British Medical Journal
07 March 2015 (vol 350, issue 7998)
http://www.bmj.com/content/350/7998

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Editorials
The evidence base for new drugs
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h952 (Published 02 March 2015) Cite this as: BMJ 2015;350:h952
Peter Doshi, associate editor1,
Tom Jefferson, reviewer2
Author affiliations

New legislation in Germany provides another piece of a complex puzzle
Marketing campaigns cast new drugs as “must haves.” In reality, the public evidence base for new drugs often leaves more questions than answers.1 2 While marketing authorization indicates that regulators judged the risk-benefit profile to be favorable, product labels rarely list and quantify these benefits and harms. Publications of premarketing trials might fill in some gaps, but readers beware: not all trials are published and those that are may be inaccurately or incompletely reported.3 4

Data transparency in clinical trials has emerged as a way to tackle the reporting biases that affect literature, enabling independent scrutiny of trials.5 But it is not enough. Even with open data we rarely know how new drugs compare with existing options or whether they improve patient centered outcomes. An analysis published in this issue (doi:10.1136/bmj.h796) suggests that new legislation in Germany may provide another piece of the puzzle.6

The German act on the reform of the market for medicinal products (AMNOG) was introduced in 2011 to inform drug pricing for all new drugs. To control costs, sponsors must submit a standardized dossier including evidence of the drug’s added benefit over already available drugs. This dossier is then reviewed by scientists, usually at the Institute for Quality and Efficiency in Health Care (IQWiG), who produce an assessment report.

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Editorials
Health literacy: towards system level solutions
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1026 (Published 24 February 2015) Cite this as: BMJ 2015;350:h1026
Trisha Greenhalgh, professor of primary care health sciences
Author affiliations

A new World Health Organization toolkit aimed at low and middle income countries could help reduce health inequalities in the rest of the world too
A new resource aimed at low and middle income countries, the World Health Organization has redefined health literacy as “the personal characteristics and social resources needed for individuals and communities to access, understand, appraise and use information and services to make decisions about health.”1

Low health literacy is associated with poor engagement with health services, health knowledge, concordance with prescribed medication, self management of illness, markers of disease progression, overall health status, and survival. It is also associated with high rates of hospital admission and use of emergency care.2 3 4 5 6 7

Low health literacy is more common in low income and minority ethnic groups, immigrants, people without full citizenship, those with fewer years of education, and older people; it is especially common in people who fall into several of these risk groups.8 9 10 11 People with low health literacy may feel ashamed and try to conceal it from professional carers and family members.12 Differences in health literacy explain a substantial proportion of inequity in the uptake and use …

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Research
The impact of providing rapid diagnostic malaria tests on fever management in the private retail sector in Ghana: a cluster randomized trial
BMJ 2015; 350 :h1019 (Published 04 March 2015)
Open Access
Abstract
Objective
To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present, with the aim of reducing current massive overdiagnosis and overtreatment of malaria.
Design
Cluster randomized trial of 24 clusters of shops.
Setting
Dangme West, a poor rural district of Ghana.
Participants
Shops and their clients, both adults and children.
Interventions
Providing rapid diagnostic tests with realistic training.
Main outcome measures
The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial. Secondary outcomes were use of antibiotics and antipyretics, and safety.
Results Of 4603 clients, 3424 (74.4%) tested negative by double-read research slides. The proportion of slide-negative clients who received any antimalarial was 590/1854 (32%) in the intervention arm and 1378/1570 (88%) in the control arm (adjusted risk ratio 0.41 (95% CI 0.29 to 0.58), P<0.0001). Treatment was in high agreement with rapid diagnostic test result. Of those who were slide-positive, 690/787 (87.8%) in the intervention arm and 347/392 (88.5%) in the control arm received an artemisinin combination therapy (adjusted risk ratio 0.96 (0.84 to 1.09)). There was no evidence of antibiotics being substituted for antimalarials. Overall, 1954/2641 (74%) clients in the intervention arm and 539/1962 (27%) in the control arm received appropriate treatment (adjusted risk ratio 2.39 (1.69 to 3.39), P<0.0001). No safety concerns were identified.
Conclusions
Most patients with fever in Africa present to the private sector. In this trial, providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria, did not reduce prescribing of antimalarials to true malaria cases, and appeared safe. Rapid diagnostic tests should be considered for the informal private drug retail sector.
Registration Clinicaltrials.gov NCT01907672

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Information on new drugs at market entry: retrospective analysis of health technology assessment reports versus regulatory reports, journal publications, and registry reports
BMJ 2015; 350 :h796 (Published 26 February 2015)
Open Access
Abstract
Background
When a new drug becomes available, patients and doctors require information on its benefits and harms. In 2011, Germany introduced the early benefit assessment of new drugs through the act on the reform of the market for medicinal products (AMNOG). At market entry, the pharmaceutical company responsible must submit a standardised dossier containing all available evidence of the drug’s added benefit over an appropriate comparator treatment. The added benefit is mainly determined using patient relevant outcomes. The “dossier assessment” is generally performed by the Institute for Quality and Efficiency in Health Care (IQWiG) and then published online. It contains all relevant study information, including data from unpublished clinical study reports contained in the dossiers. The dossier assessment refers to the patient population for which the new drug is approved according to the summary of product characteristics. This patient population may comprise either the total populations investigated in the studies submitted to regulatory authorities in the drug approval process, or the specific subpopulations defined in the summary of product characteristics (“approved subpopulations”).
Objective
To determine the information gain from AMNOG documents compared with non-AMNOG documents for methods and results of studies available at market entry of new drugs. AMNOG documents comprise dossier assessments done by IQWiG and publicly available modules of company dossiers; non-AMNOG documents comprise conventional, publicly available sources—that is, European public assessment reports, journal publications, and registry reports. The analysis focused on the approved patient populations.
Design
Retrospective analysis.
Data sources
All dossier assessments conducted by IQWiG between 1 January 2011 and 28 February 2013 in which the dossiers contained suitable studies allowing for a full early benefit assessment. We also considered all European public assessment reports, journal publications, and registry reports referring to these studies and included in the dossiers.
Data analysis
We assessed reporting quality for each study and each available document for eight methods and 11 results items (three baseline characteristics and eight patient relevant outcomes), and dichotomised them as “completely reported” or “incompletely reported (including items not reported at all).” For each document type we calculated the proportion of items with complete reporting for methods and results, for each item and overall, and compared the findings.
Results
15 out of 27 dossiers were eligible for inclusion and contained 22 studies. The 15 dossier assessments contained 28 individual assessments of 15 total study populations and 13 approved subpopulations. European public assessment reports were available for all drugs. Journal publications were available for 14 out of 15 drugs and 21 out of 22 studies. A registry report in ClinicalTrials.gov was available for all drugs and studies; however, only 11 contained results. In the analysis of total study populations, the AMNOG documents reached the highest grade of completeness, with about 90% of methods and results items completely reported. In non-AMNOG documents, the rate was 75% for methods and 52% for results items; journal publications achieved the best rates, followed by European public assessment reports and registry reports. The analysis of approved subpopulations showed poorer complete reporting of results items, particularly in non-AMNOG documents (non-AMNOG versus AMNOG: 11% v 71% for overall results items and 5% v 70% for patient relevant outcomes). The main limitation of our analysis is the small sample size.
Conclusion
Conventional, publicly available sources provide insufficient information on new drugs, especially on patient relevant outcomes in approved subpopulations. This type of information is largely available in AMNOG documents, albeit only partly in English. The AMNOG approach could be used internationally to develop a comprehensive publication model for clinical studies and thus represents a key open access measure.

Clinical Infectious Diseases (CID)
Volume 60 Issue 6 March 15, 2015
http://cid.oxfordjournals.org/content/current

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Editor’s choice: Long-term Persistence of Zoster Vaccine Efficacy
Clin Infect Dis. (2015) 60 (6): 900-909 doi:10.1093/cid/ciu918
Vicki A. Morrison, Gary R. Johnson, Kenneth E. Schmader, Myron J. Levin, Jane H. Zhang, David J. Looney, Robert Betts, Larry Gelb, John C. Guatelli, Ruth Harbecke, Connie Pachucki, Susan Keay, Barbara Menzies, Marie R. Griffin, Carol A. Kauffman, Adriana Marques, John Toney, Kathy Boardman, Shu-Chih Su, Xiaoming Li, Ivan S. F. Chan, Janie Parrino, Paula Annunziato, and Michael N. Oxmanfor the Shingles Prevention Study Group
Abstract
Background.
The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination.
Methods.
Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups.
Results.
The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8.
Conclusions.
Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.

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Editor’s choice: Editorial Commentary: Waning Efficacy of the Herpes Zoster Vaccine
Richard J. Whitley
Clin Infect Dis. (2015) 60 (6): 910-911 doi:10.1093/cid/ciu922
Extract
In this issue of Clinical Infectious Diseases, Morrison and colleagues report the waning efficacy of the herpes zoster (HZ) vaccine with long-term follow-up [1]. This report is the third that defines efficacy of vaccination. The first clinical trial reported the unequivocal efficacy of vaccination of individuals >60 years of age for burden of illness (BOI), incidence of postherpetic neuralgia (PHN), and incidence of HZ [2]. These 3 endpoints were assessed through 4 years postvaccination. A subsequent follow-up study through 7 years of postvaccination evaluation noted persistence of efficacy with slightly lower evidence of benefit than the original clinical trial [3], albeit not statistically significant. With the report of Morrison et al, we are able to reasonably estimate the efficacy of vaccination through year 10, and to a significantly lesser extent year 11…

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Vaccines Against Malaria
Amed Ouattara and Matthew B. Laurens
Clin Infect Dis. (2015) 60 (6): 930-936 doi:10.1093/cid/ciu954
Abstract
Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease.

Developing World Bioethics
April 2015 Volume 15, Issue 1 Pages ii–iii, 1–57
http://onlinelibrary.wiley.com/doi/10.1111/dewb.2015.15.issue-1/issuetoc

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EDITORIAL
Empirical Research and Bioethics
Debora Diniz
Article first published online: 3 MAR 2015
DOI: 10.1111/dewb.12078
Extract
What counts as empirical evidence in bioethics? Differently from epidemiology or social sciences, bioethics is more argumentative than demonstrative, more normative than explanatory. Saying that, I am suggesting some parameters for the field: we need strong concepts, yet pieces of data. My provocative argument is that we should not import the epistemic criteria of what counts as data from epidemiology or social sciences to evaluate a contribution as relevant to bioethics. An ethical argument is more important than a long deep description of data…

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ARTICLE
Cultural Conundrums: The Ethics of Epidemiology and the Problems of Population in Implementing Pre-Exposure Prophylaxis
Kirk Fiereck*
Article first published online: 23 DEC 2013
DOI: 10.1111/dewb.12034
Abstract
The impending implementation of pre-exposure prophylaxis (PrEP) has prompted complicated bioethical and public health ethics concerns regarding the moral distribution of antiretroviral medications (ARVs) to ostensibly healthy populations as a form of HIV prevention when millions of HIV-positive people still lack access to ARVs globally. This manuscript argues that these questions are, in part, concerns over the ethics of the knowledge production practices of epidemiology. Questions of distribution, and their attendant cost-benefit calculations, will rely on a number of presupposed, and therefore, normatively cultural assumptions within the science of epidemiology specifically regarding the ability of epidemiologic surveillance to produce accurate maps of HIV throughout national populations. Specifically, ethical questions around PrEP will focus on who should receive ARVs given the fact that global demand will far exceed supply. Given that sexual transmission is one of the main modes of HIV transmission, these questions of ‘who’ are inextricably linked to knowledge about sexual personhood. As a result, the ethics of epidemiology, and how the epidemiology of HIV in particular conceives, classifies and constructs sexual populations will become a critical point of reflection and contestation for bioethicists, health activists, physicians, nurses, and researchers in the multi-disciplinary field of global health. This paper examines how cultural conundrums within the fields of bioethics and public health ethics are directly implicated within the ethics of PrEP, by analyzing the problems of population inaugurated by the construction of the men who have sex with men (MSM) epidemiologic category in the specific national context of South Africa.

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ARTICLE
Not Fit for Purpose: The Ethical Guidelines of the Indian Council of Medical Research
Priya Satalkar* and David Shaw
Article first published online: 8 NOV 2013
DOI: 10.1111/dewb.12036
Abstract
In 2006, the Indian Council of Medical Research (ICMR) published its ‘Ethical guidelines for Biomedical Research on human participants’. The intention was to translate international ethical standards into locally and culturally appropriate norms and values to help biomedical researchers in India to conduct ethical research and thereby safeguard the interest of human subjects. Unfortunately, it is apparent that the guideline is not fit for purpose. In addition to problems with the structure and clarity of the guidelines, there are several serious omissions and contradictions in the recommendations. In this paper, we take a close look at the two key chapters and highlight some of the striking flaws in this important document. We conclude that ethics committees and national authorities should not lose sight of international ethical standards while incorporating local reality and cultural and social values, as focusing too much on the local context could compromise the safety of human subjects in biomedical research, particularly in India.

Eurosurveillance
Volume 20, Issue 9, 05 March 2015
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

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Rapid communications
An ongoing measles outbreak in the Federation of Bosnia and Herzegovina, 2014 to 2015
by M Hukic, J Ravlija, S Karakas, M Mulaomerovic, A Dedeic Ljubovic, I Salimović-Besic, M Seremet, S Ahmetagic, A Comor, E Feric

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Research articles
Characteristics and practices of National Immunisation Technical Advisory Groups in Europe and potential for collaboration, April 2014
by A Takla, O Wichmann, P Carrillo-Santisteve, S Cotter, D Lévy-Bruhl, I Paradowska-Stankiewicz, P Valentiner-Branth , F D’Ancona, the VENICE III NITAG Survey Group

Global Health: Science and Practice (GHSP)
March 2015 | Volume 3 | Issue 1
http://www.ghspjournal.org/content/current

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EDITORIALS
ARVs: The Next Generation. Going Boldly Together to New Frontiers of HIV Treatment
New antiretrovirals (ARVs), particularly the potentially “game-changing” ARV dolutegravir, offer major potential to meet the compelling need for simpler and better HIV treatment for tens of millions of people in the coming decade. Advantages include substantially lower manufacturing cost, fewer side effects, and less risk of resistance. But key obstacles must be addressed in order to develop and introduce new ARVs in specific combinations optimized for the needs of low- and middle-income countries. Strong leadership will be essential from the global health community to nurture more focused collaboration between the private and public sectors.
Matthew Barnhart, James D Shelton
Glob Health Sci Pract 2015;3(1):1-11. First published online January 27, 2015. http://dx.doi.org/10.9745/GHSP-D-14-00243

Stunning Popularity of LARCs With Good Access and Quality: A Major Opportunity to Meet Family Planning Needs
Given true choice, a very high proportion of women, perhaps most, would select one of the long-acting reversible contraceptives (LARCs)—implants or IUDs—for contraception. If implemented on a wide scale, it would not only drastically alter the current method mix but also serve client needs much better and prevent unintended pregnancy more successfully.
Glob Health Sci Pract 2015;3(1):12-13. First published online February 25, 2015. http://dx.doi.org/10.9745/GHSP-D-15-00044

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ORIGINAL ARTICLES
Delivering High-Quality Family Planning Services in Crisis-Affected Settings I: Program Implementation
Dora Ward Curry, Jesse Rattan, Jean Jose Nzau, Kamlesh Giri
Glob Health Sci Pract 2015;3(1):14-24. First published online February 4, 2015. http://dx.doi.org/10.9745/GHSP-D-14-00164
ABSTRACT
In 2012, about 43 million women of reproductive age experienced the effects of conflict. Provision of basic sexual and reproductive health services, including family planning, is a recognized right and need of refugees and internally displaced people, but funding and services for family planning have been inadequate. This article describes lessons learned during the first 2.5 years of implementing the ongoing Supporting Access to Family Planning and Post-Abortion Care in Emergencies (SAFPAC) initiative, led by CARE, which supports government health systems to deliver family planning services in 5 crisis-affected settings (Chad, Democratic Republic of the Congo, Djibouti, Mali, and Pakistan). SAFPAC’s strategy focuses on 4 broad interventions drawn from public health best practices in more stable settings: competency-based training for providers, improved supply chain management, regular supervision, and community mobilization to influence attitudes and norms related to family planning. Between July 2011 and December 2013, the initiative reached 52,616 new users of modern contraceptive methods across the 5 countries (catchment population of 698,053 women of reproductive age), 61% of whom chose long-acting methods of implants or intrauterine devices. Prudent use of data to inform decision making has been an underpinning to the project’s approach. A key approach to ensuring sustained ability to train and supervise new providers has been to build capacity in clinical skills training and supervision by establishing in-country training centers. In addition, monthly supervision using simple checklists has improved program and service quality, particularly with infection prevention procedures and stock management. We have generally instituted a “pull” system to manage commodities and other supplies, whereby health facilities place resupply orders as needed based on actual consumption patterns and stock-alert thresholds. Finally, reaching the community with mobilization efforts appropriate to the cultural context has been integral to meeting unmet family planning needs rapidly in these crisis-affected settings. Despite the constraints in crisis-affected countries, such as travel difficulties due to security issues, in our experience, we have been able to extend access to a range of contraceptive methods, including long-acting reversible contraceptives, in such settings using best practice approaches established in more stable environments.

