New trial of TKM-Ebola treatment to start in Sierra Leone
Wellcome Trust Press Release: 11 March 2015
A clinical trial of a potential Ebola therapy called TKM-Ebola-Guinea will start today in Sierra Leone.

The phase II study, led by Professor Peter Horby of the University of Oxford on behalf of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), is the second drug trial to be funded through the Wellcome Trust’s £3.2 million Ebola therapeutics platform.

TKM-Ebola-Guinea, developed and manufactured by Tekmira Pharmaceuticals, is a synthetic small interfering RNA (siRNA) therapeutic designed specifically to target the strain of the Ebola virus responsible for the present outbreak in Guinea, Liberia and Sierra Leone. It works by blocking certain genes of the virus, thereby reducing viral replication.

An earlier version of the TKM-Ebola drug (targeted at a different strain) has been tested in healthy human volunteers. The efficacy of the Guinea version will now be evaluated in patients with a confirmed diagnosis of Ebola virus infection in a single-arm study called RAPIDE-TKM (Phase II Rapid Assessment of Potential Interventions & Drugs for Ebola-TKM). Results of the trial are expected in the second half of 2015.

The RAPIDE-TKM study will be led by the University of Oxford in partnership with the Sierra Leone College of Medicine and Allied Health Sciences, the Sierra Leone Ministry for Health, the WHO-based Special Programme for Research and Training in Tropical Diseases (TDR), the UK Department for International Development (DFID), Public Health England and GOAL Global.
Professor Peter Horby, Associate Professor of Infectious Diseases and Global Health at University of Oxford, who is leading the trial, said: “There are still around 10 new cases of Ebola being diagnosed every day in Sierra Leone. It’s therefore essential that we push forward with clinical trials while we still have a realistic chance of getting answers about which, if any, of the candidate treatments can save lives in this, and in future outbreaks.”

Colonel Professor Foday Sahr, Commanding Officer of the joint medical unit in Sierra Leone and a principal investigator on the study, said: “The start of this trial is a very important event for Sierra Leone and the other countries affected by Ebola, it is an exciting development because research is essential in this outbreak so that we can determine what might work for these cases. This clinical trial is a highly collaborative effort and we are working closely with international partners so that together we can get the evidence that is needed. The team working with the patients in the treatment centres demonstrate this partnership in action because they are a mix of local and overseas staff who are working side by side to deliver these trial treatments to the patients.”

Dr Jeremy Farrar, Director of the Wellcome Trust, which is funding the trial, added: “The recent surge in new Ebola infections in Guinea and Sierra Leone should serve as a stark warning that this epidemic is far from over. Almost a year on from the first confirmed case, we’ve reached a crucial stage where several large scale trials are gathering steam, but we still don’t have any proven treatments. It’s therefore heartening to see this latest trial of TKM-Ebola getting underway after so much hard work from the research team and partner agencies. We’re very proud to be supporting their important work.”

The Wellcome Trust Ebola therapeutics platform was set up in September 2014 to enable multiple partners to quickly establish clinical trials at existing Ebola treatment centres. TKM-Ebola-Guinea is the second candidate drug to be evaluated through the platform. A previous trial of the antiviral brincidofovir was abandoned earlier this year following a sharp fall in the number of Ebola cases at the study site in Liberia.

POLIO [to 14 March 2015]
Public Health Emergency of International Concern (PHEIC)

GPEI Update: Polio this week – As of 11 March 2015
Global Polio Eradication Initiative
[Editor’s Excerpt and text bolding]
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: On International Women’s Day 2015 we celebrated the essential role women play in polio eradication efforts around the world. More
Pakistan
:: Three new wild poliovirus type 1 (WPV1) cases were reported in the past week. One case was reported in Peshawar district in Khyber Pakhtunkhwa province; 1 in Dadu district in Sindh; and one in Lorelai district in Balochistan. The latter two districts were previously uninfected with WPV in 2015. The total number of WPV1 cases in 2014 remains 306, and 16 for 2015. The most recent onset of paralysis was on 10 February in Dadu district.

PATH Watch [to 14 March 2015]
http://www.path.org/news/index.php

March 12, 2015
India rolls out ROTAVAC® in private sector
On Monday, March 9, 2015, India’s Prime Minister Narenda Modi rolled out an indigenously developed and manufactured rotavirus vaccine, ROTAVAC®, for the private market.
ROTAVAC®’s Phase 3 clinical trial data demonstrated excellent safety and efficacy, with reductions of severe rotavirus diarrhea by more than half – 56 percent during the first year of life, with protection continuing into the second year of life. This compares favorably with the efficacy of currently globally available rotavirus vaccines in low-resource countries.

PATH, a key partner in the development of ROTAVAC® since 2001, worked with the Indian Department of Biotechnology, the Society for Applied Studies, and Bharat Biotech on the clinical trials that demonstrated the safety and efficacy of the vaccine. PATH welcomed the news that Bharat Biotech launched ROTAVAC® in the private sector as “an exciting and encouraging first step towards the public health goal of improving the supply of affordable rotavirus vaccine, both in India and worldwide.”

In July 2014, Prime Minister Modi announced the introduction of ROTAVAC® into India’s publically funded Universal Immunization Programme (UIP), and in September 2014, Dr. Harsh Vardhan, India’s Minister of Health and Family Welfare at the time, confirmed the Indian government’s commitment to introduce rotavirus vaccines into the UIP during opening remarks at the International Rotavirus Symposium, held in New Delhi. The Government of India is currently developing a plan for a phased roll-out of the vaccine in the UIP, which will benefit the poorest populations who are most at-risk of severe illness or death from rotavirus diarrhea

WHO & Regionals [to 14 March 2015]
:: WHO issues its first hepatitis B treatment guidelines
12 March 2015 — Today, WHO issued its first-ever guidance for the treatment of chronic hepatitis B, a viral infection which is spread through blood and body fluids, attacking the liver and resulting in an estimated 650 000 deaths each year. Worldwide, some 240 million people have chronic hepatitis B virus and are at increased risk of dying from cirrhosis and liver cancer. Effective medicines exist that can prevent people developing these conditions so they live longer.

:: Global Alert and Response (GAR): Disease Outbreak News (DONs)
– 13 March 2015 Meningococcal disease – Nigeria
– 11 March 2015 Human infection with avian influenza A(H7N9) virus – China
– 11 March 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) – Qatar
– 11 March 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia
– 9 March 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) – Germany

:: The Weekly Epidemiological Record (WER) 13 March 2015, vol. 90, 11 (pp. 97–108) includes:
– Recommended composition of influenza virus vaccines for use in the 2015–2016 northern hemisphere influenza season

:: WHO Regional Offices
WHO African Region AFRO
:: WHO and World Food Programme join forces to reach zero Ebola cases
11 March 2015 ¦ GENEVA – WHO and the United Nations World Food Programme (WFP) are combining their forces in a new partnership in the Ebola-affected countries of Guinea, Liberia and Sierra Leone. The arrangement combines the logistics strength of WFP with WHO’s public health expertise to help get the current Ebola outbreak down to zero cases in West Africa. The platform also establishes an alert and response infrastructure for future crises.

WHO Region of the Americas PAHO
:: PAHO and Latin American Society of Nephrology call for increased prevention and better access to treatment for kidney disease (03/09/2015)

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

WHO European Region EURO
No new digest content identified.

WHO Eastern Mediterranean Region EMRO
:: WHO Regional Director inaugurates primary health care centre and hands over urgently needed mobile medical clinics and ambulances to health authorities in Dohuk, Iraq
Erbil, Iraq, 14 March 2015 – WHO’s Regional Director for the Eastern Mediterranean Dr Ala Alwan visited Dohuk governorate of the Kurdistan region of Iraq to officially hand over 15 ambulances and 2 mobile medical clinics to Dohuk health authorities. The donation will provide health services and medical treatments for more than 60 000 beneficiaries for three months.

BMC Infectious Diseases
http://www.biomedcentral.com/bmcinfectdis/content
(Accessed 14 March 2015)

Research article
Spatial clustering of measles cases during endemic (1998–2002) and epidemic (2010) periods in Lusaka, Zambia
Jessie Pinchoff1, James Chipeta2*, Gibson Chitundu Banda2, Samuel Miti2, Timothy Shields3, Frank Curriero3 and William John Moss13
Author Affiliations
BMC Infectious Diseases 2015, 15:121 doi:10.1186/s12879-015-0842-y
Published: 10 March 2015
Abstract (provisional)
Background
Measles cases may cluster in densely populated urban centers in sub-Saharan Africa as susceptible individuals share spatially dependent risk factors and may cluster among human immunodeficiency virus (HIV)-infected children despite high vaccination coverage.
Methods
Children hospitalized with measles at the University Teaching Hospital (UTH) in Lusaka, Zambia were enrolled in the study. The township of residence was recorded on the questionnaire and mapped; SaTScan software was used for cluster detection. A spatial-temporal scan statistic was used to investigate clustering of measles in children hospitalized during an endemic period (1998 to 2002) and during the 2010 measles outbreak in Lusaka, Zambia.
Results
Three sequential and spatially contiguous clusters of measles cases were identified during the 2010 outbreak but no clustering among HIV-infected children was identified. In contrast, a space-time cluster among HIV-infected children was identified during the endemic period. This cluster occurred prior to the introduction of intensive measles control efforts and during a period between seasonal peaks in measles incidence.
Conclusions
Prediction and early identification of spatial clusters of measles will be critical to achieving measles elimination. HIV infection may contribute to spatial clustering of measles cases in some epidemiological settings.

BMC Public Health
(Accessed 14 March 2015)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Association between gender inequality index and child mortality rates: a cross-national study of 138 countries
Ethel Mary Brinda1, Anto P Rajkumar23* and Ulrika Enemark1
Author Affiliations
BMC Public Health 2015, 15:97 doi:10.1186/s12889-015-1449-3
Published: 9 March 2015
Abstract
Background
Gender inequality weakens maternal health and harms children through many direct and indirect pathways. Allied biological disadvantage and psychosocial adversities challenge the survival of children of both genders. United Nations Development Programme (UNDP) has recently developed a Gender Inequality Index to measure the multidimensional nature of gender inequality. The global impact of Gender Inequality Index on the child mortality rates remains uncertain.
Methods
We employed an ecological study to investigate the association between child mortality rates and Gender Inequality Indices of 138 countries for which UNDP has published the Gender Inequality Index. Data on child mortality rates and on potential confounders, such as, per capita gross domestic product and immunization coverage, were obtained from the official World Health Organization and World Bank sources. We employed multivariate non-parametric robust regression models to study the relationship between these variables.
Results
Women in low and middle income countries (LMICs) suffer significantly more gender inequality (p < 0.001). Gender Inequality Index (GII) was positively associated with neonatal (β = 53.85; 95% CI 41.61-64.09), infant (β = 70.28; 95% CI 51.93-88.64) and under five mortality rates (β = 68.14; 95% CI 49.71-86.58), after adjusting for the effects of potential confounders (p < 0.001).
Conclusions
We have documented statistically significant positive associations between GII and child mortality rates. Our results suggest that the initiatives to curtail child mortality rates should extend beyond medical interventions and should prioritize women’s rights and autonomy. We discuss major pathways connecting gender inequality and child mortality. We present the socio-economic problems, which sustain higher gender inequality and child mortality in LMICs. We further discuss the potential solutions pertinent to LMICs. Dissipating gender barriers and focusing on social well-being of women may augment the survival of children of both genders.

BMC Research Notes
(Accessed 14 March 2015)
http://www.biomedcentral.com/bmcresnotes/content

Research article
Understanding whose births get registered: a cross sectional study in Bauchi and Cross River states, Nigeria
Atam E Adi1, Tukur Abdu1, Amir Khan12, Musa Haruna Rashid3, Ubi E Ebri4, Anne Cockcroft5* and Neil Andersson6
Author Affiliations
BMC Research Notes 2015, 8:79 doi:10.1186/s13104-015-1026-y
Published: 13 March 2015
Abstract (provisional)
Background
It is a recognized child right to acquire a name and a nationality, and birth registration may be necessary to allow access to services, but the level of birth registration is low in Nigeria. A household survey about management of childhood illnesses provided an opportunity to examine actionable determinants of birth registration of children in Bauchi and Cross River states of Nigeria.
Methods
Trained field teams visited households in a stratified random cluster sample of 90 enumeration areas in each state. They administered a questionnaire to women 14–49 years old which included questions about birth registration of their children 0–47 months old and about socio-economic and other factors potentially related to birth registration, including education of the parents, poverty (food sufficiency), marital status of the mother, maternal antenatal care and place of delivery of the last pregnancy. Bivariate then multivariate analysis examined associations with birth registration. Facilitators later conducted separate male and female focus group discussions in the same 90 communities in each state, discussing the reasons for the findings about levels of birth registration.
Results
Nearly half (45%) of 8602 children in Cross River State and only a fifth (19%) of 9837 in Bauchi State had birth certificates (seen or unseen). In both states, children whose mothers attended antenatal care and who delivered in a government health facility in their last pregnancy were more likely to have a birth certificate, as were children of more educated parents, from less poor households, and from urban communities. Focus group discussions revealed that many people did not know about birth certificates or where to get them, and parents were discouraged from getting birth certificates because of the unofficial payments involved. Conclusion
There are low levels of birth registration in Bauchi and Cross River states, particularly among disadvantaged households. As a result of this study, both states have planned interventions to increase birth registration, including closer collaboration between the National Population Commissions and state health services.

British Medical Journal
14 March 2015(vol 350, issue 7999)
http://www.bmj.com/content/350/7999

Editorials
Germany, the G7, and global health
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1210 (Published 05 March 2015) Cite this as: BMJ 2015;350:h1210
Gavin Yamey, lead1, Sabine Campe, associate director2, Sara Fewer, policy and programme manager1
Author affiliations
Health systems, new tools, and delivery science should top the agenda
Remember global health? It had a fantastic 10 years from 2002-12—the “golden decade” of rising health aid1—but is now slipping down the international agenda. Some development experts argue that other sectors, such as agriculture, should “take centre stage.”2 This is misguided. Health investment is the largest contributor to sustainable development.3 And a retreat from health would threaten the impressive gains of the past decade in reducing infectious disease, maternal, and child mortality.4
Fortunately, there are some promising signs that Germany, this year’s chair of the G7 group of large advanced economies, may spend some of its political capital on pushing health back up the global agenda. It got off to a strong start, hosting a conference in Berlin in January at which donors pledged $7.5bn (£4.9bn; €6.7bn) to Gavi, the vaccine alliance, an amount that exceeded expectations and that could fund immunisations for an additional 300 million children.5 It has identified three global health priorities for the G7 in 2015: neglected tropical diseases, pandemics, and antimicrobial resistance.6 What should we make of these priorities, and does the G7 really have the clout to effect global change?…

Epidemiology and Infection
Volume 143 – Issue 06 – April 2015
http://journals.cambridge.org/action/displayIssue?jid=HYG&tab=currentissue

Original Papers
Vaccine studies
The introduction of dengue vaccine may temporarily cause large spikes in prevalence
A. PANDEYa1 c1 and J. MEDLOCKa2
a1 Department of Mathematical Sciences, Clemson University, Clemson, SC, USA
a2 Department of Biomedical Sciences, Oregon State University, Corvallis, OR, USA
SUMMARY
A dengue vaccine is expected to be available within a few years. Once vaccine is available, policy-makers will need to develop suitable policies to allocate the vaccine. Mathematical models of dengue transmission predict complex temporal patterns in prevalence, driven by seasonal oscillations in mosquito abundance. In particular, vaccine introduction may induce a transient period immediately after vaccine introduction where prevalence can spike higher than in the pre-vaccination period. These spikes in prevalence could lead to doubts about the vaccination programme among the public and even among decision-makers, possibly impeding the vaccination programme. Using simple dengue transmission models, we found that large transient spikes in prevalence are robust phenomena that occur when vaccine coverage and vaccine efficacy are not either both very high or both very low. Despite the presence of transient spikes in prevalence, the models predict that vaccination does always reduce the total number of infections in the 15 years after vaccine introduction. We conclude that policy-makers should prepare for spikes in prevalence after vaccine introduction to mitigate the burden of these spikes and to accurately measure the effectiveness of the vaccine programme

Eurosurveillance
Volume 20, Issue 10, 12 March 2015
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

Surveillance and outbreak reports
Impact of 10- and 13-valent pneumococcal conjugate vaccines on incidence of invasive pneumococcal disease in children aged under 16 years in Germany, 2009 to 2012
by S Weiss, G Falkenhorst, M van der Linden, M Imöhl, R von Kries

Health Research Policy and Systems
http://www.health-policy-systems.com/content
[Accessed 14 March 2015]

Review
A systematic review of implementation frameworks of innovations in healthcare and resulting generic implementation framework
Joanna C Moullin1*, Daniel Sabater-Hernández12, Fernando Fernandez-Llimos3 and Shalom I Benrimoj1
Author Affiliations
Health Research Policy and Systems 2015, 13:16 doi:10.1186/s12961-015-0005-z
Published: 14 March 2015
Abstract (provisional)
Background
Implementation science and knowledge translation have developed across multiple disciplines with the common aim of bringing innovations to practice. Numerous implementation frameworks, models, and theories have been developed to target a diverse array of innovations. As such, it is plausible that not all frameworks include the full range of concepts now thought to be involved in implementation. Users face the decision of selecting a single or combining multiple implementation frameworks. To aid this decision, the aim of this review was to assess the comprehensiveness of existing frameworks.
Methods
A systematic search was undertaken in PubMed to identify implementation frameworks of innovations in healthcare published from 2004 to May 2013. Additionally, titles and abstracts from Implementation Science journal and references from identified papers were reviewed. The orientation, type, and presence of stages and domains, along with the degree of inclusion and depth of analysis of factors, strategies, and evaluations of implementation of included frameworks were analysed.
Results
Frameworks were assessed individually and grouped according to their targeted innovation. Frameworks for particular innovations had similar settings, end-users, and ‘type’ (descriptive, prescriptive, explanatory, or predictive). On the whole, frameworks were descriptive and explanatory more often than prescriptive and predictive. A small number of the reviewed frameworks covered an implementation concept(s) in detail, however, overall, there was limited degree and depth of analysis of implementation concepts. The core implementation concepts across the frameworks were collated to form a Generic Implementation Framework, which includes the process of implementation (often portrayed as a series of stages and/or steps), the innovation to be implemented, the context in which the implementation is to occur (divided into a range of domains), and influencing factors, strategies, and evaluations.
Conclusions
The selection of implementation framework(s) should be based not solely on the healthcare innovation to be implemented, but include other aspects of the framework’s orientation, e.g., the setting and end-user, as well as the degree of inclusion and depth of analysis of the implementation concepts. The resulting generic structure provides researchers, policy-makers, health administrators, and practitioners a base that can be used as guidance for their implementation efforts.

The Lancet
Mar 14, 2015 Volume 385 Number 9972 p915-1044 e21-e22
http://www.thelancet.com/journals/lancet/issue/current

Editorial
The future of health in Nigeria
The Lancet
Summary
In a letter in today’s issue, Seye Abimbola and colleagues highlight the health effects of the 6 year Boko Haram insurgency in Nigeria. The militant group now controls three states in the northeast of the country. Maternal and child mortality are worse in these states than in the rest of Nigeria, there are fears about undetected polio cases, and more than 980 000 people are internally displaced. Conditions are dire for the internally displaced population who live in informal and formal camps with minimum access to health care and other basic needs, such as food and clean water.

Special Report
Syrian crisis: health experts say more can be done
Sophie Cousins
DOI: http://dx.doi.org/10.1016/S0140-6736(15)60515-3
As the Syrian conflict enters its fifth year this month, doctors and public health experts highlight the major health problems and the actions needed to address them. Sophie Cousins reports.

Global trends and projections for tobacco use, 1990–2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control
Ver Bilano, Stuart Gilmour, Trevor Moffiet, Edouard Tursan d’Espaignet, Gretchen A Stevens, Alison Commar, Frank Tuyl, Irene Hudson, Kenji Shibuya

Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)
Claudia Allemani, Hannah K Weir, Helena Carreira, Rhea Harewood, Devon Spika, Xiao-Si Wang, Finian Bannon, Jane V Ahn, Christopher J Johnson, Audrey Bonaventure, Rafael Marcos-Gragera, Charles Stiller, Gulnar Azevedo e Silva, Wan-Qing Chen, Olufemi J Ogunbiyi, Bernard Rachet, Matthew J Soeberg, Hui You, Tomohiro Matsuda, Magdalena Bielska-Lasota, Hans Storm, Thomas C Tucker, Michel P Coleman, the CONCORD Working Group
Open Access

Nature
Volume 519 Number 7542 pp129-256 12 March 2015
http://www.nature.com/nature/current_issue.html

Comment
Global change: Put people at the centre of global risk management
Jan Willem Erisman, Guy Brasseur, Philippe Ciais, Nick van Eekeren & Thomas L. Theis
11 March 2015

An individual focus is needed to assess interconnected threats and build resilience worldwide, urge Jan Willem Erisman and colleagues.
Globalization is changing the nature of risk. Natural and social systems — from climate to energy, food, water and economies — are tightly coupled. Abrupt changes in one have a domino effect on others. Floods in Thailand in 2010, for example, led to a global shortage of computer hard disks as a result of factories closing, as well as more than US$330 million in damage and around 250 deaths.
The exposure of people and assets to risks is increasing worldwide. From 1980 to 2012, annual economic losses from environmental disasters rose more than sevenfold, from about $20 billion to $150 billion a year1.
Yet most risk assessments ignore networked threats2, 3. The annual Global Risks report of the World Economic Forum considers risks qualitatively, based on the views of experts4. But global outlooks remain sectorial and too coarse to guide individuals, organizations, municipalities or nations.
Risk reports also neglect the collective impacts of personal choices3. For example, eating more beef causes deforestation and biodiversity loss in the Amazon. Local dams for hydropower or water storage alter sediment flows to fertile coastal regions. The movement of people from the countryside to cities affects water, food, climatic and energy systems planet-wide.
Understanding networked risks is essential for achieving the United Nations Sustainable Development Goals, which are being defined this year5. The 17 proposed goals are interdependent. For example, the stimulation of renewable energies and biofuels to address climate change also affects food production and water resources…

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

Special Article
Compliance with Results Reporting at ClinicalTrials.gov
Monique L. Anderson, M.D., Karen Chiswell, Ph.D., Eric D. Peterson, M.D., M.P.H., Asba Tasneem, Ph.D., James Topping, M.S., and Robert M. Califf, M.D.
N Engl J Med 2015; 372:1031-1039 March 12, 2015
DOI: 10.1056/NEJMsa1409364
Abstract
Background
The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results.
Full Text of Background…
Methods
Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period.
Full Text of Methods…
Results
From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions.
Full Text of Results…
Conclusions
Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.)

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
(Accessed 14 March 2015)

Modeling the 2014 Ebola Virus Epidemic – Agent-Based Simulations, Temporal Analysis and Future Predictions for Liberia and Sierra Leone
March 9, 2015 • Research
We developed an agent-based model to investigate the epidemic dynamics of Ebola virus disease (EVD) in Liberia and Sierra Leone from May 27 to December 21, 2014. The dynamics of the agent-based simulator evolve on small-world transmission networks of sizes equal to the population of each country, with adjustable densities to account for the effects of public health intervention policies and individual behavioral responses to the evolving epidemic. Based on time series of the official case counts from the World Health Organization (WHO), we provide estimates for key epidemiological variables by employing the so-called Equation-Free approach. The underlying transmission networks were characterized by rather random structures in the two countries with densities decreasing by ~19% from the early (May 27-early August) to the last period (mid October-December 21). Our estimates for the values of key epidemiological variables, such as the mean time to death, recovery and the case fatality rate, are very close to the ones reported by the WHO Ebola response team during the early period of the epidemic (until September 14) that were calculated based on clinical data. Specifically, regarding the effective reproductive number Re, our analysis suggests that until mid October, Re was above 2.3 in both countries; from mid October to December 21, Re dropped well below unity in Liberia, indicating a saturation of the epidemic, while in Sierra Leone it was around 1.9, indicating an ongoing epidemic. Accordingly, a ten-week projection from December 21 estimated that the epidemic will fade out in Liberia in early March; in contrast, our results flashed a note of caution for Sierra Leone since the cumulative number of cases could reach as high as 18,000, and the number of deaths might exceed 5,000, by early March 2015. However, by processing the reported data of the very last period (December 21, 2014-January 18, 2015), we obtained more optimistic estimates indicative of a remission of the epidemic in Sierra Leone, as reflected by the derived Re (~0.82, 95% CI: 0.81-0.83)

PLoS Medicine
(Accessed 14 March 2015)
http://www.plosmedicine.org/

Policy Forum
A Public Health Approach to Hepatitis C Control in Low- and Middle-Income Countries
Amitabh B. Suthar, Anthony D. Harries
Published: March 10, 2015
DOI: 10.1371/journal.pmed.1001795
Summary Points
:: New oral short-duration regimens using direct-acting antiviral medicines for hepatitis C virus (HCV) have the potential to facilitate treatment and improve outcomes.
:: Translating scientific advances into reduced disease burden requires well-designed programmes encompassing prevention, screening, treatment, and strategic information.
:: Engagement from countries, civil society, donors, and policymakers is needed to generate political commitment, mobilise resources, and reduce diagnostic and medicine costs for HCV.
:: Countries should estimate the resources required to implement planned HCV prevention, screening, and treatment strategies and their expected health, societal, and financial benefits to mobilise domestic and international funding.
:: Countries could integrate HCV prevention, screening, treatment, and strategic information into HIV/AIDS programmes for financial, infrastructural, and health workforce efficiencies.

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 14 March 2015)

Viewpoints
Good and Bad News about Ebola
A. Townsend Peterson
Published: March 12, 2015
DOI: 10.1371/journal.pntd.0003509
[Concluding text]
…If the present situation with Ebola is to offer any lessons, they are that the only hope for serious investment in reducing the incidence and impact of such diseases is via spread to developed countries. Once such spread occurs, research and pharmaceutical investment will most likely follow. Ebola is a positive example, and clearly Ebola research will enter a new phase of progress, innovation, funding, production of key pharmaceuticals, and improved care, hopefully for all who might be infected by this virus.
In effect, what Ebola did was to cross the line between being a “neglected tropical disease” and being an “emerging infection.” The former set of diseases collectively exert an enormous burden in the developing world that may be constant or episodic, but are rather ubiquitous in those regions, affecting the affluent only when they venture into those regions [13,14]. The latter, on the other hand, are much less predictable, but garner more immediate attention on the world scene, precisely because they may affect affluent countries. How many other neglected diseases must await this process of spread to affluent regions and infection of affluent people, making the transition from neglected tropical disease to emerging infection, before they also will see investment and innovation?

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 14 March 2015)

Flexibility of Oral Cholera Vaccine Dosing—A Randomized Controlled Trial Measuring Immune Responses Following Alternative Vaccination Schedules in a Cholera Hyper-Endemic Zone
Suman Kanungo, Sachin N. Desai, Ranjan Kumar Nandy, Mihir Kumar Bhattacharya, Deok Ryun Kim, Anuradha Sinha, Tanmay Mahapatra, Jae Seung Yang, Anna Lena Lopez, Byomkesh Manna, Barnali Bannerjee, Mohammad Ali, Mandeep Singh Dhingra, Ananga Mohan Chandra, John D. Clemens, Dipika Sur, Thomas F. Wierzba
Research Article | published 12 Mar 2015 | PLOS Neglected Tropical Diseases 10.1371/journal.pntd.0003574
Abstract
Background
A bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response.
Methodology/Principal Findings
In this double blind randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55%) vs the 28 day interval (58%). Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%).
Conclusions/Significance
Comparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.
Author Summary
The five year efficacy results of the bivalent, killed whole cell oral cholera vaccine was shown to offer 65% protection in cholera endemic Kolkata. Currently, two oral cholera vaccines (OCV) are prequalified by the World Health Organization: the whole cell recombinant cholera toxin B subunit vaccine (Dukoral), and the bivalent killed whole cell only OCV (Shanchol). Shanchol, which is less expensive and possibly associated with longer protection, is recommended in a two dose schedule to be given at two weeks apart. Large scale cholera outbreaks often affect vulnerable populations with limited access to care. Strict dosing schedules can create further logistical barriers, hindering proper vaccine delivery to affected residents returning for their second OCV dose. In this study, 356 participants aged 1 year or older were randomized to receive two doses of OCV at 14 or 28 day intervals, for which vibriocidal immune responses were compared. Similar immune responses were demonstrated between a two and four week OCV dosing schedule, which can increase flexibility when offered as part of a targeted vaccination program. This can further serve to increase adherence and completion of the recommended dosing regimen, as well as providing a platform to increase coverage of other beneficial non-vaccine interventions.

PLoS One
[Accessed 14 March 2015]
http://www.plosone.org/

Cost Evaluation of Reproductive and Primary Health Care Mobile Service Delivery for Women in Two Rural Districts in South Africa
Kathryn Schnippel, Naomi Lince-Deroche, Theo van den Handel, Seithati Molefi, Suann Bruce, Cynthia Firnhaber
Research Article | published 09 Mar 2015 | PLOS ONE 10.1371/journal.pone.0119236
Abstract
Background
Cervical cancer screening is a critical health service that is often unavailable to women in under-resourced settings. In order to expand access to this and other reproductive and primary health care services, a South African non-governmental organization established a van-based mobile clinic in two rural districts in South Africa. To inform policy and budgeting, we conducted a cost evaluation of this service delivery model.
Methods
The evaluation was retrospective (October 2012–September 2013 for one district and April–September 2013 for the second district) and conducted from a provider cost perspective. Services evaluated included cervical cancer screening, HIV counselling and testing, syndromic management of sexually transmitted infections (STIs), breast exams, provision of condoms, contraceptives, and general health education. Fixed costs, including vehicle purchase and conversion, equipment, operating costs and mobile clinic staffing, were collected from program records and public sector pricing information. The number of women accessing different services was multiplied by ingredients-based variable costs, reflecting the consumables required. All costs are reported in 2013 USD.
Results
Fixed costs accounted for most of the total annual costs of the mobile clinics (85% and 94% for the two districts); the largest contributor to annual fixed costs was staff salaries. Average costs per patient were driven by the total number of patients seen, at $46.09 and $76.03 for the two districts. Variable costs for Pap smears were higher than for other services provided, and some services, such as breast exams and STI and tuberculosis symptoms screening, had no marginal cost.
Conclusions
Staffing costs are the largest component of providing mobile health services to rural communities. Yet, in remote areas where patient volumes do not exceed nursing staff capacity, incorporating multiple services within a cervical cancer screening program is an approach to potentially expand access to health care without added costs.

PLoS One
[Accessed 14 March 2015]
http://www.plosone.org/

A Survey of UK Healthcare Workers’ Attitudes on Volunteering to Help with the Ebola Outbreak in West Africa
Lance Turtle, Fiona McGill, Judy Bettridge, Claire Matata, Rob Christley, Tom Solomon
Research Article | published 11 Mar 2015 | PLOS ONE 10.1371/journal.pone.0120013
Abstract
Objective
To understand the barriers and enablers for UK healthcare workers who are considering going to work in the current Ebola outbreak in West Africa, but have not yet volunteered.
Design
After focus group discussions, and a pilot questionnaire, an anonymous survey was conducted using SurveyMonkey to determine whether people had considered going to West Africa, what factors might make them more or less likely to volunteer, and whether any of these were modifiable factors.
Participants
The survey was publicised among doctors, nurses, laboratory staff and allied health professionals. 3109 people answered the survey, of whom 472 (15%) were considering going to work in the epidemic but had not yet volunteered. 1791 (57.6%) had not considered going, 704 (22.6%) had considered going but decided not to, 53 (1.7%) had volunteered to go and 14 (0.45%) had already been and worked in the epidemic.
Results
For those considering going to West Africa, the most important factor preventing them from volunteering was a lack of information to help them decide; fear of getting Ebola and partners’ concerns came next. Uncertainty about their potential role, current work commitments and inability to get agreement from their employer were also important barriers, whereas clarity over training would be an important enabler. In contrast, for those who were not considering going, or who had decided against going, family considerations and partner concerns were the most important factors.
Conclusions
More UK healthcare workers would volunteer to help tackle Ebola in West Africa if there was better information available, including clarity about roles, cover arrangements, and training. This could be achieved with a well-publicised high quality portal of reliable information.

PNAS – Proceedings of the National Academy of Sciences of the United States of America
(Accessed 14 March 2015)
http://www.pnas.org/content/early/

The effects of reputational and social knowledge on cooperation
Edoardo Galloa,b,1,2 and Chang Yanc,1,2
Author Affiliations
Edited by Martin A. Nowak, Harvard University, Cambridge, MA, and accepted by the Editorial Board February 5, 2015 (received for review August 18, 2014)
Significance
Cooperation is essential for societies to prosper. Recent experiments show that cooperation emerges in dynamic networks in which subjects can select their connections. However, these studies fixed the amount of reputation information available and did not display the network to subjects. Here, we systematically vary the knowledge available to subjects about reputation and the network to investigate experimentally their roles in determining cooperation in dynamic networks. Common knowledge about everyone’s reputation is the main driver of cooperation leading to dense and clustered networks. The addition of common knowledge about the network affects the distribution of cooperative activity: cooperators form a separate community and achieve a higher payoff from within-community interactions than members of the less cooperative community.
Abstract
The emergence and sustenance of cooperative behavior is fundamental for a society to thrive. Recent experimental studies have shown that cooperation increases in dynamic networks in which subjects can choose their partners. However, these studies did not vary reputational knowledge, or what subjects know about other’s past actions, which has long been recognized as an important factor in supporting cooperation. They also did not give subjects access to global social knowledge, or information on who is connected to whom in the group. As a result, it remained unknown how reputational and social knowledge foster cooperative behavior in dynamic networks both independently and by complementing each other. In an experimental setting, we show that global reputational knowledge is crucial to sustaining a high level of cooperation and welfare. Cooperation is associated with the emergence of dense and clustered networks with highly cooperative hubs. Global social knowledge has no effect on the aggregate level of cooperation. A community analysis shows that the addition of global social knowledge to global reputational knowledge affects the distribution of cooperative activity: cooperators form a separate community that achieves a higher cooperation level than the community of defectors. Members of the community of cooperators achieve a higher payoff from interactions within the community than members of the less cooperative community.

PNAS – Proceedings of the National Academy of Sciences of the United States of America
(Accessed 14 March 2015)
http://www.pnas.org/content/early/

Human Ebola virus infection results in substantial immune activation
Anita K. McElroya,b, Rama S. Akondyc,d, Carl W. Davisc,d, Ali H. Ellebedyc,d, Aneesh K. Mehtae, Colleen S. Krafte,f, G. Marshall Lyone, Bruce S. Ribnere, Jay Varkeye, John Sidneyg,
Alessandro Setteg, Shelley Campbella, Ute Ströhera, Inger Damona, Stuart T. Nichola, Christina F. Spiropouloua,1, and Rafi Ahmedc,d,1
Author Affiliations
Contributed by Rafi Ahmed, February 7, 2015 (sent for review January 6, 2015; reviewed by Lawrence Corey and Barton F. Haynes)
Significance
In 2014, Ebola virus became a household term. The ongoing outbreak in West Africa is the largest Ebola virus outbreak ever recorded, with over 20,000 cases and over 8,000 deaths to date. Very little is known about the human cellular immune response to Ebola virus infection, and this lack of knowledge has hindered development of effective therapies and vaccines. In this study, we characterize the human immune response to Ebola virus infection in four patients. We define the kinetics of T- and B-cell activation, and determine which viral proteins are targets of the Ebola virus-specific T-cell response in humans.
Abstract
Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10–50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1–2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients’ discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

Science
13 March 2015 vol 347, issue 6227, pages 1169-1284
http://www.sciencemag.org/current.dtl

Review
Modeling infectious disease dynamics in the complex landscape of global health
Hans Heesterbeek1,*, Roy M. Anderson2, Viggo Andreasen3, Shweta Bansal4, Daniela De Angelis5, Chris Dye6, Ken T. D. Eames7, W. John Edmunds7, Simon D. W. Frost8, Sebastian Funk4, T. Deirdre Hollingsworth9,10, Thomas House11, Valerie Isham12, Petra Klepac8, Justin Lessler13, James O. Lloyd-Smith14, C. Jessica E. Metcalf15, Denis Mollison16, Lorenzo Pellis11,
Juliet R. C. Pulliam17,18, Mick G. Roberts19, Cecile Viboud18, Isaac Newton Institute IDD Collaboration
Author Affiliations
1Faculty of Veterinary Medicine, University of Utrecht, Utrecht, Netherlands.
2School of Public Health, Imperial College, London, UK.
3Roskilde University, Roskilde, Denmark.
4Georgetown University, Washington, DC, USA.
5MRC Biostatistics Unit, Cambridge, UK.
6WHO, Geneva, Switzerland.
7Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene Tropical Medicine, London, UK.
8University of Cambridge, Cambridge, UK.
9School of Life Sciences, University of Warwick, UK.
10School of Tropical Medicine, University of Liverpool, UK.
11Warwick Mathematics Institute, University of Warwick, Coventry, UK.
12Department of Statistical Science, University College London, London, UK.
13Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
14Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, USA.
15Department of Zoology, University of Oxford, Oxford, UK, and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA.
16Heriot-Watt University, Edinburgh, UK.
17Department of Biology–Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
18Division of International Epidemiology and Population Studies, Fogarty International Center, NIH, Bethesda, MD, USA.
19Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand.
Abstract
BACKGROUND
Despite many notable successes in prevention and control, infectious diseases remain an enormous threat to human and animal health. The ecological and evolutionary dynamics of pathogens play out on a wide range of interconnected temporal, organizational, and spatial scales that span hours to months, cells to ecosystems, and local to global spread. Some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or persist in environmental reservoirs. Many factors, including increasing antimicrobial resistance, human connectivity, population growth, urbanization, environmental and land-use change, as well as changing human behavior, present global challenges for prevention and control. Faced with this complexity, mathematical models offer valuable tools for understanding epidemiological patterns and for developing and evaluating evidence for decision-making in global health.
ADVANCES
During the past 50 years, the study of infectious disease dynamics has matured into a rich interdisciplinary field at the intersection of mathematics, epidemiology, ecology, evolutionary biology, immunology, sociology, and public health. The practical challenges range from establishing appropriate data collection to managing increasingly large volumes of information. The theoretical challenges require fundamental study of many-layered, nonlinear systems in which infections evolve and spread and where key events can be governed by unpredictable pathogen biology or human behavior. In this Review, we start with an examination of real-time outbreak response using the West African Ebola epidemic as an example. Here, the challenges range from underreporting of cases and deaths, and missing information on the impact of control measures to understanding human responses. The possibility of future zoonoses tests our ability to detect anomalous outbreaks and to estimate human-to-human transmissibility against a backdrop of ongoing zoonotic spillover while also assessing the risk of more dangerous strains evolving. Increased understanding of the dynamics of infections in food webs and ecosystems where host and nonhost species interact is key. Simultaneous multispecies infections are increasingly recognized as a notable public health burden, yet our understanding of how different species of pathogens interact within hosts is rudimentary. Pathogen genomics has become an essential tool for drawing inferences about evolution and transmission and, here but also in general, heterogeneity is the major challenge. Methods that depart from simplistic assumptions about random mixing are yielding new insights into the dynamics of transmission and control. There is rapid growth in estimation of model parameters from mismatched or incomplete data, and in contrasting model output with real-world observations. New data streams on social connectivity and behavior are being used, and combining data collected from very different sources and scales presents important challenges.
All these mathematical endeavors have the potential to feed into public health policy and, indeed, an increasingly wide range of models is being used to support infectious disease control, elimination, and eradication efforts.
OUTLOOK
Mathematical modeling has the potential to probe the apparently intractable complexity of infectious disease dynamics. Coupled to continuous dialogue between decision-makers and the multidisciplinary infectious disease community, and by drawing on new data streams, mathematical models can lay bare mechanisms of transmission and indicate new approaches to prevention and control that help to shape national and international public health policy.

Science
13 March 2015 vol 347, issue 6227, pages 1169-1284
http://www.sciencemag.org/current.dtl

In Depth
Infectious Diseases
As Ebola fades, a new threat
Leslie Roberts
A second, often overlooked, public health crisis is brewing in the countries hardest hit by Ebola, epidemiologists warn. The Ebola epidemic has devastated already weak public health systems and disrupted childhood vaccinations in Liberia, Guinea, and Sierra Leone. As a result, unless action is taken quickly, preventable childhood diseases will likely soar. Measles, in particular, is considered a sentinel of a broken health system, often hitting early and hard in the aftermath of a disaster. In a paper in this week’s issue of Science, researchers put some sobering numbers on the size of a potential measles outbreak in the region post-Ebola. In the worst case, they warn, a measles outbreak could kill thousands more people than Ebola has.

Report
Reduced vaccination and the risk of measles and other childhood infections post-Ebola
Saki Takahashi1, C. Jessica E. Metcalf1,2, Matthew J. Ferrari3, William J. Moss4, Shaun A. Truelove4, Andrew J. Tatem5,6,7, Bryan T. Grenfell1,6, Justin Lessler4,*
Author Affiliations
1Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544, USA.
2Woodrow Wilson School, Princeton University, Princeton, NJ 08544, USA.
3Centre for Infectious Disease Dynamics, Pennsylvania State University, State College, PA 16801, USA.
4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
5Department of Geography and Environment, University of Southampton, Southampton SO17 1BJ, UK.
6Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.
7Flowminder Foundation, 17177 Stockholm, Sweden.
Abstract
The Ebola epidemic in West Africa has caused substantial morbidity and mortality. The outbreak has also disrupted health care services, including childhood vaccinations, creating a second public health crisis. We project that after 6 to 18 months of disruptions, a large connected cluster of children unvaccinated for measles will accumulate across Guinea, Liberia, and Sierra Leone. This pool of susceptibility increases the expected size of a regional measles outbreak from 127,000 to 227,000 cases after 18 months, resulting in 2000 to 16,000 additional deaths (comparable to the numbers of Ebola deaths reported thus far). There is a clear path to avoiding outbreaks of childhood vaccine-preventable diseases once the threat of Ebola begins to recede: an aggressive regional vaccination campaign aimed at age groups left unprotected because of health care disruptions.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

Conference report
Safety of vaccine adjuvants: Focus on autoimmunity
Pages 1507-1514
Jan Willem van der Laan, Sarah Gould, Jennifer Y. Tanir, ILSI HESI Vaccines and Adjuvants Safety Project Committe
Highlights
:: Industrial, academic, and governmental experts studied vaccine adjuvants safety.
:: Evidence of signals for autoimmune disorders associated with adjuvants was reviewed.
:: Existing adjuvants (used in marketed vaccines) and novel adjuvants were included.
:: The focus was on oil-in-water emulsion and toll-like receptor agonist adjuvants.
:: No compelling evidence was found associating adjuvants and autoimmunity in humans
Abstract
Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine
Review Article
Pages 1518-1526
Isabelle Delrieu, Didier Leboulleux, Karen Ivinson, Bradford D. Gessner, For the Malaria Transmission Blocking Vaccine Technical Consultation Group
Abstract
Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

Assessing the economic benefits of vaccines based on the health investment life course framework: A review of a broader approach to evaluate malaria vaccination
Review Article
Pages 1527-1540
Dagna Constenla
Abstract
Background
Economic evaluations have routinely understated the net benefits of vaccination by not including the full range of economic benefits that accrue over the lifetime of a vaccinated person. Broader approaches for evaluating benefits of vaccination can be used to more accurately calculate the value of vaccination.
Methodology
This paper reflects on the methodology of one such approach – the health investment life course approach – that looks at the impact of vaccine investment on lifetime returns. The role of this approach on vaccine decision-making will be assessed using the malaria health investment life course model example.
Results
We describe a framework that measures the impact of a health policy decision on government accounts over many generations. The methodological issues emerging from this approach are illustrated with an example from a recently completed health investment life course analysis of malaria vaccination in Ghana. Beyond the results, various conceptual and practical challenges of applying this framework to Ghana are discussed in this paper.
Discussion and conclusions
The current framework seeks to understand how disease and available technologies can impact a range of economic parameters such as labour force participation, education, healthcare consumption, productivity, wages or economic growth, and taxation following their introduction. The framework is unique amongst previous economic models in malaria because it considers future tax revenue for governments. The framework is complementary to cost-effectiveness and budget impact analysis. The intent of this paper is to stimulate discussion on how existing and new methodology can add to knowledge regarding the benefits from investing in new and underutilized vaccines.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

The complementary roles of Phase 3 trials and post-licensure surveillance in the evaluation of new vaccines
Review Article
Pages 1541-1548
Pier Luigi Lopalco, Frank DeStefano
Abstract
Vaccines have led to significant reductions in morbidity and saved countless lives from many infectious diseases and are one of the most important public health successes of the modern era. Both vaccines’ effectiveness and safety are keys for the success of immunisation programmes. The role of post-licensure surveillance has become increasingly recognised by regulatory authorities in the overall vaccine development process. Safety, purity, and effectiveness of vaccines are carefully assessed before licensure, but some safety and effectiveness aspects need continuing monitoring after licensure; Post-marketing activities are a necessary complement to pre-licensure activities for monitoring vaccine quality and to inform public health programmes. In the recent past, the availability of large databases together with data-mining and cross-linkage techniques have significantly improved the potentialities of post-licensure surveillance. The scope of this review is to present challenges and opportunities offered by vaccine post-licensure surveillance. While pre-licensure activities form the foundation for the development of effective and safe vaccines, post-licensure monitoring and assessment, are necessary to assure that vaccines are effective and safe when translated in real world settings. Strong partnerships and collaboration at an international level between different stakeholders is necessary for finding and optimally allocating resources and establishing robust post-licensure processes.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

Acceptability of human papillomavirus vaccines among women older than 26 years
Original Research Article
Pages 1556-1561
Amanda F. Dempsey, Sarah E. Brewer, Jennifer Pyrzanowski, Carter Sevick, Sean T. O’lea
Abstract
Objective
To examine older women’s (>26 years) acceptance of the human papillomavirus (HPV) vaccine, and factors associated with this outcome.
Study design
A convenience sample of 872 women age 26–77 years were surveyed regarding the likelihood they would accept the HPV vaccine if offered to them by their provider, and factors associated with this outcome. Binomial regression, Chi square and MacNemar’s analyses were used to determine associations of this outcome with demographic, attitudinal, and experiential variables.
Results
The response rate was 60.8%. Half the respondents indicated they would want the vaccine, even if they had to pay for it. In multivariable analyses, the only factor associated with wanting the vaccine was higher self-reported knowledge about HPV (risk ratio 1.43, 95% Confidence Interval 1.12, 1.83). A majority of participants also believed that older women in general would want the vaccine if it were covered by insurance. However, this perspective was significantly diminished if the vaccine had to be paid for out of pocket (97% vs. 22% for 26–45 year olds; 84% vs. 20% for 46–65 year olds, 60% vs. 8% for 66+ year olds, p < 0.001). Nearly all (93%) believed primary care physicians should routinely discuss the vaccine with older women.
Conclusions
A high proportion of women over 26 would want the HPV vaccine if offered by their provider, even if they had to pay for it out of pocket. This suggests that if providers were to routinely offer the HPV vaccine to their older patients, many women would choose to get vaccinated.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

Reduction in HPV 16/18-associated high grade cervical lesions following HPV vaccine introduction in the United States – 2008–2012
Original Research Article
Pages 1608-1613
Susan Hariri, Nancy M. Bennett, Linda M. Niccolai, Sean Schafer, Ina U. Park, Karen C. Bloch, Elizabeth R. Unger, Erin Whitney, Pamela Julian, Mary W. Scahill, Nasreen Abdullah, Diane Levine, Michelle L. Johnson, Martin Steinau, Lauri E. Markowitz, the HPV-IMPACT Working Group
Abstract
Background
Prevention of pre-invasive cervical lesions is an important benefit of HPV vaccines, but demonstrating impact on these lesions is impeded by changes in cervical cancer screening. Monitoring vaccine-types associated with lesions can help distinguish vaccine impact from screening effects. We examined trends in prevalence of HPV 16/18 types detected in cervical intraepithelial neoplasia 2, 3, and adenocarcinoma in situ (CIN2+) among women diagnosed with CIN2+ from 2008 to 2012 by vaccination status. We estimated vaccine effectiveness against HPV 16/18-attributable CIN2+ among women who received ≥1 dose by increasing time intervals between date of first vaccination and the screening test that led to detection of CIN2+ lesion.
Methods
Data are from a population-based sentinel surveillance system to monitor HPV vaccine impact on type-specific CIN2+ among adult female residents of five catchment areas in California, Connecticut, New York, Oregon, and Tennessee. Vaccination and cervical cancer screening information was retrieved. Archived diagnostic specimens were obtained from reporting laboratories for HPV DNA typing.
Results
From 2008 to 2012, prevalence of HPV 16/18 in CIN2+ lesions statistically significantly decreased from 53.6% to 28.4% among women who received at least one dose (Ptrend < .001) but not among unvaccinated women (57.1% vs 52.5%; Ptrend = .08) or women with unknown vaccination status (55.0% vs 50.5%; Ptrend = .71). Estimated vaccine effectiveness for prevention of HPV 16/18-attributable CIN2+ was 21% (95% CI: 1–37), 49% (95% CI: 28–64), and 72% (95% CI: 45–86) in women who initiated vaccination 25–36 months, 37–48 months, and >48 months prior to the screening test that led to CIN2+ diagnosis.
Conclusions
Population-based data from the United States indicate significant reductions in CIN2+ lesions attributable to types targeted by the vaccines and increasing HPV vaccine effectiveness with increasing interval between first vaccination and earliest detection of cervical disease

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

HPV vaccine acceptance among adolescent males and their parents in two suburban pediatric practices
Original Research Article
Pages 1620-1624
Shalinee Khurana, Heather L. Sipsma, Rachel N. Caskey
Abstract
Purpose
To measure HPV vaccine acceptance among unvaccinated adolescent males and parents and correlate acceptance with knowledge, awareness, and personal experience.
Methods
Adolescent males ages 11–21 years old and their parents completed questionnaires measuring attitudes and knowledge about HPV vaccination and personal experience. Acceptance was defined as wanting the vaccine and conditional acceptance as wanting the vaccine if it would protect against genital warts or cervical cancer.
Results
Adolescent (n = 154) and parent (n = 121) vaccine acceptance was low (16% and 34%, respectively); however, conditional acceptance was higher. While adolescents had similar conditional acceptance for a vaccine against genital warts and cervical cancer, parents reported higher conditional acceptance for protection against genital warts. Independent predictors of acceptance included personal experience and demographic variables.
Conclusions
HPV vaccine acceptance among adolescents and parents was low. Conditional acceptance levels highlight the importance of education about a few important benefits of HPV vaccination, which may increase vaccination rates.

Vaccine
Volume 33, Issue 13, Pages 1507-1628 (24 March 2015)
http://www.sciencedirect.com/science/journal/0264410X/33/13

Healthcare worker influenza immunization vaccinate or mask policy: Strategies for cost effective implementation and subsequent reductions in staff absenteeism due to illness
Original Research Article
Pages 1625-1628
P.G. Van Buynder, S. Konrad, F. Kersteins, E. Preston, P.D. Brown, D. Keen, N.J. Murray
Abstract
Background
A new policy requiring staff in clinical areas to vaccinate or wear a mask was implemented in British Columbia (BC) in the 2012/13 winter. This review assessed the impact of the policy on absenteeism in health care workers.
Methods
A retrospective cohort study of full-time HCW that worked prior to and during the 2012/13 influenza season in a health authority in BC. The rate of absenteeism due to all cause illness was compared between vaccinated and unvaccinated staff controlling for behaviors outside influenza season.
Results
Of the 10079 HCW, 77% were vaccinated. By comparison to absenteeism rates in the pre-influenza season, unvaccinated staff in winter had twice the increase in absenteeism due to all-cause illness than vaccinated staff.
Conclusion
After controlling for baseline differences between those vaccinated and unvaccinated, influenza vaccination was associated with reduced absenteeism, saving the Health Authority substantial money. Having regular staff in attendance increases the quality of care.

Value in Health
March 2015 Volume 18, Issue 2, p137-354
http://www.valueinhealthjournal.com/current

Fairness versus Efficiency of Vaccine Allocation Strategies
Ming Yi, PhD, Achla Marathe, PhD
Published Online: January 14, 2015
DOI: http://dx.doi.org/10.1016/j.jval.2014.11.009
Abstract
Objectives
To develop a framework to objectively measure the degree of fairness of any allocation rule aimed at distributing a limited stockpile of vaccines to contain the spread of influenza.
Methods
The trade-off between the efficiency and fairness of allocation strategies was demonstrated through an illustrative simulation study of an influenza epidemic in Southwestern Virginia. A Susceptible-Exposed-Infectious-Recovered model was used to represent the disease progression within the host.
Results
Our findings showed that among all the criteria considered here, the household size (largest first) combined with age (youngest first)-based strategy leads to the best outcome. At 80% fairness, highest efficiency can be achieved but in order to be 100% fair, disease prevalence will have to rise by approximately 1.5%.
Conclusions
This research provides a framework to objectively determine the degree of fairness of vaccine allocation strategies.

Gynecologic Oncology Reports
Article in Press
Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer
L. Stewart Massad, Charlesnika T. Evans, Kathleen M. Weber, Gypsyamber D’Souza, Nancy A. Hessol, Rodney L. Wright, Christine Colie, Howard D. Strickler, Tracey E. Wilson
Open Access
DOI: http://dx.doi.org/10.1016/j.gore.2015.02.007
Highlights
:: Women at high risk for cervical cancer have substantial knowledge gaps about prevention
:: Knowledge gaps improved after an intervention, but little additional improvement followed
:: Poor and less educated women have lower knowledge scores despite higher cancer risk
Abstract
Purpose
To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination.
Methods
In 2007, 2008–9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models.
Results
In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0–24) increased from 2007 (12.8, S.D. 5.8) to 2008–9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D 5.2, P < 0.0001 vs 2007 and <0.04 vs 2008–9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline.
Conclusion
Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.

The Journal of Infectious Diseases
Advance Access
A Kunjin Replicon Virus-like Particle Vaccine Provides Protection Against Ebola Virus Infection in Nonhuman Primates
Oleg V. Pyankov1, Sergey A. Bodnev1, Olga G. Pyankova1,2, Vladislav V. Solodkyi1, Stepan A. Pyankov1, Yin Xiang Setoh2, Valentina A. Volchkova4, Andreas Suhrbier2,3, Viktor V. Volchkov4, Alexander A. Agafonov1 and Alexander A. Khromykh2
Author Affiliations
1State Center for Virology and Biotechnology Vector, Koltsovo, Russian Federation
2Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia
3QIMR Berghofer Medical Research Institute, Brisbane, Australia
4Molecular Basis of Viral Pathogenicity, CIRI, INSERM, U1111-CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon, France
Abstract
The current unprecedented outbreak of Ebola virus (EBOV) disease in West Africa has demonstrated the urgent need for a vaccine. Here, we describe the evaluation of an EBOV vaccine candidate based on Kunjin replicon virus-like particles (KUN VLPs) encoding EBOV glycoprotein with a D637L mutation (GP/D637L) in nonhuman primates. Four African green monkeys (Cercopithecus aethiops) were injected subcutaneously with a dose of 109 KUN VLPs per animal twice with an interval of 4 weeks, and animals were challenged 3 weeks later intramuscularly with 600 plaque-forming units of Zaire EBOV. Three animals were completely protected against EBOV challenge, while one vaccinated animal and the control animal died from infection. We suggest that KUN VLPs encoding GP/D637L represent a viable EBOV vaccine candidate.

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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Associated Press
Accessed 14 March 2015
Liberia removes Ebola crematorium as outbreak is contained
8 March 2015
Marking the progress in controlling its Ebola outbreak, the Liberian government dismantled a crematorium and removed drums containing the ashes of more than 3,000 Ebola victims cremated during the height of the epidemic, whose last patient was discharged last week.

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Brookings
http://www.brookings.edu/
Accessed 14 March 2015
Innovation
Using mobile technology to improve maternal health and fight Ebola
March 11, 2015, Darrell M. West
In a new paper, Darrell West examines how mobile technologies have improved maternal health care and helped deal with disease outbreaks in Africa.

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Forbes
http://www.forbes.com/
Accessed 14 March 2015
Carlos Slim’s Foundation Recognized For Work On Health, Research To Develop Anti-Chagas Vaccine
The Carlos Slim Foundation has been awarded two international awards in the past week in recognition of its contribution to public health and promotion of new technologies
Dolia Estevez, Contributor Mar 10, 2015

Naturopaths–Not What The Doctor Ordered For Vaccine Exemptions
There are lots of reasons why measles, having gone to Disneyland, is enjoying a comeback around the United States and Canada. Unfounded fears of autism scare some parents. Others buy the daffy conspiracy theory that pharmaceutical companies are just pushing vaccination to make a buck. Some parents invoke religious concerns […]
Arthur Caplan, Contributor Feb 24, 2015

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The Guardian
http://www.guardiannews.com/
Accessed 14 March 2015
Meet the man leading Britain’s fight against Ebola | World news
16 hours ago … From his lab in Liverpool, Professor Tom Solomon is heading UK efforts to combat Ebola. He’s hopeful we’ll have a treatment and vaccine …

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New Yorker
http://www.newyorker.com/
Accessed 14 March 2015
Why Doctors Give in on Vaccines – The New Yorker
Mar 5, 2015 … Many parents are asking for their children’s vaccinations to be delayed, and many physicians are agreeing, even though it puts patients at risk.

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New York Times
http://www.nytimes.com/
Accessed 14 March 2015
Vaccines Face Same Mistrust That Fed Ebola
MONROVIA, Liberia — West Africa’s Ebola epidemic may be waning, but another outbreak in the future is a near certainty, health officials say.
Now, the United States is helping to lead a large study of two vaccines against Ebola. But as researchers try to compress a clinical process that can take a decade into a fraction of the time, they are confronting the same volatile mix of skepticism, fear, false rumor and understandable mistrust that helped spread Ebola in the first place.
“When we look at Ebola, it came from America,” said Sylvester George, a pastor’s assistant, expressing doubts about the clinical trials at an information session. “It’s a man-made virus. So why didn’t they do this trial in America, but they decide to come to Liberia?”
Trials of Ebola drugs and vaccines are underway or planned in Liberia, Guinea and Sierra Leone, the three countries most affected by an epidemic that has claimed about 10,000 lives. But the study in Liberia of the two vaccines is the most ambitious, with American researchers from the National Institutes of Health and their Liberian counterparts hoping to enlist more than 27,000 participants under an agreement between their governments.
The trial’s scale alone has posed tough ethical and practical questions. American and Liberian officials have debated how to attract so many volunteers, how much to pay them and how to mobilize the public to extinguish crippling rumors before they take root, like the one asserting that Ebola vaccines were being slipped into children’s immunizations.
And there is an added layer of mistrust directed at one of the most important partners in the trial: the Liberian government.
After a government minister called on Liberians to “step up” and volunteer to test a new Ebola vaccine, angry callers on talk radio asked why no high-ranking government official had gotten a shot in the arm…

Americans Evacuated After Possible Ebola Contact
By SHERI FINK
MARCH 14, 2015
The first of a group of 10 American aid workers who may have come into contact with the Ebola virus in Sierra Leone were evacuated on Saturday, an American government official said. They will be the largest group of Americans to have returned home over fears of exposure to the virus since an outbreak in three West African countries was declared last year.
The 10 worked with the American medical aid group Partners in Health and were determined to have varying degrees of risk but no symptoms, said Sheila Davis, who leads Ebola response efforts for the charity. A medical worker for the charity was confirmed to have Ebola last week and returned to the United States Friday morning.
Another American aid worker with the group, who was showing signs of illness, arrived in the United States on Friday evening. She became sick last week, but tested negative for Ebola twice, said several officials unaffiliated with the charity, speaking on the condition of anonymity. She was sent to Emory University Hospital in Atlanta, which has a specialized unit for Ebola patients. The hospital had no information to provide on the patient, an Emory spokeswoman said Saturday…

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Wall Street Journal
http://online.wsj.com/home-page?_wsjregion=na,us&_homepage=/home/us
Accessed 14 March 2015
Oregon Lawmaker Drops Bill to Ban Most Vaccine Exemptions
Legislation aiming to pressure Oregon parents to get their children vaccinated was abandoned because of formidable opposition in a state that has the nation’s highest rate of nonmedical exemptions.
03/11/15

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Washington Post
http://www.washingtonpost.com/
Accessed 14 March 2015
As Ebola’s death toll surpasses 10,000, this is how grief and recovery look in West Africa
Ebola infections are down and Liberia has reported no new cases since last week. Yet, there is still grief over the tremendous — and in some cases, ongoing — loss.
Abby Phillip | National | Mar 13, 2015
American health-care worker with Ebola virus arrives at NIH Bethesda
Officials: A person was transported by a private charter plane from Sierra Leone.
Dana Hedgpeth | Local | Mar 13, 2015

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

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

– pdf version:  A pdf of the current issue is available here: Vaccines and Global Health_The Week in Review_7 March 2015

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

– 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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– Support:  If you would like to join the growing list of individuals who support this service and its contribution to their roles in public health, clinical practice, government, IGOs/NGOs, research, industry and academia, please visit this page at The Wistar Institute, our co-founder and fiduciary, and follow the relevant steps . Thank you…

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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 7 March 2015]
Public Health Emergency of International Concern (PHEIC); “Threat to international peace and security” (UN Security Council)

WHO: Ebola Situation Report – 4 March 2015
Corrigendum as of 6 March 2015]
[Excerpt; Editor’s text bolding]
SUMMARY
:: A total of 132 new confirmed cases of Ebola virus disease (EVD) were reported in the week to 1 March, an increase on the previous week (99 new cases). Liberia reported no new confirmed cases this week, the first time since the week of 26 May 2014. The weekly number of confirmed cases has increased in both Sierra Leone and Guinea. Transmission remains widespread in Sierra Leone, which reported new confirmed cases in 8 districts during the week to 1 March. In Guinea, Forecariah and Conakry reported a marked increase in case numbers compared with the previous week.

:: Guinea reported 51 new confirmed cases in the week to 1 March, compared with 35 cases the previous week. Cases continue to arise from unknown sources with only 49% of cases arising from registered contacts. Seven prefectures reported new cases, with the largest number of new confirmed cases reported from 3 neighbouring western prefectures: Conakry (17 cases), Coyah (5 cases), and Forecariah (23 cases). Macenta also reported 2 new confirmed cases, a district that has not reported a confirmed case for 4 weeks. Low levels of transmission continue in the eastern prefecture of Lola (1 new case), bordering Côte d’Ivoire.

:: Sierra Leone reported 81 new confirmed cases from 8 districts in the week to 1 March. A previously reported cluster of cases in the Aberdeen fishing community of the capital, Freetown, has seeded outbreaks in other districts, notably Bombali which reported 22 new confirmed cases. There were 26 new confirmed cases in Freetown and 16 new cases in Port Loko over the same period.

:: Liberia has reported no new confirmed cases this week. Contacts from the last known chain of transmission, in the St Paul’s Bridge district of Monrovia, are being monitored. In the week to 1 March, 277 samples were tested for EVD nationwide, no new test results were positive.

:: The number of confirmed EVD deaths occurring in the community in Guinea and Sierra Leone remains high, suggesting that the need for early isolation and treatment is not yet understood, accepted or acted upon. In Guinea in the week to 1 March over half (53%: 17 out of 32) of reported confirmed deaths occurred in the community, an increase from 42% the previous week (9 out of 21). In Sierra Leone, 16% of confirmed EVD deaths occurred in the community in the week to 1 March, compared with 21% the previous week.

:: Unsafe burials continue to occur, with 16 reports of unsafe burials in both Guinea and Sierra Leone, respectively, during the weeks to 1 March and to 22 February.
Laboratories in Guinea, Liberia and Sierra Leone processed 270, 277 and 1531 samples, respectively, in the week to 1 March.

:: Mindful of the risk of cross border transmission, delegations from Guinea, Mali and Senegal met on 25-26 February 2015 and agreed to strengthen cross-border cooperation in case management (including the sharing of laboratory resources), community-based surveillance, risk communication and information sharing, and screening at border crossings.

:: In the week to 1 March, 1 new health worker infection was reported Guinea, bringing the total of health worker infections reported across the three most-affected countries since the start of the outbreak to 839, with 491 deaths.

COUNTRIES WITH WIDESPREAD AND INTENSE TRANSMISSION
:: There have been over 23,900 reported confirmed, probable, and suspected cases cases of EVD in Guinea, Liberia and Sierra Leone (table 1), with over 9800 reported deaths (outcomes for many cases are unknown). A total of 51 new confirmed cases were reported in Guinea, 0 in Liberia, and 81 in Sierra Leone in the 7 days to 1 March.

:: The total number of confirmed and probable cases is similar in males and females (table 2). Compared with children (people aged 14 years and under), people aged 15 to 44 are approximately three times more likely to be affected. People aged 45 and over are nearly four times more likely to be affected than children.

:: A total of 839 confirmed health worker infections have been reported in the 3 intense-transmission countries; there have been 491 reported deaths…

Ebola vaccine efficacy trial ready to launch in Guinea
Joint news release WHO/MSF/NIPH

5 March 2015 ¦ GENEVA – Based on promising data from initial clinical trials in late 2014, WHO with the Health Ministry of Guinea, Médecins Sans Frontières (MSF), Epicentre and The Norwegian Institute of Public Health (NIPH), will launch a Phase III trial in Guinea on 7 March to test the VSV-EBOV vaccine for efficacy and effectiveness to prevent Ebola. The vaccine was developed by the Public Health Agency of Canada. A second vaccine will be tested in a sequential study, as supply becomes available.

“We have worked hard to reach this point,” said WHO Director-General, Dr Margaret Chan. “There has been massive mobilization on the part of the affected countries and all partners to accelerate the development and availability of proven interventions. If a vaccine is found effective, it will be the first preventive tool against Ebola in history.”

Vaccination will take place in areas of Basse Guinée, the region that currently has the highest number of cases in the country. The trial strategy adopted will be “ring vaccination”, based on the approach used to eradicate smallpox in the 1970s. This involves the identification of a newly diagnosed Ebola case – the “index case” – and the tracing of all his/her contacts. The contacts are vaccinated if they give their consent.

“The Ebola epidemic shows signs of receding but we cannot let down our guard until we reach zero cases,” said Assistant Director-General Marie-Paule Kieny, who leads the Ebola Research and Development effort at WHO. “An effective vaccine to control current flare-ups could be the game-changer to finally end this epidemic and an insurance policy for any future ones.”

The objectives of the trial are two-fold: to assess if the vaccine protects the contacts who were vaccinated and if vaccinating the contacts will create a buffer – or ring of protected individuals – around the index case to prevent further spread of the infection. Vaccination will also be proposed to frontline workers in the area where the trial will take place.

Canadian governmental institutions are supporting the trial through the provision of critical training and support to the African research teams conducting the trial, in addition to scientific advice.

In the last six months WHO has convened a series of emergency consultations with scientists, ethicists, regulators and policy makers to identify potential preventive and therapeutic products to help stem the epidemic. Canada’s VSV and GSK cAd3 vaccines quickly emerged as promising tools due to prior successful studies on non-human primates.

“For more than a year we have been racing around the clock to stop the epidemic from spreading further,” explains Bertrand Draguez, Medical Director at MSF.

“We need to ensure that we continue our efforts to identify infection cases and follow up on their contacts, and in parallel keep promoting R&D for treatments, diagnostics and vaccines.

This epidemic remains unpredictable. We don’t know when it will end, and that’s why it remains crucial for us to keep focusing our efforts on developing a vaccine capable of protecting the population in this epidemic and any future ones. Frontline workers and the contacts of infected patients will be enrolled, if they consent, in the vaccine study.”

“Participation of the community in the study areas in Guinea is vital to enable the successful assessment of this vaccine,” stresses John-Arne Røttingen, NIPH, and chair of the study steering group. “The study process has ensured the inclusion of Guinean investigators since its inception, and is a response to a request from Guinean authorities.”

Since September 2014, the two most advanced Ebola vaccines have been evaluated in about 15 countries in Africa, Europe and North America. The testing timelines were considerably accelerated through the simultaneous organization of multiple trials and emergency procedures to expedite data sharing and analysis between the investigators and manufacturers. The VSV-EBOV vaccine was selected for the planned trial based on a framework of parameters developed by the WHO Scientific and Technical Advisory Committee on Ebola Experimental interventions (STAC-EE). Criteria included acceptable safety profile, induction of appropriate immune responses, including neutralizing antibodies, and the timely availability of sufficient supplies of vaccine doses.

Further measures were taken to accelerate the testing process by organizing multi-country emergency assessments, joint ethical and regulatory reviews of trial protocols and clearing of regulatory hurdles. For the Guinea trial, the Guinea National Regulatory Authority with support from Health Canada jointly reviewed the trial protocol.

WHO, UNICEF, US Centers for Disease Control (CDC), the Bill and Melinda Gates Foundation and GAVI (the Global Vaccine Alliance) are collaborating with the affected countries to develop plans and strategies for large-scale introduction, should this be needed. The vaccines’ manufacturers have assured that enough vaccine will be available in the coming months. Financial resources are in place to procure and make vaccines available to the Ebola affected countries. Millions of doses will be funded by GAVI, whose Executive Board approved a US$ 300 million funding envelope in December 2014. There are also U$ 90 million earmarked to support the deployment of the vaccine(s).

Note to editors:
The vaccines: VSV-EBOV was developed by the Public Health Agency of Canada. The vaccine was licenced to NewLink Genetics, and on November 24, 2014, NewLink Genetics and Merck announced their collaboration on the vaccine. GlaxoSmithKline (GSK) developed the cAd3-ZEBOV vaccine in collaboration with the United States National Institutes for Health.
Ring vaccination was selected, with a design allowing part of the rings (contacts of the newly diagnosed Ebola case) to be vaccinated immediately after the case is detected, while other rings will be vaccinated 3 weeks later (delayed ring). This design allows for all contacts to be vaccinated by the end of the study, albeit with a short delay for some of them, rather than the standard alternative to use a placebo.

The trial design was developed by an international group of experts from Canada, France, Guinea, Norway, Switzerland, United Kingdom, United States, and WHO. The group included Professor Donald Henderson, who led the WHO smallpox eradication effort.

The partners: The Guinea Ebola vaccine trial is a coordinated effort among numerous international partners. The regulatory sponsor of the study is the World Health Organization (WHO): implemented by the Ministry of Health of Guinea, Médecins sans Frontières (MSF), EPICENTRE, the Norwegian Institute of Public Health and WHO. The trial is funded by MSF; the Research Council of Norway through Norway’s Institute of Public Health; the Canadian government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development; and WHO, with support from the Wellcome Trust, United Kingdom.
– Read the news release on Ebola vaccine efficacy trial
– Q&A on Ebola phase III vaccine trial in Guinea

UNMEER [to 7 March 2015]
https://ebolaresponse.un.org/un-mission-ebola-emergency-response-unmeer
:: From emergency to recovery: EU mobilises efforts to end Ebola and alleviate its impact
European Commission – Press release
Brussels, 03 March 2015
The “Ebola: from emergency to recovery” conference is taking place in Brussels today under the organisation and patronage of the European Union. While international efforts have reduced the number of Ebola infections in recent months, it is critical to maintain the momentum to prevent a sharp increase in new cases. The conference today aims to sustain the international mobilisation and to plan the next steps in the fight both against the current outbreak and the Ebola virus in general.
The Ebola conference is co-chaired by the European Union, the Presidents of Guinea, Liberia and Sierra Leone, the United Nations, the African Union and the Economic Community of West African States (ECOWAS). It brings together all key international players to prepare the actions needed now to bring the number of Ebola infections down to zero – and the measures to help the affected countries recover from the severe blows that the epidemic has dealt their people and economies…
– EU High Representative, Federica Mogherini, at the Ebola High Level Conference in Brussels
– UNDP Administrator, Helen Clark, “Statement to the media” at the Ebola High Level Conference in Brussels
– UNDP Administrator, Helen Clark, on the Ebola Recovery Assessment at the Ebola High Level Conference in Brussels
– World Bank Group Vice President for Global Practices, Keith Hansen, at the Ebola High Level Conference in Brussels
– UN Special Envoy on Ebola, David Nabarro, Slideshow presentation at the Ebola High Level Conference in Brussels
– UN Special Envoy on Ebola, David Nabarro, Talking points at the Ebola High Level Conference in Brussels
– UNDP Administrator, Helen Clark, opening of the Ebola High Level Conference in Brussels
– Statement of the Co-chairs at the Ebola High Level Conference, Brussels
– WFP Regional Director for West Africa, Denise Brown, at the Ebola High Level Conference in Brussels
– WHO Director-General, Margaret Chan, at the Ebola High Level Conference in Brussels
– UNICEF statement at the Ebola High Level Conference in Brussels

CDC/MMWR Watch [to 7 March 2015]
http://www.cdc.gov/media/index.html

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:: MMWR Weekly, March 6, 2015 / Vol. 64 / No. 8
– Update: Influenza Activity — United States, September 28, 2014–February 21, 2015
– Systems for Rapidly Detecting and Treating Persons with Ebola Virus Disease — United States
– Notes from the Field: Increase in Reported Crimean-Congo Hemorrhagic Fever Cases — Country of Georgia, 2014

Risking Repetition: Are We Ignoring Ebola’s Lessons?
International Rescue Committee
New York 02 Mar 2015 –
IRC report outlines significant missteps in the global response to Ebola

Over-focus on treatment, insufficient support for community-led engagement and lack of protection and support for local health workers slowed international response
The International Rescue Committee (IRC) today published a set of recommendations in response to the devastating Ebola outbreak as high-level delegates gather at the European Commission in Brussels to “take stock of the fight against the outbreak, coordinate further action for the total eradication of the disease and discuss the recovery process in the most affected countries.”

“The lesson of this crisis is that if you lose the trust of the community then you can’t run an effective health system. This is the warning we have to take on board to avoid the risk of repetition,” said IRC president and CEO, David Miliband.

The report highlights three key areas that are essential in stopping an outbreak like Ebola in the future:

:: Local Leadership is essential: Quarantines are a salient example of the essential role of local leadership. Enforced quarantines, such as the disastrous closure of the Monrovia neighborhood of West Point, served to fuel the epidemic. In contrast, self-imposed quarantines such as the ones organized in partnership between the IRC and local communities in Lofa Country played a significant role in stopping the epidemic. By and large, local leaders and volunteers were the most effective agents of change.

:: Health Care Workers Must be Paid and Properly Resourced: From Lofa County, Liberia, to Bo District in Sierra Leone the IRC heard directly from doctors and nurses who have not received a regular salary in months. When Ebola struck Liberia, health care workers had just been on strike to protest a lack of wages. With donor support, the governments of both countries must commit to paying their employees a regular and reliable salary. The ongoing response and future recovery must ensure that health care workers receive ongoing training, monitoring, mentorship and supervision.

:: Infection prevention and control across the board: Over five hundred health care workers died fighting Ebola. The IRC recognized that health care workers were putting their lives on the line to fight Ebola and instituted rigorous infection and prevention control trainings across Kenema district. It is imperative that we don’t let up. Practices put in place now must be continued and supported. These efforts need to be extended to schools and other public facilities. This is important as a means to restore the public’s trust…

POLIO [to 7 March 2015]
Public Health Emergency of International Concern (PHEIC)

GPEI Update: Polio this week – As of 4 March 2015
Global Polio Eradication Initiative
[Editor’s Excerpt and text bolding]
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: • On the 27 February the Director General accepted the recommendations made by the Emergency Committee of the International Health Regulations concerning the international spread of wild poliovirus. The statement of the recommendations from this fourth meeting can be found here.
• The polio legacy is being demonstrated in action through the work of 26 surveillance experts from the National Polio Surveillance Programme in India who have been deployed to Sierra Leone to support the Ebola outbreak response. Read more.
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
:: Four new wild poliovirus type 1 (WPV1) cases were reported in the past week. Two cases were reported in Khyber agency, in the Federally Administered Tribal Areas, 1 in Killa Abdullah district of Balochistan province (previously uninfected in 2015) and 1 in Tank district, in Khyber Pakhtunkhwa. The total number of WPV1 cases in 2014 remains 306, and 13 for 2015. The most recent case had onset of paralysis on 3 February in Balochistan.
Statement on the 4th IHR Emergency Committee meeting regarding the international spread of wild poliovirus
WHO statement
27 February 2015
[Editor’s text bolding]
The fourth meeting of the Emergency Committee under the International Health Regulations (IHR) (2005) regarding the international spread of wild poliovirus in 2014 – 15 was convened via teleconference by the Director-General on 17 February 2015. The following IHR States Parties submitted an update on the implementation of the Temporary Recommendations since the Committee last met on 13 November 2014: Cameroon, Equatorial Guinea, Pakistan and the Syrian Arab Republic.

The Committee noted that the international spread of wild poliovirus has continued with one new exportation from Pakistan into neighbouring Afghanistan documented after 13 November 2014. Although there is seasonal decline in the number of reported cases in Pakistan, transmission is ongoing in each of the four provinces and the Federally Administered Tribal Areas. The Committee assessed the risk of international spread from Pakistan to be sustained. The Committee appreciated that Pakistan has prepared a new robust ‘low season’ vaccination plan, established national and provincial emergency operations centres, and resumed campaigns in South and North Waziristan. Nonetheless, the principal factors underpinning the international spread of wild poliovirus from Pakistan have not yet changed sufficiently since the date of the third meeting of the Emergency Committee on 13 November 2014.

There has been no other documented international spread of wild poliovirus since March 2014. Although the risk of new international spread from the nine other infected Member States appears to have declined, the possibility of international spread still remains a global threat worsened by the expansion of conflict-affected areas, particularly in the Middle East and Central Africa. Furthermore, countries affected by conflict inevitably experience a decline in health service delivery that leads to deterioration of immunization systems in a number of such at-risk countries.

The Committee assessed that the spread of polio still constitutes a Public Health Emergency of International Concern and recommended the extension of the Temporary Recommendations for a further 3 months.

The committee considered the following factors in reaching this unanimous conclusion:
1. The continued international spread of wild poliovirus through 2014;

2. The risk and consequent costs of failure to eradicate globally one of the world’s most serious vaccine preventable diseases;

3. The continued necessity of a coordinated international response to stop the international spread of wild poliovirus and to prevent new spread with the onset of the high transmission season in May/June 2015;

4. The serious consequences of further international spread for the increasing number of countries in which immunization systems have been disrupted by armed conflict and complex emergencies. Populations in these fragile states are vulnerable to infection and outbreaks of polio which are exceedingly difficult to control;

5. The importance of a regional approach and cooperation as much international spread of polio occurs over land borders.

The Committee sincerely appreciated the efforts that all countries have made in response to the temporary recommendations and reviewed the progress against the criteria previously established by the Committee for countries to respond to under the IHR. The Committee remains concerned that implementation of the Temporary Recommendations is incomplete in all affected countries, many of whom are affected by regional conflicts.

The Committee provided the Director-General with the following advice aimed at reducing the risk of international spread of wild poliovirus, based on an updated risk stratification of the 10 countries that had earlier met the criteria for ‘States currently exporting wild poliovirus’ or ‘States infected with wild poliovirus but not currently exporting ‘. A third risk category has been added by the Committee for ‘States no longer infected by wild poliovirus, but which remain vulnerable to international spread’. The committee also noted the feedback from the four exporting countries that highlighted the challenges of implementing polio eradication measures in situations where there is significant cross-border population movement, often across long borders and common epidemiological blocks. The committee therefore recommended that countries apply a regional approach and develop joint immunisation strategies with neighbouring countries.
[Specific recommendation for States continue…]

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Pakistani Officials Issue Arrest Warrants Over Refusals of Polio Vaccine
By ISMAIL KHAN
New York Times, FEB. 27, 2015
PESHAWAR, Pakistan — Determined to curb Pakistan’s polio crisis, police officials in the northwestern province of Khyber-Pakhtunkhwa said Friday that they had issued hundreds of arrest warrants for parents for refusing to vaccinate their children.

“We had 13,000 to 16,000 refusal cases,” the deputy police commissioner for Peshawar, Riaz Khan Mahsud, said in an interview. “There is total determination on our part. We shall convince parents of the good of vaccinating their children, but if they refuse, we shall detain them. There is no leniency.”

The police in other districts of the province also reported issuing warrants, though no official total was released.

“The number keeps fluctuating,” said a senior government official, speaking on the condition of anonymity because he was not authorized to brief the news media. “We are applying different laws. You have to resort to coercive measures when persuasion fails.”

The official added: “The application of laws is working. Some parents readily agree to vaccinate children to avoid detention. Others take a few days behind the bars to see reason. We take an affidavit from them and let them go if they bring kids for vaccination.”…

WHO & Regionals [to 7 March 2015]

:: Ten top issues for women’s health
6 March 2015 — International Women’s Day is a day to celebrate women and their achievements. It’s also a day to take stock of how women’s rights, especially the right to health, are fulfilled in the world. Women still face many health problems. 8 March is an opportunity to re-commit to addressing issues ranging from cancer to reproductive health, from mental health to HIV. That’s why WHO and its partners are developing a new global strategy for women’s, children’s, and adolescents’ health.
Read about the top 10 health issues for women

:: Global Alert and Response (GAR): Disease Outbreak News (DONs)
– 6 March 2015 Measles – WHO European Region
– 6 March 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) – Saudi Arabia

:: The Weekly Epidemiological Record (WER) 6 March 2015, vol. 90, 10 (pp. 89–96) includes:
– Soil-transmitted helminthiases: number of children treated in 2013
– Ebola virus disease (EVD) in West Africa: an extraordinary epidemic
:: WHO Regional Offices
WHO African Region AFRO
:: WHO strives to provide universal access to immunization in the African Region by 2020
Brazzaville, 6 March 2015 – In efforts to prevent vaccine preventable diseases, health experts concluded a four-day meeting from 2 to 5 March that aimed to ensure that every child in the African Region has access to life-saving vaccines. It is estimated that over three million children under five years of age die each year in the Region and a significant number of these deaths could be prevented by vaccines.
One of the recent developments in the field of immunization is the existence of a Regional Strategic Plan for Immunization 2014–2020, endorsed by Member States during the 64th session of the Regional Committee meeting in November 2014, which provides policy and programmatic guidance to Member States for their immunization programmes. This strategic plan addresses the challenges countries in the WHO African Region and their partners need to overcome to provide universal access to immunization for all eligible populations by 2020…
…The two-day meeting, which was well attended, had immunization partners like the Bill & Melinda Gates Foundation (BMGF), U.S. Centers for Disease Prevention and Control (CDC), USAID, United Nations Children’s Fund (UNICEF), Rotary International, Gavi the Vaccine Alliance, Médecins Sans Frontières (MSF), the Network for Education and Support for Immunization (NESI) as well as the different Immunization Advisory Bodies in the Region, namely, the Task Force on Immunization (TFI) in Africa, the African Regional Certification Committee (ARCC), the Measles and Rubella Technical Advisory Group among others present.

:: Sugars contributing to emerging health threats in Africa – 04 March 2015

WHO Region of the Americas PAHO
:: PAHO and WHO urge countries to reduce sugar consumption among adults and children (03/04/2015)

:: Congenital anomalies are the second-leading cause of death in children under 5 in the Americas (03/02/2015)

WHO South-East Asia Region SEARO
:: Prevent birth defects, provide care for survivors 03 March 2015

WHO European Region EURO
:: European countries to meet in April to review progress on environment and health 05-03-2015

WHO Eastern Mediterranean Region EMRO
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WHO Western Pacific Region
:: WHO First Embrace campaign to save more than 50 000 newborn babies a year in the Region
MANILA, 5 March 2015 – The World Health Organization (WHO) Region for the Western Pacific launched First Embrace today — a campaign highlighting simple steps that will save more than 50 000 newborn lives, and prevent hundreds of thousands of complications each year from unsafe practices in newborn care in the Region.
– Read the news release

BMGF – Gates Foundation Watch [to 7 March 2015]
http://www.gatesfoundation.org/Media-Center/Press-Releases

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The Bill & Melinda Gates Foundation and CureVac Collaborate to Accelerate the Development of Transformative Vaccine Technology
– Equity investment of $52 million (€ 46 million) to support construction of a new Good Manufacturing Practice (GMP) production facility
– Foundation will separately fund vaccine development programs with the potential to revolutionize the prevention of a wide range of infectious diseases

SEATTLE and TÜBINGEN, Germany, March 5, 2015 /PRNewswire-USNewswire/ — The Bill & Melinda Gates Foundation and CureVac today announced that the foundation has made a commitment to invest $52 million (€46 million) in CureVac, a leading clinical-stage biopharmaceutical company specializing in mRNA-based vaccine technologies. As part of the agreement, the foundation will also provide separate funding for several projects to develop prophylactic vaccines based on CureVac’s proprietary messenger RNA (mRNA) platform. In addition, CureVac’s longstanding investor dievini Hopp BioTech announced a commitment of $24 million (€21 million) of additional equity.

CureVac is pioneering the use of natural and chemically unmodified mRNA as a data carrier to instruct the human body to produce its own proteins capable of fighting a wide range of diseases. CureVac’s novel technology is the broadest and most advanced mRNA therapeutic platform and allows for rapid, low-cost production of multiple drugs and vaccines. Additionally, CureVac’s mRNA vaccines are thermostable, which eliminates the demand for cold-chain storage and infrastructure, a major challenge in the vaccine supply of most developing countries.

The investment will support continued development of CureVac’s platform technology and the construction of an industrial scale Good Manufacturing Practice (GMP) production facility. As part of this partnership, CureVac and the Gates Foundation will collaborate on the development and production of numerous vaccines against infectious diseases that disproportionately affect people in the world’s poorest countries.

“If we can teach the body to create its own natural defenses, we can revolutionize the way we treat and prevent diseases,” said Bill Gates, co-chair of the Bill & Melinda Gates Foundation. “Technologies like mRNA give us confidence to place big bets for the future. We are pleased to partner with CureVac who has been pioneering this technology.”

“This collaboration will ensure that one of medicine’s most promising new technologies is applied to the challenge of reaching all people with the affordable, life-saving vaccines they need,” said Sue Desmond-Hellmann, CEO of the Bill & Melinda Gates Foundation.

The Gates Foundation will provide additional funding – beyond the equity investment – for multiple projects developing vaccines for viral, bacterial and parasitic infectious diseases. The foundation has started work with CureVac on initial projects for diseases such as rotavirus and HIV.

“When I first met CureVac’s founders 10 years ago, their vision and technology reminded me of the beginnings of the software industry: mRNA is like software that is able to teach the body to reprogram itself in order to fight cancer and infectious disease. Even today I am not aware of any other biomolecule with such versatile potential,” said Dietmar Hopp, through dievini Hopp Biotech, the primary shareholder in CureVac. “I am delighted that Bill Gates and the foundation see it the same way.”

Ingmar Hoerr, co-founder and CEO of CureVac, said, “With the Bill & Melinda Gates Foundation we have found another strong and highly committed investor to support us in expanding our mRNA platform at an accelerated pace. We look forward to commencing our mutually beneficial partnership which will allow CureVac to contribute its versatile technology to combat many serious infectious diseases while also benefiting from the foundation’s significant network and expertise in the vaccine market. We also very much appreciate the additional commitment from our longstanding investor. We feel very well-positioned to scale up our GMP manufacturing capabilities in order to supply the world markets with our products.”

Under the terms of the agreement, any Gates Foundation-funded products will be made available by CureVac at an affordable price in poor countries. CureVac will be able to merchandise each Gates-funded product in developed countries on its own, through licensees or a combination of both. In addition, the new manufacturing facility will have dedicated capacity to focus on products resulting from Gates Foundation-related projects.

Development of Dengue Vaccines – Status Review and Future Considerations
REPORT OF THE ASIA-PACIFIC DENGUE PREVENTION BOARD MEETING
Seoul, Korea November 21 – 22, 2014 :: 38 pages
Pdf: http://www.denguevaccines.org/sites/default/files/APDPB%202014%20report_final_3615.pdf
Overview
In November of 2014, DVI held a two-day meeting to discuss the status of a dengue vaccine and exchange views on its licensure and introduction. Members of the Asia-Pacific Dengue Prevention Board (DPB), modelers of the impact of vaccination on dengue, public health specialists and dengue vaccine candidate representatives contributed to these conversations.

The Board convened at a critical time — 2014 marked a milestone for the fight against dengue fever, with the first ever successful completion of Phase III clinical trials on a dengue vaccine candidate (CYD-TDV). These trials demonstrated that a vaccine that can prevent dengue cases is feasible, showing both safety and overall moderate efficacy, especially against the most severe outcomes of dengue infection, in both Asia and the Americas. At the same time, other vaccine candidates continued to progress in clinical development throughout the year, as did modeling of the impact of vaccination on dengue incidence.

These updates, and the new information they contribute to the field of dengue research, warrant a reassessment of the potential implications of dengue vaccine introduction in endemic countries. DVI will continue to support countries’ efforts to successfully plan for the introduction of dengue vaccines through evidenced-based research to help inform decision-making. One of these efforts is the upcoming Americas DPB meeting in March 16 and 17 in Bogota, Colombia. DVI looks forward to what is sure to be another productive exchange — one that can complement the conversations had in Seoul and raise points for further analysis, discussion, and knowledge sharing.

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Professor Wilder-Smith Named New Senior Advisor to DVI
WASHINGTON, DC – March 6, 2015 – The members of the Dengue Vaccine Initiative (DVI) consortium, the International Vaccine Institute, the Johns Hopkins University International Vaccine Access Center, the Sabin Vaccine Institute and the World Health Organization, are delighted to announce the appointment of Professor Annelies Wilder-Smith as Senior Advisor to the DVI, effective immediately.

“We are extraordinarily pleased that Professor Wilder-Smith has joined us to provide guidance to DVI and ensure a smooth transition until a new full-time Director joins the Initiative. Her leadership in the research of dengue control and surveillance strategies will contribute to our efforts of laying the groundwork for the introduction of a dengue vaccine” said Dr. Jerome Kim, International Vaccine Institute Director General…

Financing Investments in Young Children Globally
Summary of a Joint Workshop by the Institute of Medicine, National Research Council, and The Centre for Early Childhood Education and Development, Ambedkar University, Delhi (2015)
March 6, 2015 :: 108 pages ISBN: 978-0-309-31610-1
Pdf dowmload: https://www.nap.edu/login.php?record_id=18993&page=http%3A%2F%2Fwww.nap.edu%2Fdownload.php%3Frecord_id%3D18993
Overview
On August 26–27, 2014, the Forum on Investing in Young Children Globally hosted its second workshop, in New Delhi, India. The forum’s first workshop, titled “The Cost of Inaction,” was held in Washington, DC, in April 2014 and focused on the science of promoting optimal development through investing in young children and the potential eco-nomic consequences of inaction. This second workshop, on financing investments for young children, built on the first workshop and brought together stakeholders from such disciplines as social protection, nutrition, education, health, finance, economics, and law and included practitioners, advocates, researchers, and policy makers.

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FORUM ON INVESTING IN YOUNG CHILDREN GLOBALLY – OVERVIEW
In January 2014, the Board on Children, Youth, and Families of the Institute of Medicine (IOM) and the National Research Council (NRC), in collaboration with the IOM Board on Global Health, launched the Forum on Investing in Young Children Globally. At this meeting, the participants agreed to focus on creating and sustaining, over 3 years, an evidence-driven community of stakeholders that aims to explore existing, new, and innovative science and research from around the world and translate this evidence into sound and strategic investments in policies and practices that will make a difference in the lives of children and their caregivers.

Forum activities will highlight the science and economics of integrated investments in young children living in low-resourced regions of the world across the areas of health, nutrition, education, and social protection.

As a result, the forum will explore a holistic view of children and caregivers by integrating analyses and disciplines that span from neurons to neighborhoods and discuss the science from the microbiome to culture. Moreover, the forum will support an integrative vision to strengthen human capital. This work will be done through the forum and will engage in a series of stakeholder consultative sessions or public workshops, each focusing on specific aspects of science integration, bridging equity gaps, and implementing and scaling evidence-informed efforts.

A set of forum goals includes supporting the development of integrated science on children’s health, nutrition, education, and social protection and working with policy makers, practitioners, and researchers to raise awareness of integrated approaches to improve the lives of children and their caregivers. Forum objectives to meet these goals are as follows:

1. To shape a global vision of healthy child development across cultures and contexts, extending from preconception through at least age eight, and across currently siloed areas of health, nutrition, education, and social protection.

2. To identify opportunities for intersectoral coordination among researchers, policy makers, implementers, practitioners, and advocates to improve quality practices in public and private settings and bring these practices to scale, in the context of the economics of strategic, integrated investing in young children.

3. To inform ongoing conversations and activities of groups working on issues related to young children globally, such as the sustainable development goals and indicators being developed.

4. To identify current models of program and policy financing across health, education, nutrition, and social protection within the framework of reproductive, maternal, newborn, and child health that aim to improve children’s developmental potential.

This information could be used to illuminate opportunities for new financing structures and forms of investments that may be more effective in improving child outcomes and potentially drive economic development.

BMC Public Health
(Accessed 7 March 2015)
http://www.biomedcentral.com/bmcpublichealth/content

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Research article
The HIV epidemic and sexual and reproductive health policy integration: views of South African policymakers
Diane Cooper, Joanne E Mantell, Jennifer Moodley, Sumaya Mall BMC Public Health 2015, 15:217 (4 March 2015)
Abstract (provisional)
Background
Integration of sexual and reproductive health (SRH) and HIV policies and services delivered by the same provider is prioritised worldwide, especially in sub-Saharan Africa where HIV prevalence is highest. South Africa has the largest antiretroviral treatment (ART) programme in the world, with an estimated 2.7 million people on ART, elevating South Africa’s prominence as a global leader in HIV treatment. In 2011, the Southern African HIV Clinicians Society published safer conception guidelines for people living with HIV (PLWH) and in 2013, the South African government published contraceptive guidelines highlighting the importance of SRH and fertility planning services for people living with HIV. Addressing unintended pregnancies, safer conception and maternal health issues is crucial for improving PLWH’s SRH and combatting the global HIV epidemic. This paper explores South African policymakers’ perspectives on public sector SRH-HIV policy integration, with a special focus on the need for national and regional policies on safer conception for PLWH and contraceptive guidelines implementation.
Methods
It draws on 42 in-depth interviews with national, provincial and civil society policymakers conducted between 2008–2009 and 2011–2012, as the number of people on ART escalated. Interviews focused on three key domains: opinions on PLWH’s childbearing; the status of SRH-HIV integration policies and services; and thoughts and suggestions on SRH-HIV integration within the restructuring of South African primary care services. Data were coded and analysed according to themes.
Results
Participants supported SRH-HIV integrated policy and services. However, integration challenges identified included a lack of policy and guidelines, inadequately trained providers, vertical programming, provider work overload, and a weak health system. Participants acknowledged that SRH-HIV integration policies, particularly for safer conception, contraception and cervical cancer, had been neglected. Policymakers supported public sector adoption of safer conception policy and services. Participants interviewed after expanded ART were more positive about safer conception policies for PLWH than participants interviewed earlier.
Conclusion
The past decade’s HIV policy changes have increased opportunities for SRH –HIV integration. The findings provide important insights for international, regional and national SRH-HIV policy and service integration initiatives.

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Debate
A critical review of population health literacy assessment
Diana Guzys1*, Amanda Kenny1, Virginia Dickson-Swift1 and Guinever Threlkeld2
Abstract
Background
Defining health literacy from a public health perspective places greater emphasis on the knowledge and skills required to prevent disease and for promoting health in everyday life. Addressing health literacy at the community level provides great potential for improving health knowledge, skills and behaviours resulting in better health outcomes. Yet there is a notable absence of discussion in the literature of what a health literate population looks like, or how this is best assessed.
Discussion
The emphasis in assessing health literacy has predominantly focused on the functional health literacy of individuals in clinical settings. This review examines currently available health literacy assessment tools to identify how well suited they are in addressing health literacy beyond clinical care settings and beyond the individual. Although public health literature appears to place greater emphasis on conceptualizing critical health literacy, the focus continues to remain on assessing individuals, rather than on health literacy within the context of families, communities and population groups. When a population approach is adopted, an aggregate of individual health literacy assessment is generally used. Aggregation of individual health literacy fails to capture the dynamic and often synergistic relationships within communities, and fails to reflect societal influences on health knowledge, beliefs and behaviours.
We hypothesise that a different assessment framework is required to adequately address the complexities of community health literacy. We assert that a public health approach, founded on health promotion theories provides a useful scaffold to assess the critical health literacy of population groups. It is proposed that inclusion of community members in the research process is a necessary requirement to coproduce such an appropriate assessment framework.
Summary
We contend that health literacy assessment and potential interventions need to shift to promoting the knowledge and skills essential for critical health literacy at a societal level. The challenge for researchers is to negotiate the myriad of complexities associated with each concept and component required for this task.