of Mosul humanitarian response – 26 October 2016
:: Major campaign launched to immunize 5.8 million Iraqi children against polio
25 October 2016

WHO Western Pacific Region
:: WHO stresses the importance of neonatal best practices for a healthy start to life
MANILA, 25 October 2016 – The neonatal period is one of the most crucial phases in the survival and development of a child. At the recently concluded session of the WHO Regional Committee for the Western Pacific, Member States widely acknowledged the importance of Early Essential Newborn Care (EENC) in reducing neonatal mortality in the Region, and highlighted significant progress made in countries towards scaling-up EENC.

CDC/ACIP [to 29 October 2016]
http://www.cdc.gov/media/index.html
https://www.cdc.gov/vaccines/acip/
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Media Statement
FRIDAY, OCTOBER 28, 2016
CDC, Miami-Dade and Miami Beach collaborate and make progress on better understanding and stopping the Zika outbreak
CDC continues to support local efforts to prevent new infections of Zika in Miami-Dade County. To see the latest situation firsthand, Dr. Frieden traveled to Miami on Tuesday, October 25….

Media Advisory
WEDNESDAY, OCTOBER 26, 2016
CDC Foundation’s New Business Pulse Focuses on Reducing Tobacco Use
“Business Pulse: Tobacco Use”, launched today by the CDC Foundation, focuses on how employers can improve employee health by reducing tobacco use and exposure to secondhand smoke.

Transcript
MONDAY, OCTOBER 24, 2016
Transcript for CDC Press Conference: Can polio be eradicated despite recent setbacks?
Transcript and audio recording of World Polio Day Press Conference

Media Advisory
MONDAY, OCTOBER 24, 2016
Can polio be eradicated despite recent setbacks?
The world is at the brink of a historic moment: eradication of polio, one of the most feared scourges of humanity; yet, recent setbacks threaten this long-awaited achievement. On World…

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MMWR Weekly October 28, 2016 / No. 42
:: Outbreak of Influenza A(H3N2) Variant Virus Infections Among Persons Attending Agricultural Fairs Housing Infected Swine — Michigan and Ohio, July–August 2016
:: Preparedness for Zika Virus Disease — New York City, 2016

Gavi [to 29 October 2016]
http://www.gavi.org/library/news/press-releases/

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IFFIm press release (restricted access)
IFFIm issues US$ 500 million in 3-year floating rate Vaccine Bonds
Funding to increase immunisation of children in the poorest countries

London, 26 October 2016 – The International Finance Facility for Immunisation Company (IFFIm) today priced a US dollar floating rate benchmark bond issuance. The US$ 500 million, 3-year Vaccine Bonds provide investors an opportunity to fund immunisation programmes by Gavi, the Vaccine Alliance (Gavi), helping protect millions of children in the world’s poorest countries against preventable diseases.

This marks IFFIm’s first visit to the international US dollar benchmark market since 2013, and is IFFIm’s third transaction in the public dollar markets in addition to its two successful US dollar denominated sukuk transactions. The issuance was lead managed by Citi, Deutsche Bank and J.P. Morgan. The issue maturing on 01 November 2019 has a re-offer of 100% and carries a quarterly coupon of +26 basis points over the 3-month USD Libor rate.

“IFFIm Vaccine Bonds continue to attract investors worldwide who want to “do good and do well,” says IFFIm Chair René Karsenti. “IFFIm is very pleased to re-enter the FRN market with this socially responsible transaction which helps to fund life-saving immunisation programmes for Gavi, the Vaccine Alliance.”…

Industry Watch [to 29 October 2016]
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:: PaxVax’s Vaxchora™ Now Available as the Only U.S. Approved Vaccine for Protection Against Cholera
REDWOOD CITY, Calif., Oct. 24, 2016 /PRNewswire/ — PaxVax, Inc. announced that Vaxchora™ is now available in the United States (U.S.) as the country’s only vaccine for protection against cholera, a highly contagious intestinal diarrheal infection that can cause death in less than 24 hours if left untreated.1…

Vaxchora, a single-dose vaccine, was approved by the U.S. Food and Drug Administration (FDA) in June 2016 for use in U.S. adults traveling to cholera-affected areas as an active immunization against disease caused by Vibrio cholerae serogroup O1. Also in June 2016, The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) voted unanimously to recommend Vaxchora for travelers to areas of active cholera transmission…

“We are excited that Vaxchora is now available to Americans traveling to areas affected by cholera. This is particularly timely in light of the number of U.S. citizens, including members of the U.S. military, joining relief efforts in Haiti,” said Nima Farzan, Chief Executive Officer and President of PaxVax. “Vaccinating those traveling to cholera-affected areas can help mitigate its spread and can help protect them against the disease,” said Farzan.

PaxVax has also made a donation to international medical organization Partners In Health (http://www.pih.org) to support the relief efforts in Haiti with specific focus on cholera prevention and treatment.

BMGF – Gates Foundation [to 29 October 2016]
http://www.gatesfoundation.org/Media-Center/Press-Releases

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OCTOBER 27, 2016
Global Britain, Global Health
Bill Gates backs British innovation, challenges UK government to step up investment in science and R&D
LONDON/SEATTLE (October 27, 2016) – Today Bill Gates, Sir Richard Branson, and Secretary of State for International Development, Priti Patel, will join over 1,000 of the world’s leading scientists in London to celebrate the Grand Challenges programme that finds solutions to the toughest problems in health and development. Grand Challenges partners have invested more than $1 billion into more than 2,000 innovations from 87 countries. Also today, a ground-breaking new programme to fight Zika, Dengue and Yellow Fever will be announced…

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

American Journal of Preventive Medicine
November 2016 Volume 51, Issue 5, p637-864, e119-e154
http://www.ajpmonline.org/current
Theme: Digital Health: Leveraging New Technologies to Develop, Deploy, and Evaluate Behavior Change Interventions
Guest Editors: Lucy Yardley, Tanzeem Choudhury, Kevin Patrick

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Research Articles
Concomitant Adolescent Vaccination in the U.S., 2007–2012
Jennifer L. Moss, Paul L. Reiter, Noel T. Brewer
p693–705
Published online: June 30, 2016
Abstract
Introduction
Concomitant (same-day) delivery of two or more vaccines to adolescents is effective, safe, and efficient. Increasing concomitant vaccination could improve coverage for recommended adolescent vaccines, but little is known about who receives vaccines concomitantly.
Methods
Data came from healthcare provider–verified records on 70,144 adolescents (aged 13–17 years) in the 2008–2012 versions of the National Immunization Survey–Teen who had received at least one dose of tetanus, diphtheria, and acellular pertussis (Tdap) booster; meningococcal conjugate vaccine (MenACWY); or human papillomavirus (HPV) vaccine. Separately for each vaccine, multivariable logistic regression identified adolescent and household correlates of concomitant versus single vaccination, stratified by adolescent sex. Vaccination took place in 2007–2012, data collection in 2008–2012, and data analysis in 2015.
Results
Among vaccinated adolescents, 51%–65% of girls and 25%–53% of boys received two vaccines concomitantly. Concomitant uptake of each vaccine increased over survey years (e.g., 2012 vs 2008: girls’ Tdap booster, OR=1.88, 95% CI=1.56, 2.26; boys’ Tdap booster, OR=2.62, 95% CI=2.16, 3.16), with the exception of HPV vaccination among boys. Additionally, concomitant vaccination was less common as adolescents got older and in the Northeast (all p<0.05). For MenACWY and HPV vaccine, concomitant uptake was less common for girls whose mothers had higher versus lower education and for boys who lived in metropolitan versus non-metropolitan areas (all p<0.05).
Conclusions
Missed opportunities for concomitant adolescent vaccination persist, particularly for HPV vaccine. Future interventions targeting groups with low rates of concomitant vaccination could improve population-level coverage with recommended vaccines.

American Journal of Public Health
Volume 106, Issue 11 (November 2016)
http://ajph.aphapublications.org/toc/ajph/current

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AJPH SPECIAL SECTION: WORLD HEALTH ORGANIZATION
Whither WHO? Our Global Health Leadership
Elizabeth Fee
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1903–1904.

World Health Organization Reform—A Normative or an Operational Organization?
Derek Yach
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1904–1906.

Finance and Governance: Critical Challenges for the Next WHO Director-General
Julio Frenk
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1906–1907.

A New Leader for a New World Health
Ariel Pablos-Mendez, Susanna Baker
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1907–1908.

The Election of the Next World Health Organization Director-General Explained to a Visitor From Mars
Gilles Dussault
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1908–1909.

World Health Organization: Overhaul or Dismantle?
Suwit Wibulpolprasert, Mushtaque Chowdhury
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1910–1911.

At the Roots of The World Health Organization’s Challenges: Politics and Regionalization
Elizabeth Fee, Marcu Cueto, Theodore M. Brown
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1912–1917.

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AJPH PERSPECTIVES FROM THE SOCIAL SCIENCES – ISLAM
Islamophobia and Public Health in the United States
Goleen Samari
American Journal of Public Health: November 2016, Vol. 106, No. 11: 1920–1925.

BMC Infectious Diseases
http://www.biomedcentral.com/bmcinfectdis/content
(Accessed 29 October 2016)

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Research article
The impact of active surveillance and health education on an Ebola virus disease cluster — Kono District, Sierra Leone, 2014–2015
During December 2014–February 2015, an Ebola outbreak in a village in Kono district, Sierra Leone, began following unsafe funeral practices after the death of a person later confirmed to be infected with Ebola…
Tasha Stehling-Ariza, Alexander Rosewell, Sahr A. Moiba, Brima Berthalomew Yorpie, Kai David Ndomaina, Kai Samuel Jimissa, Eva Leidman, Dingeman J. Rijken, Colin Basler, James Wood and Dumbuya Manso
BMC Infectious Diseases 2016 16:611
Published on: 27 October 2016