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Delivering High-Quality Family Planning Services in Crisis-Affected Settings II: Results
Dora Ward Curry, Jesse Rattan, Shuyuan Huang,
Elizabeth Noznesky
Glob Health Sci Pract 2015;3(1):25-33. First published online February 4, 2015. http://dx.doi.org/10.9745/GHSP-D-14-00112
ABSTRACT
An estimated 43 million women of reproductive age experienced the effects of conflict in 2012. Already vulnerable from the insecurity of the emergency, women must also face the continuing risk of unwanted pregnancy but often are unable to obtain family planning services. The ongoing Supporting Access to Family Planning and Post-Abortion Care (SAFPAC) initiative, led by CARE, has provided contraceptives, including long-acting reversible contraceptives (LARCs), to refugees, internally displaced persons, and conflict-affected resident populations in Chad, the Democratic Republic of the Congo (DRC), Djibouti, Mali, and Pakistan. The project works through the Ministry of Health in 4 key areas: (1) competency-based training, (2) supply chain management, (3) systematic supervision, and (4) community mobilization to raise awareness and shift norms related to family planning. This article presents data on program results from July 2011 to December 2013 from the 5 countries. Project staff summarized monthly data from client registers using hard-copy forms and recorded the data electronically in Microsoft Excel for compilation and analysis. The initiative reached 52,616 new users of modern contraceptive methods across the 5 countries, ranging from 575 in Djibouti to 21,191 in Chad. LARCs have predominated overall, representing 61% of new modern method users. The percentage of new users choosing LARCs varied by country: 78% in the DRC, 72% in Chad, and 51% in Mali, but only 29% in Pakistan. In Djibouti, those methods were not offered in the country through SAFPAC during the period discussed here. In Chad, the DRC, and Mali, implants have been the most popular LARC method, while in Pakistan the IUD has been more popular. Use of IUDs, however, has comprised a larger share of the method mix over time in all 4 of these countries. These results to date suggest that it is feasible to work with the public sector in fragile, crisis-affected states to deliver a wide range of quality family planning services, to do so rapidly, and to see a dramatic increase in the percentage of users choosing long-acting reversible methods.

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Successful Proof of Concept of Family Planning and Immunization Integration in Liberia
Chelsea M Coopera⇑, Rebecca Fieldsb, Corinne I Mazzeoc, Nyapu Taylord, Anne Pfitzera, Mary Momolue, Cuallau Jabbeh-Howee
ABSTRACT
Globally, unmet need for postpartum family planning remains high, while immunization services are among the most wide-reaching and equitable interventions. Given overlapping time frames, integrating these services provides an opportunity to leverage existing health visits to offer women more comprehensive services. From March through November 2012, Liberia’s government, with support from the Maternal and Child Health Integrated Program (MCHIP), piloted an integrated family planning and immunization model at 10 health facilities in Bong and Lofa counties. Vaccinators provided mothers bringing infants for routine immunization with targeted family planning and immunization messages and same-day referrals to co-located family planning services. In February 2013, we compared service statistics for family planning and immunization during the pilot against the previous year’s statistics. We also conducted in-depth interviews with service providers and other personnel and focus group discussions with clients. Results showed that referral acceptance across the facilities varied from 10% to 45% per month, on average. Over 80% of referral acceptors completed the family planning visit that day, of whom over 90% accepted a contraceptive method that day. The total number of new contraceptive users at participating facilities increased by 73% in Bong and by 90% in Lofa. Women referred from immunization who accepted family planning that day accounted for 44% and 34% of total new contraceptive users in Bong and Lofa, respectively. In Lofa, pilot sites administered 35% more Penta 1 and 21% more Penta 3 doses during the pilot period compared with the same period of the previous year, while Penta 1 and Penta 3 administration decreased in non-pilot facilities. In Bong, there was little difference in the number of Penta 1 and Penta 3 doses administered between pilot and non-pilot facilities. In both counties, Penta 1 to Penta 3 dropout rates increased at pilot sites but not in non-pilot facilities, possibly due to higher than average background dropout rates at pilot sites prior to the intervention in Lofa and the disproportionate effect of data from 1 large facility in Bong. The project provided considerable basic support to assess this proof of concept. However, results suggest that introducing a simple model that is minimally disruptive to existing immunization service delivery can facilitate integration. The model is currently being scaled-up to other counties in Liberia, which could potentially contribute to increased postpartum contraceptive uptake, leading to longer birth intervals and improved health outcomes for children and mothers

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Female Health Workers at the Doorstep: A Pilot of Community-Based Maternal, Newborn, and Child Health Service Delivery in Northern Nigeria
Charles A Uzondua, Henry V Doctora,b, Sally E Findleyb, Godwin Y Afenyadua, Alastair Agerb
Author Affiliations
aPartnership for Reviving Routine Immunization in Northern Nigeria–Maternal Newborn and Child Health Initiative, Kano, Nigeria
bColumbia University, Mailman School of Public Health, New York, NY, USA

Deployment of resident female Community Health Extension Workers (CHEWs) to a remote rural community led to major and sustained increases in service utilization, including antenatal care and facility-based deliveries. Key components to success: (1) providing an additional rural residence allowance to help recruit and retain CHEWs; (2) posting the female CHEWs in pairs to avoid isolation and provide mutual support; (3) ensuring supplies and transportation means for home visits; and (4) allowing CHEWs to perform deliveries.

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Engaging Communities With a Simple Tool to Help Increase Immunization Coverage
Use of a simple, publicly placed tool that monitors vaccination coverage in a community has potential to broaden program coverage by keeping both the community and the health system informed about every infant’s vaccination status.
Manish Jain, Gunjan Taneja, Ruhul Amin, Robert Steinglass, Michael Favin
Glob Health Sci Pract 2015;3(1):117-125. http://dx.doi.org/10.9745/GHSP-D-14-00180

Global Public Health
Volume 10, Issue 4, 2015
http://www.tandfonline.com/toc/rgph20/current#.VPudJy5nBhU

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Endgame for polio eradication? Options for overcoming social and political factors in the progress to eradicating polio
Pavan V. Ganapathirajuab*, Christiaan B. Morssinkc & James Plumbd
pages 463-473
DOI:10.1080/17441692.2014.994655
Abstract
In 1988, the Global Polio Eradication Initiative (GPEI) was launched with the goal of eradicating polio by the year 2000. After 25 years, several dynamics still challenge this large public health campaign with new cases of polio being reported annually. We examine the roots of this initiative to eradicate polio, its scope, the successes and setbacks during the last 25 years and reflect on the current state of affairs. We examine the social and political factors that are barriers to polio eradication. Options are discussed for solving the current impasse of polio eradication: using force, respecting individual freedoms and gaining support from those vulnerable to fundamentalist ‘propaganda’. The travails of the GPEI indicate the need for expanding the Convention on the Rights of the Child to address situations of war and civic strife. Such a cultural and structural reference will provide the basis for global stakeholders to engage belligerent local actors whose local political conflicts are barriers to the eradication of polio. Disregard for these actors will result in stagnation of polio eradication policy, delaying eradication beyond 2018.

Health Affairs
March 2015; Volume 34, Issue 3
http://content.healthaffairs.org/content/current

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People In Sub-Saharan Africa Rate Their Health And Health Care Among The Lowest In The World
Angus S. Deaton1,* and Robert Tortora2
Author Affiliations
1Angus S. Deaton (deaton@princeton.edu) is the Dwight D. Eisenhower Professor of International Affairs and a professor of economics and international affairs at the Woodrow Wilson School, Princeton University, in New Jersey.
2Robert Tortora was principal scientist and chief methodologist at the Gallup Organization, in Washington, D.C., when this article was written. He is now a senior fellow of survey methodology at ICF International, in Rockville, Maryland.
Abstract
The health of people in sub-Saharan Africa is a major global concern. However, data are weak, and little is known about how people in the region perceive their health or their health care. We used data from the Gallup World Poll in 2012 to document sub-Saharan Africans’ perceived health status, their satisfaction with health care, their contact with medical professionals, and the priority they attach to health care. In comparison to other regions of the world, sub-Saharan Africa has the lowest ratings for well-being and the lowest satisfaction with health care. It also has the second-lowest perception of personal health, after only the former Soviet Union and its Eastern European satellites. HIV prevalence is positively correlated with perceived improvements in health care in countries with high prevalence. This is consistent with an improvement in at least some health care services as a result of the largely aid-funded rollout of antiretroviral treatment. Even so, sub-Saharan Africans do not prioritize health care as a matter of policy, although donors are increasingly shifting their aid efforts in the region toward health.

Health Policy and Planning
Volume 30 Issue 2 March 2015
http://heapol.oxfordjournals.org/content/current

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Integrating mental health and social development in theory and practice
Sophie Plagerson*
Author Affiliations
Centre for Social Development in Africa, University of Johannesburg, Auckland Park, Johannesburg 2006, South Africa
Accepted December 17, 2013.
Abstract
In many low and middle income countries, attention to mental illness remains compartmentalized and consigned as a matter for specialist policy. Despite great advances in global mental health, mental health policy and practice dovetail only to a limited degree with social development efforts. They often lag behind broader approaches to health and development. This gap ignores the small but growing evidence that social development unavoidably impacts the mental health of those affected, and that this influence can be both positive and negative. This article examines the theoretical and practical challenges that need to be overcome for a more effective integration of social development and mental health policy. From a theoretical perspective, this article demonstrates compatibility between social development and mental health paradigms. In particular, the capability approach is shown to provide a strong framework for integrating mental health and development. Yet, capability-oriented critiques on ‘happiness’ have recently been applied to mental health with potentially detrimental outcomes. With regard to policy and practice, horizontal and vertical integration strategies are suggested. Horizontal strategies require stronger devolution of mental health care to the primary care level, more unified messages regarding mental health care provision and the gradual expansion of mental health packages of care. Vertical integration refers to the alignment of mental health with related policy domains (particularly the social, economic and political domains). Evidence from mental health research reinforces aspects of social development theory in a way that can have tangible implications on practice. First, it encourages a focus on avoiding exclusion of those affected by or at risk of mental illness. Secondly, it underscores the importance of the process of implementation as an integral component of successful policies. Finally, by retaining a focus on the individual, it seeks to avoid uneven approaches to development.

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Overcoming challenges to sustainable immunization financing: early experiences from GAVI graduating countries
Helen Saxenian1, Robert Hecht2,*, Miloud Kaddar3, Sarah Schmitt4, Theresa Ryckman2 and Santiago Cornejo5
Author Affiliations
1Consultant to Results for Development Institute, Washington, DC 20005, USA, 2Results for Development Institute, Washington, DC 20005, USA, 3World Health Organization, 1211 Geneva, Switzerland, 4Consultant to World Health Organization, 1211 Geneva, Switzerland, 5GAVI Alliance, 1202 Geneva, Switzerland
Accepted January 6, 2014.
Abstract
Over the 5-year period ending in 2018, 16 countries with a combined birth cohort of over 6 million infants requiring life-saving immunizations are scheduled to transition (graduate) from outside financial and technical support for a number of their essential vaccines. This support has been provided over the past decade by the GAVI Alliance. Will these 16 countries be able to continue to sustain these vaccination efforts? To address this issue, GAVI and its partners are supporting transition planning, entailing country assessments of readiness to graduate and intensive dialogue with national officials to ensure a smooth transition process. This approach was piloted in Bhutan, Republic of Congo, Georgia, Moldova and Mongolia in 2012. The pilot showed that graduating countries are highly heterogeneous in their capacity to assume responsibility for their immunization programmes. Although all possess certain strengths, each country displayed weaknesses in some of the following areas: budgeting for vaccine purchase, national procurement practices, performance of national regulatory agencies, and technical capacity for vaccine planning and advocacy. The 2012 pilot experience further demonstrated the value of transition planning processes and tools. As a result, GAVI has decided to continue with transition planning in 2013 and beyond. As the graduation process advances, GAVI and graduating countries should continue to contribute to global collective thinking about how developing countries can successfully end their dependence on donor aid and achieve self-sufficiency.

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Health seeking behaviour and the related household out-of-pocket expenditure for chronic non-communicable diseases in rural Malawi
Qun Wang, Stephan Brenner, Gerald Leppert, Thomas Hastings Banda, Olivier Kalmus, and Manuela De Allegri
Health Policy Plan. (2015) 30 (2): 242-252 doi:10.1093/heapol/czu004

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Policy options for pharmaceutical pricing and purchasing: issues for low- and middle-income countries
Tuan Anh Nguyen1,2,*, Rosemary Knight3, Elizabeth Ellen Roughead1, Geoffrey Brooks4 and
Andrea Mant3
Author Affiliations
1Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia 2Pharmacoeconomic and Pharmaceutical Administration Department, Hanoi University of Pharmacy, 13-15 Le Thanh Tong St., Hanoi, Vietnam 3School of Public Health and Community Medicine, University of New South Wales, High St, Kensington NSW 2052, Australia and 4Pharmaceutical Consultant, Adelaide Parade, Woollahra, NSW 2025, Australia
Accepted November 27, 2013.
Abstract
Pharmaceutical expenditure is rising globally. Most high-income countries have exercised pricing or purchasing strategies to address this pressure. Low- and middle-income countries (LMICs), however, usually have less regulated pharmaceutical markets and often lack feasible pricing or purchasing strategies, notwithstanding their wish to effectively manage medicine budgets. In high-income countries, most medicines payments are made by the state or health insurance institutions. In LMICs, most pharmaceutical expenditure is out-of-pocket which creates a different dynamic for policy enforcement. The paucity of rigorous studies on the effectiveness of pharmaceutical pricing and purchasing strategies makes it especially difficult for policy makers in LMICs to decide on a course of action. This article reviews published articles on pharmaceutical pricing and purchasing policies. Many policy options for medicine pricing and purchasing have been found to work but they also have attendant risks. No one option is decisively preferred; rather a mix of options may be required based on country-specific context. Empirical studies in LMICs are lacking. However, risks from any one policy option can reasonably be argued to be greater in LMICs which often lack strong legal systems, purchasing and state institutions to underpin the healthcare system. Key factors are identified to assist LMICs improve their medicine pricing and purchasing systems.

Health Research Policy and Systems
http://www.health-policy-systems.com/content
[Accessed 7 March 2015]

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Research
How does context influence performance of community health workers in low- and middle-income countries? Evidence from the literature
Maryse C Kok12*, Sumit S Kane1, Olivia Tulloch3, Hermen Ormel1, Sally Theobald3, Marjolein Dieleman1, Miriam Taegtmeyer3, Jacqueline EW Broerse2 and Korrie AM de Koning1
Author Affiliations
Health Research Policy and Systems 2015, 13:13 doi:10.1186/s12961-015-0001-3
Published: 7 March 2015
Abstract (provisional)
Background
Community health workers (CHWs) are increasingly recognized as an integral component of the health workforce needed to achieve public health goals in low- and middle-income countries (LMICs). Many factors intersect to influence CHW performance. A systematic review with a narrative analysis was conducted to identify contextual factors influencing performance of CHWs.
Methods
We searched six databases for quantitative, qualitative, and mixed-methods studies that included CHWs working in promotional, preventive or curative primary health care services in LMICs. We differentiated CHW performance outcome measures at two levels: CHW level and end-user level. Ninety-four studies met the inclusion criteria and were double read to extract data relevant to the context of CHW programmes. Thematic coding was conducted and evidence on five main categories of contextual factors influencing CHW performance was synthesized.
Results
Few studies had the influence of contextual factors on CHW performance as their primary research focus. Contextual factors related to community (most prominently), economy, environment, and health system policy and practice were found to influence CHW performance. Socio-cultural factors (including gender norms and values and disease related stigma), safety and security and education and knowledge level of the target group were community factors that influenced CHW performance. Existence of a CHW policy, human resource policy legislation related to CHWs and political commitment were found to be influencing factors within the health system policy context. Health system practice factors included health service functionality, human resources provisions, level of decision-making, costs of health services, and the governance and coordination structure. All contextual factors can interact to shape CHW performance and affect the performance of CHW interventions or programmes.
Conclusions
Research on CHW programmes often does not capture or explicitly discuss the context in which CHW interventions take place. This synthesis situates and discusses the influence of context on CHW and programme performance. Future health policy and systems research should better address the complexity of contextual influences on programmes. This insight can help policy makers and programme managers to develop CHW interventions that adequately address and respond to context to optimise performance

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Editorial
Health research improves healthcare: now we have the evidence and the chance to help the WHO spread such benefits globally
Stephen R Hanney1* and Miguel A González-Block2
Author Affiliations
Health Research Policy and Systems 2015, 13:12 doi:10.1186/s12961-015-0006-y
Published: 3 March 2015
Abstract
There has been a dramatic increase in the body of evidence demonstrating the benefits that come from health research. In 2014, the funding bodies for higher education in the UK conducted an assessment of research using an approach termed the Research Excellence Framework (REF). As one element of the REF, universities and medical schools in the UK submitted 1,621 case studies claiming to show the impact of their health and other life sciences research conducted over the last 20 years. The recently published results show many case studies were judged positively as providing examples of the wide range and extensive nature of the benefits from such research, including the development of new treatments and screening programmes that resulted in considerable reductions in mortality and morbidity.

Analysis of specific case studies yet again illustrates the international dimension of progress in health research; however, as has also long been argued, not all populations fully share the benefits. In recognition of this, in May 2013 the World Health Assembly requested the World Health Organization (WHO) to establish a Global Observatory on Health Research and Development (R&D) as part of a strategic work-plan to promote innovation, build capacity, improve access, and mobilise resources to address diseases that disproportionately affect the world’s poorest countries.

As editors of Health Research Policy and Systems (HARPS), we are delighted that our journal has been invited to help inform the establishment of the WHO Global Observatory through a Call for Papers covering a range of topics relevant to the Observatory, including topics on which HARPS has published articles over the last few months, such as approaches to assessing research results, measuring expenditure data with a focus on R&D, and landscape analyses of platforms for implementing R&D. Topics related to research capacity building may also be considered. The task of establishing a Global Observatory on Health R&D to achieve the specified objectives will not be easy; nevertheless, this Call for Papers is well timed – it comes just at the point where the evidence of the benefits from health research has been considerably strengthened.

International Health
Volume 7 Issue 2 March 2015
http://inthealth.oxfordjournals.org/content/current

Special issue: Digital methods in epidemiology
Digital methods in epidemiology can transform disease control
Extract
Modern society has been transformed by the digital revolution through cellular phones for communication, remote sensing of weather and other terrestrial data, cheap and plentiful digital computation and data storage, genomic sequencing and analysis, GPS for geolocation and navigation, and many other marvels. These advances have been concurrent with major changes in the burden, dynamics and distributions of diseases. The burden of disease remains intolerably high in much of the world,1 and current challenges facing epidemiology include reducing the prevalence of both communicable and non-communicable diseases,1 completing the Global Polio Eradication Initiative,2 developing strategies to control and eliminate malaria,2,3 and responding to outbreaks of emerging infectious diseases such as the recent Ebola epidemic.4 In this special issue of International Health, the authors illustrate both the ways in which modern digital methods are already being applied to these current challenges in epidemiology and also the opportunities for even greater impact.

Advancing digital methods in the fight against communicable diseases
Guillaume Chabot-Couturea,*, Vincent Y. Seamanb, Jay Wengerb, Bruno Moonenb and Alan Magillb
Author Affiliations
aInstitute for Disease Modeling, Intellectual Ventures, Bellevue, 98005, USA
bBill & Melinda Gates Foundation, Seattle, 98109, USA
Received December 23, 2014.
Revision received January 23, 2015.
Accepted January 26, 2015.
Abstract
Important advances are being made in the fight against communicable diseases by using new digital tools. While they can be a challenge to deploy at-scale, GPS-enabled smartphones, electronic dashboards and computer models have multiple benefits. They can facilitate program operations, lead to new insights about the disease transmission and support strategic planning. Today, tools such as these are used to vaccinate more children against polio in Nigeria, reduce the malaria burden in Zambia and help predict the spread of the Ebola epidemic in West Africa.

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The promise of reverse vaccinology
Ashley I. Heinson, Christopher H. Woelk* and Marie-Louise Newell
Author Affiliations
Faculty of Medicine, University of Southampton, Southampton, UK
Received October 22, 2014.
Revision received January 6, 2015.
Accepted January 7, 2015.
Abstract
Reverse vaccinology (RV) is a computational approach that aims to identify putative vaccine candidates in the protein coding genome (proteome) of pathogens. RV has primarily been applied to bacterial pathogens to identify proteins that can be formulated into subunit vaccines, which consist of one or more protein antigens. An RV approach based on a filtering method has already been used to construct a subunit vaccine against Neisseria meningitidis serogroup B that is now registered in several countries (Bexsero). Recently, machine learning methods have been used to improve the ability of RV approaches to identify vaccine candidates. Further improvements related to the incorporation of epitope-binding annotation and gene expression data are discussed. In the future, it is envisaged that RV approaches will facilitate rapid vaccine design with less reliance on conventional animal testing and clinical trials in order to curb the threat of antibiotic resistance or newly emerged outbreaks of bacterial origin.

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Poverty, health and satellite-derived vegetation indices: their inter-spatial relationship in West Africa
Luigi Sedda, Andrew J. Tatem, David W. Morley, Peter M. Atkinson, Nicola A. Wardrop, Carla Pezzulo, Alessandro Sorichetta, Joanna Kuleszo, and David J. Rogers
Int. Health (2015) 7 (2): 99-106 doi:10.1093/inthealth/ihv005
Abstract
Background
Previous analyses have shown the individual correlations between poverty, health and satellite-derived vegetation indices such as the normalized difference vegetation index (NDVI). However, generally these analyses did not explore the statistical interconnections between poverty, health outcomes and NDVI.
Methods
In this research aspatial methods (principal component analysis) and spatial models (variography, factorial kriging and cokriging) were applied to investigate the correlations and spatial relationships between intensity of poverty, health (expressed as child mortality and undernutrition), and NDVI for a large area of West Africa.
Results
This research showed that the intensity of poverty (and hence child mortality and nutrition) varies inversely with NDVI. From the spatial point-of-view, similarities in the spatial variation of intensity of poverty and NDVI were found.
Conclusions
These results highlight the utility of satellite-based metrics for poverty models including health and ecological components and, in general for large scale analysis, estimation and optimisation of multidimensional poverty metrics. However, it also stresses the need for further studies on the causes of the association between NDVI, health and poverty. Once these relationships are confirmed and better understood, the presence of this ecological component in poverty metrics has the potential to facilitate the analysis of the impacts of climate change on the rural populations afflicted by poverty and child mortality.

JAMA
http://jama.jamanetwork.com/issue.aspx

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Online First
March 05, 2015
Editorial
Emergency Treatment for Exposure to Ebola Virus: The Need to Fast-Track Promising Vaccines
Thomas W. Geisbert, PhD.
JAMA. Published online March 05, 2015. doi:10.1001/jama.2015.2057

Ebola virus is among the most deadly pathogens, with case fatality rates of up to 90%.1 Ebola virus is categorized as a tier 1 pathogen by the US government because of its potential for deliberate misuse with significant potential for mass casualties. The current outbreak of Ebola virus in West Africa with more than 23 000 cases and 9000 deaths2 also demonstrates the long-underestimated public health threat that Ebola virus poses as a natural human pathogen. There are no licensed vaccines or postexposure treatments for combating Ebola virus. However, substantial progress has been made in developing vaccines and antivirals that can protect laboratory animals against lethal disease.1,3 Advancing these interventions for human use is a matter of utmost urgency.

In this issue of JAMA, Lai et al4 report the use of a first-generation recombinant vesicular stomatitis virus–based Ebola vaccine (VSVΔG-ZEBOV)5 to treat a physician who experienced a needlestick in an Ebola treatment unit in Sierra Leone during the current Ebola virus outbreak. A single dose of the VSVΔG-ZEBOV vaccine was administered approximately 43 hours after the potential exposure. The patient experienced a transient febrile syndrome after vaccination. Importantly, no evidence of Ebola virus infection was detected, and the vaccine elicited strong innate and Ebola virus–specific adaptive immune responses. Most significantly, the vaccine, which expresses the surface glycoprotein of Ebola virus, was able to induce an IgG antibody response against the Ebola virus glycoprotein at a level that has been associated with protection of nonhuman primates.5
It is difficult to draw any definitive conclusions from a single case report. The inability to detect evidence of Ebola virus infection most likely is because there was not an actual exposure; however, it cannot be completely ruled out that the intervention was effective in controlling Ebola virus replication. Even though this patient experienced some adverse events after vaccination, the patient reported having traveler’s diarrhea prior to receiving the VSVΔG-ZEBOV vaccine; therefore, it is also not possible to draw any strong conclusions regarding any adverse events from this case in regard to the safety of the vaccine. This is the second time that the VSVΔG-ZEBOV vaccine has been used to treat a potential exposure to Ebola virus. The initial use occurred in 2009 for a laboratory worker in Germany6 and also involved a needlestick injury. The results of that incident were nearly identical; however, the severity of adverse events following vaccination was less notable in the German case compared with the patient in the case report by Lai et al…4

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Preliminary Communication
Emergency Postexposure Vaccination With Vesicular Stomatitis Virus–Vectored Ebola Vaccine After Needlestick
Lilin Lai, MD, Richard Davey, MD, Allison Beck, MPAS, et al.
JAMA. Published online March 05, 2015. doi:10.1001/jama.2015.1995
Abstract
Importance
Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick.
Objective
To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus.
Design and Setting
Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014.
Interventions
The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa.
Results
The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected.
Conclusions and Relevance
It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.

JAMA Pediatrics
March 2015, Vol 169, No. 3
http://archpedi.jamanetwork.com/issue.aspx

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Viewpoint | March 2015
A Landmark Report on Improving Medicines for Children
Geert W. ‘t Jong, MD, PhD1,2; Terry P. Klassen, MD, MSc, FRCPC1,2; Stuart M. MacLeod, BSc(Med), MD, PhD, FRCPC3
[+] Author Affiliations
Extract
This Viewpoint discusses the publication of the Council of Canadian Academies report “Improving Medicines for Children in Canada.”
Children have been classified as “therapeutic orphans” for more than 50 years, but the pediatric community has made important strides toward evidence-based safe and effective drug therapy for children through improved legislation, increased quantity and quality of research, and better stakeholder community involvement. In September 2014, another major step forward was taken with publication of the Council of Canadian Academies report “Improving Medicines for Children in Canada.”1 An international Expert Panel drafted the report, and many North American and European authorities participated in the final review. The Council of Canadian Academies was asked by Canada’s federal government to review the status of pediatric therapeutics in Canada, based on the following question: “What is the state of clinical pharmacology, in Canada and abroad, that can be applied to the ethical development of safe and effective pharmaceuticals and biologics labeled as therapies for infants, children and youth?”1

Journal of Community Health
Volume 40, Issue 2, April 2015
http://link.springer.com/journal/10900/40/2/page/1

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Commentary
Ebola Therapy and Health Equity
Neil J. Nusbaum
Abstract
Current care for Ebola patients in resource poor countries is hampered by a lack of resources to isolate patients and their close contacts. The current Ebola epidemic offers the opportunity to harvest convalescent serum to help contain this and future outbreaks. A systemic and just process to accomplish this goal can incorporate procedures to improve care for current Ebola patients and their close contacts.

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Factors Impacting Influenza Vaccination of Urban Low-Income Latino Children Under Nine Years Requiring Two Doses in the 2010–2011 Season
Annika M. Hofstetter, Angela Barrett, Melissa S. Stockwell
Abstract
The Advisory Committee on Immunization Practices (ACIP) recommends that certain children under 9 years of age receive two influenza vaccine doses in a season for optimal protection. Recent data indicate that many of these children fail to receive one or both of these needed doses. Contributing factors to under-vaccination of this population remain unclear. Caregivers of children aged 6 months–8 years requiring two influenza vaccine doses in the 2010–2011 season were identified from households enrolled in four urban Head Start programs. Recruitment and survey administration were conducted between March and June 2011. The impact of caregiver, provider, and practice-based factors on influenza vaccine receipt was assessed using bivariate and multivariable logistic regression analyses. Caregivers (n = 128) were predominantly mothers, Latina, Spanish-speaking, and non-U.S. born. Few children received one (31 %) or both (7 %) influenza vaccine doses. Caregivers who discussed influenza vaccination with providers were more likely to know their child needed two doses (55 vs. 35 %, p < 0.05) and have a fully vaccinated child (11 vs. 0 %, p < 0.05). Among caregivers whose child received the first dose, those who reported being told when to return for the second dose were also more likely to have a fully vaccinated child (35 vs. 0 %, p = 0.05). Belief in influenza vaccine effectiveness was positively associated with vaccination (p < 0.001), while safety concerns were negatively associated (p < 0.05). This study highlights the importance of provider-family communication about the two-dose regimen as well as influenza vaccine effectiveness and safety.

Journal of Epidemiology & Community Health
March 2015, Volume 69, Issue 3
http://jech.bmj.com/content/current

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Child health
The impact of the Iraq War on neonatal polio immunisation coverage: a quasi-experimental study
Valeria Cetorelli
Correspondence to Valeria Cetorelli, Department of Social Policy, London School of Economics
Abstract
Background The public health consequences of the Iraq War (2003–2011) have remained difficult to quantify, mainly due to a scarcity of adequate data. This paper is the first to assess whether and to what extent the war affected neonatal polio immunisation coverage.
Method The study relies on retrospective neonatal polio vaccination histories from the 2000, 2006 and 2011 Iraq Multiple Indicator Cluster Surveys (N=64 141). Pooling these surveys makes it possible to reconstruct yearly trends in immunisation coverage from 1996 to 2010. The impact of the war is identified with a difference-in-difference approach contrasting immunisation trends in the autonomous Kurdish provinces, which remained relatively safe during the war, with trends in the central and southern provinces, where violence and disruption were pervasive.
Results After controlling for individual and household characteristics, year of birth and province of residence, children exposed to the war were found to be 21.5 percentage points (95% CI −0.341 to −0.089) less likely to have received neonatal polio immunisation compared with non-exposed children.
Conclusions The decline in neonatal polio immunisation coverage is part of a broader war-induced deterioration of routine maternal and newborn health services. Postwar strategies to promote institutional deliveries and ensure adequate vaccine availability in primary health facilities could increase dramatically the percentage of newborns immunised.

Journal of Pediatrics
March 2015 Volume 166, Issue 3, p507-782
http://www.jpeds.com/current

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Explaining alleged pertussis vaccine associated neurologic disorders
Sarah S. Long, MD
DOI: http://dx.doi.org/10.1016/j.jpeds.2015.01.010
Extract
In 1986, the National Childhood Vaccine Injury Act established the Vaccine Injury Compensation Program to compensate children and adults or to adjudicate claims of injury related to vaccines. Along with such benefits, healthcare providers who administer vaccines are mandated to maintain vaccination records and to report certain adverse events associated with covered immunizations. In this issue of The Journal, investigators from Children’s National Medical Center, the Division of Vaccine Injury Compensation of the Department of Health and Human Services, and the National Institute of Neurologic Disorders of the National Institutes of Health report the findings of 165 claims of children younger than 2 years of age with seizures or encephalopathy as an alleged vaccine-related injury from 1995 through 2005.

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Post-Licensure Monitoring to Evaluate Vaccine Safety
Annabelle de St Maurice, MD
Division of Infectious Diseases, Department of Pediatrics, Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, Nashville, Tennessee
Kathryn M. Edwards, MD
Division of Infectious Diseases, Department of Pediatrics, Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine, Nashville, Tennessee
DOI: http://dx.doi.org/10.1016/j.jpeds.2014.12.031
Extract
Pertussis, or whooping cough, is caused by a gram-negative rod, Bordetella pertussis. Typically, pertussis causes a respiratory illness characterized by prolonged cough in adults and children. In infants, it can be complicated by apnea, pneumonia, pulmonary hypertension, and neurologic symptoms, including encephalopathy and seizures. Prior to the introduction of pertussis vaccine in the US, there were about 157 cases of pertussis per 100 000 people each year, with 1.5 deaths per 1000 infants less than 1 year of age.

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Seizures, Encephalopathy, and Vaccines: Experience in the National Vaccine Injury Compensation Program
Tarannum M. Lateef, MD, MPH, Rosemary Johann-Liang, MD, Himanshu Kaulas, MD, Rakibul Hasan, MD, Karen Williams, MS, Vito Caserta, MD, Karin B. Nelson, MD
Received: May 20, 2014; Received in revised form: September 12, 2014; Accepted: October 22, 2014; Published Online: December 02, 2014
DOI: http://dx.doi.org/10.1016/j.jpeds.2014.10.054
Abstract
Objectives
To describe the demographic and clinical characteristics of children for whom claims were filed with the National Vaccine Injury Compensation Program (VICP) alleging seizure disorder and/or encephalopathy as a vaccine injury.
Study design
The National VICP within the Department of Health and Human Services compensates individuals who develop medical problems associated with a covered immunization. We retrospectively reviewed medical records of children younger than 2 years of age with seizures and/or encephalopathy allegedly caused by an immunization, where a claim was filed in the VICP between 1995 through 2005.
Results
The VICP retrieved 165 claims that had sufficient clinical information for review. Approximately 80% of these alleged an injury associated with whole-cell diphtheria, pertussis (whooping cough), and tetanus or tetanus, diphtheria toxoids, and acellular pertussis vaccine. Pre-existing seizures were found in 13% and abnormal findings on a neurologic examination before the alleged vaccine injury in 10%. A final diagnostic impression of seizure disorder was established in 69%, of whom 17% (28 patients) had myoclonic epilepsy, including possible severe myoclonic epilepsy of infancy. Specific conditions not caused by immunization, such as tuberous sclerosis and cerebral dysgenesis, were identified in 16% of subjects.
Conclusion
A significant number of children with alleged vaccine injury had pre-existing neurologic or neurodevelopmental abnormalities. Among those developing chronic epilepsy, many had clinical features suggesting genetically determined epilepsy. Future studies that include genotyping may allow more specific therapy and prognostication, and enhance public confidence in vaccination.

The Lancet
Mar 07, 2015 Volume 385 Number 9971 p829-914 e16-e20
http://www.thelancet.com/journals/lancet/issue/current

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Comment
Morality in a time of Ebola
Arthur L Caplan
Published Online: 19 February 2015
Summary
The first true epidemic of Ebola led to widespread panic. The virus appeared in so many countries in 2014—including Guinea, Liberia, Mali, Nigeria, Senegal, Sierra Leone, Spain, and the USA—that WHO, officials at the US National Institutes of Health and Centers for Disease Control and Prevention, and many other government officials around the world declared the epidemic to be out of control.1,2 Talk of desperation and apocalypse with reference to Ebola is not uncommon.3 Previous Ebola outbreaks were rapidly contained through a combination of local attentiveness, the availability of resources, focused public education, and a bit of luck.

The Lancet Infectious Diseases
Mar 2015 Volume 15 Number 3 p249-360
http://www.thelancet.com/journals/laninf/issue/current

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Editorial
Global harmonisation in vaccine price
The Lancet Infectious Diseases
Summary
On Jan 20, 2015, Médecins Sans Frontières published the second edition of the report The right shot: bringing down barriers to affordable and adapted vaccines. The report highlighted the lack of a rational pricing system for vaccines that serves all countries and populations, and, as a consequence, private and public health providers struggle to sustain the costs of immunisation campaigns in many settings. Several factors, such as limited information on vaccine prices, introduction of costly new vaccines, absence of competition in vaccine production, and a paucity of vaccine products suited for low-resource settings, have created a market in which children in many countries are unprotected against life-threatening—but preventable—diseases.

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Comment
Novel observational study designs with new influenza vaccines
Eelko Hak
Published Online: 08 February 2015
Summary
In The Lancet Infectious Diseases, Hector Izurieta and colleagues1 presented results of a cohort study in 929 730 older people (65 years and older) who received a high-dose influenza vaccine (high-dose Fluzone, Sanofi Pasteur, PA, USA, 60 μg per strain) and compared rates of influenza-related visits and hospital admissions with 1 615 545 older people who received a standard dose of the same vaccine (15 μg per strain). The high-dose vaccine seemed to be 22% more effective than the standard-dose vaccine.

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Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis
Hector S Izurieta, Nicole Thadani, David K Shay, Yun Lu, Aaron Maurer, Ivo M Foppa, Riley Franks, Douglas Pratt, Richard A Forshee, Thomas MaCurdy, Chris Worrall, Andrew E Howery, Jeffrey Kelman
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Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance
Matthew R Moore, Ruth Link-Gelles, William Schaffner, Ruth Lynfield, Catherine Lexau, Nancy M Bennett, Susan Petit, Shelley M Zansky, Lee H Harrison, Arthur Reingold, Lisa Miller, Karen Scherzinger, Ann Thomas, Monica M Farley, Elizabeth R Zell, Thomas H Taylor, Tracy Pondo, Loren Rodgers, Lesley McGee, Bernard Beall, James H Jorgensen, Cynthia G Whitney

Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in 2014: an observational study
Ousmane Faye, Pierre-Yves Boëlle, Emmanuel Heleze, Oumar Faye, Cheikh Loucoubar, N’Faly Magassouba, Barré Soropogui, Sakoba Keita, Tata Gakou, El Hadji Ibrahima Bah, Lamine Koivogui, Amadou Alpha Sall, Simon Cauchemez

Review
The development of global vaccine stockpiles
Dr Catherine Yen, MD, Terri B Hyde, MD, Alejandro J Costa, MSc, Katya Fernandez, MSc, John S Tam, PhD, Stéphane Hugonnet, MD, Anne M Huvos, JD, Philippe Duclos, PhD, Vance J Dietz, MD, Brenton T Burkholder, MD
Published Online: 05 February 2015
Summary
Global vaccine stockpiles, in which vaccines are reserved for use when needed for emergencies or supply shortages, have effectively provided countries with the capacity for rapid response to emergency situations, such as outbreaks of yellow fever and meningococcal meningitis. The high cost and insufficient supply of many vaccines, including oral cholera vaccine and pandemic influenza vaccine, have prompted discussion on expansion of the use of vaccine stockpiles to address a wider range of emerging and re-emerging diseases. However, the decision to establish and maintain a vaccine stockpile is complex and must take account of disease and vaccine characteristics, stockpile management, funding, and ethical concerns, such as equity. Past experience with global vaccine stockpiles provide valuable information about the processes for their establishment and maintenance. In this Review we explored existing literature and stockpile data to discuss the lessons learned and to inform the development of future vaccine stockpiles.

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Personal View
Emergency Ebola response: a new approach to the rapid design and development of vaccines against emerging diseases
Claire M Tully, BA[Mod], Teresa Lambe, PhD, Prof Sarah C Gilbert, PhD, Prof Adrian V S Hill, DM
Published Online: 13 January 2015
Summary
The epidemic of Ebola virus disease has spread at an alarming rate despite containment efforts. As a result, unprecedented large-scale international response efforts have been made in an attempt to gain control of the outbreak and reduce transmission. Several international consortia have been formed in a remarkable worldwide collaborative effort to expedite trials of two candidate Ebola virus vaccines: cAd3-EBOZ and rVSV-EBOV. In parallel, both vaccines are being manufactured in large amounts to enable future rapid deployment for management of the crisis.

The Milbank Quarterly
A Multidisciplinary Journal of Population Health and Health Policy
March 2015 Volume 93, Issue 1 Pages 1–222
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1468-0009/currentissue

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Op-Ed
Good Science + Good Ethics = Good Law: Five Rules for Epidemic Preparedness
LAWRENCE O. GOSTIN*
Article first published online: 5 MAR 2015
DOI: 10.1111/1468-0009.12100
[No abstract]

Nature
Volume 519 Number 7541 pp5-124 5 March 2015
http://www.nature.com/nature/current_issue.html

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Editorial
Fatal fallout
The Ebola epidemic has had a dire effect on the health prospects of pregnant women.
04 March 2015

Features
Maternal health: Ebola’s lasting legacy
One of the most devastating consequences of the Ebola outbreak will be its impact on maternal health.
Erika Check Hayden
04 March 2015

New England Journal of Medicine
March 5, 2015 Vol. 372 No. 10
http://www.nejm.org/toc/nejm/medical-journal

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Perspective
Making Hepatitis E a Vaccine-Preventable Disease
Eyasu Teshale, M.D., and John W. Ward, M.D.
N Engl J Med 2015; 372:899-901 March 5, 2015 DOI: 10.1056/NEJMp1415240
A hepatitis E vaccine could become a powerful new tool in the prevention and control of hepatitis E virus transmission and disease. Most immediately, it can have a role in curbing outbreaks of hepatitis E in humanitarian crises.

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Original Article
Long-Term Efficacy of a Hepatitis E Vaccine
Jun Zhang, M.Sc., Xue-Feng Zhang, M.Sc., Shou-Jie Huang, M.Sc., Ting Wu, Ph.D., Yue-Mei Hu, M.Sc., Zhong-Ze Wang, B.Sc., Hua Wang, M.D., Han-Min Jiang, B.Sc., Yi-Jun Wang, M.Sc., Qiang Yan, M.Sc., Meng Guo, B.Sc., Xiao-Hui Liu, B.Sc., Jing-Xin Li, M.Sc., Chang-Lin Yang, B.Sc., Quan Tang, B.Sc., Ren-Jie Jiang, M.Sc., Hui-Rong Pan, Ph.D., Yi-Min Li, M.D., J. Wai-Kuo Shih, Ph.D., Mun-Hon Ng, Ph.D., Feng-Cai Zhu, M.Sc., and Ning-Shao Xia
N Engl J Med 2015; 372:914-922 March 5, 2015 DOI: 10.1056/NEJMoa1406011
Abstract
Background
Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.
Methods
In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years.
Results
During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.
Conclusions
Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.)

Pediatrics
March 2015, VOLUME 135 / ISSUE 3
http://pediatrics.aappublications.org/current.shtml

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Advancing Informed Consent for Vulnerable Populations
Willliam J. Heerman, MD, MPHa, Richard O. White, MD, MScb, and Shari L. Barkin, MD, MSHSa
Author Affiliations
aDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; and
bDivision of Community Internal Medicine, Mayo Clinic, Jacksonville, Florida
Extract
Informed consent is essential for the conduct of ethical biomedical research.1 Despite its importance, obtaining informed consent is often a complex process, which raises concerns about the extent to which participants are truly informed. Effective implementation is especially difficult among research participants who have limited health literacy. Often, these potential participants are from traditionally high-risk groups, including underrepresented minorities and children. With this in mind, we suggest an innovative approach that uses low health-literacy communication strategies and visual aids to augment and potentially replace the traditional approach to informed consent.
The tension is clear. To provide a comprehensive review of the proposed research, the informed consent document and process are often lengthy, complex, and burdensome.2 Consequently, research participants who sign or verbalize consent often do so without truly understanding the form that they are being asked to sign. In a recent systematic review, participants in one-third of trials assessed did not have adequate understanding in the areas of risks, benefits, randomization, study aims, withdrawal, and voluntarism.3 There are no clear standards for “how much” understanding is adequate. Furthermore, we know that lower education levels, lower literacy, and a participant’s primary language are all associated with poor comprehension of the informed consent process.4 These issues are particularly important when studies are being done in children, adding an additional dimension to vulnerable populations….

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Vaccination, Underlying Comorbidities, and Risk of Invasive Pneumococcal Disease
Inci Yildirim, MD, MSca,b, Kimberly M. Shea, DSc, MPHa,b, Brent A. Little, PhDa, Amy L. Silverio, MAa, and Stephen I. Pelton, MDa,b on behalf of the Members of the Massachusetts Department of Public Health
Author Affiliations
aSection of Pediatric Infectious Diseases, Boston University Medical Center, Boston, Massachusetts; and
bDepartment of Epidemiology, Boston University, School of Public Health, Boston, Massachusetts
Abstract
OBJECTIVES: Children with underlying conditions remain at increased risk for invasive pneumococcal diseases (IPD). This study describes the epidemiology, serotype distribution, clinical presentations, and outcomes of IPD in children with and without comorbidity.
METHODS: Cases of childhood IPD in Massachusetts were identified via enhanced surveillance from 2002 through 2014. Demographic and clinical data were collected via follow-up telephone interviews with parents and/or primary care providers. Underlying conditions were classified according to the 2012 Report of the Committee on Infectious Diseases and 2013 recommendations by the Advisory Committee on Immunization Practices.
RESULTS: Among 1052 IPD cases in Massachusetts children <18 years old, 22.1% had at least 1 comorbidity. Immunocompromising conditions (32.7%) and chronic respiratory diseases (22.4%) were most common. Children with comorbidities were older at the time of IPD diagnosis (median 54 vs 23 months, P < .001), had higher hospitalization (odds ratio 2.5; 95% confidence interval 1.7–3.6) and case-fatality rates (odds ratio 3.7; 95% confidence interval 1.5–8.9) compared with children without known underlying conditions after adjusting for age, gender, year of diagnosis, and pneumococcal vaccination status. During the last 2 years of the study, IPD among children with comorbidities was caused by non–pneumococcal conjugate vaccine 13 serotypes in 23-valent polysaccharide pneumococcal vaccine (6/12, 50%) or serotypes that are not included in any of the vaccines (6/12; 50%).
CONCLUSIONS: In children with comorbidity, IPD results in higher mortality, and a large proportion of disease is due to serotypes not included in current conjugate vaccines. Further research is needed, specifically to develop and evaluate additional strategies for prevention of IPD in the most vulnerable children.

PLoS One
[Accessed 7 March 2015]
http://www.plosone.org/

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Pertussis Post-Exposure Prophylaxis among Household Contacts: A Cost-Utility Analysis
Nisha Thampi, Ipek Gurol-Urganci, Natasha S. Crowcroft, Beate Sander
Research Article | published 06 Mar 2015 | PLOS ONE 10.1371/journal.pone.0119271
Abstract
Background
Recent pertussis outbreaks have prompted re-examination of post-exposure prophylaxis (PEP) strategies, when immunization is not immediately protective. Chemoprophylaxis is recommended to household contacts; however there are concerns of clinical failure and significant adverse events, especially with erythromycin among infants who have the highest disease burden. Newer macrolides offer fewer side effects at higher drug costs. We sought to determine the cost-effectiveness of PEP strategies from the health care payer perspective.
Methods
A Markov model was constructed to examine 4 mutually exclusive strategies: erythromycin, azithromycin, clarithromycin, or no intervention, stratified by age group of contacts (“infant”, “child”, and “adult”). Transition probabilities, costs and quality-adjusted life years (QALYs) were derived from the literature. Chronic neurologic sequelae were modeled over a lifetime, with costs and QALYs discounted at 5%. Associated health outcomes and costs were compared, and incremental cost-effectiveness ratios (ICER) were calculated in 2012 Canadian dollars. Deterministic and probabilistic sensitivity analyses were performed to evaluate the degree of uncertainty in the results.
Findings
Azithromycin offered the highest QALYs in all scenarios. While this was the dominant strategy among infants, it produced an ICER of $16,963 per QALY among children and $2,415 per QALY among adults. Total QALYs with azithromycin were 19.7 for a 5-kg infant, 19.4 for a 10-year-old child, and 18.8 for a 30-year-old adult. The costs of azithromycin PEP among infants, children and adults were $1,976, $132 and $90, respectively. While results were sensitive to changes in PEP effectiveness (11% to 87%), disease transmission (variable among age groups) and hospitalization costs ($379 to $59,644), the choice of strategy remained unchanged.
Interpretation
Pertussis PEP is a cost-effective strategy compared with no intervention and plays an important role in contact management, potentially in outbreak situations. From a healthcare payer perspective, azithromycin is the optimal strategy among all contact groups

Science
6 March 2015 vol 347, issue 6226, pages 1041-1168
http://www.sciencemag.org/current.dtl

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Perspective
Infectious Disease
A sustainable model for antibiotics
Manos Perros
Author Affiliations
AstraZeneca Innovative Medicines and Early Development, Gatehouse Drive, Waltham, MA 02451, USA.

Despite the alarming increase in the prevalence of drug-resistant bacterial infections, far fewer new antibiotics have been approved in the past decade than at the peak in the 1980s (1). The situation is particularly alarming for serious infections by Gram-negative bacteria, some of which are becoming untreatable by modern antibiotics (2–4). Particularly in low- and middle-income countries, untreatable infections are becoming an everyday reality in hospital and care settings (5). Increasing recognition of this problem is spurring a number of public and private initiatives on both sides of the Atlantic (6–8). To more effectively counter the threat of emerging resistance, we must increase the number of innovative new antibiotics in development and harness advances in diagnostic technology to preserve their efficacy.

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Perspective
Infectious Disease
A return to the pre-antimicrobial era?
Stephen Baker1,2,2
Author Affiliations
1Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
2Centre for Tropical Medicine, Oxford University, Oxford, UK.
3London School of Hygiene and Tropical Medicine, London, UK.

After many years out of the limelight, antimicrobial resistance (AMR) in bacteria is firmly back on the international political and scientific agenda (1, 2). The potential impact of AMR on hospital-acquired bacterial infections such as Staphylococcus aureus and Acinetobacter baumannii in higher-income countries has created both fear and a surge of motivation aimed at providing new solutions for the problem (3, 4). The political will and momentum to tackle AMR lies in higher-income countries, but the medical, social, and economic effects of AMR are likely to be felt more in lower-income countries, particularly those in South and Southeast Asia and in sub-Saharan Africa. The identification and development of new drugs is a potential solution but is challenging and costly; any novel therapies introduced into low-income settings without a suitable infrastructure to understand and prevent the rapid development of resistance will likely be expensive and futile.

Vaccine
Volume 33, Issue 12, Pages 1419-1506 (17 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/12

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Discussion
Should close contacts of returning travellers with typhoid fever be protected by vaccination?
Pages 1419-1421
A. Kantele
Abstract
Increasing international travel to areas endemic for typhoid fever correlates with increased risk for travellers to contract the disease. At home, the acutely ill/convalescent patients may pose some risk to their close contacts. In Finland an unofficial guideline suggests vaccination for close contacts of patients with acute typhoid fever; in other developed countries, routine typhoid vaccinations are only recommended to contacts of chronic carriers. This paper discusses the possibilities and limitations of prophylactic/post-exposure typhoid vaccination for contacts of patients with acute disease.

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Brief report
Greater freedom of speech on Web 2.0 correlates with dominance of views linking vaccines to autism
Pages 1422-1425
Anand Venkatraman, Neetika Garg, Nilay Kumar
Abstract
Introduction
It is suspected that Web 2.0 web sites, with a lot of user-generated content, often support viewpoints that link autism to vaccines.
Methods
We assessed the prevalence of the views supporting a link between vaccines and autism online by comparing YouTube, Google and Wikipedia with PubMed. Freedom of speech is highest on YouTube and progressively decreases for the others.
Results
Support for a link between vaccines and autism is most prominent on YouTube, followed by Google search results. It is far lower on Wikipedia and PubMed. Anti-vaccine activists use scientific arguments, certified physicians and official-sounding titles to gain credibility, while also leaning on celebrity endorsement and personalized stories.
Conclusions
Online communities with greater freedom of speech lead to a dominance of anti-vaccine voices. Moderation of content by editors can offer balance between free expression and factual accuracy. Health communicators and medical institutions need to step up their activity on the Internet.

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Review
Comparing vaccines: A systematic review of the use of the non-inferiority margin in vaccine trials
Review Article
Pages 1426-1432
R. Donken, H.E. de Melker, N.Y. Rots, G. Berbers, M.J. Knol
Abstract
Background
Non-inferiority (NI) randomized controlled trials (RCTs) aim to demonstrate that a new treatment is no worse than a comparator that has already shown its efficacy over placebo within a pre-specified margin. However, clear guidelines on how the NI margin should be determined are lacking for vaccine trials. A difference (seroprevalence/risk) of 10% or a geometric mean titre/concentration (GMT) ratio of 1.5 or 2.0 in antibody levels is implicitly recommended for vaccine trials. We aimed to explore which NI margins were used in vaccine RCTs and how they were determined.
Methods
A systematic search for NI vaccine RCTs yielded 177 eligible articles. Data were extracted from these articles using a standardized form and included general characteristics and characteristics specific for NI trials. Relations between the study characteristics and the NI margin used were explored.
Results
Among the 143 studies using an NI margin based on difference (n = 136 on immunogenicity, n = 2 on efficacy and n = 5 on safety), 66% used a margin of 10%, 23% used margins lower than 10% (range 1–7.5%) and 11% used margins larger than 10% (range 11.5–25%). Of the 103 studies using a NI margin based on the GMT ratio, 50% used a margin of 0.67/1.5 and 49% used 0.5/2.0. As observed, 85% of the studies did not discuss the method of margin determination; and 19% of the studies lacked a confidence interval or p-value for non-inferiority.
Conclusion
Most NI vaccine RCTs used an NI margin of 10% for difference or a GMT ratio of 1.5 or 2.0 without a clear rationale. Most articles presented enough information for the reader to make a judgement about the NI margin used and the conclusions. The reporting on the design, margins used and results of NI vaccine trials could be improved; more explicit guidelines may help to achieve this end.

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Modeling the durability of ZOSTAVAX® vaccine efficacy in people ≥60 years of age
Original Research Article
Pages 1499-1505
Xiaoming Li, Jane H. Zhang, Robert F. Betts, Vicki A. Morrison, Ruifeng Xu, Robbin F. Itzler, Camilo J. Acosta, Erik J. Dasbach, James M. Pellissier, Gary R. Johnson, Ivan S.F. Chan
Abstract
Since 2006, the vaccine, ZOSTAVAX®, has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.

Vaccines — Open Access Journal
(Accessed 7 March 2015)
http://www.mdpi.com/journal/vaccines
Review:
Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines
by Huub F. J. Savelkoul, Valerie A. Ferro, Marius M. Strioga and Virgil E. J. C. Schijns
Vaccines 2015, 3 (1), 148-171; doi:10.3390/vaccines3010148 – published 5 March 2015
Abstract
The existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease) vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. For naive T-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals. Adjuvants, for example, are used to promote the immunogenicity of antigens in vaccines, by inducing a pro-inflammatory environment that enables the recruitment and promotion of the infiltration of phagocytic cells, particularly antigen-presenting cells (APC), to the injection site. Adjuvants can enhance antigen presentation, induce cytokine expression, activate APC and modulate more downstream adaptive immune reactions (vaccine delivery systems, facilitating immune Signal 1). In addition, adjuvants can act as immunopotentiators (facilitating Signals 2 and 3) exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3). New adjuvants should also target specific (innate) immune cells in order to facilitate proper activation of downstream adaptive immune responses and homing (Signal 4). It is desirable that these adjuvants should be able to exert such responses in the context of mucosal administered vaccines. This review focuses on the understanding of the potential working mechanisms of the most well-known classes of adjuvants to be used effectively in vaccines.

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

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Health Education Journal
February 23, 2015 0017896915572705
Beliefs and knowledge about the human papillomavirus vaccine among undergraduate men
Theresa Hunter, Melissa Weinstein
Department of Applied Health Science, School of Public Health, Indiana University Bloomington, Bloomington, IN, USA
Abstract
Objective: The objective of this study was to assess male undergraduate students’ human papillomavirus (HPV) knowledge and intentions to receive the HPV vaccination.
Design: Cross-sectional survey.
Method: A sample of 116 male undergraduate students from a university in the Midwestern USA completed a survey questionnaire assessing various aspects related to their attitudes towards the HPV vaccine.
Results: Results show that awareness and levels of knowledge about HPV and the HPV vaccine were low among male undergraduate students. The study also found that intentions to receive the HPV vaccine were very low among this population.
Conclusion: The results of this study should encourage the developmental and implementation of campus-wide health education programmes which discuss the HPV vaccine and benefits for men.

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Disaster Medicine and Public Health Preparedness
Volume 9 – Issue 01 – February 2015
http://journals.cambridge.org/action/displayIssue?jid=DMP&tab=currentissue

Ebola Special Section
Ebola Virus and Public Health (Part 1)
pp 29 – 29
DOI: http://dx.doi.org/10.1017/dmp.2015.18 (About DOI), Published online: 04 March 2015

Introduction
Ebola Virus and Public Health
Charles W. Beadling, Frederick M. Burkle, Jr, Kristi L. Koenig and Trueman W. Sharp
pp 31 – 31
DOI: http://dx.doi.org/10.1017/dmp.2015.16 (About DOI), Published online: 04 March 2015

Editorial
The Ebola Epidemic and Translational Public Health
James J. James
pp 32 – 32
DOI: http://dx.doi.org/10.1017/dmp.2014.106 (About DOI), Published online: 07 October 2014

Special Reports
A Primer on Ebola for Clinicians
Eric Toner, Amesh Adalja and Thomas Inglesby
pp 33 – 37
DOI: http://dx.doi.org/10.1017/dmp.2014.115 (About DOI), Published online: 17 October 2014

Triage Management, Survival, and the Law in the Age of Ebola
Frederick M Burkle, Jr and Christopher M Burkle
pp 38 – 43
DOI: http://dx.doi.org/10.1017/dmp.2014.117 (About DOI), Published online: 24 October 2014

Commentaries
Operationalizing Public Health Skills to Resource Poor Settings: Is This the Achilles Heel in the Ebola Epidemic Campaign?
Frederick M. Burkle, Jr
pp 44 – 46
DOI: http://dx.doi.org/10.1017/dmp.2014.95 (About DOI), Published online: 07 October 2014

Global and Domestic Legal Preparedness and Response: 2014 Ebola Outbreak
James G. Hodge, Jr
pp 47 – 50
DOI: http://dx.doi.org/10.1017/dmp.2014.96 (About DOI), Published online: 10 October 2014

Hubris: The Recurring Pandemic
Tom Koch
pp 51 – 56
DOI: http://dx.doi.org/10.1017/dmp.2014.107 (About DOI), Published online: 22 October 2014

Ebola Triage Screening and Public Health: The New “Vital Sign Zero”
Kristi L. Koenig
pp 57 – 58
DOI: http://dx.doi.org/10.1017/dmp.2014.120 (About DOI), Published online: 29 October 2014

Journalists and Public Health Professionals: Challenges of a Symbiotic Relationship
Pauline Lubens
pp 59 – 63
DOI: http://dx.doi.org/10.1017/dmp.2014.127 (About DOI), Published online: 10 November 2014

The Ebola Threat: China’s Response to the West African Epidemic and National Development of Prevention and Control Policies and Infrastructure
Hao-Jun Fan, Hong-Wei Gao, Hui Ding, Bi-Ke Zhang and Shi-Ke Hou
pp 64 – 65
DOI: http://dx.doi.org/10.1017/dmp.2014.152 (About DOI), Published online: 07 January 2015

Mapping Medical Disasters: Ebola Makes Old Lessons, New
Tom Koch
pp 66 – 73
DOI: http://dx.doi.org/10.1017/dmp.2015.14 (About DOI), Published online: 09 February 2015

Brief Reports
Ebola Virus Disease: Preparedness in Japan
Yugo Ashino, Haorile Chagan-Yasutan, Shinichi Egawa and Toshio Hattori
pp 74 – 78
DOI: http://dx.doi.org/10.1017/dmp.2014.130 (About DOI), Published online: 17 November 2014

Favipiravir: A New Medication for the Ebola Virus Disease Pandemic
Takashi Nagata, Alan K. Lefor, Manabu Hasegawa and Masami Ishii
pp 79 – 81
DOI: http://dx.doi.org/10.1017/dmp.2014.151 (About DOI), Published online: 29 December 2014

Concepts in Disaster Medicine
Ebola Outbreak Response: The Role of Information Resources and the National Library of Medicine
Cynthia B. Love, Stacey J. Arnesen and Steven J. Phillips
pp 82 – 85
DOI: http://dx.doi.org/10.1017/dmp.2014.108 (About DOI), Published online: 17 October 2014

Sign Me Up: Rules of the Road for Humanitarian Volunteers During the Ebola Outbreak
preview
Ryan Wildes, Stephanie Kayden, Eric Goralnick, Michelle Niescierenko, Miriam Aschkenasy, Katherine M. Kemen, Michael Vanrooyen, Paul Biddinger and Hilarie Cranmer

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Intervention – Journal of Mental Health and Psychological Support in Conflict Affected Areas
March 2015 – Volume 13 – Issue 1 pp: 1-102
http://journals.lww.com/interventionjnl/pages/currenttoc.aspx

New Frontiers issue of Intervention
Articles
Surviving juntas (together): lessons of resilience of indigenous Quechua women in the aftermath of conflict in Peru
Suarez, Eliana Barrios

Measuring suffering: assessing chronic stress through hair cortisol measurement in humanitarian settings
Cunningham, Tim

Special Section
Ebola: reflections from the field
Introduction to the Special Section on Ebola: reflections from the field
Tankink, Marian

Personal reflections
Mental health and psychosocial support in the face of Ebola in Liberia: the personal and professional intersect. A personal account
Cooper, Janice L.

The travellers dance: how Ebola prevention measures affect day to day life
Gonzalez, Teresa

Field reports
Mental illness and health in Sierra Leone affected by Ebola: lessons for health workers
Hughes, Peter

An outbreak of fear, rumours and stigma: psychosocial support for the Ebola Virus Disease outbreak in West Africa
Cheung, Eliza Y.L.

Psychosocial support during the Ebola outbreak in Kailahun, Sierra Leone
Garoff, Ferdinand

How to eat an elephant: psychosocial support during an Ebola outbreak in Sierra Leone
Jónasdóttir, Elín

Announcement
Reaching out a helping hand during Ebola: adaptation of the Psychological First Aid guide

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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The Huffington Post
http://www.huffingtonpost.com/
How We Can End the Anti-vaccination Feud
5 March 2015
by John Hewko, General secretary of Rotary International
It is time to move beyond the blame game regarding childhood vaccinations and replace it with honest dialogue and outreach in order to ensure the current measles outbreak — which has infected more than 170 people in 17 states — doesn’t happen again. This follows a record 644 cases in 2014, the highest caseload since the U.S. Centers for Disease Control and Prevention declared that measles had been eliminated in our country in 2000.
Continuing the current tone of confrontation will only aggravate the growing schism between those who refuse vaccinations and those of us who believe vaccines are the public’s best defense against communicable diseases. The real public health solution is to identify common ground and talk to each other…

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New York Times
http://www.nytimes.com/
Accessed 7 March 2015
Last Known Ebola Patient in Liberia Is Discharged
5 March 2015
Liberia’s last Ebola patient was discharged on Thursday after a ceremony in the capital, Monrovia, bringing to zero the number of known cases in the country and marking a milestone in West Africa’s battle against the disease. Officials in Monrovia, the city where the raging epidemic littered the streets with bodies only five months ago, celebrated even as they warned that Liberia was at least weeks away from being officially declared free of Ebola. They also noted that the disease had flared up recently in neighboring Sierra Leone and Guinea, the two other countries hardest hit by it…

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Wall Street Journal
http://online.wsj.com/home-page?_wsjregion=na,us&_homepage=/home/us
Accessed 7 March 2015
Virulent Flu Strain in Europe Hits Economy
Europe’s convalescent economy faces a new burden: an unusually virulent strain of flu that is shutting down schools, stopping commuter trains, and keeping workers and consumers in bed. In Germany, the cost of the epidemic could reach $2.4 billion, according to an economic institute.
Yesterday 11:51:00 AM

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

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– 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.
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David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy
a program of the
– Division of Medical Ethics, NYU Medical School
– The Wistar Institute Vaccine Center
– Children’s Hospital of Philadelphia Vaccine Education Center
Associate Faculty, Division of Medical Ethics, NYU Medical School

EBOLA/EVD [to 28 February 2015]
Public Health Emergency of International Concern (PHEIC); “Threat to international peace and security” (UN Security Council)

WHO: Ebola Situation Report – 25 February 2015
[Excerpt; Editor’s text bolding]
SUMMARY
:: A total of 99 new confirmed cases of Ebola virus disease (EVD) were reported in the week to 22 February. Guinea reported 35 new confirmed cases. Cases continue to arise from unknown chains of transmission. Transmission remains widespread in Sierra Leone, with 63 new confirmed cases. A spike of 20 new confirmed cases in Bombali is linked to the previously reported cluster of cases in the Aberdeen fishing community of the capital, Freetown. There were 14 new confirmed cases in Freetown over the same period, with cases still arising from unknown chains of transmission in Freetown and elsewhere. Transmission continues at very low levels in Liberia, with 1 new confirmed case reported in the 7 days to 22 February: a registered contact associated with a known chain of transmission in the capital, Monrovia.

:: Engaging effectively with communities remains a challenge in several geographical areas. Nearly one-third of prefectures in Guinea reported at least one security incident in the week to 22 February, often as a result of rumours and misinformation linking response efforts with the spread of EVD. A total of 16 new confirmed cases were identified in Guinea and Sierra Leone after post-mortem testing of individuals who died in the community, indicating that a significant number of individuals are still either unable or reluctant to seek treatment. Ideally these individuals would have been identified as contacts associated with known chains of transmission, and have been rapidly diagnosed, isolated, and treated after the initial onset of symptoms. In Guinea and Sierra Leone, 19 and 15 unsafe burials were reported, respectively.

:: Most new cases in Guinea were reported from 3 neighbouring western prefectures: Conakry (6 new confirmed cases), Coyah (8 new confirmed cases), and Forecariah (16 confirmed cases). However, the eastern prefecture of Lola, on the border with Côte d’Ivoire, reported 1 new confirmed case. Case incidence has fluctuated in this prefecture. The northern prefecture of Mali, which borders Senegal, also reported 1 new confirmed case.

:: The steep decline in case incidence nationally in Sierra Leone from December until the end of January has halted. Transmission remains widespread, with 8 districts reporting new confirmed cases. A significant proportion of cases are still arising from unknown chains of transmission.

:: Of laboratories that report results to the relevant ministry of health, between 84% and 98% of laboratory samples were tested within 1 day of collection in the 22 days to 22 February. At present there are no data on how rapidly results are communicated to patients.

:: In the week to 22 February, 3 new health worker infections were reported (2 from Guinea, 1 from Sierra Leone), bringing the total of health worker infections reported since the start of the outbreak to 837, with 490 deaths.

COUNTRIES WITH WIDESPREAD AND INTENSE TRANSMISSION
:: There have been over 23,500 reported confirmed, probable, and suspected cases cases of EVD in Guinea, Liberia and Sierra Leone (table 1), with over 9,500 reported deaths (outcomes for many cases are unknown). A total of 35 new confirmed cases were reported in Guinea, 1 in Liberia, and 63 in Sierra Leone in the 7 days to 22 February….

NIH Watch [to 28 February 2015]
http://www.nih.gov/news/index.html

:: Liberia-U.S. clinical research partnership opens trial to test Ebola treatments
Initial study will evaluate experimental drug cocktail ZMapp
February 27, 2015
In partnership with the Liberian government, the National Institute of Allergy and Infectious Diseases (NIAID) today launched a clinical trial to obtain safety and efficacy data on the investigational drug ZMapp as a treatment for Ebola virus disease. The study, which will be conducted in Liberia and the United States, is a randomized controlled trial enrolling adults and children with known Ebola virus infection.

“Although ZMapp has been used to treat several Ebola-infected patients in recent months, we cannot determine if the drug actually benefitted those patients because it was not administered within the context of a clinical trial,” said Anthony S. Fauci, M.D., director of the NIAID, at the National Institutes of Health (NIH). “This clinical trial will help us determine if ZMapp and other treatments are safe and effective for use in the current devastating outbreak in West Africa as well as in future outbreaks.”…

…All participants will receive the optimized standard of care for treating Ebola infection, which includes providing intravenous fluids, balancing electrolytes, maintaining oxygen status and blood pressure and treating other infections if they occur. Participants will then be assigned randomly to one of two groups: the first group, which will act as the control, will continue to receive the current optimized standard of care. The second group will receive the optimized standard of care plus three separate intravenous infusions of ZMapp administered three days apart. The total dose of ZMapp at each infusion will depend on the weight of the participant. Study participants will be monitored up to 30 days following discharge from the hospital and may return for outpatient visits for additional follow up.

Researchers designed the study protocol to include a series of two-arm comparisons (the first being ZMapp compared to the current standard of care) to establish a framework to evaluate multiple potential Ebola treatments in the future. If one investigational treatment proves to be statistically more effective, it will then become the basis of the new standard of care against which additional investigational Ebola interventions could be tested and compared. Each experimental therapy will be examined in up to 100 participants per arm. If scientists are unable to establish a significant difference after enrolling 100 participants per arm, then that particular treatment will be declared ineffective and scientists will begin testing the next therapy.

These additional treatments may also include the following:
– Tekmira siRNA from Tekmira Pharmaceuticals Corp., based in Burnaby, British Columbia
– Favipiravir from Toyama Chemical Co. LTD, based in Tokyo
– Convalescent or post-immunization plasma collected from recent Ebola infection survivors. It is possible that this category could potentially be expanded to include plasma donors who have participated in Phase 1 Ebola vaccine clinical trials and whose plasma shows high neutralizing activity against the virus.
– BCX4430 from BioCryst, based in Durham, North Carolina
– AVI-7537 from Sarepta, based in Cambridge, Massachusetts…

MSF: Preliminary Results of the JIKI Clinical Trial to test the Efficacy of Favipiravir in Reducing Mortality in Individuals Infected by Ebola Virus in Guinea
February 24, 2015
NEW YORK—Preliminary data from the JIKI clinical trial, which is testing the efficacy of favipiravir in reducing mortality associated with Ebola, provide two important pieces of information:
– absence of efficacy in individuals who arrive at treatment centers with a very high level of viral replication and who already have serious visceral involvement, and
– encouraging signs of efficacy in individuals arriving at treatment centers with a high or moderate level of viral replication, who have not yet developed overly severe visceral lesions.

With this classification into two groups, we have a much better understanding of Ebola virus disease, and can redefine the role of antiviral monotherapies in the therapeutic arsenal used against the disease.

The trial, sponsored by INSERM and funded by the European Commission from the Horizon 2020 Initiative under the project title REACTION, is supported by two NGOs, Doctors Without Borders/Médecins Sans Frontières (MSF) and Alliance for International Medical Action (ALIMA); two laboratory networks, Belgian First Aid and Support Team (B-FAST) and European Mobile Laboratory (EMLab); the French Red Cross, and the French Military Health Service.

These preliminary data are being presented on Wednesday, February 25, as a late-breaking abstract at the CROI international conference (Conference on Retroviruses and Opportunistic Infections) in Seattle.

Given the high mortality associated with Ebola virus despite high-quality symptomatic treatment, study of specific innovative therapeutic agents is essential. Potentially useful drugs against the virus include favipiravir (T-705), an antiviral drug already tested against influenza virus in adult humans (and well tolerated). The latter (no more than other potential treatments) has never been tested in humans for treating Ebola, but its efficacy has been demonstrated in vitro and in mice.

As part of the mission given to Aviesan to organize the research as a matter of urgency, the JIKI clinical trial, a phase II multicentre non-comparative trial, began in Guinea on December 17, 2014, to test the ability of favipiravir to reduce mortality in individuals infected by Ebola virus.

Sponsored by INSERM, and jointly funded by the European Commission, the JIKI trial is being conducted in partnership with MSF, ALIMA, the French Red Cross, EMLab, B-Fast and the French Military Health Service, and is taking place in four Ebola treatment centers in Guékédou (MSF), Nzérékoré (ALIMA), Macenta (French Red Cross) and Conakry (carers’ treatment centre).

In these centers, adults and children over one year of age with a positive Ebola PCR test who agree to take part (parental consent in the case of minors) receive treatment with favipiravir for 10 days along with basic care. Favipiravir comes in the form of 20 mg tablets (the tablets can be dissolved in a drink) and is administered according to the following dose regimen[1]:
– Adults: Day 0: 2,400 mg at H0, 2,400 mg at H8 and 1,200 mg at H16, then 1,200 mg twice a day for nine days;
– Children: doses adjusted to body weight.

The JIKI trial is being followed by an independent monitoring committee, which met on December 11, 2014, and on January 5, January 14, and January 26, 2015. At this last meeting, the committee authorized the investigators to publish the interim data, which they judged to contain messages that should be quickly shared with the international community. These messages, obtained from the first 80 participants (69 adolescents or adults, and 11 children) are as follows:
– 42 percent of participants arrived at the treatment centers with a strongly positive PCR test (cycle threshold value, CT, < 20), reflecting a very high viral load[2]. Of these patients, 81 percent had refractory renal failure and 93 percent died. In the three months preceding the trial, mortality among individuals presenting with the same features was 85 percent. Comparison of the trial and pretrial data shows that it is highly unlikely that favipiravir monotherapy will ultimately be proven to reduce mortality in this population with advanced disease.
– 58 percent of participants arrived in the treatment centers with a cycle threshold (CT) ≥ 20, reflecting a high or moderate viral load. Of these patients, 42 percent had renal failure, but only 15 percent died. In the three months preceding the trial, mortality among individuals presenting with a CT ≥ 20 was 30 percent. Comparison of the trial and pretrial data therefore leads us to hope that favipiravir monotherapy may reduce mortality in this population with less advanced disease.

For the researchers, these preliminary data encourage us:
– to continue the trial while trying to provide favipiravir treatment as soon as possible after the symptoms appear, so as to treat patients in whom viral multiplication can be controlled, and who have not yet developed visceral lesions (especially renal lesions);
– to explore other therapeutic options for patients who come to the treatment centers when their disease is too far advanced.

Yves Levy, the chairman and CEO of INSERM said: “The results of this non-comparative trial have to be confirmed using a larger number of patients. However, they open up other therapeutic opportunities in drug combinations, in particular for the treatment of patients suffering from more advanced stages of this disease. They also clearly show that research plays an essential role in tackling such epidemics. I would also like to stress that without the excellent Guinean-French cooperation, the pioneering role of MSF in this research, the fruitful partnerships with all NGOs involved, and the European Commission’s responsiveness, this progress could not have been accomplished.”

Commissioner Moedas said: “I am excited about the encouraging results of one of our EU-funded projects to tackle Ebola. We have preliminary evidence that the antiviral drug favipiravir may be effective against early Ebola disease. If these results are confirmed by the ongoing clinical trial, it will be the first-ever treatment to be deployed against this deadly disease during the current outbreak. These results show the success of the European Commission’s quick reaction to the Ebola outbreak to support urgent research on several potential treatments and vaccines against Ebola with funding from our Horizon 2020 research program. This is an astounding example of what the best brains can achieve with EU support when there is so much at stake. It shows how EU funding can lead to discoveries that save people’s lives and which are the result of rapid EU, international, and industry cooperation.”

According to Agustin Augier, Secretary-General of Alima, “Those positive results will reinforce the confidence between affected populations and the treatment center. This therapeutic solution, even if partial, will significatively attract ebola patients to the treatment center. It is a significant step towards tackling the outbreak in the villages where it still goes on.”

“MSF is pleased to see that favipiravir seems to have a positive effect for certain patients suffering from Ebola Viral Disease (EVD). But it also seems that the most vulnerable patients, the people that are most likely to die from the disease, don’t benefit at all from favipiravir. That fact, and the fact that these are only preliminary results, show that it is really too soon to start using favipiravir outside a trial environment. Research into favipiravir, and into other potential treatments for EVD, must be continued, and MSF is willing to play a role in these clinical trials,” says Dr. Bertrand Draguez, medical director of MSF.

[1] Details of this dose regimen are the subject of a publication in the journal The Lancet Infectious Diseases.
[2] In the laboratories taking part in the trial, a CT < 20 is equivalent to a viral load of over 108 copies of the virus per ml of blood.

CDC/MMWR Watch [to 28 February 2015]
http://www.cdc.gov/media/index.html

:: MMWR Weekly, February 27, 2015 / Vol. 64 / No. 7
– Rapid Intervention to Reduce Ebola Transmission in a Remote Village — Gbarpolu County, Liberia, 2014
– Community Quarantine to Interrupt Ebola Virus Transmission — Mawah Village, Bong County, Liberia, August–October, 2014
– Implementation of Ebola Case–Finding Using a Village Chieftaincy Taskforce in a Remote Outbreak — Liberia, 2014
– Update: Ebola Virus Disease Epidemic — West Africa, February 2015
– Rapid Response to Ebola Outbreaks in Remote Areas — Liberia, July–November 2014

African Union [to 28 February 2015]
http://www.au.int/en/
Feb.24.2015
:: African Unions Welcomes Back the First Group of its Heroines and Heroes in the Fight Against Ebola
Addis Ababa, 24 February 2014- 17 ASEOWA (African Union Support to the Ebola Outbreak in West Africa) health workers, who were the first to be deployed to fight Ebola, returned from Liberia on 22nd February, upon completion of their tour of duty and were welcomed back by the Chairperson of the African Union Commission Dr Nkosazana Dlamini Zuma.
Attending the meeting were the AUC Commissioner for Social Affairs Dr Mustapha Sidiki Kaloko, the Director of Social Affairs Dr Olawale Maiyegun, ambassadors from the health workers’ member states and a representative from Liberia. It was a unique event- the first time ever that the AU had welcomed back heroines and heroes in the fight against Ebola, and, without any infections among the health workers.
Dr Dlamini Zuma thanked the health workers for their pioneering role and assured them that the AU’s is determined to defeat Ebola: “You personified Pan Africanism and solidarity. The African Union will stay the course until the affected countries are declared Ebola free. We are very happy that you undertook this mission”, she told them.
All returnees were awarded certificates of service in recognition of their contribution to the fight against Ebola and their selfless dedication. The returnees were from Nigeria, Rwanda, Ethiopia, Uganda and the Democratic Republic of Congo. Among them were doctors, hygienists and communications experts. One of them was a trainer of other medical personnel in the treatment of Ebola patients….

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World Bank [to 28 February 2015]
http://www.worldbank.org/en/news/all
:: Ebola: World Bank and Liberia to Work with Japan to Launch a Psychological Support Project
Some 18,000 Beneficiaries to Receive Mental Health and Psychosocial Support to Alleviate Consequences of Epidemic
MONROVIA, February 25, 2015 – The Liberian Government and the World Bank Group in partnership with the Government of Japan, today launched a new $3 million project to address the psychological effects of Liberia’s Ebola crisis and to promote psychosocial health in the country. The ceremony was held at the World Bank Liberia Office.The project, Supporting Psychosocial Health and Resilience in Liberia, is funded by Japan through the Japanese Social Development Fund (JSDF), a trust fund administered by the World Bank. The Carter Center will implement this three-year project, which is expected to reach approximately 18,000 beneficiaries in Montserrado (hosting Monrovia) and Margibi counties.
Date: February 25, 2015

:: Households Begin Returning To Work in Liberia as Ebola Crisis Wanes
Long-term welfare remains a concern as country moves toward economic recovery
WASHINGTON, February 24, 2015— Nearly 20 percent of the Liberians who had stopped working since the Ebola crisis have returned to work in the last month, according to the World Bank Group’s most recent round of cell-phone surveys, signaling both important progress and the magnitude of the challenge ahead. This improvement, an encouraging sign of a shift toward economic normalization, was mainly driven by a large increase in wage work in urban areas. A substantial percentage of those working pre-crisis remain out of work, however; those in self-employment continue to be the hardest hit by the Ebola crisis, pointing to a lack of working capital and a lack of customers as the main barriers to their operation. As the pressing health crisis in Liberia slows, it will be important to identify and support those who are most vulnerable to a sluggish economy…
Date: February 24, 2015

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USAID [to 28 February 2015]
http://www.usaid.gov/news-information/press-releases
:: USAID Announces Education Crisis Response Program in Liberia
February 25, 2015
The U.S. Agency for International Development (USAID) announced the $18.7 million Education Crisis Response program today to assist the Government of Liberia in restoring basic education in the Ebola-affected country and help return children to school safely. The program was announced today while Liberian President Ellen Johnson Sirleaf visited with staff from USAID.

:: U.S. Government Launches President’s Malaria Initiative Next Six-Year Strategy for 2015-2020
February 25, 2015
The U.S. President’s Malaria Initiative, led by the U.S. Agency for International Development and implemented together with the Centers for Disease Control and Prevention (CDC), launched its next six-year strategy to further reduce malaria deaths and substantially decrease malaria illness, toward the long-term goal of elimination at the White House today.

POLIO [to 28 February 2015]
Public Health Emergency of International Concern (PHEIC)

GPEI Update: Polio this week – As of 25 February 2014
Global Polio Eradication Initiative
[Editor’s Excerpt and text bolding]
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: The fourth meeting of the International Health Regulations Emergency Committee concerning the international spread of wild poliovirus was convened last week. Outcomes and the Committee’s final report will be made available on www.polioeradication.org

Selected country report content:
Afghanistan
:: One new case of wild poliovirus type 1 (WPV1) has been reported in the past week in Reg district, Hilmand province. This was the first case reported in 2015, with onset of paralysis on 21 January. The total number of WPV1 cases for 2014 remains 28. Most of the cases from 2014 were linked to cross-border transmission with neighbouring Pakistan.
Pakistan
:: Two new wild poliovirus type 1 (WPV1) cases were reported in the past week. One case was reported in Khyber district in the Federally Administered Tribal Areas, and the other in Peshawar, in Khyber Pakhtunkhwa. The total number of WPV1 cases in 2014 remains 306, and 9 for 2015. The most recent onset of paralysis was on 31 January in Peshawar.
:: A panel of experts was convened on 14 – 15 February for a consultation to review the current epidemiological situation and the status of implementation of the existing ‘low transmission season’ polio eradication plan. With 8 weeks remaining until the end of the low season, the panel urged that Emergency Operations Centres continue strengthening the roll-out of the plan and that, at the provincial level, teams more completely and accurately track its’ implementation.
West Africa
:: Even as polio programme staff across West Africa help to control the Ebola outbreak affecting the region, efforts are being made in those countries not affected by Ebola to vaccinate children against polio to create a buffer zone surrounding the affected countries. The Ebola crisis in western Africa continues to have an impact on the implementation of polio eradication activities in Liberia, Guinea and Sierra Leone. Twenty two experts from the National Polio Surveillance Programme (NPSP) in India have been deployed for 3 months to strengthen surveillance systems and data collection for the Ebola response, demonstrating the polio legacy in action.

WHO & Regionals [to 28 February 2015]

:: Health crises in Central African Republic, Iraq, South Sudan and Syria need US$1 billion
24 February, 2015 Geneva – Raging conflict and beleaguered health services are threatening the health of tens of millions of people across the Central African Republic, Iraq, South Sudan and Syria. To respond, the World Health Organization today called on the international community to provide $US1 billion to support its on-going efforts – and those of partners – to treat, immunize and provide the wide range of life-saving health services needed to populations in need.
– Read the full news release on WHO’s increased funding needed to meet health needs
– More information on Central African Republic
– More information on Iraq
– More information on South Sudan
– More information on Syrian Arabic Republic

:: Warning signals from the volatile world of influenza viruses
26 February 2015 — The current global influenza situation is characterized by a number of trends that must be closely monitored. These include: an increase in the variety of animal influenza viruses co-circulating and exchanging genetic material, giving rise to novel strains; continuing cases of human H7N9 infections in China; and a recent spurt of human H5N1 cases in Egypt. Changes in the H3N2 seasonal influenza viruses, which have affected the protection conferred by the current vaccine, are also of particular concern

:: WHO/Europe calls for scaled-up vaccination against measles
Over 22 000 cases reported in Europe in 2014–2015
Copenhagen, 25 February 2015
The WHO Regional Office for Europe calls on policy-makers, health care workers and parents immediately to step up vaccination against measles across age groups at risk. This will help to put an end to the outbreaks occurring in countries in the WHO European Region and to prevent similar outbreaks in the future.
Seven countries in the Region have reported 22 567 cases of measles in 2014 and thus far in 2015. This threatens the Region’s goal of eliminating the disease by the end of 2015. Even though measles cases fell by 50% from 2013 to 2014, large outbreaks continue.
“When we consider that over the past two decades we have seen a reduction of 96% in the number of measles cases in the European Region, and that we are just a step away from eliminating the disease, we are taken aback by these numbers. We must collectively respond, without further delay, to close immunization gaps,” says Dr Zsuzsanna Jakab, WHO Regional Director for Europe. “It is unacceptable that, after the last 50 years’ efforts to make safe and effective vaccines available, measles continues to cost lives, money and time.”…

:: Global Alert and Response (GAR): Disease Outbreak News (DONs)
– 26 February 2015 Human infection with avian influenza A(H7N9) virus – China
– 26 February 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia

:: GIN February 2015

:: The Weekly Epidemiological Record (WER) 27 February 2015, vol. 90, 09 (pp. 69–88) includes:
– Japanese Encephalitis Vaccines: WHO position paper – February 2015
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:: WHO Regional Offices
WHO African Region AFRO
:: WHO identifying innovative ways to strengthen immunization services in Central Africa – 26 February 2015
Douala, 25 February 2015 –- The World Health Organization (WHO) Inter-country Support Team (IST) for Central Africa is convening its Expanded Programme on Immunization (EPI) Managers’ meeting in Douala, Cameroon from 23 to 27 February 2015 to strengthen and improve access to immunization services in 10 countries in Central Africa.
:: Kenya hosts commemoration to accelerate comprehensive implementation of WHO FCTC in the African Region – 25 February 2015

WHO Region of the Americas PAHO
:: Tobacco: 10 years fighting a top killer in the Americas (02/26/2015)

:: PAHO/WHO supports CDC-led effort to eliminate malaria on Hispaniola by 2020 (02/25/2015)

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

WHO European Region EURO
:: WHO/Europe calls for scaled-up vaccination against measles 25-02-2015

WHO Eastern Mediterranean Region EMRO
:: WHO supports tax increase on cigarettes in Egypt 26 February 2015

:: Save lives: Recommit to implementing WHO’s Framework Convention on Tobacco Control  26 February 2015

:: More progress needed to control the Middle East respiratory syndrome coronavirus (MERS-COV) in Saudi Arabia
23 February 2015
Riyadh, Saudi Arabia | 23 February 2015 – A team of experts from the World Health Organization (WHO), the UN’s Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE) and Institut Pasteur, France concluded a mission to Saudi Arabia to assess the current situation of the Middle East respiratory syndrome (MERS-CoV) following a surge of cases in the past few weeks and to make recommendations for improving the surveillance, prevention and control of the virus. Already this month, more than 50 cases have been reported in several locations in the Kingdom, including infections acquired in health facilities (called nosocomial infections) in Riyadh, Qassim Region and Damman City, eastern region
Members of the joint mission held discussions with high-level representatives from the Ministry of Health, visited the Command and Control Centre that has been leading all activities related to the control of the MERS-CoV, and toured the emergency and isolation facilities of the Prince Mohammed Bin Abdulaziz Hospital. Government officials and the WHO-led mission shared their concern about the rising number of MERS-CoV cases in recent weeks and in particular in health care facilities….
…The mission, along with the Saudi Arabian health authorities, identified main areas that should be urgently addressed:
– Understanding the animal/human interface, that is, modes of infection and transmission;
– Filling critical knowledge gaps in the science and epidemiology of MERS-CoV by conducting further research studies and by sharing the findings widely and rapidly;
– Improving disease prevention, especially in health facilities that continue to experience avoidable infections;
– Intensifying social mobilization, community engagement activities and communications. The mission also stressed the need for intersectoral cooperation and coordination, especially between health, agriculture, and other sectors….

WHO Western Pacific Region
No new digest content identified.

Global Fund Watch [to 28 February 2015]
http://www.theglobalfund.org/en/mediacenter/

:: Global Health Partners Begin Building a New Approach to Ensure Equitable Access to Medicines
26 February 2015
Global health partners met in Geneva to begin the process of building a new approach to better determine health needs and constraints and addressing them in countries.

The new framework, the Equitable Access Initiative, aims to better inform international decision making processes on health and development, particularly where they rely on traditional gross-national-income classification as a measure of where to invest global health resources.

Relying solely on gross national income to determine investment priorities in global health has been increasingly questioned by partners.

Economic growth is lifting many countries from low- to middle-income status, yet those classifications and criteria may be too simple to capture overall needs and capacities.
Countries classified as middle-income are often in need of substantial resources to respond to disease burden, as a steadily larger percentage of those affected by the diseases live in middle-income countries.

Participants in the meeting discussed how the absence of new strategies to ease the transition of countries from low-income to middle-income status has led to a substantial risk of countries not being able to maintain or improve health outcomes. The initial meeting of the Equitable Access initiative was held on 23 February 2015 and co-chaired by Pascal Lamy, the Honorary President of Notre Europe, and Donald Kaberuka, the President of African Development Bank Group. The meeting, hosted by the WHO, was co-convened by Gavi, the Vaccine Alliance; The Global Fund to fight AIDS, TB, Malaria; UNAIDS; UNICEF; UNDP; UNFPA; UNITAID; WHO and the World Bank.

The meeting looked at a process of engagement that may culminate in recommendations on how to support countries as they make vital health investments as they transition from low-income to middle-income status.

The Equitable Access Initiative seeks to establish a new way to measure a country’s health needs and capacities, aimed towards sustainability, and in addition to propose nuanced health classifications that go beyond traditional economic metrics such as national income levels and are more relevant for better health outcomes. The initiative will be firmly grounded in human rights and will uphold the need for zero discrimination in access to medicines.

WIPO Re:Search Gains Momentum in the Fight Against Neglected Tropical Diseases, Malaria and Tuberculosis
World Intellectual Property Organization
Geneva, February 26, 2015 – PR/2015/773

WIPO Re:Search signed on more than a dozen new members in 2014, including two leading pharmaceutical firms, and nearly doubled the number of research agreements using shared intellectual property to promote the fight against neglected tropical diseases, tuberculosis and malaria.

During WIPO Re:Search’s third full year of operation, the consortium welcomed 14 new members including Merck KGaA and Kineta Inc., as well as six institutions from the developing world, where the targeted diseases are most prevalent.

As 2014 closed, 82 collaborations were in place among the 94 members, including 38 new agreements, nearly doubling the numbers of managed partnerships and surpassing the goal of 15 new agreements for the year.

“We are very pleased with the level of engagement and interest in WIPO Re:Search by the various providers and users,” said WIPO Director General Francis Gurry. “We are hopeful that these positive results will continue to grow in the coming years and lead to outcomes to alleviate the huge burden of neglected tropical diseases on already vulnerable populations.”

WIPO Re:Search allows organizations to share their intellectual property, compounds, expertise, facilities and know-how royalty-free with qualified researchers worldwide working on new solutions for these maladies, which affect more than one billion people across the globe.

Malaria and tuberculosis represented 44% of all partnerships established by the end of 2014. Other collaboration cover an additional 12 neglected tropical diseases, with drug discovery continuing to be the primary focus of agreements established in 2014.

Industry Watch [to 28 February 2015]
:: Merck’s 9-Valent HPV Vaccine, GARDASIL®9, Recommended by CDC’s Advisory Committee on Immunization Practices for Females Aged 9-26 and Males Aged 9-21
February 26, 2015

:: CDC Advisory Committee on Immunization Practices Votes to Recommend Serogroup B Meningococcal Disease Vaccination for Persons at Increased Risk [Pfizer]
February 26, 2015

:: Pfizer Announces Positive Top-line Results Of A Phase 2 Study Of TRUMENBA® (Meningococcal Group B Vaccine) Co-Administered With Routine Meningococcal (A, C, Y, and W) And Tetanus, Diptheria And Pertussis (Tdap) Vaccines In Adolescents
February 24, 2015

:: Sanofi joins Be He@lthy, Be Mobile initiative
Partnership harnessing power of ICTs to deliver health-care solutions
Geneva, 26 February 2015 – Multinational pharmaceutical firm Sanofi has joined the International Telecommunication Union’s Be He@lthy, Be Mobile initiative, which ITU leads in collaboration with the World Health Organization (WHO).
Be He@lthy Be Mobile partners include Bupa, Verizon, The World Lung Foundation, the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), the Non-Communicable Disease (NCD) Alliance, Novartis and GSK. Participating organizations are currently contributing to the initiative through funds, in-kind contributions and knowledge, as well as supporting country projects. They will join forces to provide multidisciplinary expertise, health information and mobile technology to fight chronic non-communicable diseases (NCDs), including diabetes, cancer, cardiovascular and chronic respiratory diseases, in low- and middle-income countries…

Ranking Vaccines: Applications of a Prioritization Software Tool: Phase III: Use Case Studies and Data Framework (2014)
Authors: Guruprasad Madhavan; Charles Phelps; Rino Rappuoli; Rose Marie Martinez; Lonnie King; Committee on Identifying and Prioritizing New Preventive Vaccines for Development, Phase III; Board on Population Health and Public Health Practice; Board on Global Health; Institute of Medicine; National Research Council
February 20145 :: 128 pages :: Download pdf: https://www.nap.edu/login.php?record_id=18763&page=http%3A%2F%2Fwww.nap.edu%2Fdownload.php%3Frecord_id%3D18763

Description
SMART Vaccines – Strategic Multi-Attribute Ranking Tool for Vaccines – is a prioritization software tool developed by the Institute of Medicine that utilizes decision science and modeling to help inform choices among candidates for new vaccine development. A blueprint for this computer-based guide was presented in the 2012 report Ranking Vaccines: A Prioritization Framework: Phase I. The 2013 Phase II report refined a beta version of the model developed in the Phase I report.

Ranking Vaccines: Applications of a Prioritization Software Tool: Phase III: Use Case Studies and Data Framework extends this project by demonstrating the practical applications of SMART Vaccines through use case scenarios in partnership with the Public Health Agency of Canada, New York State Department of Health, and the Serum Institute of India. This report also explores a novel application of SMART Vaccines in determining new vaccine product profiles, and offers practical strategies for data synthesis and estimation to encourage the broader use of the software.

American Journal of Infection Control
March 2015 Volume 43, Issue 3, p199-312
http://www.ajicjournal.org/current

Commentary
Nebraska Biocontainment Unit patient discharge and environmental decontamination after Ebola care
Katelyn C. Jelden, Shawn G. Gibbs, Philip W. Smith, Michelle M. Schwedhelm, Peter C. Iwen, Elizabeth L. Beam, A. Kim Hayes, Nedra Marion, Christopher J. Kratochvil, Kathleen C. Boulter, Angela L. Hewlett, John J. Lowe
p203–205
Published online: January 27, 2015
Preview
The Nebraska Biocontainment Unit (NBU), which operates through collaboration of Nebraska Medicine, the University of Nebraska Medical Center, and the Nebraska Department of Health and Human Services, recently treated patients with Ebola virus disease (EVD) evacuated from West Africa to the United States. EVD is transmitted by contact with infected blood or bodily fluids with an infectious dose of <10 viruses and high virus concentrations in blood 108 virus particles/mL.1 Although negative for virus by molecular testing (quantitative polymerase chain reaction [qPCR] assay), discharged NBU patients successfully treated for EVD are at risk of touching EVD contaminated surfaces within the patient room and may serve as a disease vector to areas outside of isolation on discharge from the unit.

Infection prevention and mass vaccination training for U.S. point of dispensing staff and volunteers: A national study
Terri Rebmann, Travis M. Loux, Thomas K. Zink, Zachary Swick, Mary Wakefield
p222–227
Published online: January 27, 2015
Preview
Points of dispensing (PODs) are deployed for medical countermeasure mass dispensing. However, infection prevention and vaccine administration pre-event training offered and just-in-time (JIT) education planned for POD workers have not been assessed.

Employee influenza vaccination in a large cancer center with high baseline compliance rates: Comparison of carrot versus stick approaches
Sara Podczervinski, Zach Stednick, Lois Helbert, Judith Davies, Barbara Jagels, Ted Gooley, Corey Casper, Steven A. Pergam
p228–233
Preview
Influenza is a major complication in patients with cancer and hematopoietic cell transplant recipients. We set out to maximize influenza vaccination rates in health care personnel at our large ambulatory cancer center with high baseline compliance and to assess alternatives to mandatory policies.

Geospatial patterns in influenza vaccination: Evidence from uninsured and publicly insured children in North Carolina
Justin G. Trogdon, Thomas Ahn
p234–240
Published online: January 27, 2015
Highlights
– Our study explores spatial patterns in influenza vaccination among children.
– ZIP codes tend to have influenza vaccination rates similar to neighboring ZIP codes.
– Clustering is partially, but not wholly, explained by area characteristics.
– Spatial targeting of vaccination could reduce the spread of pandemic influenza.
Abstract
Background
The purpose of this study was to explore geospatial patterns in influenza vaccination.
Methods
We conducted an ecological analysis of publicly funded influenza vaccinations at the ZIP code tabulation area (ZCTA) level using secondary data for publicly funded influenza vaccinations among eligible school-aged children (age range, 5-17 years) for the 2010-2011 and 2011-2012 influenza seasons from the North Carolina Immunization Registry (NCIR). NCIR data were merged by ZCTA with other publicly available data. We tested for spatial autocorrelation in unadjusted influenza vaccination rates using choropleth maps and Moran’s I. We estimated nonspatial and spatial negative binomial models with spatially correlated random effects adjusted for demographic, economic, and health care variables. The study was conducted at the University of North Carolina at Chapel Hill in the spring of 2014.
Results
The NCIR demonstrated spatial autocorrelation in publicly funded influenza vaccinations among uninsured and means-tested, publicly insured school-aged children; ZCTAs tended to have influenza vaccination rates that were similar to their neighbors. This result was partially explained by included ZCTA characteristics, but not wholly.
Conclusion
To the extent that the geospatial clustering of vaccination rates is the result of social influences, targeting interventions to increase influenza vaccination among school-aged children in one area could also lead to increases in neighboring areas.

BMC Infectious Diseases
http://www.biomedcentral.com/bmcinfectdis/content
(Accessed 28 February 2015)

Research article
Effectiveness of rotavirus vaccines, licensed but not funded, against rotavirus hospitalizations in the Valencia Region, Spain
Silvia Pérez-Vilar1, Javier Díez-Domingo1*, Mónica López-Lacort1, Sergio Martínez-Úbeda1 and Miguel Á Martínez-Beneito23
Author Affiliations
BMC Infectious Diseases 2015, 15:92 doi:10.1186/s12879-015-0811-5
Published: 25 February 2015
Abstract (provisional)
Background
Although rotavirus vaccines have been licensed in Spain for over 8 years, they are not funded by its public health systems. The analysis of their effectiveness in the Valencia Region could better inform decisions about potential inclusion in the official immunization schedule. Our aim was to assess the effectiveness of Rotarix® (RV1) and RotaTeq® (RV5) against rotavirus hospitalizations.
Methods
We conducted a retrospective cohort study using the region’s health care databases, among resident children aged &lt;3 years covered by the National Health System, during January 2007-June 2012. We compared two cohorts of vaccinated children: the first included children who received at least one dose of a rotavirus vaccine, and the second included children who were not vaccinated with rotavirus vaccines but received at least one dose of a pneumococcal vaccine, another licensed but non-funded vaccine. The main outcome was rotavirus hospitalization, either laboratory-confirmed (confirmed) or codified as rotavirus (probable). Rotavirus vaccine effectiveness (RVE) by vaccine brand was assessed using Cox proportional hazards models.
Results
The study included 78,281 rotavirus and 96,643 pneumococcal vaccinees. Adjusted RVE against probable or confirmed rotavirus hospitalizations was 86% (95% CI: 78-91%) and 88% (95% CI: 81-92%) for a complete series of RV1 and RV5 respectively.
Conclusions
Both rotavirus vaccines were over 85% effective against rotavirus hospitalization among young children. The high effectiveness shown argues in favor of their inclusion in the official schedule. Additional information on rotavirus vaccine safety, duration of protection, and benefit-risk will also be needed to inform such deliberations.

BMC Medical Ethics
(Accessed 28 February 2015)
http://www.biomedcentral.com/bmcmedethics/content

Debate
Innovations in research ethics governance in humanitarian settings
Doris Schopper12*, Angus Dawson3, Ross Upshur4, Aasim Ahmad56, Amar Jesani7, Raffaella Ravinetto89, Michael J Segelid10, Sunita Sheel11 and Jerome Singh12
Author Affiliations
BMC Medical Ethics 2015, 16:10 doi:10.1186/s12910-015-0002-3
Published: 26 February 2015
Abstract (provisional)
Background
Médecins Sans Frontières (MSF) is one of the world’s leading humanitarian medical organizations. The increased emphasis in MSF on research led to the creation of an ethics review board (ERB) in 2001. The ERB has encouraged innovation in the review of proposals and the interaction between the ERB and the organization. This has led to some of the advances in ethics governance described in this paper.
Findings
We first update our previous work from 2009 describing ERB performance and then highlight five innovative practices:
• A new framework to guide ethics review
• The introduction of a policy exempting a posteriori analysis of routinely collected data
• The preapproval of “emergency” protocols • General ethical approval of “routine surveys”
• Evaluating the impact of approved studies
The new framework encourages a conversation about ethical issues, rather than imposing quasi-legalistic rules, is more engaged with the specific MSF research context and gives greater prominence to certain values and principles. Some of the innovations implemented by the ERB, such as review exemption or approval of generic protocols, may run counter to many standard operating procedures. We argue that much standard practice in research ethics review ought to be open to challenge and revision. Continued interaction between MSF researchers and independent ERB members has allowed for progressive innovations based on a trustful and respectful partnership between the ERB and the researchers. In the future, three areas merit particular attention.
First, the impact of the new framework should be assessed. Second, the impact of research needs to be defined more precisely as a first step towards being meaningfully assessed, including changes of impact over time. Finally, the dialogue between the MSF ERB and the ethics committees in the study countries should be enhanced.
Conclusions
We hope that the innovations in research ethics governance described may be relevant for other organisations carrying out research in fragile contexts and for ethics committees reviewing such research.

BMC Public Health
(Accessed 28 February 2015)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Diarrhea and health inequity among Indigenous children in Brazil: results from the First National Survey of Indigenous People’s Health and Nutrition
Ana Lúcia Escobar1, Carlos EA Coimbra2*, James R Welch2, Bernardo L Horta3, Ricardo Ventura Santos24 and Andrey M Cardoso2
Author Affiliations
BMC Public Health 2015, 15:191 doi:10.1186/s12889-015-1534-7
Published: 27 February 2015
Abstract (provisional)
Background
Globally, diarrhea is the second leading cause of death among children under five. In Brazil, mortality due to diarrhea underwent a significant reduction in recent decades principally due to expansion of the primary healthcare network, use of oral rehydration therapy, reduced child undernutrition, and improved access to safe drinking water. The First National Survey of Indigenous People’s Health and Nutrition in Brazil, conducted in 2008–2009, was the first survey based on a nationwide representative sample to study the prevalence of diarrhea and associated factors among Indigenous children in the country.
Methods
The survey assessed the health and nutritional status of Indigenous children &lt; 5 years of age based on a representative sample of major Brazilian geopolitical regions. A stratified probabilistic sampling was carried out for Indigenous villages. Within villages, children &lt; 5 years of age in sampled households were included in the study. Interviews were based on a seven day recall period. Prevalence rates of acute diarrhea were calculated for independent variables and hierarchical multivariable analyses were conducted to assess associations.
Results
Information on diarrhea was obtained for 5,828 children (95.1% of the total sample). The overall prevalence of diarrhea was 23.5%. Regional differences were observed, with the highest rate being in the North (38.1%). Higher risk of diarrhea was observed among younger children and those who had less maternal schooling, lower household socioeconomic status, undernutrition (weight-for-age deficit), presence of another child with diarrhea in the household, and occurrence of upper respiratory infection.
Conclusions
According to results of the First National Survey of Indigenous People’s Health and Nutrition, almost a quarter of Indigenous children throughout the country had diarrhea during the previous week. This prevalence is substantially higher than that documented in 2006 for Brazilian children &lt; 5 years generally (9.4%). Due to its exceedingly multicausal nature, the set of associated variables that remained associated with child diarrhea in the final multivariable model provide an excellent reflection of the diverse social and health inequities faced by Indigenous peoples in contemporary Brazil.

Research article
Public preferences for vaccination and antiviral medicines under different pandemic flu outbreak scenarios
Helena Rubinstein1, Afrodita Marcu2, Lucy Yardley2 and Susan Michie1*
Author Affiliations
BMC Public Health 2015, 15:190 doi:10.1186/s12889-015-1541-8
Published: 27 February 2015
Abstract (provisional)
Background
During the 2009-2010 A(H1N1) pandemic, many people did not seek care quickly enough, failed to take a full course of antivirals despite being authorised to receive them, and were not vaccinated. Understanding facilitators and barriers to the uptake of vaccination and antiviral medicines will help inform campaigns in future pandemic influenza outbreaks. Increasing uptake of vaccines and antiviral medicines may need to address a range of drivers of behaviour. The aim was to identify facilitators of and barriers to being vaccinated and taking antiviral medicines in uncertain and severe pandemic influenza scenarios using a theoretical model of behaviour change, COM-B.
Methods
Focus groups and interviews with 71 members of the public in England who varied in their at-risk status. Participants responded to uncertain and severe scenarios, and to messages giving advice on vaccination and antiviral medicines. Data were thematically analysed using the theoretical framework provided by the COM-B model.
Results
Influences on uptake of vaccines and antiviral medicines – capabilities, motivations and opportunities – are part of an inter-related behavioural system and different components influenced each other. An identity of being healthy and immune from infection was invoked to explain feelings of invulnerability and hence a reduced need to be vaccinated, especially during an uncertain scenario. The identity of being a ‘healthy person’ also included beliefs about avoiding medicine and allowing the body to fight disease ‘naturally’. This was given as a reason for using alternative precautionary behaviours to vaccination. This identity could be held by those not at-risk and by those who were clinically at-risk.
Conclusions
Promoters and barriers to being vaccinated and taking antiviral medicines are multi-dimensional and communications to promote uptake are likely to be most effective if they address several components of behaviour. The benefit of using the COM-B model is that it is at the core of an approach that can identify effective strategies for behaviour change and communications for the future. Identity beliefs were salient for decisions about vaccination. Communications should confront identity beliefs about being a ‘healthy person’ who is immune from infection by addressing how vaccination can boost wellbeing and immunity.

Research article
Child survival and BCG vaccination: a community based prospective cohort study in Uganda
Victoria Nankabirwa12*, James K Tumwine3, Proscovia M Mugaba3, Thorkild Tylleskär4, Halvor Sommerfelt25 and for the PROMISE- EBF Study Group
Author Affiliations
BMC Public Health 2015, 15:175 doi:10.1186/s12889-015-1497-8
Published: 22 February 2015
Abstract
Background
Data on non-specific effects of BCG vaccination in well described, general population African cohorts is scanty. We report the effects of BCG vaccination on post-neonatal infant and post-infancy mortality in a cohort of children in Mbale, Eastern Uganda.
Methods
A community-based prospective cohort study was conducted between January 2006 and February 2014. A total of 819 eligible pregnant women were followed up for pregnancy outcomes and survival of their children up to 5 years of age. Data on the children’s BCG vaccination status was collected from child health cards at multiple visits between 3 weeks and 7 years of age. Data was also collected on mothers’ residence, age, parity, household income, self-reported HIV status as well as place of birth. Multivariable Cox proportional hazards regression models taking into account potential confounders were used to estimate the association between BCG vaccination and child survival.
Results
The neonatal mortality risk was 22 (95% CI: 13, 35), post-neonatal infant mortality 21 (12, 34) per 1,000 live births and the mortality risk among children between 1 and 5 years of age (post-infancy) was 63 (47, 82) per 1,000 live births. The median age at BCG vaccination was 4 days. Out of 819 children, 647 (79%) had received the BCG vaccine by 24 weeks of age. In the adjusted analysis, the rate of post-neonatal death among infants vaccinated with BCG tended to be nearly half of that among those who had not received the vaccine (adjusted HR: 0.47; 95% CI: 0.14, 1.53). BCG vaccination was associated with a lower rate of death among children between 1 and 5 years of age (adjusted HR: 0.26; 95% CI: 0.14, 0.48).
Conclusion
The risk of early childhood death in Mbale, Uganda is unacceptably high. BCG vaccination was associated with an increased likelihood of child survival.

British Medical Journal
28 February 2015(vol 350, issue 7997)
http://www.bmj.com/content/350/7997

Clinical Review
Multidrug resistant tuberculosis
James Millard, clinical lecturer in global health1,
Cesar Ugarte-Gil, epidemiologist2,
David A J Moore, professor of infectious diseases & tropical medicine3
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h882 (Published 26 February 2015) Cite this as: BMJ 2015;350:h882

The bottom line
– Multidrug resistant tuberculosis refers to tuberculosis with resistance to at least rifampicin and isoniazid
– Multidrug resistant tuberculosis is increasingly common; however, there is a large shortfall between the estimated total number of cases and the numbers diagnosed and treated
– Diagnosis is hampered by lack of access to quality assured diagnostics, although newer, rapid molecular and phenotypic methods may go some way to improving this situation
– Compared with drug susceptible tuberculosis, treatment for multidrug resistant tuberculosis requires the use of drug regimens that are prolonged (18-24 months), less efficacious, and noticeably more toxic; new drugs and regimens are becoming available for the first time in decades and ongoing trials should define how best they should be used
– Worldwide, treatment success is only around 50%; however, several settings, including some low income countries, have proved that higher success rates are achievable

Bulletin of the World Health Organization
Volume 93, Number 3, March 2015, 133-208
http://www.who.int/bulletin/volumes/93/3/en/

Research
Assessing the potential for improvement of primary care in 34 countries: a cross-sectional survey
Willemijn LA Schäfer, Wienke GW Boerma, Anna M Murante, Herman JM Sixma, François G Schellevis & Peter P Groenewegen
Abstract
Objective
To investigate patients’ perceptions of improvement potential in primary care in 34 countries.
Methods
We did a cross-sectional survey of 69 201 patients who had just visited general practitioners at primary-care facilities. Patients rated five features of person-focused primary care – accessibility/availability, continuity, comprehensiveness, patient involvement and doctor–patient communication. One tenth of the patients ranked the importance of each feature on a scale of one to four, and nine tenths of patients scored their experiences of care received. We calculated the potential for improvement by multiplying the proportion of negative patient experiences with the mean importance score in each country. Scores were divided into low, medium and high improvement potential. Pair-wise correlations were made between improvement scores and three dimensions of the structure of primary care – governance, economic conditions and workforce development.
Findings
In 26 countries, one or more features of primary care had medium or high improvement potentials. Comprehensiveness of care had medium to high improvement potential in 23 of 34 countries. In all countries, doctor–patient communication had low improvement potential. An overall stronger structure of primary care was correlated with a lower potential for improvement of continuity and comprehensiveness of care. In countries with stronger primary care governance patients perceived less potential to improve the continuity of care. Countries with better economic conditions for primary care had less potential for improvement of all features of person-focused care.
Conclusion
In countries with a stronger primary care structure, patients perceived that primary care had less potential for improvement.

Systematic Review
The burden of child maltreatment in China: a systematic review
Xiangming Fang, Deborah A Fry, Kai Ji, David Finkelhor, Jingqi Chen, Patricia Lannen & Michael P Dunne
Abstract
Objective
To estimate the health and economic burdens of child maltreatment in China.
Methods
We did a systematic review for studies on child maltreatment in China using PubMed, Embase, PsycInfo, CINAHL-EBSCO, ERIC and the Chinese National Knowledge Infrastructure databases. We did meta-analyses of studies that met inclusion criteria to estimate the prevalence of child neglect and child physical, emotional and sexual abuse. We used data from the 2010 global burden of disease estimates to calculate disability-adjusted life-years (DALYs) lost as a result of child maltreatment.
Findings
From 68 studies we estimated that 26.6% of children under 18 years of age have suffered physical abuse, 19.6% emotional abuse, 8.7% sexual abuse and 26.0% neglect. We estimate that emotional abuse in childhood accounts for 26.3% of the DALYs lost because of mental disorders and 18.0% of those lost because of self-harm. Physical abuse in childhood accounts for 12.2% of DALYs lost because of depression, 17.0% of those lost to anxiety, 20.7% of those lost to problem drinking, 18.8% of those lost to illicit drug use and 18.3% of those lost to self-harm. The consequences of physical abuse of children costs China an estimated 0.84% of its gross domestic product – i.e. 50 billion United States dollars – in 2010. The corresponding losses attributable to emotional and sexual abuse in childhood were 0.47% and 0.39% of the gross domestic product, respectively.
Conclusion
In China, child maltreatment is common and associated with large economic losses because many maltreated children suffer substantial psychological distress and might adopt behaviours that increase their risk of chronic disease.

Systematic Review
Participants’ understanding of informed consent in clinical trials over three decades: systematic review and meta-analysis
Nguyen Thanh Tam, Nguyen Tien Huy, Le Thi Bich Thoa, Nguyen Phuoc Long, Nguyen Thi Huyen Trang, Kenji Hirayama & Juntra Karbwang
Abstract
Objective
To estimate the proportion of participants in clinical trials who understand different components of informed consent.
Methods
Relevant studies were identified by a systematic review of PubMed, Scopus and Google Scholar and by manually reviewing reference lists for publications up to October 2013. A meta-analysis of study results was performed using a random-effects model to take account of heterogeneity.
Findings
The analysis included 103 studies evaluating 135 cohorts of participants. The pooled proportion of participants who understood components of informed consent was 75.8% for freedom to withdraw at any time, 74.7% for the nature of study, 74.7% for the voluntary nature of participation, 74.0% for potential benefits, 69.6% for the study’s purpose, 67.0% for potential risks and side-effects, 66.2% for confidentiality, 64.1% for the availability of alternative treatment if withdrawn, 62.9% for knowing that treatments were being compared, 53.3% for placebo and 52.1% for randomization. Most participants, 62.4%, had no therapeutic misconceptions and 54.9% could name at least one risk. Subgroup and meta-regression analyses identified covariates, such as age, educational level, critical illness, the study phase and location, that significantly affected understanding and indicated that the proportion of participants who understood informed consent had not increased over 30 years.
Conclusion
The proportion of participants in clinical trials who understood different components of informed consent varied from 52.1% to 75.8%. Investigators could do more to help participants achieve a complete understanding.

Policy & Practice
Big data in global health: improving health in low- and middle-income countries
Rosemary Wyber, Samuel Vaillancourt, William Perry, Priya Mannava, Temitope Folaranmi & Leo Anthony Celi
Abstract
Over the last decade, a massive increase in data collection and analysis has occurred in many fields. In the health sector, however, there has been relatively little progress in data analysis and application despite a rapid rise in data production. Given adequate governance, improvements in the quality, quantity, storage and analysis of health data could lead to substantial improvements in many health outcomes. In low- and middle-income countries in particular, the creation of an information feedback mechanism can move health-care delivery towards results-based practice and improve the effective use of scarce resources. We review the evolving definition of big data and the possible advantages of – and problems in – using such data to improve health-care delivery in low- and middle-income countries. The collection of big data as mobile-phone based services improve may mean that development phases required elsewhere can be skipped. However, poor infrastructure may prevent interoperability and the safe use of patient data. An appropriate governance framework must be developed and enforced to protect individuals and ensure that health-care delivery is tailored to the characteristics and values of the target communities.

Epidemics
Volume 11, In Progress (June 2015)
http://www.sciencedirect.com/science/journal/17554365

Optimal prophylactic vaccination in segregated populations: When can we improve on the equalising strategy?
Original Research Article
Pages 7-13
Matt J. Keeling, J.V. Ross
Abstract
Highlights
– Allocating prophylactic vaccination in a segregated population is a key issue.
– The equalising strategy (ES) has been proposed as an optimal means of vaccination.
– However, the ES only holds for density-dependent transmission,
– We consider more realistic types of transmission and show the ES can be improved.
– This highlights the possibility of more targeted vaccination strategies

Pneumococcal vaccination in older adults in the era of childhood vaccination: Public health insights from a Norwegian statistical prediction study
Original Research Article
Pages 24-31
Anneke Steens, Didrik F. Vestrheim, Birgitte Freiesleben de Blasio
Abstract
Highlights
– Prediction analysis estimates a nearly elimination of PCV13-IPD among the 65+.
– Combining PCV13 and PPV23 likely has highest impact on IPD prevention in the 65+.
– Increasing PPV23 uptake will prevent more IPD cases than adding PCV13 to PPV23.
– The preventive potential of pneumococcal vaccines may decrease among the 65+.

Eurosurveillance
Volume 20, Issue 8, 26 February 2015
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

Rapid communications
Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results
by J Puig-Barberà, A Mira-Iglesias, M Tortajada-Girbés, FX López-Labrador, A Belenguer-Varea, M Carballido-Fernández, E Carbonell-Franco, C Carratalá-Munuera, R Limón-Ramírez, J Mollar-Maseres, M del Carmen Otero-Reigada, G Schwarz-Chavarri, J Tuells, V Gil-Guillén, for the Valencia Hospital Network for the Study of Influenza and Respiratory Viruses Disease

Globalization and Health
[Accessed 28 February 2015]
http://www.globalizationandhealth.com/

Debate
Why language matters: insights and challenges in applying a social determination of health approach in a North-South collaborative research program
Spiegel JM, Breilh J and Yassi A Globalization and Health 2015, 11:9 (27 February 2015)

Debate
Preparing for Ebola Virus Disease in West African countries not yet affected: perspectives from Ghanaian health professionals
Nyarko Y, Goldfrank L, Ogedegbe G, Soghoian S, de-Graft Aikins A and NYU-UG-KBTH Ghana Ebola Working Group Globalization and Health 2015, 11:7 (26 February 2015)
Abstract (provisional)
Background
The current Ebola Virus Disease (EVD) epidemic has ravaged the social fabric of three West African countries and affected people worldwide. We report key themes from an agenda-setting, multi-disciplinary roundtable convened to examine experiences and implications for health systems in Ghana, a nation without cases but where risk for spread is high and the economic, social and political impact of the impending threat is already felt.
Discussion
Participants’ personal stories and the broader debates to define fundamental issues and opportunities for preparedness focused on three inter-related themes. First, the dangers of the fear response itself were highlighted as a threat to the integrity and continuity of quality care. Second, healthcare workers’ fears were compounded by a demonstrable lack of societal and personal protections for infection prevention and control in communities and healthcare facilities, as evidenced by an ongoing cholera epidemic affecting over 20,000 patients in the capital Accra alone since June 2014. Third, a lack of coherent messaging and direction from leadership seems to have limited coordination and reinforced a level of mistrust in the government’s ability and commitment to mobilize an adequate response. Initial recommendations include urgent investment in the needed supplies and infrastructure for basic, routine infection control in communities and healthcare facilities, provision of assurances with securities for frontline healthcare workers, establishment of a multi-sector, “all-hazards” outbreak surveillance system, and engaging directly with key community groups to co-produce contextually relevant educational messages that will help decrease stigma, fear, and the demoralizing perception that the disease defies remedy or control.
Summary
The EVD epidemic provides an unprecedented opportunity for West African countries not yet affected by EVD cases to make progress on tackling long-standing health systems weaknesses. This roundtable discussion emphasized the urgent need to strengthen capacity for infection control, occupational health and safety, and leadership coordination. Significant commitment is needed to raise standards of hygiene in communities and health facilities, build mechanisms for collaboration across sectors, and engage community stakeholders in creating the needed solutions. It would be both devastating and irresponsible to waste the opportunity.

Health Research Policy and Systems
http://www.health-policy-systems.com/content
[Accessed 28 February 2015]

Research
Developing and refining the methods for a ‘one-stop shop’ for research evidence about health systems
John N Lavis, Michael G Wilson, Kaelan A Moat, Amanda C Hammill, Jennifer A Boyko, Jeremy M Grimshaw and Signe Flottorp
Health Research Policy and Systems 2015, 13:10 doi:10.1186/1478-4505-13-10
Published: 25 February 2015
Abstract (provisional)
Background
Policymakers, stakeholders and researchers have not been able to find research evidence about health systems using an easily understood taxonomy of topics, know when they have conducted a comprehensive search of the many types of research evidence relevant to them, or rapidly identify decision-relevant information in their search results.
Methods
To address these gaps, we developed an approach to building a ‘one-stop shop’ for research evidence about health systems. We developed a taxonomy of health system topics and iteratively refined it by drawing on existing categorization schemes and by using it to categorize progressively larger bundles of research evidence. We identified systematic reviews, systematic review protocols, and review-derived products through searches of Medline, hand searches of several databases indexing systematic reviews, hand searches of journals, and continuous scanning of LISTSERVS and websites. We developed an approach to providing ‘added value’ to existing content (e.g., coding systematic reviews according to the countries in which included studies were conducted) and to expanding the types of evidence eligible for inclusion (e.g., economic evaluations and health system descriptions). Lastly, we developed an approach to continuously updating the online one-stop shop in seven supported languages.
Results
The taxonomy is organized by governance, financial, and delivery arrangements and by implementation strategies. The ‘one-stop shop’, called Health Systems Evidence, contains a comprehensive inventory of evidence briefs, overviews of systematic reviews, systematic reviews, systematic review protocols, registered systematic review titles, economic evaluations and costing studies, health reform descriptions and health system descriptions, and many types of added-value coding. It is continuously updated and new content is regularly translated into Arabic, Chinese, English, French, Portuguese, Russian, and Spanish.
Conclusions
Policymakers and stakeholders can now easily access and use a wide variety of types of research evidence about health systems to inform decision-making and advocacy. Researchers and research funding agencies can use Health Systems Evidence to identify gaps in the current stock of research evidence and domains that could benefit from primary research, systematic reviews, and review overviews.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
Volume 11, Issue 1, 2015
http://www.tandfonline.com/toc/khvi20/11/1#.VPJsQS5nBhU

Impact of universal vaccination against varicella in Italy-Experiences from eight Italian Regions
Angela Bechini, Sara Boccalini, Vincenzo Baldo, Silvia Cocchio, Paolo Castiglia, Tolinda Gallo, Sandro Giuffrida, Francesco Locuratolo, Silvio Tafuri, Domenico Martinelli, Rosa Prato, Emanuele Amodio, Francesco Vitale & Paolo Bonanni
pages 63-71

Effectiveness of interventions that apply new media to improve vaccine uptake and vaccine coverage – A systematic review
Anna Odone, Antonio Ferrari, Francesca Spagnoli, Sara Visciarelli, Abigail Shefer, Cesira Pasquarella & Carlo Signorelli
pages 72-82

Routine surveillance of adverse events following immunization as an important tool to monitor vaccine safety – The two-years’ experience of the Liguria Region, Italy
Cristiano Alicino, Caterina Merlano, Simona Zappettini, Sergio Schiaffino, Giovanni Della Luna, Cristina Accardo, Roberto Gasparini, Paolo Durando & Giancarlo Icardi
pages 91-94

Influenza vaccination among healthcare workers in Italy – the experience of a large tertiary acute-care teaching hospital
Cristiano Alicino, Rocco Iudici, Ilaria Barberis, Chiara Paganino, Roberto Cacciani, Monica Zacconi, Angela Battistini, Dorotea Bellina, Anna Maria Di Bella, Antonella Talamini, Laura Sticchi, Alessandra Morando, Filippo Ansaldi & Paolo Durando
pages 95-100

Adult vaccination – Current recommendations and future prospects
Kena A Swanson, H Josef Schmitt, Kathrin U Jansen & Annaliesa S Anderson
pages 150-155

Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly
An observational study in Liguria Region, Italy
Paolo Durando, Roberto Rosselli, Ilaria Cremonesi, Andrea Orsi, Erika Albanese, Ilaria Barberis, Chiara Paganino, Cecilia Trucchi, Mariano Martini, Lorenzo Marensi, Valter Turello, the Ligurian Pneumococcal Study Group, Alessandro Bregante, Roberto Cacciani, Rocco Iudici, Diego La Marca, Leonardo Pedano, Amadio Franco Petrucci, Maria Santolini, Valentina Sbisà & Monica Zacconi
pages 172-177

Facilitators and barriers HPV unvaccinated girls after 5 years of program implementation
Alberto Firenze, Maria Grazia Laura Marsala, Valentina Bonanno, Marianna Maranto, Clara Ferrara, Lucia Giovannelli & Vincenzo Restivo
pages 240-244

Implication of health care personnel in measles transmission – The need for updated immunization status in the move towards eradication of measles in Catalonia
Núria Torner, Ruben Solano, Cristina Rius, Angela Domínguez & the Measles Elimination Program Surveillance Network of Catalonia, Spain
pages 288-292