Nature Medicine
December 2014, Volume 20 No 12 pp1355-1492
http://www.nature.com/nm/journal/v20/n12/index.html

Nature Medicine | Editorial
Principled compassion
oi:10.1038/nm.3772
Published online
04 December 2014
Abstract
Investigational drugs can save or extend lives, and seriously ill patients not able to take part in clinical trials should have access to such drugs whenever possible. In a climate of increased public pressure for this access—often termed compassionate use—five states in the US have passed so-called ‘right to try’ legislation. These laws are ill advised, as they are not likely to substantially increase access and have the potential to compromise the clinical trial system.

Nature Medicine | News
University travel bans and quarantines may impede Ebola response
Cassandra Willyard
doi:10.1038/nm1214-1359
Published online
04 December 2014

Travel to and from West Africa has become increasingly burdensome for researchers and health workers helping to curb the spread of an Ebola outbreak that has killed nearly 5,000 people in the past year. In October, US universities began banning campus-sponsored travel to Liberia, Sierra Leone and Guinea and began strongly discouraging travel to these countries for personal reasons, including volunteer work. As of 29 October, the guidelines set by the US Centers for Disease Control and Prevention advise health officials to monitor the condition of those arriving from Ebola-affected countries for 21 days—the maximum incubation period for the disease. But some institutions are also asking these individuals to stay away from campus during that time, regardless of their exposure to the virus. Although these policies are designed to prevent the spread of Ebola, they may also be hampering the response to the outbreak in West Africa.

“Universities in a time of crisis have historically been able to step up and provide not just research and other resources like that, but really personnel and expertise,” says Phuoc Le, a physician at the University of California, San Francisco (UCSF) who was headed to Liberia on 6 November to work with a nonprofit called Last Mile Health. Whereas UCSF is encouraging doctors and nurses to go to West Africa, Le adds, others are “putting up multiple barriers that are hard for individual faculty or staff to overcome.”

For example, as of early November, when this story went to press, Stanford University School of Medicine is prohibiting Stanford-related travel to the countries affected by Ebola and is adopting the 21-day rule, regardless of whether travelers are symptomatic or came into contact with infected individuals. Columbia University in New York has advised staff and students to avoid traveling to West Africa. Anyone wishing to make the trip must apply for an exception and sign a letter emphasizing that “evacuation of patients with Ebola symptoms may not be achievable.” Travelers must also submit an evacuation plan in case of emergency…

New England Journal of Medicine
December 4, 2014 Vol. 371 No. 23
http://www.nejm.org/toc/nejm/medical-journal

Online First
Perspective
Evaluating Ebola Therapies — The Case for RCTs
Edward Cox, M.D., M.P.H., Luciana Borio, M.D., and Robert Temple, M.D.
December 3, 2014
DOI: 10.1056/NEJMp1414145
The worst Ebola epidemic in history is ongoing. With the number of deaths from Ebola virus disease (EVD) already in the thousands and predicted to rise to tens of thousands,1 the situation is tragic. No treatments have yet been shown to be safe and effective in patients with EVD. Some candidate therapies have shown benefit in animal models of infection, and others have shown activity against certain Ebola strains in cell culture, but concerns have been raised about possible toxicity of some of these agents. There is an urgent need to identify therapies that are effective and safe, and well-designed clinical trials are the fastest and most reliable way to achieve that goal.

Studying investigational therapies for EVD presents scientific, practical, and ethical challenges. Not surprisingly, there has been substantial debate about the best and most appropriate study approaches.2,3 It is generally agreed that a trial with a concurrent control group, in which patients are randomly assigned to receive the test drug plus the best available supportive care (BASC) or to BASC alone, would be the most efficient and reliable way to evaluate the safety and effectiveness of candidate products. Some people in the health care community, however, have argued against such trials, urging instead use of a historical control — that is, making investigational drugs as widely available as their supply allows and then comparing mortality rates among treated patients with rates that would have been expected absent the drugs, on the basis of past experience with EVD. The desire to allow all patients access to investigational drugs is understandable, but there are strong reasons to doubt the ability of such “historically controlled” studies to distinguish effective therapies from ineffective ones.
Insofar as such studies cannot reliably identify effective treatments, their use could have tragic consequences. If historical comparisons falsely suggest a benefit or fail to detect modest but meaningful clinical effectiveness, the investigational drug might be erroneously adopted as effective or discarded as ineffective. Possible consequences include exposure of subsequent patients to harm or to lack of effect from the mistakenly adopted treatment and failure to use a drug with a real, though modest, ability to improve survival, as well as failure to further develop an intervention that provides meaningful benefit.
Historically controlled studies compare study outcomes with outcomes in an external group that is thought to be similar to the study participants. The challenge of such trials is identifying a pertinent historical experience. If the two groups are not similar, observed differences in results may be unrelated to the therapy, instead reflecting underlying differences between the groups or differences in supportive care.

Case fatality rates in past outbreaks of EVD have ranged from less than 50% to more than 80%,4 and even limited supportive care probably improves survival rates. Thus, the historical case fatality rates are irrelevant if current study patients receive better supportive care. Without clear knowledge of the mortality that would be expected with the study’s level of supportive care, a historically controlled study cannot determine whether a treatment has helped or harmed patients.5 In a randomized trial, by contrast, all patients would receive similar supportive care, so that the effect (or lack of effect) of the added treatment could be assessed. Moreover, such a trial could detect even a small but meaningful benefit that a historically controlled trial could not credibly identify.

Randomized, controlled trials (RCTs) with a BASC control group are a powerful tool for evaluating effects of an investigational therapy. Randomization ensures reasonable similarity of the test and control groups and protects against various imbalances and biases that could lead to erroneous conclusions. Properly designed RCTs that give reliable answers are critical to identifying urgently needed treatments for responding to the ongoing Ebola crisis and any future outbreaks.

The number of infected patients greatly exceeds the supply of certain investigational agents. Regardless of debates over trial design or ethics, when there are only limited supplies, most patients cannot receive specific antiviral therapy. RCTs for evaluating these agents will therefore not be depriving patients of treatment but will provide a pathway for identifying effective treatments as rapidly and reliably as possible. Even when sufficient supplies are available, RCTs will provide the definitive answer on effectiveness, in a generally quicker fashion than alternative trial designs.

When preclinical data suggest that a candidate treatment has a low likelihood of clinical effectiveness or may have substantial toxicity, RCTs including a BASC group are the most efficient and reliable way to identify benefits or harm. Given the accelerated development of Ebola drugs (which involves, for example, proceeding on the basis of only limited phase 1 data and little or no traditional phase 2 data) and preliminary data suggesting potential for adverse effects, such drugs need to be evaluated in RCTs with an appropriate control group so that any harm can be detected. Otherwise, it may not be possible to distinguish serious adverse drug effects from manifestations of EVD.

Some public health authorities are reluctant to support RCTs, which they see as traditional and slow trials.3 However, advances in trial design can and should be incorporated into Ebola RCTs. For example, such trials should include ongoing monitoring of results (e.g., group-sequential designs), adaptive elements, and other trial efficiencies to reduce the time required to identify an effective treatment, particularly a very effective treatment. If one investigational drug clearly shows benefit, trials should incorporate it into the new standard of care for all treatment groups thereafter. Then a regimen adding a different investigational therapy to the new standard of care could be compared with the new standard of care alone. If multiple investigational drugs are simultaneously available for clinical testing, an RCT could include more than one drug and a shared control group. Trials could be designed to assess effects on survival (recovery from disease) as the most important and measurable end point.

RCTs will yield the safety and effectiveness data that are so desperately needed and will do so ethically, giving all patients in a study an equal opportunity to receive the often limited supply of investigational drugs. So far, investigational drugs have generally been used in the few patients treated in the United States or Europe. An RCT with sites in West Africa, the United States, and Europe could result in more equitable distribution, because random allocation provides a fair means of deciding who has access to limited quantities of an investigational drug.

Scientists at the National Institutes of Health, in collaboration with the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Defense, and clinicians caring for patients with EVD in the United States, are leading efforts to develop and implement such trials. They have developed a protocol for an RCT with a BASC control group that will use Bayesian analytic methods, allow for the study of more than one investigational drug using a shared control group, and permit incorporation of a therapy into the regimen for the standard-of-care group once it has been shown to be effective against Ebola. The trial will be initiated first in the United States, with an opportunity for subsequent expansion to affected countries in West Africa. Establishing such trials in those countries is likely to have additional beneficial effects, such as improving supportive care.

Conducting such trials in affected regions will be challenging. It is critical for public health leaders to articulate the rationale for conducting scientifically valid trials, to work closely with local health authorities, and to engage community leaders so that trials can be acceptable to the affected populations. Such efforts are essential if we are to correctly identify therapies that will benefit patients with EVD now and in the future.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on December 3, 2014, at NEJM.org.
Source Information
From the Center for Drug Evaluation and Research (E.C., R.T.) and the Office of the Commissioner (L.B.), Food and Drug Administration, Silver Spring, MD.

New England Journal of Medicine
December 4, 2014 Vol. 371 No. 23
http://www.nejm.org/toc/nejm/medical-journal

Original Article
Chimpanzee Adenovirus Vector Ebola Vaccine — Preliminary Report
Julie E. Ledgerwood, D.O., Adam D. DeZure, M.D., Daphne A. Stanley, M.S., Laura Novik, M.A., Mary E. Enama, M.A., Nina M. Berkowitz, M.P.H., Zonghui Hu, Ph.D., Gyan Joshi, M.S., Aurélie Ploquin, Ph.D., Sandra Sitar, M.S., Ingelise J. Gordon, R.N., Sarah A. Plummer, C.R.N.P., LaSonji A. Holman, F.N.P., Cynthia S. Hendel, C.R.N.P., Galina Yamshchikov, M.S., Francois Roman, M.D., Alfredo Nicosia, Ph.D., Stefano Colloca, Ph.D., Riccardo Cortese, M.D., Robert T. Bailer, Ph.D., Richard M. Schwartz, Ph.D., Mario Roederer, Ph.D., John R. Mascola, M.D., Richard A. Koup, M.D., Nancy J. Sullivan, Ph.D., Barney S. Graham, M.D., and the VRC 207 Study Team
November 26, 2014DOI: 10.1056/NEJMoa1410863
Abstract
Background
The unprecedented 2014 epidemic of Ebola virus disease (EVD) has prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3–vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation.
Full Text of Background…
Methods
We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×1010 particle units or 2×1011 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 weeks after vaccination.
Full Text of Methods…
Results
In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×1011 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×1011 particle-unit dose than in the group that received the 2×1010 particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2×1011 particle-unit dose than among those who received the 2×1010 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07).
Full Text of Results…
Conclusions
Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×1011 particle-unit dose, glycoprotein Zaire–specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates. Clinical trials assessing cAd3-EBO are ongoing. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866.)

The Pediatric Infectious Disease Journal
December 2014 – Volume 33 – Issue 12 pp: 1211-1312,e316-e337
http://journals.lww.com/pidj/pages/currenttoc.aspx

Trends of Pneumococcal Meningitis in Children After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in France
Levy, Corinne MD; Varon, Emmanuelle MD; Picard, Capucine MD; Béchet, Stéphane MSc; Martinot, Alain MD; Bonacorsi, Stéphane MD; Cohen, Robert MD
Abstract
Background:
Streptococcus pneumoniae remains an important cause of bacterial meningitis in children younger than 2 years. Here, we analyzed data from an active surveillance network established 12 years ago by the Pediatric Infectious Disease Group and the Pediatric Clinical and Therapeutical Association to analyze the impact of pneumococcal conjugate vaccine (PCV7 implemented in 2002 and PCV13 in 2010) on pneumococcal meningitis (PM).
Methods:
Two hundred twenty-seven pediatric wards working with 168 microbiology departments throughout France were asked to report all cases of PM.
Results:
From 2001 to 2012, among 4808 bacterial meningitis cases, 1406 cases of PM (29.2%) were reported. After PCV13 implementation, from 2009 to 2012, the number of cases significantly decreased by 27.4% (P = 0.041, Cuzick trend test). For children younger than 2 years, the decrease was 28.2% (P = 0.039, Cuzick trend test). In the same period, the decrease was 66.7% in cases due to 6 additional PCV13 types, and the number of cases due to nonvaccine types remained stable. In 2012, the non-PCV13 serotype represented 67.6% of cases and were mainly represented by 12F (15%), 24F (15%), 22F (7%) and 15B/C (7%). For 88.6% of cases, initial antibiotic treatment was vancomycin with a third-generation cephalosporin. Overall mortality was 10.6%, most deaths (86.4%) occurred before day 15.
Conclusions:
Two years after the PCV13 implementation, we found an impact on PM cases particularly for children younger than 2 years.

Pediatrics
December 2014, VOLUME 134 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Article
Sinusitis and Pneumonia Hospitalization After Introduction of Pneumococcal Conjugate Vaccine
Ann Lindstrand, MD, MPHa,b, Rutger Bennet, MD, PhDc, Ilias Galanis, MSca, Margareta Blennow, MD, PhDd,e, Lina Schollin Ask, MDd, Sofia Hultman Dennison, MDf, Malin Ryd Rinder, MD, PhDd, Margareta Eriksson, MD, PhDc, Birgitta Henriques-Normark, MD, PhDa,g,h, Åke Örtqvist, MD, PhDi,j, and Tobias Alfvén, MD, PhDb,d
Author Affiliations
aPublic Health Agency of Sweden, Solna, Sweden;
Departments of bPublic Health Sciences, Division of Global Health,
eClinical Sciences and Education, and
gMicrobiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;
cAstrid Lindgren Children’s Hospital, and
hDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Solna, Sweden;
dSachs’ Children and Youth Hospital, South General Hospital, Stockholm, Sweden;
fDepartment of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden;
iDepartment of Communicable Disease Control and Prevention, Stockholm County Council, Sweden; and
jDepartment of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska, Solna, Sweden
Abstract
BACKGROUND AND OBJECTIVE:Streptococcus pneumoniae is a major cause of pneumonia and sinusitis. Pneumonia kills >1 million children annually, and sinusitis is a potentially serious pediatric disease that increases the risk of orbital and intracranial complications. Although pneumococcal conjugate vaccine (PCV) is effective against invasive pneumococcal disease, its effectiveness against pneumonia is less consistent, and its effect on sinusitis is not known. We compared hospitalization rates due to sinusitis, pneumonia, and empyema before and after sequential introduction of PCV7 and PCV13.
METHOD: All children 0 to <18 years old hospitalized for sinusitis, pneumonia, or empyema in Stockholm County, Sweden, from 2003 to 2012 were included in a population-based study of hospital registry data on hospitalizations due to sinusitis, pneumonia, or empyema. Trend analysis, incidence rates, and rate ratios (RRs) were calculated comparing July 2003 to June 2007 with July 2008 to June 2012, excluding the year of PCV7 introduction.
RESULTS: Hospitalizations for sinusitis decreased significantly in children aged 0 to <2 years, from 70 to 24 cases per 100 000 population (RR = 0.34, P < .001). Hospitalizations for pneumonia decreased significantly in children aged 0 to <2 years, from 450 to 366 per 100 000 population (RR = 0.81, P < .001) and in those aged 2 to <5 years from 250 to 212 per 100 000 population (RR = 0.85, P = .002). Hospitalization for empyema increased nonsignificantly. Trend analyses showed increasing hospitalization for pneumonia in children 0 to <2 years before intervention and confirmed a decrease in hospitalizations for sinusitis and pneumonia in children aged 0 to <5 years after intervention.
CONCLUSIONS: PCV7 and PCV13 vaccination led to a 66% lower risk of hospitalization for sinusitis and 19% lower risk of hospitalization for pneumonia in children aged 0 to <2 years, in a comparison of 4 years before and 4 years after vaccine introduction.

Article
Changes in Child Mortality Over Time Across the Wealth Gradient in Less-Developed Countries
Eran Bendavid, MD, MSa,b
Author Affiliations
aDivision of General Medical Disciplines, and
bCenter for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, California
Abstract
BACKGROUND: It is unknown whether inequalities in under-5 mortality by wealth in low- and middle-income countries (LMICs) are growing or declining.
METHODS: All Demographic and Health Surveys conducted between 2002 and 2012 were used to measure under-5 mortality trends in 3 wealth tertiles. Two approaches were used to estimate changes in under-5 mortality: within-survey changes from all 54 countries, and between-survey changes for 29 countries with repeated survey waves. The principal outcome measures include annual decline in mortality, and the ratio of mortality between the poorest and least-poor wealth tertiles.
RESULTS: Mortality information in 85 surveys from 929 224 households and 1 267 167 women living in 54 countries was used. In the subset of 29 countries with repeat surveys, mortality declined annually by 4.36, 3.36, and 2.06 deaths per 1000 live births among the poorest, middle, and least-poor tertiles, respectively (P = .031 for difference). The mortality ratio declined from 1.68 to 1.48 during the study period (P = .006 for trend). In the complete set of 85 surveys, the mortality ratio declined in 64 surveys (from 2.11 to 1.55), and increased in 21 surveys (from 1.58 to 1.88). Multivariate analyses suggest that convergence was associated with good governance (P ≤ .03 for 4 governance indicators: government effectiveness, rule of law, regulatory quality, and control of corruption).
CONCLUSIONS: Overall, under-5 mortality in low- and middle-income countries has decreased faster among the poorest compared with the least poor between 1995 and 2012, but progress in some countries has lagged, especially with poor governance.

Article
Adolescent Vaccine Co-administration and Coverage in New York City: 2007–2013
Monica Sull, MPHa, Joanna Eavey, MSPHa,b, Vikki Papadouka, PhD, MPHa, Rebecca Mandell, MSa,c, Michael A. Hansen, MPHa,d, and Jane R. Zucker, MD, MSca,e
Author Affiliations
aBureau of Immunization, New York City Department of Health and Mental Hygiene, New York, New York;
bCenter for Health Statistics, Washington Department of Health,
cDepartment of Health Behavior and Health Education, University of Michigan, Ann Arbor, Michigan;
dAtlantic Management Center, Inc., Columbus, Ohio; and
eImmunization Services Division/National Center for Immunization and Respiratory Diseases/Centers for Disease Control & Prevention, Atlanta, Georgia
Abstract
OBJECTIVES: To investigate adolescent vaccination in New York City, we assessed tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal conjugate (MCV4), and human papillomavirus (HPV) vaccine uptake, vaccine co-administration, and catch-up coverage over time.
METHODS: We analyzed data from the Citywide Immunization Registry, a population-based immunization information system, to measure vaccine uptake and co-administration, defined as a Tdap vaccination visit where MCV4 or HPV vaccine was co-administered, among 11-year-olds. Catch-up vaccinations were evaluated through 2013 for adolescents born 1996 to 2000, by birth cohort. HPV vaccination among boys included data from 2010 to 2013.
RESULTS: Adolescent vaccine administration was greatest during the back-to-school months of August to October and was highest for Tdap. Although MCV4 uptake improved over the study years, HPV vaccine uptake among girls stagnated; boys achieved similar uptake of HPV vaccine by 2012. By 2013, 65.4% had MCV4 co-administered with Tdap vaccine, whereas 28.4% of girls and 25.9% of boys had their first dose of HPV vaccine co-administered. By age 17, Tdap and MCV4 vaccination coverage increased to 97.5% and 92.8%, respectively, whereas ≥1-dose and 3-dose HPV vaccination coverage were, respectively, 77.5% and 53.1% for girls and 49.3% and 21.6% for boys. Age-specific vaccination coverage increased with each successive birth cohort (P < .001).
CONCLUSIONS: From 2007 to 2013, there were greater improvements in Tdap and MCV4 vaccination than HPV vaccination, for which co-administration with Tdap vaccine and coverage through adolescence remained lower. Parent and provider outreach efforts should promote timely HPV vaccination for all adolescents and vaccine co-administration.

PLoS One
[Accessed 6 December 2014]
http://www.plosone.org/

Research Article
Quantifying the Impact of Expanded Age Group Campaigns for Polio Eradication
Bradley G. Wagner mail, Matthew R. Behrend, Daniel J. Klein, Alexander M. Upfill-Brown, Philip A. Eckhoff, Hao Hu
Published: December 01, 2014
DOI: 10.1371/journal.pone.0113538
Abstract
A priority of the Global Polio Eradication Initiative (GPEI) 2013–2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5–14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage—representing less than one tenth of additional vaccinations required for the six SIA EAG scenario—increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.

PLoS One
[Accessed 6 December 2014]
http://www.plosone.org/
Research Article
What Are Fair Study Benefits in International Health Research? Consulting Community Members in Kenya
Maureen Njue, Francis Kombe, Salim Mwalukore, Sassy Molyneux, Vicki Marsh mail
Published: December 03, 2014
DOI: 10.1371/journal.pone.0113112
Abstract
Background
Planning study benefits and payments for participants in international health research in low- income settings can be a difficult and controversial process, with particular challenges in balancing risks of undue inducement and exploitation and understanding how researchers should take account of background inequities. At an international health research programme in Kenya, this study aimed to map local residents’ informed and reasoned views on the effects of different levels of study benefits and payments to inform local policy and wider debates in international research.
Methods and Findings
Using a relatively novel two-stage process community consultation approach, five participatory workshops involving 90 local residents from diverse constituencies were followed by 15 small group discussions, with components of information-sharing, deliberation and reflection to situate normative reasoning within debates. Framework Analysis drew inductively and deductively on voice- recorded discussions and field notes supported by Nvivo 10 software, and the international research ethics literature. Community members’ views on study benefits and payments were diverse, with complex contextual influences and interplay between risks of giving ‘too many’ and ‘too few’ benefits, including the role of cash. While recognising important risks for free choice, research relationships and community values in giving ‘too many’, the greatest concerns were risks of unfairness in giving ‘too few’ benefits, given difficulties in assessing indirect costs of participation and the serious consequences for families of underestimation, related to perceptions of researchers’ responsibilities.
Conclusions
Providing benefits and payments to participants in international research in low-income settings is an essential means by which researchers meet individual-level and structural forms of ethical responsibilities, but understanding how this can be achieved requires a careful account of social realities and local judgment. Concerns about undue inducement in low-income communities may often be misplaced; we argue that greater attention should be placed on avoiding unfairness, particularly for the most-poor.

PLoS Medicine
(Accessed 6 December 2014)
http://www.plosmedicine.org/

Health in Action
Tracking Rural Health Facility Financial Data in Resource-Limited Settings: A Case Study from Rwanda
Chunling Lu mail, Sandy Tsai, John Ruhumuriza, Grace Umugiraneza, Solange Kandamutsa, Phillip P. Salvatore, Zibiao Zhang, Agnes Binagwaho, Fidele Ngabo
Published: December 02, 2014
DOI: 10.1371/journal.pmed.1001763
Summary Points
:: Tracking financial data for rural health facilities is difficult in low-income countries because of unstandardized accounting practices and the absence of effective health financial information tracking systems.
:: Poor-quality financial data hinders monitoring and evaluation of health facility performance.
:: We present a five-step procedure developed for gathering financial data from 21 health centers in two rural districts of Rwanda.
:: The five-step procedure generated financial data with internal consistency and a low percentage of reports of “missing” for in-kind support (donated goods and services). In-kind support (mainly medicine and equipment) accounted for a large proportion of the total expenditure of health centers.
:: We report challenges faced by the project and make suggestions for how Rwanda’s national web-based financial data collection system can be improved.
Knowledge gained from the Rwanda field experience may inform other low-income countries on how to establish an information system to track health facility financial data.

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 6 December 2014)
Research Article
Comparative Effectiveness of Different Strategies of Oral Cholera Vaccination in Bangladesh: A Modeling Study
Dobromir T. Dimitrov, Christopher Troeger, M. Elizabeth Halloran, Ira M. Longini, Dennis L. Chao mail
Published: December 04, 2014
DOI: 10.1371/journal.pntd.000334
Abstract
Background
Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies.
Methods & Findings
We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies.
Conclusions
We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions.

Author Summary
Bangladesh has a high burden of cholera and may become the first country to use cholera vaccine on a large scale. Mass cholera vaccination may be hard to justify to international funding agencies because of the modest efficacy of existing vaccines and their limited duration of protection. However, mass cholera vaccination can induce high levels of indirect protection in a population, i.e., protecting even unvaccinated individuals by lowering cholera incidence, and a case for cost-effective cholera vaccination could be made. Mathematical modeling is one way to predict the magnitude of indirect protection conferred by a proposed vaccination program. Here, we predict the effectiveness of various mass cholera vaccination strategies in Bangladesh using a mathematical model. We found that maintaining high levels of vaccination coverage in children could be very effective in reducing the burden of cholera, and secondary transmission of cholera would virtually stop when 70% of the population is vaccinated. Mathematical modeling may play a key role in planning widespread cholera vaccination efforts in Bangladesh and other countries.

PLoS Pathogens
http://journals.plos.org/plospathogens/
(Accessed 6 December 2014)

Pearls
War and Infectious Diseases: Challenges of the Syrian Civil War
Sima L. Sharara, Souha S. Kanj mail
Published: November 13, 2014
DOI: 10.1371/journal.ppat.100443
Overview
Syria’s ongoing three-year civil war has displaced 6.5 million Syrians, left hundreds of thousands wounded or killed by violence, and created a vacuum in basic infrastructures that will reverberate throughout the region for years to come. Beyond such devastation, the civil war has introduced epidemics of infections that have spread through vulnerable populations in Syria and neighboring countries. In this article, we discuss the growing epidemics of poliomyelitis, measles, and cutaneous leishmaniasis in Syria and the region to examine the impact of conditions of war on the spread of infectious diseases in a public health emergency of global concern.

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

BMC Biology
http://www.biomedcentral.com/bmcbiol/content
Interview
Vaccines, emerging viruses, and how to avoid disaster
Rino Rappuoli
Author Affiliations
Novartis Vaccines, Siena 53100, Italy
BMC Biology 2014, 12:100 doi:10.1186/s12915-014-0100-6
29 November 2014
Abstract
Rino Rappuoli is a graduate of Siena University, where he also earned his PhD before moving to the Sclavo Research Center, the Italian vaccine institute, also in Siena. He then spent two years in the USA, mostly at Harvard with John Murphy and Alwin Pappenheimer working on a new diphtheria vaccine based on a non-toxic mutant of diphtheria toxin which has since become the basis for conjugate vaccines against haemophilus, meningococcus, and pneumococcal infections, before returning to the Sclavo Research Center where he developed an acellular vaccine based on a mutant pertussis toxin. With many achievements in vaccine development to his credit, he is now Global Head of Vaccines Research and Development for Novartis Vaccines in Siena, and has most recently pioneered reverse vaccinology, in which the genome of the pathogen is screened for candidate antigenic and immunogenic vaccine components. We spoke to him about the potential for outbreaks of the kind we are now seeing with Ebolavirus in West Africa, and what can be done to prevent them.

Q. Ebolavirus disease has been much in the news recently because of the horrendous outbreak in West Africa – but how many other rare, sporadic but severe infections are there that pose an equal threat?
Well, during the last few years, more or less with every 6 months to a year there has been a new outbreak of an emerging infection. Examples are the influenza viruses – for instance H1N1 in 2009, and H7N9 and H5N1 more recently [1] – the MERS rotavirus in Saudi Arabia [2], and Chikungunya virus in St Martin in 2013 [3], and of course now Ebola virus [4]. So there are many rare but potentially very dangerous diseases or emerging infections regularly breaking out. Ebola virus is by far the most lethal that we have now, but all of the others are very dangerous.

Q. I know that there are ’flu vaccines, but are there licensed vaccines for any of the others?
The answer is no – there are no vaccines for SARS, which emerged in 2003, there is no licensed vaccine for MERS, there is no licensed vaccine for Chikungunya, there is no licensed vaccine for Ebola – so for most of these diseases there are no vaccines, because they are too rare to justify the economic investment.

Q. Is that the only difficultly, or are there other difficulties in developing vaccines for these sorts of diseases? I realise it may be impossible to generalise.
Most of the time we do have the technologies to make these vaccines. I remember for example when SARS came in 2003/2004 we made a vaccine pretty quickly and brought it to the stage where it was ready to go to phase 1, but when we got to phase 1 the disease had gone away, there was no interest, no incentive to bring it even to phase 1, so we dropped it. For Ebola I think that the technology to make a vaccine has been there for many years, but nobody wanted to invest in it because there was no market, no demand.

Q. Do you think this is going to have to change in the light of what has happened with Ebola?
I hope that this humanitarian and health disaster is going to help us to become a little bit smarter in planning the future. I see these emerging infectious diseases as a constant threat. They pose a risk, just as in other areas we have a risk of earthquakes, we have a risk when we drive a car of car accidents, when we buy a house there is a risk of burning the house, and so on – and for all of those risks we prepare ahead of time. We have insurance for cars or we have insurance for houses and we build buildings that are earthquake-resistant. It looks as though the only place where we are not able to make investments ahead of time is health – we always have to wait for the disaster to happen and then we rush and usually with the vaccine we come too late and when the disease is no longer there then everyone forgets and we go from one disaster to another.

Q. How forward-thinking do we need to be? – How long does it actually take to develop a vaccine, generally?
For a normal commercial vaccine the time is between 10 and 15 years. Under very accelerated circumstances, like those we have now for Ebola, you can take advantage of previous studies that have been done and try to rush the development of the vaccine, but we do take risks with safety and efficacy when we accelerate so much, so I think we will be wise to develop those vaccines ahead of time.
Q. How much of a problem is viral mutation?
It depends on the virus, so for Ebola it is not a problem at all, for MERS it does not seem to be a problem, for SARS it does not seem to be a problem, for Chikungunya it does not seem to be a problem. For influenza it is a problem and for HIV it is a big problem, so it depends on the virus.

Q. What about the possibility, aired in the Press, that Ebola might become transmissible in an airborne form? Do you have any view on that possibility?
I believe that it is extremely unlikely. This virus has been there for a long time in the wild in Africa and it has never done it. It has had many opportunities to do it. I don’t think that a small exposure to mankind right now is going to do it and the preliminary data from the genetics and genomics of the virus show very good stability so I don’t think this is a risk in the short term.

So a little bit of good news. But you say one of these diseases pops out about every six months.

Q. Do you expect that we’ll be continuing to see emerging infections we haven’t seen before?
Oh yes, I believe that in six months we will have a new emerging disease. Hopefully the Ebola outbreak will be under control. It will not be in the news and there will be other news about another emerging infection and we will rush into the new one, and instead of doing that I think it would be nice to be able to plan ahead of time. I think we have technologies today by which we could prepare multiple vaccine platforms that could be tested for safety and efficacy against multiple diseases and where you could plug in an antigen from a new emerging infection quickly. We already effectively have this for influenza virus, for which as the virus mutates each year we just plug in the most prevalent haemagglutinin variants to the existing vaccine platform. If the regulatory authorities could approve platforms suitable for use against other pathogens – thus already of proven safety and efficacy – we could have a way of being as ready as possible for unexpected events.
The Lancet Respiratory Medicine
Online First
Comment
Paediatric influenza vaccination: time to better protect high-risk groups?
Harish Nair, Marc-Alain Widdowson
4 December 2014
Preview
Paediatric influenza vaccination: time to better protect high-risk groups?
Influenza is an important contributor to severe acute lower respiratory infection (ALRI). It is estimated to cause 20 million cases of influenza-associated ALRI per year worldwide, including 1 million severe ALRI cases, and 28 000—111 500 deaths in children younger than 5 years, mostly in the first 2 years of life… In many countries with few resources, children are very rarely vaccinated against influenza, and antivirals are usually unavailable. Moreover, children could be more susceptible to well documented sequelae of influenza infection, especially Streptococcus pneumoniae. Unfortunately, pneumococcal vaccine has been introduced in only 40 of the Gavi-eligible countries, and even where introduced, the coverage remains poor.

Identification of children at risk of influenza-related complications in primary and ambulatory care: a systematic review and meta-analysis
Peter J Gill DPhil a b, Helen F Ashdown MRCGP a, Dr Kay Wang DPhil a, Prof Carl Heneghan DPhil a, Nia W Roberts MSc Econ c, Prof Anthony Harnden FRCGP a, Susan Mallett DPhil a
Summary
Background
Interventions to prevent influenza-related complications are recommended for individuals at the greatest risk of serious clinical deterioration. However, guidelines are based on consensus opinion rather than evidence, and do not specify risk factors in children. We aimed to provide an evidence-based definition of children who are most at risk of such complications.
Methods
In this systematic review, we searched the Medline and Medline In Process, Embase, Science Citation Index, and CINAHL databases for studies published between inception and April 3, 2013. We included studies that reported data for underlying disorders and complications in children presenting in primary or ambulatory care with influenza or influenza-like illness. We requested unpublished data from investigators of studies that had obtained, but not published, relevant data. We analysed data with univariable meta-analysis and individual patient data multivariable meta-analysis methods. The primary outcome was admission to hospital as a proxy for complications of influenza or influenza-like illness.
Findings
We included 28 articles that reported data from 27 studies (14 086 children). Strong risk factors for hospital admission were neurological disorders (univariable odds ratio [OR] 4• 62, 95% CI 2•82—7•55), prematurity (4•33, 2•47—7•58), sickle cell disease (3•46, 1•63—7•37), immunosuppression (2•39, 1•24—4•61), diabetes (2•34, 1•20—4•58), and age younger than 2 years (2•51, 1•71—3•69). However, reactive airways disease including asthma (1•36, 0•82—2•26) and obesity (0•99, 0•61—1•62) were not found to be risk factors. On the basis of individual patient data multivariable analysis (1612 children, four studies), the risk of hospital admission was higher in children with more than one risk factor than in children with just one risk factor, when age younger than 2 years was included as a risk factor (92 [74%] of 124 vs 428 [52%] of 817; difference 22%, 95% CI 13—30%, p<0•0001).
Interpretation
We identified prematurity as a new strong risk factor for influenza-related complications in children. Our findings also support the inclusion of neurological disorders, sickle cell disease, immunosuppression, diabetes, and age younger than 2 years as risk factors in existing guidelines. Interventions to prevent influenza-related complications should be prioritised in these groups, but should also be considered for other children, especially those with more than one risk factor or severe underlying comorbidities.
Funding
UK National Institute for Health Research.

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.

AP (Associated Press)
http://hosted.ap.org/dynamic/fronts/HOME?SITE=AP
Accessed 6 December 2014 Dec 5, 1:22 PM EST
Sierra Leone seeing 80-100 new Ebola cases daily
By EDITH M. LEDERER
Associated Press UNITED NATIONS (AP) — Sierra Leone said Friday that between 80 and 100 new cases of Ebola are being reported every day and the country now hardest-hit by the deadly virus desperately needs over 1,000 beds to treat victims.
Sierra Leone’s Finance Minister Kaifalah Marah painted a grim picture to the U.N. Economic and Social Council Friday of the challenges facing his West African nation which failed to meet a World Health Organization interim goal of isolating 70 percent of Ebola patients and safely burying 70 percent of victims by Dec. 1…

Council on Foreign Relations
http://www.cfr.org/
Accessed 6 December 2014
Transcript
DC Event: Launch of the CFR-Sponsored Independent Task Force Report on the Emerging Global Health Crisis of Noncommunicable Diseases
with Mitchell E. Daniels Jr., Thomas E. Donilon, Thomas J. Bollyky, Massimo F. T. Calabresi December 5, 2014
Experts discuss the newly published Council on Foreign Relations (CFR)-sponsored Independent Task Force on Noncommunicable Diseases, which assesses the NCD crisis in developing countries and recommends a practical, scalable strategy for intervention.

New York Times
http://www.nytimes.com/
Accessed 6 December 2014
Chronic Diseases Are Killing More in Poorer Countries
4 December 2014
Chronic diseases like cancer and heart disease are rising fast in low- and middle-income countries, striking far younger populations than in rich countries and causing much worse outcomes, according to a new report. Deaths from chronic diseases have risen by more than 50 percent in low- and middle-income countries over the past two decades, according to the report (The Emerging Global Health Crisis), by the Council on Foreign Relations. The increase is part of a shift in global mortality patterns in which infectious diseases, such as malaria and tuberculosis, have declined substantially and are no longer the leading cause of death in the developing world.

Wall Street Journal
http://online.wsj.com/home-page?_wsjregion=na,us&_homepage=/home/us
Accessed 6 December 2014
Haider Javed Warraich: The Measles Outbreak Coming Near You
Parents who won’t vaccinate their children are reviving once-dead diseases. Will a vaccine mandate be needed?

Washington Post
http://www.washingtonpost.com/
Accessed 6 December 2014
U.S. designates 35 hospitals to treat Ebola patients
President Obama says the fight against Ebola in West Africa “is not even close to being over.”
Lena H. Sun | Health & Science | December 2, 2014

UNMEER [UN Mission for Ebola Emergency Response] @UNMEER #EbolaResponse
UNMEER’s website is aggregating and presenting content from various sources including its own External Situation Reports, press releases, statements and what it titles “developments.” We present a composite below from the week ending 6 December 2014.

UNMEER site: Press Releases & Statement
:: UN employs ‘district-by district’ approach in fight against Ebola (1 December 2014)

:: Remarks by David Nabarro, Special Envoy of the Secretary-General on Ebola, to mark the first 60 days of UNMEER, Freetown, Sierra Leone (1 December 2014)

UNMEER External Situation Reports
UNMEER External Situation Reports are issued daily (excepting Saturday) with content organized under these headings:
– Highlights
– Key Political and Economic Developments
– Human Rights
– Response Efforts and Health
– Logistics
– Outreach and Education
– Resource Mobilisation
– Essential Services
– Upcoming Events
The “Week in Review” will present highly-selected elements of interest from these reports. The full daily report is available as a pdf using the link provided by the report date.

5 December 2014 | UNMEER External Situation Report
Key Political and Economic Developments
2. The government of Guinea-Bissau announced on 4 December that it would reopen the country’s official border crossings with Guinea within 5 days. Guinea-Bissau had closed the border in August 2014 in an effort to prevent cross-border transmission of EVD. Surveillance measures will be strengthened along the border. The recent summit of Heads of State of the Economic Community of West African States (ECOWAS) held in Ghana had recommended the reopening of borders with the most affected countries to accelerate response efforts and avoid stigmatization of their populations.
3. The United Nations Mission in Liberia (UNMIL) on Thursday said that a member of its military personnel had tested positive for EVD. The patient is receiving treatment at an Ebola Treatment Unit in Monrovia. In line with WHO protocols, the medical team of UNMIL has immediately conducted robust contact tracing to ensure that all those who came into contact with the individual while he was symptomatic have been assessed and quarantined. All areas where the individual is known to have been while symptomatic have been decontaminated.
4. A ceremony scheduled on 4 December for Guinea’s Prime Minister to lay the first stone of a new ETC in Matoto commune in Conakry, was cancelled when groups of local youth ransacked the premises. They were reportedly protesting against the establishment of the ETC, arguing that it would lead to a spike in EVD cases in their community. Government officials, diplomats and representatives of non-governmental organizations were forced to leave the site of the planned ceremony due to the tensions.
Response Efforts and Health
7. 17,256 confirmed, probable, and suspected cases of EVD have been reported in the three most affected countries, where there have been 6,113 reported deaths.
Resource Mobilisation
11. The OCHA Ebola Virus Outbreak Overview of Needs and Requirements, now totaling US$ 1.5 billion, has been funded for $ 993 million, which is around 66 percent of the total ask.
Essential Services
15. The EVD crisis is destroying livelihoods, according to a newly released UNDP socioeconomic study. The study shows disproportionate numbers of economically active people are getting infected. In Sierra Leone, for instance, 65% of the sick were in the 15-49 age group. As caregivers, women are especially vulnerable. They represent up to 74% of the people who get infected in some areas of Guinea. Because women are often responsible for growing and trading food in all three countries, these sectors are also particularly impacted. 97% of respondents in a recent survey reported reduced incomes from farming, petty trading and service delivery. Employment in the informal sector and in education is especially affected in all three countries. The report calls for boosting informal and formal loan schemes and microfinance; investments in the next planting season; promotion of value chains in export-oriented primary commodities; and continuing to build skills among the workforce.
16. As schools remain closed, two million children in Sierra Leone are affected. The Emergency Radio Education Programme (EREP) continues to broadcast daily lessons through 41 radio stations nationwide. Some 47% of 2,489 surveyed households have children listening. The Ministry of Education and UNICEF are working to increase listenership through community outreach. UNICEF is in the process of procuring 50,000 solar powered radios for the most vulnerable households.

4 December 2014 | UNMEER External Situation Report
Key Political and Economic Developments
1. Europe must send more medical staff to West Africa to help rebuild local health systems and tackle the outbreak of EVD, EU Ebola coordinator Christos Stylianides has said, adding that he was in touch with European capitals on additional assistance to counter the disease in Guinea, Liberia, Sierra Leone, and Mali. At European level the mobilisation is “satisfactory but we must not relax our efforts” he indicated. Sweden has already announced that it will send 42 healthcare workers, while Greece is readying its first team. The EU’s medical evacuation system is “fully operational” with four planes on standby in Luxembourg and the US, and nine countries ready to treat repatriated staff. Mr. Stylianides is due to present an EVD action plan in December. Brussels is counting on more help;
2. MSF expressed concern on Tuesday about what it called a slow and uneven international response that portends further setbacks. MSF president Dr. Joanne Liu acknowledged an outpouring of financial and construction help from abroad in the past few months, but added that most of the work on tracking, isolating and treating patients, burying the dead and raising awareness to minimize contagion had fallen to the three countries at the heart of the outbreak: Guinea, Liberia and Sierra Leone. “It is extremely disappointing that states with biological disaster response capacities have chosen not to utilize them,” Dr. Liu said. “How is it that the international community has left the
Response Efforts and Health
8. The WFP-led Emergency Telecommunications Cluster is equipping rapid response teams in Sierra Leone with tools such as satellite phones and portable internet to ensure efficient and effective communication even in the remotest of areas. These teams of 15-20 people include a burial team, medical professionals and contact tracers amongst others, and are managed by the government of Sierra Leone.
Resource Mobilisation
13. Guinea, Liberia and Sierra Leone will each receive US$ 500,000 to help curb the impact of EVD on food security and on the livelihoods of people in rural areas. The $ 1.5 million grant from the Africa Solidarity Trust Fund will be used in support of FAO’s recently launched Regional Response Programme to tackle agriculture and food security issues related to the EVD outbreak in West Africa.
Outreach and Education
18. UNDP in Sierra Leone, working with local NGO One Family People, has completed the first stage of a sensitization campaign for people living with disability, having reached out to 10,000 women, men and children. Thanks to the campaign, people who are deaf, blind or physically impaired received messages in braille, sign language and pictures on how to protect themselves and others.

3 December 2014 | UNMEER External Situation Report
Key Political and Economic Developments
2. The World Bank said Tuesday that EVD is costing the three most affected countries more than US$ 2 billion, as the virus causes their economies to slow down or shrink. The bank sharply revised down its 2014 and 2015 economic growth estimates for Sierra Leone and Guinea, but said the outlook for Liberia was improving slightly. For 2015, it now forecasts Sierra Leone’s economy will shrink 2.0%, down from a 7.7% growth forecast in October and 8.9% before the crisis. Guinea will shrink 0.2% versus October’s estimate of 2% growth and a pre-outbreak forecast of 4.3%. In Liberia, where there are signs of progress and increasing economic activity, the bank increased its 2015 GDP growth estimate to 3.0%, up from 1.0% in October, but still less than half the pre-crisis estimate of 6.8%.
3. With more than half of its population already under lockdown, Sierra Leone has now quarantined a sixth district. Tonkolili, in the centre of the country, was added to the growing list of districts which no one is allowed to leave or enter without special dispensation, in an effort to combat the outbreak. The northern districts of Port Loko and Bombali were closed off indefinitely in September, along with the southern district of Moyamba – effectively sealing in more than one million people. With the eastern districts of Kenema and Kailahun also under quarantine, more than half of the population of six million, in six of the nation’s 14 districts, now finds itself unable to move freely. Tonkolili is expected to end its quarantine on December 15, according to health ministry officials.
Response Efforts and Health
5. Community resistance, denial and resorting to traditional healers remain prevalent in Gbarpolu and Grand Cape Mount counties, Liberia. The high mortality rates in the remote communities affected by the EVD flare ups (e.g. 17 deaths vs 2 survivors as last reported by the Glensyasu community), combined with limited outreach in hard to reach places, contribute to maintaining a worrying trend in the two counties.
10. UNICEF has provided EVD prevention (hygiene and sanitation) supplies and infection control training to wardens and staff of 14 prisons housing juvenile offenders across Liberia.
Logistics
12. The WFP-led Emergency Telecommunications Cluster is providing technical support to the International Rescue Committee (IRC) to programme 400 mobile phones to be used for data collection by health workers in Bo, Sierra Leone. Internet equipment provided by standby partners Emergency and Ericsson Response will be sent to the International Humanitarian Partnership camp in Port Loko, to provide 80 organisations with internet access by the end of this week.

2 December 2014 | UNMEER External Situation Report
Key Political and Economic Developments
2. In his press conference, the SRSG also reported on performance against the targets the UN had set for 1 December: 70 per cent of burials being done safely and 70 per cent of new cases isolated in a treatment facility. He indicated that those targets have been exceeded in most cases. In the case of safe burials, those targets are exceeded in all three countries. The other target – 70 per cent of new cases being isolated – is being exceeded in two of the three countries, in Liberia and Guinea. And it is being exceeded in many places in Sierra Leone – but some areas remain in serious crisis, and there, targets are not yet being met. Those areas are the focus of UNMEER’s efforts now. Nonetheless, the 70/70 target in 60 days was set so the crisis could be turned around, and that has been achieved.
3. Despite the positive news, the SRSG also emphasized that there was still a long way to go. Special Envoy David Nabarro said the disease was slowing down in some districts and increasing in others. He cautioned that the distribution changes from week to week, and the situation can worsen unexpectedly. EVD remains a very complex, multidimensional crisis, and additional efforts remain needed. The strategy that has been designed to get it under control has proven to work, SRSG Banbury said – putting people in treatment facilities, ensuring safe burials, contact tracing and social mobilization. But it needs to be present everywhere, and it need to be supported with logistics, with payments to response workers, with the information management needed for these activities.
4. The SRSG stressed that to achieve the goal of zero cases, the response needs to be present everywhere. As numbers get lower, more and more emphasis needs to be on contact tracing, on surveillance, and on rapid response capabilities. UNMEER and its partners are looking at putting in place a district-by-district strategy for 62 districts in the three countries, with interventions in every district that are appropriate to the circumstances there. That will be the focus for the next 60 days. SRSG Banbury expressed his confidence that 60 days from now the three countries will be in a much better condition than they are now, though that will still require a lot of hard work. There remains a lot to be done to get to zero cases, but the global EVD response is on the right track.
Response Efforts and Health
9. The Global Fund to Fight AIDS, Tuberculosis and Malaria has agreed to contribute € 500,000 to bolster UNDP’s support to the Malian Ministry of Health. The funds will be used to strengthen preventive measures in health facilities; train and pay health staff, and purchase protective gear.
Essential Services
19. Beyla prefecture in Guinea has 45 community agents working as contact tracers in EVD affected areas. Out of these 45 personnel, only 13 staff members received their salaries in November. The 32 others have not been paid for more than a month. UNMEER’s FCM has followed up with the prefectoral Ebola response coordinator on this payments issue, and has requested the coordinator to bring this to the attention of the National Ebola Response Cell.
20. In Montserrado, where Monrovia is located, UNDP and the Liberian Ministry of Health have set up a task force to increase communication within communities around denial, stigma, safe burials and hiding of sick people. The group will dispel widely held fears that no one comes back from ETUs, and help locate contacts, secret burials and households hiding sick people.

1 December 2014 | UNMEER External Situation Report
Response Efforts and Health
7. On Thursday 27 November, the UNMEER ECM in Liberia hosted the first NGO partnership meeting, to seek inputs from a broad range of implementing partners. Building county level capacity to decentralize policy discussions and coordination was deemed of high importance. Partners agreed that UNMEER has a central role in this regard. In addition, partners agreed to rationalize ad hoc coordination and create specific task groups to address issues such as CCC strategy and funding imbalances. The NGO partnership meeting will be held on a bi-weekly basis.
Outreach and Education
20. According to UNICEF, women in Samana sub-prefecture (Beyla prefecture), an area where there has been community resistance to EVD response, abandoned plans to march in protest against the presence of EVD responders after a sensitization by women leaders via rural radio. Also in Beyla, an agreement was reached for the establishment of a rapid response team within the prefectural communication commission. This cell plans advocacy activities to overcome community resistance.
21. In Liberia’s Grand Geddeh county, WHO, UNICEF, IRC and other partners conducted community engagement activities in Zwedru together with the county health team. The main aim was to have an interactive and informative session with community members and to share health information on EVD. More than 200 EVD posters were distributed. Teams also brought the emergency hotline telephone numbers to the attention of the communities.
Essential Services
22. UNICEF formed a partnership with Africa Humanitarian Action this week to expand the coverage of essential health services to 14 primary healthcare facilities in Montserrado County, Liberia, serving 158,181 people, including 26,890 children under five and 7,909 pregnant women. The provision of lifesaving medical and nutritional supplies is key in enabling access to lifesaving interventions.
World Bank [to 6 December 2014]
http://www.worldbank.org/en/news/all
:: Transcript of Press Conference with World Bank Group President Jim Yong Kim and President of Sierra Leone Ernest Bai Koroma December 3, 2014

:: Remarks by World Bank Group President Jim Yong Kim in Press Conference with President of Guinea Alpha Condé December 3, 2014

:: Transcript of Press Conference with World Bank Group President Jim Yong Kim and President of Liberia Ellen Johnson Sirleaf December 2, 2014

:: Ebola: New World Bank Group Report Shows Growth Shrinking, Economic Impact Worsening in Guinea, Liberia, and Sierra Leone
December 2, 2014
WASHINGTON, December 2, 2014 – The Ebola epidemic continues to cripple the economies of Guinea, Liberia, and Sierra Leone, and is projected to result in negative or contracting growth in these countries next year as they work to eradicate the virus, according to an Ebola Economic Impact Update released today by the World Bank Group. The report comes as World Bank Group President Jim Yong Kim begins a two-day visit to West Africa to assess the epidemic’s impact and discuss with governments and international agencies what steps need to be taken to reach the goal of zero cases as soon as possible.

This report updates the World Bank Group’s October 8 analysis of the economic effects of the Ebola crisis on the three hardest-hit countries. GDP growth estimates for 2014 have been revised sharply downward since pre-crisis estimates to 2.2 percent for Liberia (versus 5.9 percent pre-crisis and 2.5 percent in October); and 4.0 percent for Sierra Leone (versus 11.3 percent pre-crisis and 8.0 percent in October); and 0.5 percent for Guinea (versus 4.5 percent pre-crisis and 2.4 percent in October). All three countries had been growing rapidly in recent years and into the first half of 2014.

In addition, the World Bank Group is now projecting negative growth for 2015 of -0.2% in Guinea (down from pre-crisis estimates of 4.3 percent and 2.0 percent in October) and -2.0% in Sierra Leone (down from 8.9 percent and 7.7 percent in October). In Liberia, where there are signs of progress in containing the epidemic and some increasing economic activity, the updated 2015 growth estimate is 3.0 percent, an increase from 1.0 percent in October but still less than half the pre-crisis estimate of 6.8 percent. These latest projections imply forgone income across the three countries in 2014–15 totaling more than $2 billion.

“This report reinforces why zero Ebola cases must be our goal. While there are signs of progress, as long as the epidemic continues, the human and economic impact will only grow more devastating,” said Jim Yong Kim, President of the World Bank Group. “As we accelerate the immediate health response, the international community must also do everything we can to help the affected countries back on the road to economic recovery and development.”…

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

.– Request an Email Summary: Vaccines and Global Health : The Week in Review is published as a single email summary, scheduled for release each Saturday evening before midnight (EDT in the U.S.). If you would like to receive the email version, please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.
.
– pdf version:  A pdf of the current issue is available here: Vaccines and Global Health_The Week in Review_29 November 2014

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

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

.
.
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

Editor’s Note:
We continue to lead this weekly digest with extensive coverage of polio and EVD – both designated as Public Health Emergencies of International Concern (PHEIC). Please note that Ebola/EVD content is threaded through this edition.

See Journal Watch [Nature, NEJM, PLoS Currents: Outbreaks, Science +) and Media Watch.

POLIO [to 29 November 2014]
Public Health Emergency of International Concern (PHEIC)

GPEI Update: Polio this week – As of 26 November 2014
Global Polio Eradication Initiative
[Editor’s Excerpt and text bolding]
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: In response to the outbreak of circulating vaccine-derived poliovirus (cVDPV) in South Sudan, over 19,000 children were vaccinated last week in Bentiu Poc, where the two cases were reported. Outbreak response plans are in place to hold three rounds of supplementary immunization activities (SIAs) in high risk areas to stop transmission of the virus.
:: In the north of Madagascar, SIAs are planned for December in response to the outbreak of cVDPV. National Immunization Days are planned for January. The aim is to boost immunity across the country against all strains of poliovirus.
:: A planning meeting was held in Pakistan last week to develop a strategy for the low poliovirus transmission season, December 2014 to May 2015, using lessons learned from high risk areas. There is national consensus for the low season plan, including increased support from the Pakistan law enforcement and security services. The structure of the planned Emergency Operations Centre for polio eradication at the Federal and Provincial levels is being finalized.
:: For the first time ever, only 1 case of wild poliovirus has been reported in Africa in the last 4 months, despite the high season for polio transmission. The most recent case had onset of paralysis on 11 August in Somalia.
Afghanistan
:: One new wild poliovirus type 1 (WPV1) case was reported in the past week in Afghanistan in Kandahar district, with onset of paralysis on the 5 November. The total number of WPV1 cases for 2014 in Afghanistan is now 21.
Pakistan
:: Fourteen new wild poliovirus type 1 (WPV1) cases were reported in the past week. Five were from the Federally Administered Tribal Areas (FATA) (2 in Khyber Agency, 2 in South Waziristan Agency and 1 in Frontier Region Bannu); 3 from Balochistan province (1 in Quetta district, 1 in Killa Abdullah district and 1 in Khuzdar district, which has not previously been infected in 2014); 5 from Khyber Pakhtunkhwa province (4 from Peshawar district and 1 from Karak district, which has not reported cases so far in 2014); and 1 from Karachi Site town in Sindh province. The total number of WPV1 cases in Pakistan in 2014 is now 260, compared to 64 at this time last year. The most recent WPV1 case had onset of paralysis on 11 November, from Quetta district, Balochistan.
:: Immunization activities are continuing with particular focus on known high-risk areas, in particular newly opened previously inaccessible areas of FATA. At exit and entry points of conflict-affected areas that are still inaccessible during polio campaigns, 100 permanent vaccination points are being used to reach internally displaced families as they move in and out of the inaccessible area. Over 1 million people have been vaccinated in the past few months at transit points and in host communities, including over 850,000 children under 10 years old.
Horn of Africa
:: Following confirmation of two cases of circulating vaccine derived poliovirus type 2 (cVDPV2) in a refugee camp area of Unity state, South Sudan, outbreak response plans are in place to hold rounds of supplementary immunization activities (SIAs) in high risk areas. Over 19,000 children were vaccinated on 13 – 15 November in Bentiu Poc where the 2 cases were reported in September. The objective is to rapidly stop the cVDPV2 in the infected area, while further boosting immunity to type 1 wild poliovirus and to minimize the risk of renewed outbreaks following virus re-introduction from infected countries and areas.
West Africa
:: The Ebola crisis in western Africa is impacting on the implementation or polio eradication activities in Liberia, Guinea and Sierra Leone. Supplementary immunization activities in these countries have been postponed and the quality of acute flaccid paralysis surveillance has markedly decreased this year.
:: Even as polio programme staff across West Africa support efforts to control the Ebola outbreak affecting the region, efforts are being made in those countries not affected by Ebola to vaccinate children against polio.
.

The Weekly Epidemiological Record (WER) for 28 November 2014, vol. 89, 48 (pp. 529–544) includes:
:: Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2014 :: Review of the 2014 influenza season in the southern hemisphere
http://www.who.int/entity/wer/2014/wer8948.pdf?ua=1
.

Polio Crisis Deepens in Pakistan, With New Cases and Killings
By DECLAN WALSH
New York Times
NOV. 26, 2014
LONDON — Pakistan’s polio crisis has reached new depths this year, health officials say, intensified by a deadly mix of ruthless militant violence, large-scale refugee displacement and political chaos that has cemented the country’s role as the central global incubator of a disease that other conflict-torn countries have managed to hold in check.

The number of new Pakistani polio cases this year hit 260 this week, four times as many as at the same point last year, making a mockery of promises by Prime Minister Nawaz Sharif and other politicians from across the spectrum to halt the galloping progress of the disease.

Even as domestic vaccination drives and extensive international aid have put huge numbers of anti-polio workers in the field, Pakistan’s militants have seen it as an opportunity to strike at symbols of authority, portraying the workers as agents in a sinister Western plot. On Wednesday, four more health workers were gunned down, bringing the death toll among anti-polio workers to 65 since the first targeted attack in December 2012.

The attackers, who struck in Quetta, the capital of Baluchistan Province, opened fire on the workers’ vehicle after demanding to know if they were involved in the anti-polio campaign. Television footage showed emergency workers carrying three other wounded workers from a van that contained abandoned slippers and blood-smeared iceboxes with polio vaccines.

The wounded, and three of the dead, were women, whose greater access to private households in conservative rural areas of Pakistan have put them in high demand as health workers.

The attackers escaped, and there was no claim of responsibility, although a Taliban splinter group said it had carried out a gun attack near Peshawar on Monday that wounded a polio worker and a student. Polio vaccinations are “dangerous to health and against Islam,” a spokesman for that group, Jamaat-e-Ahrar, said after the attack, echoing longstanding claims that Western countries are using immunization to sterilize Muslim children…

NIH Watch [to 29 November 2014]
http://www.nih.gov/news/index.html

:: NIAID/GSK experimental Ebola vaccine appears safe, prompts immune response
Results from NIH Phase 1 clinical trial support accelerated development of candidate vaccine
November 28, 2014
An experimental vaccine to prevent Ebola virus disease was well-tolerated and produced immune system responses in all 20 healthy adults who received it in a phase 1 clinical trial conducted by researchers from the National Institutes of Health. The candidate vaccine, which was co-developed by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and GlaxoSmithKline (GSK), was tested at the NIH Clinical Center in Bethesda, Maryland. The interim results are reported online in advance of print in the New England Journal of Medicine.

“The unprecedented scale of the current Ebola outbreak in West Africa has intensified efforts to develop safe and effective vaccines, which may play a role in bringing this epidemic to an end and undoubtedly will be critically important in preventing future large outbreaks,” said NIAID Director Anthony S. Fauci, M.D. “Based on these positive results from the first human trial of this candidate vaccine, we are continuing our accelerated plan for larger trials to determine if the vaccine is efficacious in preventing Ebola infection.”

The candidate NIAID/GSK Ebola vaccine was developed collaboratively by scientists at the NIAID Vaccine Research Center (VRC) and at Okairos, a biotechnology company acquired by GSK. It contains segments of Ebola virus genetic material from two virus species, Sudan and Zaire. The Ebola virus genetic material is delivered by a carrier virus (chimpanzee-derived adenovirus 3 or cAd 3) that causes a common cold in chimpanzees but causes no illness in humans. The candidate vaccine does not contain Ebola virus and cannot cause Ebola virus disease.

The trial enrolled volunteers between the ages of 18 and 50. Ten volunteers received an intramuscular injection of vaccine at a lower dose and 10 received the same vaccine at a higher dose. At two weeks and four weeks following vaccination, the researchers tested the volunteers’ blood to determine if anti-Ebola antibodies were generated. All 20 volunteers developed such antibodies within four weeks of receiving the vaccine. Antibody levels were higher in those who received the higher dose vaccine.

The investigators also analyzed the research participants’ blood to learn whether the vaccine prompted production of immune system cells called T cells. A recent study by VRC scientist Nancy J. Sullivan, Ph.D., and colleagues showed that non-human primates inoculated with the candidate NIAID/GSK vaccine developed both antibody and T-cell responses, and that these were sufficient to protect vaccinated animals from disease when they were later exposed to high levels of Ebola virus.

The experimental NIAID/GSK vaccine did induce a T-cell response in many of the volunteers, including production of CD8 T cells, which may be an important part of immune protection against Ebola viruses. Four weeks after vaccination, CD8 T cells were detected in two volunteers who had received the lower dose vaccine and in seven of those who had received the higher dose.

“We know from previous studies in non-human primates that CD8 T cells played a crucial role in protecting animals that had been vaccinated with this NIAID/GSK vaccine and then exposed to otherwise lethal amounts of Ebola virus,” said Julie E. Ledgerwood, D.O., a VRC researcher and the trial’s principal investigator. “The size and quality of the CD8 T cell response we saw in this trial are similar to that observed in non-human primates vaccinated with the candidate vaccine.”

There were no serious adverse effects observed in any of the volunteers, although two people who received the higher dose vaccine did develop a briefly lasting fever within a day of vaccination…

Industry Watch [to 29 November 2014]
Selected media releases and other content from industry.

:: Merck and NewLink Genetics Enter Into Licensing and Collaboration Agreement for Investigational Ebola Vaccine
Clinical Development, Manufacturing Expertise, and Scale Critical to Success
November 24, 2014
WHITEHOUSE STATION, N.J. & AMES, IA–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada, and NewLink Genetics Corporation (NASDAQ:NLNK), announced today that they have entered into an exclusive worldwide license agreement to research, develop, manufacture, and distribute NewLink’s investigational rVSV-EBOV (Ebola) vaccine candidate.

The vaccine candidate, originally developed by the Public Health Agency of Canada (PHAC), is currently being evaluated in Phase I clinical trials. Pending the results of ongoing Phase I trials the U.S. National Institutes of Health (NIH) has announced plans to initiate, in early 2015, a large randomized, controlled Phase III study to evaluate the safety and efficacy of the rVSV-EBOV vaccine and another investigational Ebola vaccine co-developed by the National Institute of Allergy and Infectious Diseases (NIAID) and GlaxoSmithKline.

“Effective Ebola vaccines will be a critical component of comprehensive prevention and control measures for people at risk of Ebola virus infection and to stem future outbreaks globally,” said Dr. Julie Gerberding, president of Merck Vaccines. “Merck is committed to applying our vaccine expertise to address important global health needs and, through our collaboration with NewLink, we hope to advance the public health response to this urgent international health priority.”

According to Dr. Charles Link, chairman and chief executive officer of NewLink Genetics, “Merck’s vaccine development expertise, commercial leadership and history of successful strategic alliances make it an ideal partner to expedite the development of rVSV-EBOV and, if demonstrated to be efficacious and well-tolerated, to make it available to individuals and communities at risk of Ebola virus infection around the world.”

Under the terms of the agreement, Merck will be granted the exclusive rights to the rVSV-EBOV vaccine candidate as well as any follow-on products. The vaccine candidate is under an exclusive licensing arrangement with a wholly-owned subsidiary of NewLink Genetics. Under these license arrangements, the PHAC retains non-commercial rights pertaining to the vaccine candidate.

Phase I clinical trials of the rVSV-EBOV vaccine are now underway at the Walter Reed Army Institute of Research and the NIAID at the NIH. Additional Phase I studies are underway or planned to begin in the near future at clinical research centers in Switzerland, Germany, Kenya, and Gabon in a World Health Organization-coordinated effort, and in Canada by the Canadian Immunization Research Network.

“This vaccine is the result of years of hard work and innovation by Canadian scientists. We are pleased that this new alliance coupled with the clinical trials currently underway will further strengthen the possibility that the vaccine will make a difference in the global response to the Ebola outbreak,” said Canada’s Minister of Health, Rona Ambrose.

About rVSV Vaccine Platform
This vaccine platform is based on an attenuated strain of vesicular stomatitis virus that has been modified to express an Ebola virus protein that plays an essential role in establishing virus infection. The rVSV-EBOV vaccine was created by scientists at the Public Health Agency of Canada’s National Microbiology Laboratory. A significant portion of the funding for the further development of the vaccine came from the CBRN Research and Technology Initiative, a federal program led by Defence Research and Development Canada. In 2010, the PHAC signed a licensing arrangement with BioProtection Systems (BPS), a wholly-owned subsidiary of NewLink Genetics, as the sole licensee for these vaccines and the underlying technology. BPS has worked with the PHAC to produce clinical trial materials and to move this vaccine candidate into Phase I studies.

WHO: African regulators’ meeting looking to expedite approval of vaccines and therapies for Ebola
November 2014
pdf of slides: http://www.who.int/entity/immunization_standards/vaccine_regulation/avaref_meeting_recommendations_14nov2014.pdf?ua=1

Aiming to make potential Ebola therapies and vaccines available as quickly as possible, the ninth African Vaccine Regulatory Forum (AVAREF), was convened in Pretoria, South Africa, from 3-7 November. The first two days focused on a collaborative mechanism for fast tracking approvals for clinical trials and registration of these (Ebola) products in the affected countries.

The mechanism would cover:
:: Clear pathways and timelines for expedited ethical and regulatory review of clinical trial applications and approval of products;
:: Agreement on timelines and joint safety and efficacy assessments of the new products to fast-track national registration;
:: Endorsement of a panel of safety experts for expedited review of safety data of new products with relevant communication to National Regulatory Authorities (NRAs);
:: Technical assistance from the World Health Organization (WHO) to facilitate these processes.

Following are summary recommendations from this meeting as adapted from a WHO PowerPoint Presentation:

Recommendations: 9th Annual Meeting of the African Vaccine Regulatory Forum (AVAREF)
Pretoria, 3 to 7 November 2014
Background
:: The 9th annual meeting of the African Vaccine Regulatory Forum (AVAREF) was held in Pretoria South Africa, 3 to 7 November 2014
:: The meeting brought together NRAs, EC/IRB, in Africa, Manufacturers, developers, Research Institutions, US-FDA, EMA and BMGF and representatives of NRAs and ethics committees of 20 AVAREF countries
:: Participants reviewed progresses in development of vaccines and medicines for Ebola and other priority diseases

Recommendations to SPONSORS/Manufacturers
1. To immediately release the planned time line for submission of clinical trial applications indicating specific trial sites
2. To hold pre-submission meetings with each participating NRAs, EC and to attend
3. Manufacturers to attend the joint review sessions with their appropriate staff;
4. Manufacturers to file clinical trial applications through the focal persons identified by Heads of NRAs
5. To use the AVAREF clinical trials format for the submissions of clinical trial applications.
6. To include in their submissions all pertinent data that is available at the time of submission
7. To respond swiftly to any query from NRAs or EC/IRB

Recommendations to supporting regulatory authorities (EMA, USFDA, HC)
1. In collaboration with WHO, do everything in their power to share data relevant to clinical trials with the NRAs of participating countries
2. To provide expertise to support NRAs in the joint reviews when requested

Recommendations to WHO
1. To request Heads of regulatory Agencies to:
a) Identify and named senior regulators staff as the agency entry focal points for Ebola
b) Designate named reviewer(s) to participate in a joint review process with the mandate to take regulatory/ethics decisions (reviewers are empowered to take decisions during the joint review meeting).
2. To facilitate a joint review session of the clinical trial applications with a target date of 15 December 2014
3. To involve the NRAs of the Ebola affected countries in the joint review process
4. To provide expertise and develop briefing materials for ethics committees
5. To develop additional briefing materials on the vaccines, and novel clinical trial designs, to assist the national/regional reviews
6. To proactively play the needed broker role in facilitating the interaction between manufacturers and countries
7. Engage with heads of Institutions and research institutions and provide necessary support to countries to develop procedures for accelerated review of Ebola related research.
8. Ensure that ethics committees have the necessary support to follow up approved trials and research studies through site monitoring and having mechanisms to rapidly review amendments etc.

Recommendations to NRAs and EC/IRB
:: To prioritize assessment of clinical trial applications in parallel (regulatory/ethics) to minimize delays and to apply fast-track procedures’
:: To immediately release all national/regional provisions governing the area of clinical trials and highlight aspects favourable to fast track procedures
:: To accept to review all clinical trials submitted by manufacturers/sponsors

Other recommendations from the meeting
To NRAs and EC/IRB
:: To gradually strengthen Regional Harmonization of Technical processes and procedures
:: To emphasize on utilization of joint process implementation
:: To establish mechanisms for strengthening Transparency on processes/procedures and on country/regional performance (including adapting indicators for research ethics systems)
:: To interact actively with AMRH (EAC, SADC, WAHO, OCEAC, UEMOA)

Overall recommendations for the meeting To WHO
:: To support and strengthen collaborative mechanisms among NRAs and ethics committees including capacity building through regular trainings
:: To encourage multiplication of joint implementation of regulatory activities including joint reviews and joint inspections
:: To host and manage the AVAREF virtual community platform developed by Health Canada, the secretariat to implement the transition by end January 2015
:: WHO to provide specific guidelines for evaluation of clinical trial applications for vaccines against TB and HIV, build Capacity to efficiently address other anticipated products in the pipeline Issues to be considered by AVAREF
:: Bio-samples management and regulation at national, regional and global levels
:: WHO to support workshops on ethical issues in relation to bio-repositories

Acknowledgements
:: Recommendations drafted by Dr Nikiema with input from
:: Dr D. Akanmori, Dr V Ahonkhai, Dr A. Bellah, Dr R. Cushman, Dr L. Elmgren, Dr T. M. Lapnet, Dr D. Wood
:: Representatives of GSK, NEW LINK, J&J
:: Botswana, Burkina Faso, Central Africa Republic, Congo, Democratic Republic of Congo, Equatorial Guinea, Gambia, Ghana, Guinea, Kenya, Malawi, Mali, Mozambique, Niger, Nigeria, Senegal, South Africa, Tanzania, Uganda, Zambia and Zimbabwe.

WHO & Regionals [to 29 November 2014]
:: GIN November 2014 pdf, 1.38Mb 28 November 2014

:: World AIDS Day 2014: Closing the gap in HIV prevention and treatment 1 December 2014

:: Closing the gap in HIV prevention and treatment
27 November 2014 — In 2013, a record 13 million people were able to access life-saving antiretrovirals (ARVs). But many people still lack comprehensive HIV treatment and prevention services. This feature story describes how a centre in South Africa offers emergency HIV prevention medication, as well as support and advice to rape victims. On World AIDS Day 2014, WHO will release new guidelines on providing ARVs as emergency prevention following HIV exposure, and on the use of the antibiotic co-trimoxazole to prevent HIV-related infections.
Read the feature story on emergency HIV prevention service in South Africa
World AIDS Day 2014
.

WHO Regional Offices
WHO African Region AFRO
:: When Ebola came calling: how communities in Sierra Leone faced the challenge – 24 November 2014

WHO Region of the Americas PAHO
:: PAHO/WHO to provide training in clinical management of Ebola for doctors and nurses in Latin America and the Caribbean (11/28/2014)
:: Antiretroviral treatment for people with HIV is increasing in Latin America and the Caribbean (11/26/2014)

WHO South-East Asia Region SEARO
World AIDS Day – Close the gap
On this World AIDS Day with the theme “Close the gap”, the World Health Organization, Regional Offices for South-East Asia and Western Pacific are calling on Member States to recognize that in order to close the significant gaps that remain for millions of people to access to HIV prevention, treatment and care, key populations most vulnerable to HIV must be equal partners with governments and health authorities.
Joint press release – Closing the gap

WHO European Region EURO
:: High cancer burden due to overweight and obesity in most European countries 28-11-2014
:: Europe’s HIV response falls short in curbing the epidemic: 80% more new HIV cases compared to 2004 27-11-2014
:: WHO project to combat noncommunicable diseases with major grant from Russian Federation 26-11-2014

WHO Eastern Mediterranean Region EMRO
:: Yemen vaccinates more than 11 million children in measles/rubella campaign
23 November 2014 – Yemen conducted a national measles/rubella vaccination campaign from 9 to 20 November 2014, in which more than 11 million children from 9 months to 15 years were vaccinated. In spite of political unrest and insecurity, vaccination teams achieved a coverage rate of 98%, which included children from high-risk groups, such as refugees and internally displaced persons. Effective partnership was crucial to successful implementation of the campaign with the GAVI Alliance supporting 80% of operational costs and the cost of the vaccine and many other partners on the ground providing support to the campaign.
Read more

WHO Western Pacific Region WPRO
:: Asia-Pacific countries need to improve affordable access to healthcare
27 November 2014 – Most countries in the Asia-Pacific region need to step up their efforts to give more people access to affordable, quality health care. Too many people, especially women, cannot get the medical treatment they need due to high costs, difficulties in getting permission to see a doctor or a lack of health care providers in rural areas, according to Health at a Glance: Asia/Pacific 2014, a joint publication by the World Health Organization and the Organisation for Economic Co-operation and Development.

GAVI Watch [to 29 November 2014]
http://www.gavialliance.org/library/news/press-releases/

:: Canada commits C$ 500 million to support immunisation in developing countries
28 November 2014
Gavi welcomed the announcement by Canada of a C$ 500 million contribution to support immunisation in developing countries between 2016 and 2020.

:: International Finance Facility for Immunisation issues first Sukuk, raising US$ 500 million
Dubai, UAE, 27 November 2014 – The International Finance Facility for Immunisation Company (IFFIm) today issued its inaugural Sukuk, raising US$ 500 million for children’s immunisation in the world’s poorest countries through Gavi, the Vaccine Alliance. This landmark transaction is the first socially responsible Sukuk with funds to be utilised for this purpose. This successful transaction marks the largest Sukuk al-Murabaha issuance in the public markets and is also the largest inaugural Sukuk offering from a Supranational.

The 3-year Sukuk – a financial certificate that complies with Islamic law – provides institutional investors with a socially responsible investment that will help protect tens of millions of children against preventable diseases.

The Sukuk was coordinated by Standard Chartered Bank, working with joint lead managers Barwa Bank, CIMB, National Bank of Abu Dhabi (NBAD) and NCB Capital Company (NCB Capital). The issue, maturing on 4 December 2017 has an issue price of 100% and carries a quarterly coupon of +15 basis points over 3-month USD LIBOR.

The Sukuk was oversubscribed, even with its unique structure for Sukuk market participants. IFFIm achieved strong diversification in its investor base with 85% of the order book coming from new and primarily Islamic investors. The regional distribution of investors was 21% based in Asia, 11% in Europe and 68% in the Middle East and Africa. Banks took 74%, and central banks / official institutions took 26%.

“IFFIm is dedicated to issuing socially responsible instruments for investors everywhere to make a real difference in saving children’s lives,” said IFFIm Chair René Karsenti. “The funds will be used to protect children near and far – in countries like Yemen and Mali to Afghanistan and Indonesia – from deadly diseases.”

IFFIm raises funds in the international capital markets to accelerate the availability of funds for immunisation programmes and health system strengthening by Gavi, the Vaccine Alliance. IFFIm’s financial base consists of legally binding grant payments (approximately US$ 6.3 billion) from its nine sovereign donors. The World Bank is IFFIm’s Treasury Manager.

“We are delighted to bring this landmark Sukuk to the growing Islamic Finance market. The use of proceeds – to help finance the delivery of life-saving vaccines and related health system strengthening support to many of the world’s poorest nations – is well aligned with the core principles of Islamic finance. We are grateful for the strong support from investors who value the diversification benefit of IFFIm as a new highly rated name in the Islamic capital markets and appreciate its purpose,” said Madelyn Antoncic, Vice President and Treasurer of the World Bank, IFFIm’s Treasury Manager.

From its inception in 2006 up until today’s announcement, IFFIm had raised about US$ 5 billion equivalent in the capital markets to support Gavi, whose mission is to save children’s lives and protect people’s health by increasing access to immunisation in poor countries…

IAVI Watch [29 November 2014]

World AIDS Day 2014: Honoring their memories. Partnering toward a vaccine.
December 1, 2014
There have been major advances in treatment and prevention since AIDS was first diagnosed 33 years ago. But the HIV virus continues to devastate millions of people, families and communities around the world.

HIV has infected 78 million people – and half of them have died. Last year alone, 1.5 million people died from HIV/AIDS and 2.1 million – that’s 5,750 a day – became infected. Some 35 million people globally live with HIV today, including almost 6 million people under the age of 25 in sub-Saharan Africa.

Yet many people today mistakenly view HIV/AIDS as a manageable disease, as no longer an urgent priority. Funding for prevention research has flattened – despite optimism about promising advances in scientific progress.

“The tragedy of Ebola has been a stark reminder of the dangers of complacency,” said Margie McGlynn, IAVI President and CEO. “Now, more than ever before, we need to invest in the innovative research it will take to end these deadly diseases.”

On this World AIDS Day, IAVI and our many partners remember the millions of lives taken and torn apart by HIV/AIDS. And we honor their memories with a renewed commitment to build on the scientific momentum that will lead to a vaccine. Together, we can achieve a world without AIDS.

PATH Watch [to 29 November 2014]
http://www.path.org/news/

:: PATH names Dr. David Fleming as vice president for Public Health Impact
Global public health expert to serve on PATH executive leadership team and oversee diverse portfolio

Seattle, November 24, 2014—PATH has named Dr. David Fleming as its vice president for Public Health Impact. Dr. Fleming will begin January 5, 2015 and be based in PATH’s Seattle headquarters.

Dr. Fleming will lead PATH’s Public Health Impact division, which houses the organization’s reproductive health, maternal and child health and nutrition, noncommunicable diseases, malaria control and elimination, and HIV/AIDS and tuberculosis programs. He also will oversee cross-programmatic collaboration at PATH, which seeks to maximize the impact of the organization’s work across the value chain in critical health areas, including maternal and neonatal health, diarrheal disease, and malaria….

Global Fund Watch [to 29 November 2014]
:: Global Fund Calls for End to Compulsory Treatment
26 November 2014
The Global Fund called for the closure of compulsory treatment programs to change sexual orientation, compulsory rehabilitation of sex workers and compulsory drug detention centers. The Global Fund committed not to finance programs in such facilities.

The Strategy, Investment and Impact Committee of the Global Fund Board reported to a meeting of the full Board on 20-21 November that under a new policy the Global Fund explicitly refuses to fund programs with compulsory treatment.

The Global Fund is committed to ensuring that programs it supports do not infringe upon human rights. The United Nations Special Rapporteur on the Right to Health and other UN experts have found that these programs frequently include torture, cruel, inhuman and degrading treatment, as well as forced labor, among other abuses. Twelve UN agencies have called for the closure of compulsory drug detention and rehabilitation programs.

“The evidence is overwhelming that compulsory treatment facilities for sex workers and drug users, and programs that seek to change sexual orientation, are not scientifically valid and undermine the fight against HIV, TB and malaria,” said Mark Dybul, Executive Director of the Global Fund. “Trust is essential in the relationship between health workers and patients. The fear of compulsory treatment drives people underground and makes it harder to reach them.”

While opposing compulsory treatment facilities, the Global Fund may in exceptional circumstances finance scientifically sound medical services to save lives, where there are heightened processes and scrutiny. For instance, to provide lifesaving treatment to people detained in a compulsory treatment facility, the Global Fund may fund health services for detainees in a voluntary, community-based treatment program located outside the detention facility. Exceptions would be determined based on consultation with UN partners.

:: Global Fund Analysis of Audits and Investigations
25 November 2014
At the 32nd Board meeting of the Global Fund to Fight AIDS, Tuberculosis and Malaria, held 20-21 November, the Board was informed of an analysis of audits and investigations, reaffirming a policy of zero tolerance for corruption and a commitment to a high degree of transparency. The Global Fund reports all cases of misused funds, publishing audits and investigations reports on its website.

The analysis found that 1.8 percent of funding that was audited or investigated from 2005-2014 was misspent, fraudulently misappropriated or inadequately accounted for. The Global Fund has recovered a key portion of those funds, and is actively pursuing the remaining amount…

…Of the 1.8 percent of funds that were detected as misused, 0.4 percent were lost to fraud, 0.7 percent were unsupported by proper accounting, and 0.6 percent were deemed ineligible, or spent on activities not covered by the grant agreements. A further 0.1 percent were not adequately reported.

Cees Klumper, Chief Risk Officer, reported to the Board that the analysis is a factual rendering of the percentages of funding revealed in audits and investigations to be ineligible, misappropriated or inadequately accounted for. He cautioned that the analysis did not reflect a representative sampling of all Global Fund grants, as audits and investigations tend to focus where specific risks have been identified.

The analysis shows that US$103 million were misused and recoverable by the Global Fund, equivalent to 1.8 percent of US$5.7 billion in grants that were audited or investigated. US$30.4 million has already been recovered. Written commitments to repay a further US$16.8 million have been received and US$1 million has been adjusted. Efforts are being pursued to recover the remaining amount….

1st Amref Health Africa International Conference
Theme: From Evidence to Action – Lasting Health Change in Africa
November 24 – 26, 2014, Nairobi,
Organised in Collaboration with the World Health Organization

Conference Communiqué
Preamble
We, the organisers, keynote speakers, scientists and researchers, leaders from governments, multilateral agencies, the private sector and civil society, representatives of development partners, delegates, participants and the media, came together in this inaugural Amref Health Africa International Health conference to:
:: Share cutting edge research on health and health systems in Africa
:: Identify and discuss priorities in addressing Africa’s health in the post-2015 agenda
:: Bring together stakeholders to reflect on home-grown solutions to health system challenges in Africa.

In the past three days, we have had rich sharing and discussion around the deep knowledge shared by keynote speakers, the findings of researchers, and the experience and skills of the private sector in innovation to find solutions to improved service delivery in Africa.

We Note That:
:: Africa has made progress in improving the health of her peoples in the MDG era, but that this progress has been inadequate to achieve the MDG targets for health.
:: Serious challenges in health persist in relation to the health of women and children, communicable diseases and infectious diseases that have long been eliminated or mitigated in other continents.
:: Africa additionally faces an emerging health burden from non-communicable diseases (NCDs).
:: More than one-third of African children are stunted due to chronic malnutrition, which seriously reduces their future economic productivity. This is a root cause of Africa’s under-development as malnutrition reduces national GDP by up to 3%.
:: In some countries, up to 40% of healthcare expenditure is out of pocket
:: African governments and the private sector must work together to invest in systems of production of human resources for health, taking maximum advantage of current technologies like e- and m-learning to lower the cost of training.
:: Accountability, efficiency, value for money, and transparent tracking of health expenditure must become standard principles in utilisation of health care resources by both state and non-state health stakeholders.
:: African governments must put in place enabling policies, invest in quality health services, and show greater political will to address the root causes of ill health and galvanise other stakeholders to contribute towards sustainable universal health care coverage.
:: African governments should enact polices that adopt task shifting to address the shortage of human resources for health.
:: African governments must urgently create the policy framework, legislation and investment to rapidly improve the health research output in the continent.
:: Implementers, researchers and policy makers must create the platforms that ensure that research is translated into evidence-based policy-making and action to improve health in Africa.
:: African governments should create policies to facilitate networking of African researchers to generate evidence from research for practice and policy change.
:: Non-governmental organisations must advocate with the key stakeholders to focus attention continuously on translation of evidence to investment decisions for sustainable health systems in Africa.
– Conference Bulletin Issue No. 1
– Conference Bulletin Issue No. 2
– Conference Bulletin Issue No. 3

American Journal of Infection Control
Volume 42, Issue 12, p1255-1346 December 2014
http://www.ajicjournal.org/current

Commentary
Nebraska Biocontainment Unit perspective on disposal of Ebola medical waste
John J. Lowe, Shawn G. Gibbs, Shelly S. Schwedhelm, John Nguyen, Philip W. Smith
p1256–1257
Preview
Clinical practices surrounding the current Ebola epidemic have been center stage in discourse concerning research and practice of care. As the medical community becomes more sophisticated in understanding the many facets of treating and containing this virus, the Nebraska Biocontainment Unit has identified Ebola medical waste disposal as a key area of concern for U.S. hospitals. The requirements for processing Ebola medical waste stand to impact most U.S. hospitals currently preparing readiness plans to receive and treat patients with suspected or confirmed Ebola virus disease (EVD).

Middle East respiratory syndrome coronavirus infection control: The missing piece?
Ziad A. Memish, Jaffar A. Al-Tawfiq
p1258–1260
Preview
Since the initial occurrence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012,1,2 the disease had caused 837 cases, with a case fatality rate of 34.7%.3 As with any emerging infectious diseases of pandemic potential there is a concern of the global spread of the disease. It is therefore the first priority of the global public health community to develop and implement the required infection control practices to prevent the dissemination of these emerging organisms within health care facilities (HCFs) and worldwide based on the best available evidence and previous experience with similar or related groups of pathogens.

Middle East respiratory syndrome coronavirus: Implications for health care facilities
Helena C. Maltezou, MD, PhD, Sotirios Tsiodras, MD, PhD
DOI: http://dx.doi.org/10.1016/j.ajic.2014.06.019
Highlights
:: Health care–associated transmission plays a pivotal role in the Middle East respiratory syndrome coronavirus epidemic.
:: Gaps in infection control were noted in all health care–associated events.
:: There is a need to increase infection control capacity.
:: Studies about the effectiveness of infection control measures are needed.
:: Vaccines and antiviral agents against Middle East respiratory syndrome coronavirus are urgently needed.
Abstract
Background
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate. Starting in March 2014, a dramatic increase of cases has occurred in the Arabian Peninsula, many of which were acquired in health care settings. As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported globally.
Methods
Review of publicly available data about MERS-CoV health care–associated transmission.
Results
We identified 11 events of possible or confirmed health care–associated transmission with high morbidity and mortality, mainly among patients with comorbidities. Health care workers are also frequently affected; however, they tend to have milder symptoms and better prognosis. Gaps in infection control were noted in all events. Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula.
Conclusion
There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings. Vaccines and antiviral agents are urgently needed. Overall, our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. As the MERS-CoV epidemic continues to evolve, issues concerning best infection control measures will arise, and studies to better define their effectiveness in real life are needed.

Environmental sampling for respiratory pathogens in Jeddah airport during the 2013 Hajj season
Ziad A. Memish, MD, Malak Almasri, RN, Abdullah Assirri, MD, Ali M. Al-Shangiti, PhD, Gregory C. Gray, MD, John A. Lednicky, PhD, Saber Yezli, PhD
DOI: http://dx.doi.org/10.1016/j.ajic.2014.07.027
Abstract
Background
Respiratory tract infections (RTIs) are common during the Hajj season and are caused by a variety of organisms, which can be transmitted via the air or contaminated surfaces. We conducted a study aimed at sampling the environment in the King Abdul Aziz International (KAAI) Airport, Pilgrims City, Jeddah, during Hajj season to detect respiratory pathogens.
Methods
Active air sampling was conducted using air biosamplers, and swabs were used to sample frequently touched surfaces. A respiratory multiplex array was used to detect bacterial and viral respiratory pathogens.
Results
Of the 58 environmental samples, 8 were positive for at least 1 pathogen. One air sample (1 of 18 samples, 5.5%) tested positive for influenza B virus. Of the 40 surface samples, 7 (17.5%) were positive for pathogens. These were human adenovirus (3 out of 7, 42.8%), human coronavirus OC43/HKU1 (3 out of 7, 42.8%), Haemophilus influenzae (1 out of 7, 14.2%), and Moraxella catarrhalis (1 out of 7, 14.2%). Chair handles were the most commonly contaminated surfaces. The handles of 1 chair were cocontaminated with coronavirus OC43/HKU1 and H influenzae.
Conclusion
Respiratory pathogens were detected in the air and on surfaces in the KAAI Airport in Pilgrims City. Larger-scale studies based on our study are warranted to determine the role of the environment in transmission of respiratory pathogens during mass gathering events (eg, Hajj) such that public health preventative measures might be better targeted.

American Journal of Preventive Medicine
Volume 47, Issue 6, p689-852, e11-e14 December 2014
http://www.ajpmonline.org/current

Adult Vaccination Disparities Among Foreign-Born Populations in the U.S., 2012
Peng-jun Lu, MD, PhD, Alfonso Rodriguez-Lainz, PhD, DVM, MPVM, Alissa O’Halloran, MSPH, Stacie Greby, DVM, Walter W. Williams, MD, MPH
Published Online: October 06, 2014
DOI: http://dx.doi.org/10.1016/j.amepre.2014.08.009
Abstract
Background
Foreign-born persons are considered at higher risk of undervaccination and exposure to many vaccine-preventable diseases. Information on vaccination coverage among foreign-born populations is limited.
Purpose
To assess adult vaccination coverage disparities among foreign-born populations in the U.S.
Methods
Data from the 2012 National Health Interview Survey were analyzed in 2013. For non-influenza vaccines, the weighted proportion vaccinated was calculated. For influenza vaccination, Kaplan–Meier survival analysis was used to assess coverage among individuals interviewed during September 2011–June 2012 and vaccinated in August 2011–May 2012.
Results
Overall, unadjusted vaccination coverage among U.S.-born respondents was significantly higher than that of foreign-born respondents: influenza, age ≥18 years (40.4% vs 33.8%); pneumococcal polysaccharide vaccine (PPV), 18–64 years with high-risk conditions (20.8% vs 13.7%); PPV, ≥65 years (62.6% vs 40.5%); tetanus vaccination, ≥18 years (65.0% vs 50.6%); tetanus, diphtheria, and acellular pertussis (Tdap), ≥18 years (15.5% vs 9.3%); hepatitis B, 18–49 years (37.2% vs 28.4%); shingles, ≥60 years (21.3% vs 12.0%); and human papilloma virus (HPV), women 18–26 years (38.7% vs 14.7%). Among the foreign born, vaccination coverage was generally lower for non-U.S. citizens, recent immigrants, and those interviewed in a language other than English. Foreign-born individuals were less likely than U.S.-born people to be vaccinated for pneumococcal (≥65 years), tetanus, Tdap, and HPV (women) after adjusting for confounders.
Conclusions
Vaccination coverage is lower among foreign-born adults than those born in the U.S. It is important to consider foreign birth and immigration status when assessing vaccination disparities and planning interventions.

Effect of Decision Support on Missed Opportunities for Human Papillomavirus Vaccination
Stephanie L. Mayne, MHS, Nathalie E. duRivage, MPH, Kristen A. Feemster, MD, MPH, MSHP, A. Russell Localio, PhD, Robert W. Grundmeier, MD, Alexander G. Fiks, MD, MSCE
DOI: http://dx.doi.org/10.1016/j.amepre.2014.08.010
Abstract
Background
Missed opportunities for human papilloma virus (HPV) vaccination are common, presenting a barrier to achieving widespread vaccine coverage and preventing infection.
Purpose
To compare the impact of clinician- versus family-focused decision support, none, or both on captured opportunities for HPV vaccination.
Design
Twelve-month cluster randomized controlled trial conducted in 2010–2011.
Setting/participants
Adolescent girls aged 11–17 years due for HPV Dose 1, 2, or 3 receiving care at primary care practices.
Intervention
Twenty-two primary care practices were cluster randomized to receive a three-part clinician-focused intervention (educational sessions, electronic health record–based alerts, and performance feedback) or none. Within each practice, girls were randomized at the patient level to receive family-focused, automated, educational phone calls or none. Randomization resulted in four groups: clinician-focused, family-focused, combined, or no intervention.
Main outcome measures
Standardized proportions of captured opportunities (due vaccine received at clinician visit) were calculated among girls in each study arm. Analyses were conducted in 2013.
Results
Among 17,016 adolescent girls and their 32,472 visits (14,247 preventive, 18,225 acute), more HPV opportunities were captured at preventive than acute visits (36% vs 4%, p<0.001). At preventive visits, the clinician intervention increased captured opportunities by 9 percentage points for HPV-1 and 6 percentage points for HPV-3 (p≤0.01), but not HPV-2. At acute visits, the clinician and combined interventions significantly improved captured opportunities for all three doses (p≤0.01). The family intervention was similar to none. Results differed by practice setting; at preventive visits, the clinician intervention was more effective for HPV-1 in suburban than urban settings, whereas at acute visits, the clinician intervention was more effective for all doses at urban practices.
Conclusions
Clinician-focused decision support is a more effective strategy than family-focused to prevent missed HPV vaccination opportunities. Given the persistence of missed opportunities even in intervention groups, complementary strategies are needed. This study is registered at clinicaltrials.gov NCT01159093.

BMC Public Health
(Accessed 29 November 2014)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Health economic analysis of human papillomavirus vaccines in women of Chile: perspective of the health care payer using a Markov model
Jorge Alberto Gomez, Alejandro Lepetic and Nadia Demarteau
Author Affiliations
BMC Public Health 2014, 14:1222 doi:10.1186/1471-2458-14-1222
Published: 26 November 2014
Abstract (provisional)
Background
In Chile, significant reductions in cervical cancer incidence and mortality have been observed due to implementation of a well-organized screening program. However, it has been suggested that the inclusion of human papillomavirus (HPV) vaccination for young adolescent women may be the best prospect to further reduce the burden of cervical cancer. This cost-effectiveness study comparing two available HPV vaccines in Chile was performed to support decision making on the implementation of universal HPV vaccination.
Methods
The present analysis used an existing static Markov model to assess the effect of screening and vaccination. This analysis includes the epidemiology of low-risk HPV types allowing for the comparison between the two vaccines (HPV-16/18 AS04-adjuvanted vaccine and the HPV-6/11/16/18 vaccine), latest cross-protection data on HPV vaccines, treatment costs for cervical cancer, vaccine costs and 6% discounting per the health economic guideline for Chile.
Results
Projected incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratio (ICERs) for the HPV-16/18 AS04-adjuvanted vaccine was 116 United States (US) dollars per quality-adjusted life years (QALY) gained or 147 US dollars per life-years (LY) saved, while the projected ICUR/ICER for the HPV-6/11/16/18 vaccine was 541 US dollars per QALY gained or 726 US dollars per LY saved. Introduction of any HPV vaccine to the present cervical cancer prevention program of Chile is estimated to be highly cost-effective (below 1X gross domestic product [GDP] per capita, 14278 US dollars). In Chile, the addition of HPV-16/18 AS04-adjuvanted vaccine to the existing screening program dominated the addition of HPV-6/11/16/18 vaccine. In the probabilistic sensitivity analysis results show that the HPV-16/18 AS04-adjuvanted vaccine is expected to be dominant and cost-saving in 69.3% and 77.6% of the replicates respectively.
Conclusions
The findings indicate that the addition of any HPV vaccine to the current cervical screening program of Chile will be advantageous. However, this cost-effectiveness model shows that the HPV-16/18 AS04-adjuvanted vaccine dominated the HPV-6/11/16/18 vaccine. Beyond the context of Chile, the data from this modelling exercise may support healthcare policy and decision-making pertaining to introduction of HPV vaccination in similar resource settings in the region.

Research article
The evolution of health literacy assessment tools: a systematic review
Sibel Vildan Altin, Isabelle Finke, Sibylle Kautz-Freimuth and Stephanie Stock
Author Affiliations
BMC Public Health 2014, 14:1207 doi:10.1186/1471-2458-14-1207
Published: 24 November 2014
Abstract (provisional)
Background
Health literacy (HL) is seen as an increasingly relevant issue for global public health and requires a reliable and comprehensive operationalization. By now, there is limited evidence on how the development of tools measuring HL proceeded in recent years and if scholars considered existing methodological guidance when developing an instrument.
Methods
We performed a systematic review of generic measurement tools developed to assess HL by searching PubMed, ERIC, CINAHL and Web of Knowledge (2009 forward). Two reviewers independently reviewed abstracts/ full text articles for inclusion according to predefined criteria. Additionally we conducted a reporting quality appraisal according to the survey reporting guideline SURGE.
Results
We identified 17 articles reporting on the development and validation of 17 instruments measuring health literacy. More than two thirds of all instruments are based on a multidimensional construct of health literacy. Moreover, there is a trend towards a mixed measurement (self-report and direct test) of health literacy with 41% of instruments applying it, though results strongly indicate a weakness of coherence between the underlying constructs measured. Overall, almost every third instrument is based on assessment formats modeled on already existing functional literacy screeners such as the REALM or the TOFHLA and 30% of the included articles do not report on significant reporting features specified in the SURGE guideline.
Conclusions
Scholars recently developing instruments that measure health literacy mainly comply with recommendations of the academic circle by applying multidimensional constructs and mixing up measurement approaches to capture health literacy comprehensively. Nonetheless, there is still a dependence on assessment formats, rooted in functional literacy measurement contradicting the widespread call for new instruments. All things considered, there is no clear “consensus” on HL measurement but a convergence to more comprehensive tools. Giving attention to this finding can help to offer direction towards the development of comparable and reliable health literacy assessment tools that effectively respond to the informational needs of populations.

British Medical Journal
29 November 2014(vol 349, issue 7985)
http://www.bmj.com/content/349/7985

Research
Selective reporting bias of harm outcomes within studies: findings from a cohort of systematic reviews
BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g6501 (Published 21 November 2014) Cite this as: BMJ 2014;349:g6501
Pooja Saini, research associate1, Yoon K Loke, professor2, Carrol Gamble, professor3, Douglas G Altman, professor4, Paula R Williamson, professor3, Jamie J Kirkham, lecturer3
Abstract
Objective
To determine the extent and nature of selective non-reporting of harm outcomes in clinical studies that were eligible for inclusion in a cohort of systematic reviews.
Design
Cohort study of systematic reviews from two databases.
Setting
Outcome reporting bias in trials for harm outcomes (ORBIT II) in systematic reviews from the Cochrane Library and a separate cohort of systematic reviews of adverse events.
Participants 92 systematic reviews of randomised controlled trials and non-randomised studies published in the Cochrane Library between issue 9, 2012 and issue 2, 2013 (Cochrane cohort) and 230 systematic reviews published between 1 January 2007 and 31 December 2011 in other publications, synthesising data on harm outcomes (adverse event cohort).
Methods
A 13 point classification system for missing outcome data on harm was developed and applied to the studies.
Results
86% (79/92) of reviews in the Cochrane cohort did not include full data from the main harm outcome of interest of each review for all of the eligible studies included within that review; 76% (173/230) for the adverse event cohort. Overall, the single primary harm outcome was inadequately reported in 76% (705/931) of the studies included in the 92 reviews from the Cochrane cohort and not reported in 47% (4159/8837) of the 230 reviews in the adverse event cohort. In a sample of primary studies not reporting on the single primary harm outcome in the review, scrutiny of the study publication revealed that outcome reporting bias was suspected in nearly two thirds (63%, 248/393).
Conclusions
The number of reviews suspected of outcome reporting bias as a result of missing or partially reported harm related outcomes from at least one eligible study is high. The declaration of important harms and the quality of the reporting of harm outcomes must be improved in both primary studies and systematic reviews.

Conflict and Health
[Accessed 29 November 2014]
http://www.conflictandhealth.com/

Research
Evaluating the use of locally-based health facility assessments in Afghanistan: a pilot study of a novel research method
Jack S Rowe, Kayhan Natiq, Olakunle Alonge, Shivam Gupta, Anubhav Agarwal and David H Peters
Author Affiliations
Conflict and Health 2014, 8:24 doi:10.1186/1752-1505-8-24
Published: 25 November 2014
Abstract (provisional)
Background
Through the Balanced Scorecard program there have been independent, annual and nationwide assessments of the Afghan health system from 2004 to 2013. During this period, Afghanistan remained in a dynamic state of conflict, requiring innovative approaches to health service evaluation in insecure areas. The primary objective of this pilot study was to evaluate the reliability of health facility assessments conducted by a novel, locally-based data collection method compared to a standard survey team.
Methods
In this cross-sectional study, one standard survey team of clinicians and multiple rapidly trained locally-based survey teams of teachers conducted health facility assessments in Badghis province, Afghanistan from March – August, 2010. Outpatient facilities covered under the country’s Basic Package of Health Services were eligible for inclusion. Both approaches attempted to survey as many health facilities as safely possible, up to 25 total facilities per method. Each facility assessed was scored on 23 health services indicators used to evaluate performance in the annual Balanced Scorecard national assessment. For facilities assessed by both survey methods, the indicator scores produced by each method were compared using Spearman’s correlation coefficients and linear regression analysis with generalized estimating equations.
Results
The standard survey team was able to assess 11 facilities; the locally-based approach was able to assess these 11 facilities, as well as 13 additional facilities in areas of greater insecurity. Among the 11 facilities assessed by both approaches, 19 of 23 indicators were statistically similar by survey method (p < .05). Spearman’s coefficients varied widely from (-0.39) to (0.71). The differences were greatest for items requiring specialized data collector knowledge on reviewing patient records, patient examination and counseling, and health worker reported satisfaction.
Conclusions
This pilot study of a novel method of data collection in health facility assessments showed that an approach using locally-based survey teams provided markedly increased access to areas of insecurity. Though analysis was limited by small sample size, indicator scores used for facility evaluation were relatively comparable overall, but less reliable for items requiring clinical knowledge or when asking health worker opinions, suggesting that alternative approaches may be needed to assess these parameters in insecure environments.

Cost Effectiveness and Resource Allocation
(Accessed 29 November 2014)
http://www.resource-allocation.com/

Research
System dynamics model of cervical cancer vaccination and screening interventions in Kenya
Lucy W Kivuti-Bitok, Geoff McDonnell, Roudsari Abdul and Ganesh P Pokhariyal
Author Affiliations
Cost Effectiveness and Resource Allocation 2014, 12:26 doi:10.1186/1478-7547-12-26
Published: 27 November 2014
Abstract (provisional)
Objectives
This paper presents a simulation model for evaluating the possible effects of a screening and vaccination campaign against Human Papillomavirus [HPV] in Kenya.
Method
A System Dynamics model was developed using the iThinkTM computer simulation package. The model was based on data extracted from epidemiological, demographic and published research and where data was not available, expert opinion was sought. The deterministic model stratified the population by vaccination status, screening status and HPV infection status. The model was simulated to estimate outputs for the next 50 years from 2011. Cost Utility indicators of Disability Adjusted Life Years (DALYs) and cost per averted DALY were used for economic evaluation.
Results
The model predicted that catch up vaccination had the greatest impact in reducing the prevalence of cervical cancer. This was followed by Primary vaccination, with early detection through Screening having the lowest impact of the three choices of interventions in respect of averted cases of cervical cancer and DALY estimates.
Conclusion
Kenya as a country should consider adoption of secondary /catch up vaccination as an immediate measure to curb cervical cancer followed by primary vaccination of pre-adolescent girls. Screening should be a complementary measure(s). This model provides a policy decision support vehicle that can allow for choice between different interventions based on their expected outcomes. It also allows modification to accommodate new research results and information to assess the clinical impact of different policies and interventions in cervical cancer management in Kenya.

The European Journal of Public Health
Volume 24, Issue 6, 01 December 2014
http://eurpub.oxfordjournals.org/content/24/6

Impact of physicians’ attitude to vaccination on local vaccination coverage for pertussis and measles in Germany
Martin Weigel, Kerstin Weitmann, Christiane Rautmann, Judith Schmidt, Roswitha Bruns, Wolfgang Hoffmann
DOI: http://dx.doi.org/10.1093/eurpub/cku013 1008-1015 First published online: 5 March 2014
Abstract
Background: Vaccination rates of children in Germany are unsatisfying and regional endemic outbreaks have been reported. Few studies have analysed physicians’ attitude towards vaccination. We investigated whether there is an association between physicians’ attitude and vaccination coverage on the regional level for Germany.
Methods: In a representative cross-sectional survey, anonymized questionnaires were sent to random samples of all paediatricians (50%) and general practitioners (10%) in private practice in Germany. Attitude towards vaccination was operationalized in three scores. Measles and pertussis vaccination coverage rates were obtained from the 16 Federal States’ Health Departments. Geographic methods and linear regression models were used for analysis.
Results: A total of 2010 paediatricians (response proportion: 64.1%) and 1712 general practitioners (response proportion 39.1%) were included in the analysis. We found an association of physicians’ attitude towards vaccination and vaccination coverage rate (P < 0.0001). There is also an important association between vaccination coverage and the geographic location, with lower coverage rates especially in the States of former Western Germany (compared with our reference State Mecklenburg – Western Pomerania; pertussis: maximum −5.86% in Bavaria, P < 0.0001; measles: maximum −20.20% in Berlin, P = 0.0002).
Conclusions: The regional association between vaccination coverage rates and physicians’ attitude towards vaccination seems to be superposed by population-related variables. An increase of vaccination coverage requires better information and training of both, physicians and the general population.

The European Journal of Public Health
Volume 24, Issue 6, 01 December 2014
http://eurpub.oxfordjournals.org/content/24/6

Cultures of evidence across policy sectors: systematic review of qualitative evidence
Theo Lorenc, Elizabeth F. Tyner, Mark Petticrew, Steven Duffy, Fred P. Martineau, Gemma Phillips, Karen Lock
DOI: http://dx.doi.org/10.1093/eurpub/cku038 1040-1046 First published online: 28 March 2014
Abstract
Background: It is important to understand the decision-making process, and the role of research evidence within it, across sectors other than health, as interventions delivered within these sectors may have substantial impacts on public health and health inequalities. Methods: Systematic review of qualitative evidence. Twenty-eight databases covering a range of sectors were searched. Studies were eligible if they included local decision-makers in a policy field relevant to the social determinants of health (including housing, transport, urban planning and regeneration, crime, licensing or trading standards), were conducted in a high-income country, and reported primary qualitative data on perceptions of research evidence. Study quality was assessed and a thematic synthesis undertaken. Results: Sixteen studies were included, most using interview designs, and most focusing on planning or transport policy. Several factors are seen to influence decision-makers’ views of evidence, including practical factors such as resources or organizational support; the credibility of the evidence; its relevance or applicability to practice; considerations of political support or feasibility; and legislative constraints. There are limited data on how evidence is used: it is sometimes used to not only support decision-making, but also to lend legitimacy to decisions that have already been made. Conclusion: Although cultures of evidence in non-health sectors are similar to those in health in some ways, there are some key differences, particularly as regards the political context of decision-making. Intersectoral public health research could benefit from taking into account non-health decision makers’ needs and preferences, particularly around relevance and political feasibility.

Eurosurveillance
Volume 19, Issue 47, 27 November 2014
http://www.eurosurveillance.org/Public/Articles/Archives.aspx?PublicationId=11678

Editorials
Death from AIDS is preventable, so why are people still dying of AIDS in Europe?
V Delpech, J Lundgren2
Public Health England, London, United Kingdom
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
Excerpt
It is almost two decades since life-saving treatment for human immunodeficiency virus (HIV) became available. Life expectancy among people living with HIV, for whom optimal therapy is initiated timely, is now close to that of the general population [1]. Despite this, an estimated 1.6 million people died from acquired immunodeficiency syndrome (AIDS)-related illnesses globally in 2012, and the number who died within the World Health Organization (WHO) European Region reached almost 100,000 [2]. A large proportion of these deaths occur in the eastern part of the Region, and without changes in the HIV response, the death toll in this region is likely to continue to increase in the coming years [3]. Conversely, in the west, the risk of AIDS-related death continues to decline [3], reflecting some positive progress…

Infectious Diseases of Poverty
[Accessed 29 November 2014]
http://www.idpjournal.com/content

Opinion
Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus
Kang Yiu Lai, Wing Yiu Ng and Fan Fanny Cheng
Author Affiliations
Infectious Diseases of Poverty 2014, 3:43 doi:10.1186/2049-9957-3-43
Published: 28 November 2014
Abstract (provisional)
The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV.

The Lancet
Nov 29, 2014 Volume 384 Number 9958 p1901 – 1998 e58 – 61
http://www.thelancet.com/journals/lancet/issue/current

Editorial
The health of India: a future that must be devoid of caste
The Lancet
Preview |
In 2011, The Lancet published a special Series on the progress and future of health in India. The central message was a call for universal health coverage by 2020. Despite India’s Prime Minister at the time, Manmohan Singh, being supportive of this goal, the move towards universal health coverage in India has gained little traction. Public health spending remains desperately low at 1•3% of gross domestic product, while more than 40 million Indians are driven into impoverishment from out-of-pocket health expenditure every year.

Migrants’ health in China
The Lancet
Preview |
During the past three decades, China has experienced the largest migration in human history, with hundreds of millions of rural inhabitants moving temporarily or permanently to cities. By the end of 2013, China’s internal migrant population was 245 million, comprising more than a sixth of the nation’s total population, according to the Development Report on China’s Migrant Population 2014 released by China’s National Health and Family Planning Commission last week.

Nature
Volume 515 Number 7528 pp465-600 27 November 2014
http://www.nature.com/nature/current_issue.html

Nature | Editorial
Ebola opportunity – A slowdown in new cases offers a chance for control efforts to get ahead of the epidemic.
26 November 2014
An apparent slowdown in new cases of Ebola disease in Liberia and Guinea should be taken advantage of. Almost one year after an Ebola epidemic began in West Africa there are at last encouraging signs that it may be receding in some regions. But those responding to the epidemic must not drop their guard — rather, they should seize upon the chance to finish the job.

“Today, we — two dumbfounded doctors — stare at our empty blackboard. We have no more patients.” Last week, that declaration was blogged by a doctor with the humanitarian agency Médecins Sans Frontières (MSF), also known as Doctors Without Borders, at an Ebola treatment centre in the Foya region of Liberia. It is the same story in many parts of the country: empty beds that would have been unthinkable just a few weeks ago when Ebola treatment centres were overflowing. Nationally, the growth in the numbers of those infected in Liberia, the worst-affected country, is no longer exponential but has flattened off.

The epidemic has also stabilized in Guinea. But a resurgence of cases in Sierra Leone is a timely reminder that until Ebola is eliminated throughout West Africa, it remains a major threat. As of 18 November, Ebola has infected at least 15,000 people and killed 5,440 of them in these three main affected countries. But the worst-case scenarios predicted by mathematical modellers, which projected a steady apocalyptic rise in Ebola case numbers, have proved far off the mark (see Nature 515,18; 2014).

Although complacency is as unwise as it is hopefully unlikely — a lull in Ebola cases in the spring prompted authorities to drop their guard, only to see the virus return with a vengeance — there are reasons to believe that the current lull in Liberia and Guinea may continue. And that offers an opportunity to roll back the epidemic at last.

The exact causes of the lull are unclear. Belated international Ebola control efforts are only now beginning to kick in, and have no doubt contributed. But much of the slowdown is perhaps due to Africans themselves coming to terms with the epidemic and blocking its main routes of transmission. In particular, there has been a reduction in traditional burial practices, which are a key source of spread.

The slowing of new cases in Liberia and Guinea is a welcome reprieve for the health-care workers and scientists who have toiled to control a virus that for months has held the advantage. It is an opportunity to regroup, to consolidate gains, and to go all the more on the offensive.

Until recently, MSF, based in Geneva, Switzerland, was the only serious international presence fighting Ebola on the ground, but logistics meant that it could operate only a few large centralized treatment centres. These large centres, often with hundreds of beds, are still needed to absorb any resurgence, particularly in urban areas. But having only large centres is not ideal. Patients often have to travel for many hours or even days to reach them, and by the time they make it are often beyond recovery. They are also likely to have contaminated others en route, so fuelling the spread of the virus.

With its caseloads falling in recent weeks, MSF is coming out of the trenches and taking the fight to the virus, sending mobile teams and smaller treatment centres to the sites of new outbreaks to try to nip them in the bud. MSF sensibly wants other aid groups to adapt in a similar way. It will be a challenge for the more bureaucratic UN Mission for Ebola Emergency Response, and the US and other national Ebola-treatment efforts, to quickly change their plans, because they are mainly based around large centres. But it is crucial that the response to Ebola is flexible in the face of the shifting epidemiology.

The slowdown is also buying precious time for the testing of drugs and vaccines: clinical trials of vaccines in particular are being fast-tracked, with the first results due at the end of 2014. Unfortunately, however, drugs and vaccines have captured the spotlight and resources, while more mundane interventions that could have an immediate impact have been neglected. Better rehydration and electrolyte control can dramatically reduce mortality: the case fatality rate for patients treated in rich countries has been a fraction of the 70% seen in West Africa. Testing convalescent blood and serum from survivors — a potentially game-changing treatment — should also be a priority.

At the start of October, the United Nations and the World Health Organization set quantitative targets for safe burials, contact tracing and other key public-health control measures, which the international community was to meet by 1 December. It is already obvious that most of these targets will not be met. The breathing space offered by the current lull in Liberia and Guinea offers an opportunity to fill gaps and ramp up coverage of countermeasures. It must not be wasted.

New England Journal of Medicine
November 20, 2014 Vol. 371 No. 21
http://www.nejm.org/toc/nejm/medical-journal

Perspective
Ebola Virus Disease in West Africa — Clinical Manifestations and Management
Daniel S. Chertow, M.D., M.P.H., Christian Kleine, M.D., Jeffrey K. Edwards, M.D., M.P.H., Roberto Scaini, M.D., Ruggero Giuliani, M.D., and Armand Sprecher, M.D., M.P.H.
N Engl J Med 2014; 371:2054-2057
November 27, 2014
DOI: 10.1056/NEJMp1413084
In resource-limited areas, isolation of the sick from the population at large has been the cornerstone of control of Ebola virus disease (EVD) since the virus was discovered in 1976.1 Although this strategy by itself may be effective in controlling small outbreaks in remote settings, it has offered little hope to infected people and their families in the absence of medical care. In the current West African outbreak, infection control and clinical management efforts are necessarily being implemented on a larger scale than in any previous outbreak, and it is therefore appropriate to reassess traditional efforts at disease management. Having cared for more than 700 patients with EVD between August 23 and October 4, 2014, in the largest Ebola treatment unit in Monrovia, Liberia (see diagrams Diagrams of ELWA 3 Ebola Management Center, Monrovia, Liberia.), we believe that our cumulative clinical observations support a rational approach to EVD management in resource-limited settings.

Early symptoms of EVD include high fever (temperature of up to 40°C), malaise, fatigue, and body aches (see table Clinical Features of Ebola Virus Disease.).2,3 The fever persists, and by day 3 to 5 of illness, gastrointestinal symptoms typically begin, with epigastric pain, nausea, vomiting, and diarrhea. Patients routinely presented to our facility after 2 or 3 days of severe vomiting or diarrhea, during which they posed a substantial risk to their communities and had a high probability of testing positive for Ebola virus in blood by polymerase chain reaction (PCR). Although some patients tested positive on PCR within 24 hours after symptom onset, we found that a negative test result could not be relied on to rule out disease until 72 hours after symptoms began. Of the patients who tested positive for Ebola, none that we were aware of had contracted disease from an infected contact during the early febrile phase of illness. No ancillary testing was available in our facility.

We observed that recurrent episodes of emesis resulted in an inability to tolerate oral intake. Large volumes of watery diarrhea estimated at 5 or more liters per day (a manifestation not unlike that of cholera) presented suddenly, persisted for up to 7 days or (rarely) longer, and gradually tapered off. Associated signs and symptoms included asthenia, headache, conjunctival injection, chest pain, abdominal pain, arthralgias, myalgias, and hiccups. Respiratory symptoms, such as cough, were rare. Commonly observed neurologic symptoms included delirium, both hypoactive and hyperactive, manifested by confusion, slowed cognition, or agitation, and less frequently, seizures. In the absence of adequate fluid and electrolyte replacement, severe lethargy and prostration developed.

In approximately 60% of the patients we cared for, the development of shock was manifested by diminished level of consciousness or coma, rapid thready pulses, oliguria or anuria, and tachypnea. The distal extremities were cold despite high ambient temperature, and peripheral vasoconstriction was apparent. In aggregate, these clinical findings suggested metabolic acidosis due to severe hypovolemic shock. Evidence of hyperdynamic or distributive shock was infrequently observed and if present was a late finding. Clinically significant hemorrhage from the upper or lower gastrointestinal tract or both occurred in less than 5% of patients before death. Sudden death occurred in a small fraction of patients who were in the recovery phase of their illness, possibly as the result of fatal arrhythmias. Most deaths occurred between days 7 and 12 of illness.

Symptoms began to improve in approximately 40% of patients around day 10 of illness. We observed the development of oral ulcers and thrush around this time, associated with throat pain and dysphagia. Nearly all patients who survived to day 13 ultimately lived. Our discharge criteria included 3 days without gastrointestinal symptoms and a negative PCR test for Ebola virus in blood. We noted that some patients with initial evidence of clinical improvement developed neck rigidity and diminished levels of consciousness. These symptoms were associated with a slight increase in late mortality. The role of central nervous system involvement by EVD, secondary infection, or aseptic processes could not be assessed.

Particularly vulnerable patient populations included children less than 5 years of age, the elderly, and pregnant women. Of the four women who presented with late second- or third-trimester pregnancies, three died shortly after miscarrying, and none successfully carried a fetus to term. Four Liberian staff members became infected with Ebola virus, and three of them died. According to individual investigations, these infections were not attributable to any known breaches in infection-control procedures in the Ebola treatment unit; instead they are thought to be possibly related to transmission in the community where the outbreak was active.

Health care workers in West Africa remain overwhelmed and challenged by the scarcity of resources that would be available in developed countries for improving the care of patients with EVD.4 When patients arrived at our facility, they were moderately to severely ill, and each physician was responsible for the care of 30 to 50 patients. Direct patient contact in the Ebola treatment center was typically limited to intervals of 45 to 60 minutes two to three times a day, owing to substantial heat exposure and fluid losses that providers experienced while wearing full personal protective equipment (PPE). Under these conditions, physicians had 1 to 2 minutes per patient to evaluate needs and establish a care plan.

Rapid clinical assessment required triage of patients into one of three categories: those who were clinically hypovolemic, not in shock, and able to provide self-care; those who were hypovolemic, not in shock, but unable to provide self-care; and those in shock with evidence of organ failure whose outcome would not be altered by any available medical intervention. The majority of patients we cared for were in the first category. We believe that this group had the highest likelihood of having a response to our limited available interventions.

We observed that patients who were hypovolemic, not in shock, and able to care for themselves had potential for recovery with oral antiemetics, antidiarrheal therapy, and adequate rehydration with oral electrolyte solutions. Given the massive fluid losses observed with EVD, oral antiemetics and antidiarrheal therapy appear to be important early interventions that may limit life-threatening dehydration and shock. In our experience, these regimens were successful at controlling symptoms, facilitated oral intake, reduced gastrointestinal fluid losses, and helped to reduce environmental contamination by body fluids. Health care workers with limited time in PPE were then able to direct their efforts toward encouraging and facilitating oral intake.

It was our impression that the cohort of patients who were hypovolemic and not in shock but unable to provide self-care would benefit the most from short-term intravenous fluid therapy and electrolyte replacement. Establishing intravenous access, delivering an adequate volume of fluid, and ensuring safe management of needles and devices required intensive individual-level patient care. Routine use of intravenous fluid therapy in our facility was prohibited by massive caseloads, limited number of health care workers, and limited time in PPE.

The central purpose of Ebola treatment units has historically been to isolate infected persons early in the course of disease — often soon after fever onset — in order to break the chain of disease transmission in the community. However, all efforts must be made to optimize the level of medical care provided within these facilities. Resistance by infected people to voluntary admission will persist unless the treatment facilities are seen as a place to go for treatment and recovery and not as a place to die isolated from loved ones and the community. Our observations support aggressive use of antiemetics, antidiarrheal medications, and rehydration solution to reduce massive gastrointestinal losses and the consequences of hypovolemic shock. Selective use of intravenous fluid therapy in the population that is most likely to benefit is a rational approach under the current circumstances. When possible, broader use of intravenous fluid therapy and electrolyte replacement, guided by point-of-service laboratory testing, is likely to significantly improve outcomes.
References

Original Article
Ebola Virus Disease in the Democratic Republic of Congo
Gaël D. Maganga, D.V.M., Ph.D., Jimmy Kapetshi, M.D., Nicolas Berthet, Pharm.D., Ph.D., Benoît Kebela Ilunga, M.D., Felix Kabange, M.D., Placide Mbala Kingebeni, M.D., Vital Mondonge, M.D., Jean-Jacques T. Muyembe, M.D., Ph.D., Eric Bertherat, M.D., Sylvie Briand, M.D., Joseph Cabore, M.D., Alain Epelboin, M.D., Pierre Formenty, D.V.M., M.P.H., Gary Kobinger, M.D., Licé González-Angulo, M.Sc., Ingrid Labouba, Ph.D., Jean-Claude Manuguerra, Ph.D., Jean-Marie Okwo-Bele, M.D., Christopher Dye, D. Phil., and Eric M. Leroy, D.V.M., Ph.D.
N Engl J Med 2014; 371:2083-2091 November 27, 2014 DOI: 10.1056/NEJMoa1411099
[Free full text]
Conclusions
The current EVD outbreak in the DRC has clinical and epidemiologic characteristics that are similar to those of previous EVD outbreaks in equatorial Africa. The causal agent is a local EBOV variant, and this outbreak has a zoonotic origin different from that in the 2014 epidemic in West Africa. (Funded by the Centre International de Recherches Médicales de Franceville and others.)

Original Article
Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone
John S. Schieffelin, M.D., M.S.P.H., Jeffrey G. Shaffer, Ph.D., Augustine Goba, B.Sc., Michael Gbakie, R.N., Stephen K. Gire, M.P.H., Andres Colubri, Ph.D., Rachel S.G. Sealfon, S.M., Lansana Kanneh, Alex Moigboi, R.N., Mambu Momoh, Mohammed Fullah, Lina M. Moses, Ph.D., Bethany L. Brown, M.S.C.S., Kristian G. Andersen, Ph.D., Sarah Winnicki, M.S., Stephen F. Schaffner, Ph.D., Daniel J. Park, Ph.D., Nathan L. Yozwiak, Ph.D., Pan-Pan Jiang, Ph.D., David Kargbo, Simbirie Jalloh, Mbalu Fonnie, R.N., Vandi Sinnah, Issa French, Alice Kovoma, Fatima K. Kamara, R.N., Veronica Tucker, Edwin Konuwa, R.N., Josephine Sellu, R.N., Ibrahim Mustapha, Momoh Foday, Mohamed Yillah, Franklyn Kanneh, Sidiki Saffa, James L.B. Massally, Matt L. Boisen, Luis M. Branco, Ph.D., Mohamed A. Vandi, M.B., Ch.B., Donald S. Grant, M.B., Ch.B., Christian Happi, Ph.D., Sahr M. Gevao, M.B., Ch.B., Thomas E. Fletcher, M.D., Robert A. Fowler, M.D., Daniel G. Bausch, M.D., M.P.H.T.M., Pardis C. Sabeti, M.D., D.Phil., S. Humarr Khan, M.B., Ch.B., and Robert F. Garry, Ph.D. for the KGH Lassa Fever Program, the Viral Hemorrhagic Fever Consortium, and the WHO Clinical Response Team
N Engl J Med 2014; 371:2092-2100 November 27, 2014 DOI: 10.1056/NEJMoa1411680
[Free full text]
Conclusions
The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.)

PLoS One
[Accessed 29 November 2014]
http://www.plosone.org/

Research Article
The Definition of Placebo in the Informed Consent Forms of Clinical Trials
Astrid Hernández, Josep-E. Baños mail, Cristina Llop, Magí Farré
Published: November 25, 2014
DOI: 10.1371/journal.pone.0113654
Abstract
Aim
Lack of knowledge concerning the nature of placebo and why it is necessary may influence the participation of patients in clinical trials. The objective of the present study is to review how placebo is described in written information for participants in clinical trials to be evaluated by a Human Research Ethics Committee.
Methods
All research protocols submitted for evaluation in a Spanish hospital during 2007–2013 were reviewed. The main characteristics of the studies using a placebo were collected. Three authors read each of them to determine how the term “placebo” was explained and if there was any comment on its efficacy and safety.
Results
Two thousand seven-hundred and forty research protocols were evaluated, of which three hundred and fifty-nine used a placebo. Pharmaceutical companies sponsored most placebo-controlled clinical trials (91.9%), and phase III studies were the commonest (59.9%). Oncology (15.0%), cardiology (14.2%), and neurology (13.1%) made the greatest contributions. A review of the informed consent forms showed that placebo was described in a similar manner in most studies: the explanation was limited to between four and eight words. Very few gave information about the risks of its use or adverse reactions from its administration. None of the studies provided details about the placebo effect. And 23 lacked any information about placebo at all.
Conclusions
Explanations about placebo in informed consent forms is often scarce, and information about the placebo effect and associated risks are absent. This situation may influence a full understanding of placebo by participants in clinical trials and might reduce their informed decision to participate.

PLoS Medicine
(Accessed 29 November 2014)
http://www.plosmedicine.org

Editorial
(How) Can We Reduce Violence Against Women by 50% over the Next 30 Years?
Rachel Jewkes mail
Published: November 25, 2014
DOI: 10.1371/journal.pmed.1001761
Open Access
[Initial text]
Each year, interpersonal violence is experienced and perpetrated by millions of people worldwide. In 2010, it was the 27th cause of death globally, causing an estimated 456,268 deaths worldwide [1]. Violence against women has been shown to be highly prevalent globally, with partner violence affecting one in three women, and one in 15 women (7%) having been raped by a man who was not a partner [2],[3]. Recognising this huge global burden, the 67th World Health Assembly adopted the resolution “Strengthening the Role of the Health System in Addressing Violence, in Particular against Women and Girls, and against Children” [4] and mandated countries globally to develop violence prevention through their health sector. The goal of reducing violence by 50% over the next 30 years has been mooted by the World Health Organization as a rallying point for the global violence prevention community and was the subject of critical debate at the recent Global Violence Reduction Conference 2014 at King’s College, Cambridge University, UK, which was hosted by the Institute of Criminology Violence Research Centre and the World Health Organization [5]. Whilst ostensibly ambitious, several high-income countries, including the United States, have reduced rates of some forms of violence by 50% or more over a very short period of time, and such reductions are supported by historical trends of reduced homicide over several centuries in several European countries [6]–[8]. There is no real evidence, however, that violence against women is reducing in low- and middle-income countries [3]. Indeed, in South Africa, where there has been considerable gender activism and growth in women’s empowerment, non-fatal rape and intimate partner violence seem quite resistant to change, notwithstanding the measured reductions in female homicide [9],[10]. The key question, then, is how can we secure substantial reductions in violence against women in low- and middle-income countries?

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
(Accessed 29 November 2014)

Estimating Potential Incidence of MERS-CoV Associated with Hajj Pilgrims to Saudi Arabia, 2014
Justin Lessler Isabel Rodriguez-Barraquer, Derek A.T. Cummings, Tini Garske, Maria Van Kerkhove, Harriet Mills, Shaun Truelove, Rafat Hakeem, Ali Albarrak, Neil M. Ferguson, – The MERS-CoV Scenario Modeling Working Group
November 24, 2014 • Research
Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1–17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0–12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32–66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17–43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries.

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
(Accessed 29 November 2014)

Projected Impact of Vaccination Timing and Dose Availability on the Course of the 2014 West African Ebola Epidemic
David Fisman, Ashleigh Tuite
November 21, 2014 • Research
Abstract
Background: The 2014 West African Ebola outbreak has evolved into an epidemic of historical proportions and catastrophic scope. Prior outbreaks have been contained through the use of personal protective equipment, but such an approach has not been rapidly effective in the current epidemic. Several candidate vaccines have been developed against the Ebola virus, and are undergoing initial clinical trials.
Methods: As removal of population-level susceptibility through vaccination could be a highly impactful control measure for this epidemic, we sought to estimate the number of vaccine doses and timing of vaccine administration required to reduce the epidemic size. Our base model was fit using the IDEA approach, a single equation model that has been successful to date in describing Ebola growth. We projected the future course of the Ebola epidemic using this model. Vaccination was assumed to reduce the effective reproductive number. We evaluated the potential impact of vaccination on epidemic trajectory under different assumptions around timing of vaccine availability.
Results: Using effective reproductive (Re) number estimates derived from this model, we estimate that 3-4 million doses of vaccine, if available and administered, could reduce Re to 0.9 in the interval from January-March 2015. Later vaccination would be associated with a progressively diminishing impact on final epidemic size; in particular, vaccination to the same Re at or after the epidemic is projected to peak (April-May 2015) would have little impact on final epidemic size, though more intensive campaigns (e.g., Re reduced to 0.5) could still be effective if initiated by summer 2015. In summary, there is a closing window of opportunity for the use of vaccine as a tool for Ebola epidemic control.
Conclusions: Effective vaccination, used before the epidemic peaks, would be projected to prevent tens of thousands of deaths; this does not minimize the ethical challenges that would be associated with wide-scale application of vaccines that have undergone only limited evaluation for safety and efficacy.

Science
28 November 2014 vol 346, issue 6213, pages 1029-1148
http://www.sciencemag.org/current.dtl

In Depth
Infectious Diseases
A new phase in the Ebola war
Kai Kupferschmidt*
Summary
The number of new Ebola cases in Liberia, one of the hardest hit countries in the current epidemic, has come down to about 20 per day, far fewer than models predicted a few months ago. Ebola treatment units now have hundreds of empty beds, and the fight against the virus is entering a new phase. Back in September, the key job was building clinics, removing the dead, and keeping as many patients as possible isolated. Now, it’s about setting up a flexible system to respond to new outbreaks, identifying patients quickly, and tracing their contacts to prevent more infections. Meanwhile, outbreaks are still flaring up in the remote districts, making it unlikely that Liberia can put a stop to the epidemic anytime soon

Perspective
Medicine
Big data meets public health
Muin J. Khoury1,2, John P. A. Ioannidis3
Author Affiliations
1Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
2Epidemiology and Genomics Research Program, National Cancer Institute, Bethesda, MD 20850, USA.
3Stanford Prevention Research Center and Meta-Research Innovation Center at Stanford, Stanford University, Palo Alto, CA 94305, USA.
Summary
In 1854, as cholera swept through London, John Snow, the father of modern epidemiology, painstakingly recorded the locations of affected homes. After long, laborious work, he implicated the Broad Street water pump as the source of the outbreak, even without knowing that a Vibrio organism caused cholera. “Today, Snow might have crunched Global Positioning System information and disease prevalence data, solving the problem within hours” (1). That is the potential impact of “Big Data” on the public’s health. But the promise of Big Data is also accompanied by claims that “the scientific method itself is becoming obsolete” (2), as next-generation computers, such as IBM’s Watson (3), sift through the digital world to provide predictive models based on massive information. Separating the true signal from the gigantic amount of noise is neither easy nor straightforward, but it is a challenge that must be tackled if information is ever to be translated into societal well-being.

Vaccine
Volume 32, Issue 52, Pages 7033-7184 (12 December 2014)
http://www.sciencedirect.com/science/journal/0264410X/32/52

Meeting Report
Considerations around the introduction of a cholera vaccine in Bangladesh
Pages 7033-7036
Christopher B. Nelson, Vittal Mogasale, Tajul Islam A. Bari, John D. Clemens
Abstract
Cholera is an endemic and epidemic disease in Bangladesh. On 3 March 2013, a meeting on cholera and cholera vaccination in Bangladesh was convened by the Foundation Mérieux jointly with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B). The purpose of the meeting was to discuss the investment case for cholera vaccination as a complimentary control and prevention strategy. The performance of a new low cost oral cholera vaccine, Shanchol™, used in recent trials in Bangladesh, was also reviewed in the context of a potential large-scale public-sector vaccination program. Findings showed the oral vaccine to be highly cost-effective when targeting ages 1–14y, and cost-effective when targeting ages 1+y, in high-burden/high-risk districts. Other vaccination strategies targeting urban slums and rural areas without improved water were found to be cost-effective. Regardless of cost-effectiveness (value), the budget impact (affordability) will be an important determinant of which target population and vaccination strategy is selected. Most importantly, adequate vaccine supply for the proposed vaccination programs must be addressed in the context of global efforts to establish a cholera vaccine stockpile and supply other control and prevention efforts.

Commentaries
Seasonal and pandemic influenza vaccine: Demand, supply and vaccine availability
Pages 7037-7039
Bruce G. Gellin, William K. Ampofo
[No abstract]

Increasing engagement of clinicians in adult immunizations: Reflections on a decade and a half of research
Pages 7040-7042
Richard K. Zimmerman
[No abstract]

Brief Report
Monitoring coverage of fully immunized children
Pages 7047-7049
Asnakew Tsega, Fussum Daniel, Robert Steinglass
Abstract
Immunization programs monitor 3rd dose of DPT-containing vaccine coverage as a principal indicator; however, this does not inform about coverage with other vaccines. A mini-survey was conducted to assess the status of monitoring coverage of fully immunized children (FIC) in Eastern and Southern African countries. We designed and distributed a structured self-administered questionnaire to all 19 national program managers attending a meeting in March 2014 in Harare, Zimbabwe. We learned that most countries already monitor FIC coverage and managers appreciate the importance of monitoring this as a national indicator, as it aligns with the full benefits of immunization. This mini-survey concluded that at national level, FIC coverage could be used as a principal indicator; however, at global level DPT3 has some additional advantages across all countries in standardizing the capacity of the immunization program to deliver multiple doses of the same vaccine to all children by 12 months of age.

Safety of immunization during pregnancy: A review of the evidence of selected inactivated and live attenuated vaccines
Review Article
Pages 7057-7064
Brigitte Keller-Stanislawski, Janet A. Englund, Gagandeep Kang, Punam Mangtani, Kathleen Neuzil, Hanna Nohynek, Robert Pless, Philipp Lambach, Patrick Zuber
Abstract
Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus.
This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.

Vaccine
Volume 32, Issue 52, Pages 7033-7184 (12 December 2014)
http://www.sciencedirect.com/science/journal/0264410X/32/52

Variation in exemptions to school immunization requirements among New York State private and public schools
Original Research Article
Pages 7070-7076
Yun-Kuang Lai, Jessica Nadeau, Louise-Anne McNutt, Jana Shaw
Abstract
Background and objectives
School immunization requirements have ensured high vaccination rates and have helped to control vaccine-preventable diseases. However, vaccine exemptions have increased in the last decade. This study compared New York State private versus public schools with respect to medical and religious exemption rates.
Methods
This retrospective study utilizes New York State Department of Health Immunization Survey data from the 2003 through 2012 academic years. Schools were categorized as private or public, the former further categorized by religious affiliation. Rates of medical and religious vaccine exemptions were compared by school category.
Results
From 2003 to 2012, religious exemptions increased in private and public schools from 0.63% to 1.35% and 0.17% to 0.29% (Spearman’s R: 0.89 and 0.81), respectively. Among private schools, increases in religious exemption rates during the study period were observed in Catholic/Eastern Orthodox, Protestant/Other Christian, Jewish, and secular schools (Spearman’s R = 0.66, 0.99, 0.89, and 0.93), respectively. Exemption rate ratios in private schools compared to public schools were 1.39 (95% CI 1.15–1.68) for medical and 3.94 (95% CI: 3.20–4.86) for religious exemptions. Among private school students, all school types except for Catholic/Eastern Orthodox and Episcopal affiliates were more likely to report religious exemptions compared to children in public schools.
Conclusions
Medical and religious exemption rates increased over time and higher rates were observed among New York State private schools compared to public schools. Low exemption rates are critical to minimize disease outbreaks in the schools and their community.

Vaccine
Volume 32, Issue 52, Pages 7033-7184 (12 December 2014)
http://www.sciencedirect.com/science/journal/0264410X/32/52

Qualitative motivators and barriers to pandemic vs. seasonal influenza vaccination among healthcare workers: A content analysis
Original Research Article
Pages 7128-7134
Chatura Prematunge, Kimberly Corace, Anne McCarthy, Rama C. Nair, Virginia Roth, Kathryn N. Suh, Gary Garb
Abstract
Introduction
Influenza is a major concern across healthcare environments. Annual vaccination of healthcare workers (HCW) remains a key mode of influenza prevention in healthcare settings. Yet influenza vaccine coverage among HCWs continues to be below recommended targets, in pandemic and non-pandemic settings. Thus, the primary objective of this analysis is to identify motivators and barriers to pandemic (panINFLU) and seasonal influenza vaccination (sINFLU) through the qualitative analysis of HCW provided reasons driving HCW’s personal vaccination decisions.
Methods
Data were collected from a multi-professional sample of HCWs via a cross-sectional survey study, conducted at a tertiary-care hospital in Ontario, Canada. HCW provided and ranked qualitative reasons for personal (1) panINFLU (pH1N1) and (2) sINFLU (2008/2009 season) vaccine uptake and avoidance were used to identify key vaccination motivators and barriers through content analysis methodology.
Results
Most HCW vaccination motivators and barriers were found to be similar for panINFLU and sINFLU vaccines. Personal motivators had the greatest impact on vaccination (panINFLU 29.9% and sINFLU 33.9%). Other motivators included preventing influenza in loved ones, patients, and community, and awareness of HCW role in influenza transmission. In contrast, concerns of vaccine safety and limited HCW knowledge of influenza vaccines (panINFLU 46.2% and sINFLU 37.3%).
HCW vaccination during the pandemic was motivated by panINFLU related fear, epidemiology, and workplace pro-vaccination policies. HCW perceptions of accelerated panINFLU vaccine development and vaccine safety compromises, negative views of external sources (i.e. media, pharmaceutical companies, and regulatory agencies) and pandemic management strategies were barriers specific to panINFLU vaccine.
Conclusions
HCW panINFLU and sINFLU vaccine coverage can increase if future vaccination programs (1) highlight personal vaccination benefits (2) emphasize the impact HCW non-vaccination on family members, patients and community, (3) address HCW vaccine related knowledge gaps, and (4) implement pro-vaccination workplace policies consistent with those in place at the study site during pH1N1.

Vaccine
Volume 32, Issue 52, Pages 7033-7184 (12 December 2014)
http://www.sciencedirect.com/science/journal/0264410X/32/52

Special Section: Vaccination Ethics
Vaccination ethics
Pages 7161-7162
A.M. Viens, Angus Dawson
[No abstract]

What is the responsibility of national government with respect to vaccination?
Original Research Article
Pages 7163-7166
Marcel F. Verweij, Hans Houweling
Highlights
:: Governments have a dual responsibility in relation to collective vaccination.
:: First, to protect conditions for public health and societal life.
:: Second, to secure equitable access to basic preventive care.
:: Judgments about seriousness of risk and disease are inevitable in applying these principles.

How high is a high risk? Prioritising high-risk individuals in an influenza pandemic
Original Research Article
Pages 7167-7170
Jasper Littmann
Highlights
:: Pandemic contingency plans often prioritise high-risk patients for immunisation.
:: Inclusion and exclusion criteria for this group are poorly defined.
:: Many pandemic plans fail to define how great a risk must be to merit prioritisation.
:: Personal responsibility for a risk factor is not normally taken into account.
:: The resulting categorisation of high-risk individuals is often arbitrary.

Ethical considerations in post-market-approval monitoring and regulation of vaccines
Original Research Article
Pages 7171-7174
Alison Thompson, Ana Komparic, Maxwell J. Smith
Highlights
:: We articulate ethical considerations for regulators involved in post-market vaccine monitoring and regulation.
:: The protection of the public from harm is both a strong obligation of governments and the main ethical consideration.
:: There are four subsequent considerations that need to be considered when aiming to protect the public from vaccine harms related to safety and effectiveness.
:: These are highest quality of evidence possible, anticipatory decision making, duty to warn and proportionate monitoring.
:: In addition to these considerations, we identify further ethical issues that need consideration, including: transparency, a publicly acceptable risk-benefit profile, minimization of stigma, special obligations to vulnerable populations and public trust.

Varicella-zoster virus vaccination under the exogenous boosting hypothesis: Two ethical perspectives
Original Research Article
Pages 7175-7178
Jeroen Luyten, Benson Ogunjimi, Philippe Beutels
Highlights
:: Childhood chickenpox vaccination may increase zoster incidence in older age groups.
:: This ‘exogenous boosting’ effect gives VZV policy an important equity dimension.
:: We discuss the justifiability of childhood vaccination from two ethical perspectives.
:: Classic utilitarianism offers a basis for a policy that discourages VZV-vaccination.
:: Contractualism lends support to children’s freedom to become vaccinated.

The ethics of disease eradication
Original Research Article
Pages 7179-7183
James Wilson
Highlights
:: The endgame of eradication policies will often involve some individuals being vaccinated against their medical best interests.
:: Eradication policies can nonetheless be ethically appropriate, as they should be thought of through the lens of public health ethics, rather than clinical medical ethics.
:: Some common arguments for eradication, such as its symbolic value or that it is a global public good, fail to convince.
:: The same considerations that should guide public health policy more generally – reducing the burden of disease equitably and efficiently – make eradication a compelling goal where it is feasible.

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

Journal of Bioethical Inquiry
November 2014
Date: 25 Nov 2014
Using the Ebola Outbreak as an Opportunity to Educate on Vaccine Utility
Brandon Brown
Excerpt
The first domestic death from Ebola in the United States occurred in Texas in October 2014. Family members who were potentially exposed to the infected individual were legally and involuntarily quarantined. Quarantine may not be a recent normal practice in the United States, but it was used extensively during the influenza pandemic in the early 20th century. However, health care ethics comes into play when we quarantine someone whose infection status is unknown versus active. To prevent the spread of a pathogen, one person may be held against his or her will and that person’s freedom is terminated. Quarantine may be acceptable in the case of Ebola, as it is particularly virulent and there have been more and more potential cases in the United States (and elsewhere). As a result, the general population may understand how isolation and quarantine may help prevent the spread of Ebola. We must use this epidemic as an opportunity to educate the general population on ways to prevent the spread…

.

International Journal of Research in Medical Sciences
2014; 2(4): 1607-1611
Awareness and attitude regarding human papilloma virus and its vaccine among medical students in a medical school in India
N Challa, V Madras, S Challa -, 2014
doi: 10.5455/2320-6012.ijrms20141168
Abstract
Background: Human papilloma virus is the major cause of cervical cancer in women and HPV vaccine is the most effective option. Prevention of cancer with vaccine is a new concept. Medical students should be aware of cervical cancer, HPV and its vaccine. This calls for assessment of the knowledge of HPV infection and the acceptability of HPV vaccine among medical students. The aim of this study was to assess awareness of HPV infection and HPV vaccine and to assess attitude toward these vaccines among final year medical students in Sri Venkateswara Medical College, Tirupati.
Methods: It is a cross-sectional study. A total of 127 (59 males and 68 females) final year M.B.B.S. students participated. Data regarding HPV and its vaccine were collected using questionnaire based survey. The questionnaire sought student responses pertaining to the knowledge of cervical cancer, HPV and its vaccine. The data were analyzed using Microsoft Access and Excel software.
Results: Most of the participants know well about the etiology and prevention of cervical cancer but information regarding the dosage, schedule, site and route of administration was lacking in majority of them.
Conclusion: The medical students know the association between Human Papilloma Virus and cervical cancer, but the awareness about HPV vaccine was low among study population. Medical schools should modify their curricula to include teaching methods aimed at improving awareness regarding HPV and its vaccine.

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.

Al Jazeera
http://www.aljazeera.com/Services/Search/?q=vaccine
Accessed 29 November 2014
Syria struggles to vaccinate residents
Inoculation campaigns have faced massive challenges amid the country’s plummeting security situation.
Sophie Cousins Last updated: 23 Nov 2014 10:40
Beirut – Since the beginning of the Syrian crisis in early 2011, war has all but destroyed the country’s healthcare system. Hundreds of doctors and health practitioners have been killed or have fled to neighbouring countries, drug supply routes have been destroyed, and government forces have routinely and indiscriminately targeted hospitals.
As a result – and on top of unsanitary living conditions and a sharp drop in overall vaccination coverage – there have been outbreaks of communicable diseases such as hepatitis, leishmaniasis, polio, and tuberculosis.
Polio, eliminated in Syria in 1995, re-emerged last year and spread across large swaths of the country’s opposition-held north.The highly contagious disease also re-emerged in Iraq this year for the first time since 2000, infecting a baby boy and a young girl. The World Health Organisation (WHO) and UNICEF responded by launching a mass polio vaccination campaign across the region, but health workers say the response was too slow.
“The first cases of flaccid paralysis were diagnosed clinically in July of 2013, and they weren’t confirmed by WHO until October,” