Health Economics, Policy and Law
Volume 11 – Issue 03 – July 2016
http://journals.cambridge.org/action/displayIssue?jid=HEP&tab=currentissue

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Articles
Out-of-pocket payments and community-wide health outcomes: an examination of influenza vaccination subsidies in Japan
Yoko Ibukaa1 c1 and Shun-ichiro Besshoa2
a1 Graduate School of Economics and Management, Tohoku University, Miyagi, Japan
a2 Faculty of Economics, Keio University, Tokyo, Japan
Abstract
While studies have shown that reductions in out-of-pocket payments for vaccination generally encourages vaccination uptake, research on the impact on health outcomes has rarely been examined. Thus, the present study, using municipal-level survey data on a subsidy programme for influenza vaccination in Japan that covers the entire country, examines how reductions in out-of-pocket payments for vaccination among non-elderly individuals through a subsidy programme affected regional-level influenza activity. We find that payment reductions are negatively correlated with the number of weeks with a high influenza alert in that region, although the correlation varied across years. At the same time, we find no significant correlation between payment reductions and the total duration of influenza outbreaks (i.e. periods with a moderate or high alert). Given that a greater number of weeks with a high alert indicates a severer epidemic, our findings suggest that reductions in out-of-pocket payments for influenza vaccination among the non-elderly had a positive impact on community-wide health outcomes, indicating that reduced out-of-pocket payments contributes to the effective control of severe influenza epidemics. This suggests that payment reductions could benefit not only individuals by providing them with better access to preventive care, as has been shown previously, but also communities as a whole by shortening the duration of epidemics.

Infectious Diseases of Poverty
http://www.idpjournal.com/content
[Accessed 4 June 2016]

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Research Article
Productivity losses associated with tuberculosis deaths in the World Health Organization African region
In 2014, almost half of the global tuberculosis deaths occurred in the World Health Organization (WHO) African Region. Approximately 21.5 % of the 6 060 742 TB cases (new and relapse) reported to the WHO in 20…
Joses Muthuri Kirigia and Rosenabi Deborah Karimi Muthuri
Infectious Diseases of Poverty 2016 5:43
Published on: 1 June 2016

The Lancet
Jun 04, 2016 Volume 387 Number 10035 p2263-2350
http://www.thelancet.com/journals/lancet/issue/current
Editorial
World Humanitarian Summit: next steps crucial
The Lancet
Summary
Ban Ki-moon’s final flagship initiative for his tenure as UN Secretary-General, the World Humanitarian Summit, was held in Istanbul, Turkey, last week (May 23–24). The meeting, the first of its kind, was marred in controversy before it started, with Médecins Sans Frontières boycotting the event because it did not believe that it would address the weaknesses in humanitarian action and emergency response. Other non-governmental organisations (NGOs) were sceptical too. Were they right?

The Lancet Infectious Diseases
Jun 2016 Volume 16 Number 6 p619-752 e82-e107
http://www.thelancet.com/journals/laninf/issue/current

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Comment
Mandating influenza vaccine for Hajj pilgrims
Mohammad Alfelali, Amani S Alqahtani, Osamah Barasheed, Robert Booy, Harunor Rashid
DOI: http://dx.doi.org/10.1016/S1473-3099(16)30064-0
The risk of acquisition and transmission of respiratory tract infections including influenza is considerably enhanced among attendees of the Hajj pilgrimage.1 Influenza vaccine has been recommended by the Saudi Ministry of Health since 2005 for all pilgrims, particularly for those at increased risk of severe disease.2 The Saudi Ministry of Health is now seriously considering mandating influenza vaccine for all pilgrims,3 and the Saudi Thoracic Society has already urged consideration of a “strict vaccination strategy” for Hajj and Umrah visitors.

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Articles
Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study
Grant A Mackenzie, Philip C Hill, David J Jeffries, Ilias Hossain, Uchendu Uchendu, David Ameh, Malick Ndiaye, Oyedeji Adeyemi, Jayani Pathirana, Yekini Olatunji, Bade Abatan, Bilquees S Muhammad, Augustin E Fombah, Debasish Saha, Ian Plumb, Aliu Akano, Bernard Ebruke, Readon C Ideh, Bankole Kuti, Peter Githua, Emmanuel Olutunde, Ogochukwu Ofordile, Edward Green, Effua Usuf, Henry Badji, Usman N A Ikumapayi, Ahmad Manjang, Rasheed Salaudeen, E David Nsekpong, Sheikh Jarju, Martin Antonio, Sana Sambou, Lamin Ceesay, Yamundow Lowe-Jallow, Momodou Jasseh, Kim Mulholland, Maria Knoll, Orin S Levine, Stephen R Howie, Richard A Adegbola, Brian M Greenwood, Tumani Corrah
703
Open Access
Summary
Background
Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011.
Methods
We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008–May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013–Dec 31, 2014), adjusting for changes in case ascertainment over time.
Findings
We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30–71) in the 2–23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64–91) reduction in serotypes covered by the PCV13 vaccine. In the 2–4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25–75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39–83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2–59 months increased by 47% (−21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time.
Interpretation
The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2–59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2–4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease.
Funding
GAVI’s Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council.

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Articles
The global burden of dengue: an analysis from the Global Burden of Disease Study 2013
Jeffrey D Stanaway, Donald S Shepard, Eduardo A Undurraga, Yara A Halasa, Luc E Coffeng, Oliver J Brady, Simon I Hay, Neeraj Bedi, Isabela M Bensenor, Carlos A Castañeda-Orjuela, Ting-Wu Chuang, Katherine B Gibney, Ziad A Memish, Anwar Rafay, Kingsley N Ukwaja, Naohiro Yonemoto, Christopher J L Murray
Summary
Background
Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013.
Methods
We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries.
Findings
We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353–10 649) in 1992, to a peak of 11 302 (6790–13 722) in 2010. This yielded a total of 576 900 (330 000–701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8·3 million (3·3 million–17·2 million) apparent cases in 1990, to 58·4 million (23·6 million–121·9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000–1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1·14 million (0·73 million–1·98 million) disability-adjusted life-years in 2013.
Interpretation
Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher.
Funding
Bill & Melinda Gates Foundation.

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Review
HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination
Ceri Evans, MBBCh, Christine E Jones, PhD, Dr Andrew J Prendergast, DPhil
Published Online: 31 March 2016
DOI: http://dx.doi.org/10.1016/S1473-3099(16)00055-4
Summary
The number of infants infected with HIV is declining with the rise in interventions for the elimination of paediatric HIV infection, but the number of uninfected infants exposed to HIV through their HIV-infected mothers is increasing. Interest in the health outcomes of HIV-exposed, uninfected infants has grown in the past decade, with several studies suggesting that these infants have increased mortality rates, increased infectious morbidity, and impaired growth compared with HIV-unexposed infants. However, heterogeneous results might reflect the inherent challenges in studies of HIV-exposed, uninfected infants, which need large populations with appropriate, contemporaneous comparison groups and repeated HIV testing throughout the period of breastfeeding. We review the effects of HIV exposure on mortality, morbidity, and growth, discuss the immunological abnormalities identified so far, and provide an overview of interventions that could be effective in this susceptible population. As the number of infants infected with HIV declines, the health needs of HIV-exposed, uninfected infants should be prioritised further, to ensure that post-2015 Sustainable Development Goals are achieved.

Lancet Global Health
Jun 2016 Volume 4 Number 6 e344-e426
http://www.thelancet.com/journals/langlo/issue/current

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Articles
Achieving maternal and child health gains in Afghanistan: a Countdown to 2015 country case study
Nadia Akseer, Ahmad S Salehi, S M Moazzem Hossain, M Taufiq Mashal, M Hafiz Rasooly, Zaid Bhatti, Arjumand Rizvi, Zulfiqar A Bhutta

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Articles
Child health and nutrition in Peru within an antipoverty political agenda: a Countdown to 2015 country case study
Luis Huicho, Eddy R Segura, Carlos A Huayanay-Espinoza, Jessica Niño de Guzman, Maria Clara Restrepo-Méndez, Yvonne Tam, Aluisio J D Barros, Cesar G Victora, Peru Countdown Country Case Study Working Group

New England Journal of Medicine
June 2, 2016 Vol. 374 No. 22
http://www.nejm.org/toc/nejm/medical-journal

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Editorial
Clinical Trials Series
Janet Woodcock, M.D., James H. Ware, Ph.D., Pamela W. Miller, John J.V. McMurray, M.D., David P. Harrington, Ph.D., and Jeffrey M. Drazen, M.D.
N Engl J Med 2016; 374:2167 June 2, 2016 DOI: 10.1056/NEJMe1601510
Clinical trials are our best vehicle for turning medical information that we may think is true into evidence that we know, within reasonable limits, to be true. Since the introduction of random assignments to treatment in the 1930s,1 the clinical trial has been in continuous evolution. Among the major milestones have been the development of methods to perform randomization; the convening of data and safety monitoring committees; the formulation of stopping guidelines for safety, efficacy, and futility; and many others. Indeed, the clinical trial landscape is far different today from what it was over 80 years ago, when investigators first confronted the conundrum of how to obtain unbiased data that could be used to guide clinical practice. Today, trials range from a single person2 to 100,000 people, from a single lab to hundreds of centers around the world, from simple two-arm randomizations to increasingly complex study designs.

In this issue, we inaugurate a series of articles called “The Changing Face of Clinical Trials,” in which we examine the current challenges in the design, performance, and interpretation of clinical trials. The series will deal with contemporary challenges that affect clinical trialists today. It is not meant to be a course in clinical trial performance; rather, the articles are written by trialists for trialists about issues that face us all. We plan to cover new trial designs, current issues related to the performance of clinical trials, how to deal with unexpected events during the progress of trials, difficulties in the interpretation of trial findings, and challenges faced by specific sectors of trialists, including those working for large or small companies; the viewpoint of regulators who use trial data in their decision making will also be included. Each review article will define a specific issue of interest and illustrate it with examples from actual practice. The articles will occasionally be accompanied by Perspective pieces to bring additional history and color to the topic. We begin with an article on integrating comparative effectiveness trials into patient care,3 accompanied by a history of clinical trials.4 We have enjoyed putting the series together for you, and we hope that it will stimulate thought and discussion.

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Review Article
Integrating Randomized Comparative Effectiveness Research with Patient Care
Louis D. Fiore, M.D., M.P.H., and Philip W. Lavori, Ph.D.
N Engl J Med 2016; 374:2152-2158 June 2, 2016 DOI: 10.1056/NEJMra1510057
Clinical trials of interventions in common practice can be built into the workflow of an electronic medical record. The authors review four such trials and highlight the strengths and weaknesses of this approach to gathering information.

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Medicine and Society
Assessing the Gold Standard — Lessons from the History of RCTs
Laura E. Bothwell, Ph.D., Jeremy A. Greene, M.D., Ph.D., Scott H. Podolsky, M.D., and David S. Jones, M.D., Ph.D.
N Engl J Med 2016; 374:2175-2181 June 2, 2016 DOI: 10.1056/NEJMms160459
Over the past 70 years, randomized, controlled trials (RCTs) have reshaped medical knowledge and practice. Popularized by mid-20th-century clinical researchers and statisticians aiming to reduce bias and enhance the accuracy of clinical experimentation, RCTs have often functioned well in that role. Yet the past seven decades also bear witness to many limitations of this new “gold standard.” The scientific and political history of RCTs offers lessons regarding the complexity of medicine and disease and the economic and political forces that shape the production and circulation of medical knowledge…

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
(Accessed 4 June 2016)

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Research Article
Maintaining Maternal and Child Health Services During the Ebola Outbreak: Experience from Pujehun, Sierra Leone
June 2, 2016 ·
Background: During the Ebola outbreak the overall confidence of the population in the national health system declined in Sierra Leone, with a reduction in the use of health services. The objective of this study is to provide information on understanding of how Ebola impacted maternal and child health services in Sierra Leone. Data come from an operational setting which is representative of the communities affected by the outbreak.
Methods: By integrating hospital registers and contact tracing form data with healthcare workers and local population interviews, the transmission chain was reconstructed. Data on the utilization of maternal and neonatal health services were collected from the local district’s Health Management Information System. The main measures put in place to control the Ebola epidemic were: the organization of a rapid response to the crisis by the local health authorities; triage, contact tracing and quarantine; isolation, clinical management and safe burials; training and community sensitization.
Results: A total of 49 case patients were registered between July and November 2014 in the Pujehun district. Hospitalization rate was 89%. Overall, 74.3% of transmission events occurred between members of the same family, 17.9% in the community and 7.7% in hospital. The mean number of contacts investigated per case raised from 11.5 in July to 25 in September 2014. The 2014 admission trend in the pediatric ward shows a decrease after beginning of June: the reduction was almost significant in the period July-December (p 0.05). The admission in the maternity ward showed no statistical differences in comparison with the previous year (p 0.07). Also the number of deliveries appeared to be similar to the previous year, without significant variations (p 0.41).
Conclusion: The Ebola outbreak reduced the number of patients at hospital level in Pujehun district. However, the activities undertaken to manage Ebola, reduced the spread of infection and the impact of the disease in mothers and children. A number of reasons which may explain these results are presented and discussed.

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Travel Volume to the United States from Countries and U.S. Territories with Local Zika Virus Transmission
May 31, 2016 · Research Article
Introduction: Air, land, and sea transportation can facilitate rapid spread of infectious diseases. In May 2015 the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed Zika virus infection in Brazil. As of March 8, 2016, the U.S. Centers for Disease Control and Prevention (CDC) had issued travel notices for 33 countries and 3 U.S. territories with local Zika virus transmission.
Methods: Using data from five separate datasets from 2014 and 2015, we estimated the annual number of passenger journeys by air and land border crossings to the United States from the 33 countries and 3 U.S. territories listed in the CDC’s Zika travel notices as of March 8, 2016. We also estimated the annual number of passenger journeys originating in and returning to the United States (primarily on cruises) with visits to seaports in areas with local Zika virus transmission. Because of the adverse pregnancy and birth outcomes that have been associated with Zika virus disease, the number of passenger journeys completed by women of childbearing age and pregnant women was also estimated.
Results: An estimated 216.3 million passenger journeys by air, land, and sea are made annually to the United States from areas with local Zika virus transmission (as of March 8). The destination states with the largest numbers of arrivals were Texas (by land) and Florida (by air and sea). An estimated 51.7 million passenger journeys were made by women of childbearing age and an estimated 2.3 million were made by pregnant women.
Conclusion: Travel volume analyses provide important information that can be used to effectively target public health interventions as well as direct public health resources and efforts at local, regional, and country-specific levels.

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Using Phenomenological Models to Characterize Transmissibility and Forecast Patterns and Final Burden of Zika Epidemics
May 31, 2016 · Research Article
Background: The World Health Organization declared the ongoing Zika virus (ZIKV) epidemic in the Americas a Public Health Emergency of International Concern on February 1, 2016. ZIKV disease in humans is characterized by a “dengue-like” syndrome including febrile illness and rash. However, ZIKV infection in early pregnancy has been associated with severe birth defects, including microcephaly and other developmental issues. Mechanistic models of disease transmission can be used to forecast trajectories and likely disease burden but are currently hampered by substantial uncertainty on the epidemiology of the disease (e.g., the role of asymptomatic transmission, generation interval, incubation period, and key drivers). When insight is limited, phenomenological models provide a starting point for estimation of key transmission parameters, such as the reproduction number, and forecasts of epidemic impact.
Methods: We obtained daily counts of suspected Zika cases by date of symptoms onset from the Secretary of Health of Antioquia, Colombia during January-April 2016. We calibrated the generalized Richards model, a phenomenological model that accommodates a variety of early exponential and sub-exponential growth kinetics, against the early epidemic trajectory and generated predictions of epidemic size. The reproduction number was estimated by applying the renewal equation to incident cases simulated from the fitted generalized-growth model and assuming gamma or exponentially-distributed generation intervals derived from the literature. We estimated the reproduction number for an increasing duration of the epidemic growth phase.
Results: The reproduction number rapidly declined from 10.3 (95% CI: 8.3, 12.4) in the first disease generation to 2.2 (95% CI: 1.9, 2.8) in the second disease generation, assuming a gamma-distributed generation interval with the mean of 14 days and standard deviation of 2 days. The generalized-Richards model outperformed the logistic growth model and provided forecasts within 22% of the actual epidemic size based on an assessment 30 days into the epidemic, with the epidemic peaking on day 36.
Conclusion: Phenomenological models represent promising tools to generate early forecasts of epidemic impact particularly in the context of substantial uncertainty in epidemiological parameters. Our findings underscore the need to treat the reproduction number as a dynamic quantity even during the early growth phase, and emphasize the sensitivity of reproduction number estimates to assumptions on the generation interval distribution.

PLoS Medicine
http://www.plosmedicine.org/
(Accessed 4 June 2016)

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Research Article
Prices, Costs, and Affordability of New Medicines for Hepatitis C in 30 Countries: An Economic Analysis
Swathi Iyengar, Kiu Tay-Teo, Sabine Vogler, Peter Beyer, Stefan Wiktor, Kees de Joncheere, Suzanne Hill
Research Article | published 31 May 2016 | PLOS Medicine
http://dx.doi.org/10.1371/journal.pmed.1002032

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Perspective
A Revolution in Treatment for Hepatitis C Infection: Mitigating the Budgetary Impact
Elliot Marseille, James G. Kahn
| published 31 May 2016 | PLOS Medicine
http://dx.doi.org/10.1371/journal.pmed.1002031

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

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Viewpoints
Control of Urban Zika Vectors: Should We Return to the Successful PAHO/WHO Strategy?
Paul Reiter
| published 01 Jun 2016 | PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0004769

PLoS One
http://www.plosone.org/
[Accessed 4 June 2016]

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Research Article
Rapid Ethical Assessment on Informed Consent Content and Procedure in Hintalo-Wajirat, Northern Ethiopia: A Qualitative Study
Serebe Abay, Adamu Addissie, Gail Davey, Bobbie Farsides, Thomas Addissie
Research Article | published 03 Jun 2016 | PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0157056

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Cross-Border Cholera Outbreaks in Sub-Saharan Africa, the Mystery behind the Silent Illness: What Needs to Be Done?
Godfrey Bwire, Maurice Mwesawina, Yosia Baluku, Setiala S. E. Kanyanda, Christopher Garimoi Orach
Research Article | published 03 Jun 2016 | PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0156674

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Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study
Francesca Lombardi, Simone Belmonti, Massimiliano Fabbiani, Matteo Morandi, Barbara Rossetti, Giacinta Tordini, Roberto Cauda, Andrea De Luca, Simona Di Giambenedetto, Francesca Montagnani
Research Article | published 03 Jun 2016 | PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0156523

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Understanding Vaccine Hesitancy in Canada: Results of a Consultation Study by the Canadian Immunization Research Network
Eve Dubé, Dominique Gagnon, Manale Ouakki, Julie A. Bettinger, Maryse Guay, Scott Halperin, Kumanan Wilson, Janice Graham, Holly O. Witteman, Shannon MacDonald, William Fisher, Laurence Monnais, Dat Tran, Arnaud Gagneur, Juliet Guichon, Vineet Saini, Jane M. Heffernan, Samantha Meyer, S. Michelle Driedger, Joshua Greenberg, Heather MacDougall, Canadian Immunization Research Network
Research Article | published 03 Jun 2016 | PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0156118

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Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants
Olga Visser, Jeannine L. A. Hautvast, Koos van der Velden, Marlies E. J. L. Hulscher
Research Article | published 02 Jun 2016 | PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0155861

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Scoping Review of the Zika Virus Literature
Lisa A. Waddell, Judy D. Greig
Research Article | published 31 May 2016 | PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0156376

PNAS – Proceedings of the National Academy of Sciences of the United States of America
http://www.pnas.org/content/early/
(Accessed 4 June 2016)
Biological Sciences – Ecology:
Digital epidemiology reveals global childhood disease seasonality and the effects of immunization
Kevin M. Bakker, Micaela Elvira Martinez-Bakker, Barbara Helm, and Tyler J. Stevenson
PNAS 2016 ; published ahead of print May 31, 2016, doi:10.1073/pnas.1523941113
Significance
Disease surveillance systems largely focus on infectious diseases with high mortality, whereas less severe diseases often go unreported. Using chicken pox as an example, we demonstrate that Internet queries can be used as a proxy for disease incidence when reporting is lacking. We established that Google Trends accurately reflected clinical cases in countries with surveillance, and thus population-level dynamics of chicken pox. Then, we discovered robust seasonal variation in query behavior, with a striking latitudinal gradient on a global scale. Next, we showed that real-time data-mining of queries could forecast the timing and magnitude of outbreaks. Finally, our analyses revealed that countries with government-mandated vaccination programs have significantly reduced seasonality of queries, indicating vaccination efforts mitigated chicken pox outbreaks.
Abstract
Public health surveillance systems are important for tracking disease dynamics. In recent years, social and real-time digital data sources have provided new means of studying disease transmission. Such affordable and accessible data have the potential to offer new insights into disease epidemiology at national and international scales. We used the extensive information repository Google Trends to examine the digital epidemiology of a common childhood disease, chicken pox, caused by varicella zoster virus (VZV), over an 11-y period. We (i) report robust seasonal information-seeking behavior for chicken pox using Google data from 36 countries, (ii) validate Google data using clinical chicken pox cases, (iii) demonstrate that Google data can be used to identify recurrent seasonal outbreaks and forecast their magnitude and seasonal timing, and (iv) reveal that VZV immunization significantly dampened seasonal cycles in information-seeking behavior. Our findings provide strong evidence that VZV transmission is seasonal and that seasonal peaks show remarkable latitudinal variation. We attribute the dampened seasonal cycles in chicken pox information-seeking behavior to VZV vaccine-induced reduction of seasonal transmission. These data and the methodological approaches provide a way to track the global burden of childhood disease and illustrate population-level effects of immunization. The global latitudinal patterns in outbreak seasonality could direct future studies of environmental and physiological drivers of disease transmission.

Risk Management and Healthcare Policy
Volume 9, 2016
https://www.dovepress.com/risk-management-and-healthcare-policy-archive56

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Original Research
Video
Haiti’s progress in achieving its 10-year plan to eliminate cholera: hidden sickness cannot be cured
Koski-Karell V, Farmer PE, Isaac B, Campa EM, Viaud L, Namphy PC, Ternier R, Ivers LC
Risk Management and Healthcare Policy 2016, 9:87-100
Published Date: 24 May 2016
Abstract:
Since the beginning of the cholera epidemic in Haiti 5 years ago, the prevalence of this deadly water-borne disease has fallen far below the initial rates registered during its explosive outset. However, cholera continues to cause extensive suffering and needless deaths across the country, particularly among the poor. The urgent need to eliminate transmission of cholera persists: compared to the same period in 2014, the first 4 months of 2015 saw three times the number of cholera cases. Drawing upon epidemiology, clinical work (and clinical knowledge), policy, ecology, and political economy, and informed by ethnographic data collected in a rural area of Haiti called Bocozel, this paper evaluates the progress of the nation’s 10-year Plan for the Elimination of Cholera. Bocozel is a rice-producing region where most people live in extreme poverty. The irrigation network is decrepit, the land is prone to environmental shocks, fertilizer is not affordable, and the government’s capacity to assist farmers is undermined by resource constraints. When peasants do have rice to sell, the price of domestically grown rice is twice that of US-imported rice. Canal water is not only used to irrigate thousands of acres of rice paddies and sustain livestock, but also to bathe, wash, and play, while water from wells, hand pumps, and the river is used for drinking, cooking, and bathing. Only one out of the three government-sponsored water treatment stations in the research area is still functional and utilized by those who can afford it. Latrines are scarce and often shared by up to 30 people; open defecation remains common. Structural vulnerabilities cut across all sectors – not just water, sanitation, health care, and education, but agriculture, environment, (global and local) commerce, transportation, and governance as well. These are among the hidden sicknesses that impede Haiti and its partners’ capacity to eliminate cholera.

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Review
Critical role of ethics in clinical management and public health response to the West Africa Ebola epidemic
Folayan MO, Haire BG, Brown B
Risk Management and Healthcare Policy 2016, 9:55-65
Published Date: 12 May 2016
Abstract:
The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis. These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak. Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries. The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development. In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions. Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups. The compassionate use of experimental drugs intersects both with research ethics and clinical care. The role of developed countries also came under scrutiny, and we concluded that developed countries have an obligation to contribute to the containment of EVD infection by contributing to the strengthening of local health care systems and infrastructure in an effort to provide fair benefits to communities engaged in research, ensuring that affected countries have ready and affordable access to any therapeutic or preventative interventions developed, and supporting affected countries on their way to recovery from the impact of EVD on their social and economic lives.

Science Translational Medicine
01 June 2016 Vol 8, Issue 341
http://stm.sciencemag.org/

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Perspective
What does research reproducibility mean?
By Steven N. Goodman, Daniele Fanelli, John P. A. Ioannidis
Science Translational Medicine01 Jun 2016 : 341ps12
The language and conceptual framework of “research reproducibility” are nonstandard and unsettled across the sciences.

Vaccine
Volume 34, Issue 26, Pages 2863-3006 (3 June 2016)
http://www.sciencedirect.com/science/journal/0264410X/34/25

Issue Focus: WHO Product Development for Vaccines Advisory Committee (PDVAC) Pipeline Analyses for 25 Pathogens
Edited by Birgitte K. Giersing, Kayvon Modjarrad and Vasee S. Moorthy

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Preface
The 2016 Vaccine Development Pipeline: A special issue from the World Health Organization Product Development for Vaccine Advisory Committee (PDVAC)
Under a Creative Commons license
Birgitte K. Giersing, Kayvon Modjarrad, David C. Kaslow, Jean-Marie Okwo-Bele, Vasee S. Moorthy
doi:10.1016/j.vaccine.2016.04.041
Open Access
Infectious diseases are the leading cause of death among children and adolescents globally, and one of the primary causes of mortality in adults. Most of these deaths disproportionately burden low- and middle-income countries (LMICs) and are attributable to infectious diseases that include diarrheal illnesses, lower respiratory infections, human immunodeficiency virus, tuberculosis and malaria. Socio-economic gains have translated into improvements in sanitation systems, clean water supplies, early diagnosis and healthcare accessibility and delivery, with consequent reductions in infectious disease incidence and mortality. However, for the majority of the world’s population, large scale advancements in public health infrastructure are still far off. For these communities, high-impact, low-cost public health interventions remain a key strategy for driving down the preventable infectious disease incidence and mortality. Principal among these cost-effective measures is immunization; however, some vaccines are unavailable, inaccessible, and/or unaffordable for the populations most in need. Global national immunization programmes, partially financed through the Gavi vaccine alliance, are estimated to save 2–3 million lives per year with the existing vaccines – and these could be even more impactful if greater levels of coverage could be achieved. Investments into the research, development and deployment of vaccines and delivery technologies against the deadliest and most widespread pathogens are, therefore, likely to yield considerable dividends in global health.

There are approximately 600 vaccine candidates in development against an estimated 110 pathogens [1]. Considering the resource constraints in vaccine development, there is a need to rationally identify the approaches that are most likely to succeed and then prioritize among these candidates. Additionally, as the routine immunization schedule expands, it becomes increasingly important to have strong, evidence-based justifications for investing in the development of new vaccines with a high likelihood of success. Just as innovation should be applied to the domain of vaccines in the development pipeline, there is room for improvement of some licensed vaccines with respect to cost-effectiveness and coverage in order to maximize their public health impact. This special issue, however, focuses its review on the research and development (R&D) pipeline of vaccines against 25 pathogens for which no licensed vaccines currently exists but for which there is high public health importance, as identified by the World Health Organization (WHO) Product Development for Vaccines Advisory Committee (PDVAC). PDVAC is a body of independent experts that was established in 2014 to guide WHO and the vaccine development community along the pathway toward the goal of licensure and deployment in countries of highest disease burden. As such, PDVAC’s remit is to advise on the acceleration of vaccine candidates at Phase 2 of clinical evaluation or earlier and report its proceedings from its meetings to the WHO’s principal committee on immunization policy recommendations: the Strategic Advisory Group of Experts on Immunization (SAGE).

PDVAC also has a contributory role within the framework of the R&D Blueprint at WHO for R&D preparedness and emergency research response in the emerging pathogen area. When WHO declares a Public Health Emergency of International Concern (PHEIC), PDVAC may be tasked with forming a working group to facilitate development of guidance tools for the vaccine development community in the context of the emergency. For example, as this issue goes to press, a PDVAC Working Group is developing a WHO Zika vaccine Target Product Profile [2].

The landscape analyses in this issue are intended as structured overviews of the key considerations for vaccine development, not as exhaustive literature reviews. They are authored by independent subject matter experts in each field and follow a template set forth by the PDVAC committee. Each report summarizes the biological evidence for a vaccine’s feasibility, the data on proof-of-concept studies, existing knowledge gaps, the technical and regulatory hurdles to vaccine licensure, and the prospects for donor funding and procurement of the product. The compendium of pathogens highlighted in this issue was agreed upon by PDVAC in 2015 [3]. Each year, pathogens and diseases to be reviewed is modified to incorporate new areas where vaccine development activity is progressing, and in 2016, Zika will be discussed. In this way, PDVAC remains at the cutting edge of product development issues, with oversight across a broad spectrum of R&D activity, ensuring that its contributions are relevant and impactful to vaccine developers, regulators, donors and policy makers.

[References at link above]

Health Education Journal
May 31, 2016 0017896916647988

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HPV vaccine decision-making among young men who have sex with men
Christopher W Wheldona, Ellen M Daleya, Eric R Buhib, Julie A Baldwinc, Alan G Nyitrayd, Anna R Giulianoe
Abstract
Objective: Human papilloma virus (HPV) vaccination is recommended for all men who have sex with men (MSM) in the USA until the age of 26 years. Despite this recommendation, vaccine uptake remains low. The purpose of this study was to (1) describe salient beliefs related to HPV vaccination among young MSM; (2) determine factors that underlie these beliefs; and (3) describe a model for HPV vaccine decision-making.
Design: Qualitative descriptive study.
Setting: Central Florida, USA.
Method: Semi-structured interviews (N = 22).
Results: The majority of respondents had heard of the HPV vaccine, but generally perceived HPV as a women’s health issue. Salient behavioural beliefs about HPV vaccination described physical (such as lowering risk and promoting overall health) and psychological benefits (such as protecting sex partners and providing peace of mind). There was some concern regarding the risks of vaccination including contracting HPV from the vaccine, not knowing if it would be effective, and side effects. Normative influences on decision-making were minimal. Availability, cost and convenience were among the most salient external control factors discussed. Issues surrounding disclosure of sexual orientation, as well as the competence and sensitivity of healthcare providers in dealing with issues of sexuality, were key factors in HPV-related beliefs.
Conclusion: Addressing the specific beliefs and concerns expressed by MSM can help to improve the effectiveness of health education interventions promoting vaccination.

The Journal of Immunology
May 1, 2016 vol.196

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A multivariate approach to data analysis of vaccine clinical trials.
M Coccia1, F Nozay1, L De Mot1, Avisek Deyati1, E Jogert1, R van der Most1 and R van den Berg1
Author Affiliations
1GlaxoSmithKline, Belgium
Abstract
Despite significant progress in prevention, diagnosis and treatment, Malaria and Tuberculosis (TB) remain major health challenges. In 2014 WHO estimated that ≈438000 people died from Malaria and ≈1.5 million from TB, mainly in resource-poor countries. Vaccines represent a cost-effective and efficient method of preventing infectious diseases. The development of vaccines for TB and Malaria would significantly contribute to reducing disease burden, particularly with the emergence of drug-resistant pathogens. GSK’s Malaria vaccine, Mosquirix™ (RTS,S/AS01), received a positive opinion from European regulators for the prevention of Malaria in young children in sub-Saharan Africa. GSK’s candidate vaccine for TB (M72/AS01) induces robust TB-specific CD4 T-cell responses in humans, and it is undergoing phase IIb clinical trials. System biology approaches can support vaccines at different stages of development by identifying molecular signatures that drive responses to vaccination. Here, we describe the application of systems vaccinology to the analysis of gene expression data from clinical trials for Malaria and TB candidate vaccines. Our analysis aimed to identify early predictors of vaccine efficacy in Malaria clinical trials and to detect signatures associated with reactogenicity in the early development of a TB vaccine. To better capture the multidimensional nature of the data, we used multivariate analysis approaches such as Partial Least Squares regression. Additionally, biological interpretation of our results allowed us to pinpoint biological processes linked with response to vaccination, advancing our understanding of vaccine mode of action.

Media/Policy Watch
This section is intended to alert readers to substantive news, analysis and opinion from the general media 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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Forbes
http://www.forbes.com/
Accessed 4 June 2016
Preemies Get Boost in Pertussis Protection From Mom’s Vaccination
Preemies can also benefit from a pertussis vaccine in pregnancy.
Tara Haelle, Contributor Jun 02, 2016 [No new, unique, relevant content]

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Foreign Affairs
http://www.foreignaffairs.com/
Accessed 4 June 2016
1 June 2016
Pakistan’s Quiet Revolution Against Polio
While Pakistan’s path to eradication hasn’t been easy, there is now reason for optimism.
…Unfortunately, violent attacks — which have, at times, affected health workers and those who protect them — have overshadowed this remarkable progress.

These incidents are tragic, although not entirely unexpected. The polio virus has, historically, thrived in regions experiencing political turmoil and conflict. In fact, many of the places where polio still has a strong hold are insecure areas of Afghanistan and Pakistan. So health workers like Naseeba, who go bravely and tirelessly door-to-door, are working in some of the most challenging environments on Earth.

Even in the face of this violence, the dedication to stopping polio in Pakistan extends to all levels of society. In order to reach all of Pakistan’s 35 million children, nearly a quarter of a million clinicians, mothers, religious leaders, security personnel, community members, and government officials have come together to support eradication efforts…

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Foreign Policy
http://foreignpolicy.com/
Accessed 4 June 2016
27 May 2016
Laurie Garrett: WHO’s Fairy Dust Financing
…The organization responsible for international public health is increasing its budget by millions of dollars — but its plan for coming up with the cash to help battle epidemics like Zika isn’t grounded in reality.… That kind of preparedness begins with leadership and mutual trust between the institutions of public health, political leaders, and the populations they are supposed to serve. This is a feat that WHO has not, by any measure, accomplished…

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New York Times
http://www.nytimes.com/
Accessed 4 June 2016
The Opinion Pages | Editorial
Hustling Dollars for Public Health
By THE EDITORIAL BOARD
JUNE 2, 2016
On Tuesday, a woman infected with the Zika virus gave birth to a girl with microcephaly, a malformed head, in New Jersey. Federal officials say there are more than 300 pregnant women possibly infected with Zika around the country. Yet every time an emergency like this happens, public health officials must go begging bowl in hand to Congress for the funds to deal with it. And as the current squabble between Republicans and President Obama over money for the Zika virus shows, there’s no guarantee of significant or even timely relief.

The obvious answer is to establish a permanent pool of money that federal health authorities can tap into quickly, much like the disaster relief fund that enables the Federal Emergency Management Agency to respond quickly to hurricanes and other natural disasters.

Such a fund would allow agencies like the Centers for Disease Control and Prevention to mobilize their resources to contain emerging threats like Zika and Ebola before they become large-scale problems. The money would be used for research, for vaccine development and to prevent the spread of the disease in the United States and overseas.

Zika is just such a threat. It is primarily transmitted by mosquitoes, can cause birth defects and has been linked to neurological disorders in adults. A study published in The New England Journal of Medicine last week estimated that the risk of microcephaly in newborns ranged from 1 percent to 13 percent for women infected with Zika in the first trimester.

A bill introduced by Representative Rosa DeLauro, a Connecticut Democrat, would put $5 billion into an existing public health emergency fund that was created in 1983 but has been largely dormant. The fund currently has a balance of just $57,000. In the Senate, Bill Cassidy, a Louisiana Republican and a doctor, has said he plans to introduce a bill that would provide emergency funds, though he has offered few details.

Some Republicans are likely to oppose setting aside the money. Many in the House have been reluctant to spend money on Zika; last month they passed a bill to provide $622 million to fight the disease, which is a lot less than the $1.1 billion the Senate approved and the $1.9 billion Mr. Obama has asked for.

Despite the concerns of fiscal conservatives, the health emergency fund could save lives and money. Consider Ebola. Had the American government moved quickly to help Guinea, Liberia and Sierra Leone fight that virus early in 2014, the disease might not have killed more than 11,000 people or caused a global panic. But the United States was slow to react, approving $5.4 billion for the disease in December 2014, months after it had caused or was suspected to have caused nearly 7,000 deaths and after Ebola cases had been confirmed in the United States.

That money was used to send doctors and nurses to West Africa, to help strengthen health systems in the affected countries, and for research. Some Ebola projects are still active, including vaccine development and testing. In public health, “the sooner you can get there the more effective you can be,” said Dr. Thomas Frieden, the C.D.C. director. “You can change the trajectory of an epidemic in a way that is very, very important.”

Giving public health officials a blank check would be unwise. But creating a system that is at once generous and disciplined by strong internal controls should be possible. Money in the present health emergency fund, for instance, can be used only when the secretary of health and human services declares an emergency. The secretary has to notify Congress of that decision and report how the money was spent within 90 days of the end of the fiscal year.
Without a less restricted fund, health officials fighting Zika have had to move money and scientists away from programs focused on other diseases, like Ebola, malaria and dengue. Robbing existing programs is sure to hurt public health the longer it goes on.

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Wall Street Journal
http://online.wsj.com/home-page?_wsjregion=na,us&_homepage=/home/us
Accessed 4 June 2016
Zika Draws U.S. Researchers Into a Race for Understanding
By Jo Craven McGinty
June 3, 2016 10:13 am ET

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Washington Post
http://www.washingtonpost.com/
Accessed 4 June 2016
Health officials now confirm 11 cases of measles in Arizona
An outbreak of measles that began with an inmate at a federal detention center for immigrants in central Arizona has now grown to 11 confirmed cases, officials said Monday.
Associated Press | National | May 30, 2016

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Think Tanks et al
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Center for Global Development
http://www.cgdev.org/
Accessed 4 June 2016
Innovation for Development: Why Are We not Getting to Scale?
Event
6/13/16
Development depends on innovation. New ideas, new funding mechanisms and new technologies save and improve lives, from vaccines to solar lamps to Development Impact Bonds. But even if innovations reach a million people, they still fall short of the billion who live in poverty.

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Council on Foreign Relations
http://www.cfr.org/
Accessed 4 June 2016
Expert Brief
| 31 May 2016
Back to the Future of Global Health Security
Authors: Thomas J. Bollyky, Senior Fellow for Global Health, Economics, and Development, and Steve Davis, President and CEO of PATH
…To improve pandemic preparedness we must embrace the hard-won lessons of the past decade in global health, not ignore them. This is true in deploying people and resources to prepare for the inevitability of future outbreaks, but even more so when it comes to accelerating the development of the medical tools to diagnose, treat, and prevent those infectious disease outbreaks from turning into epidemics, or even pandemics…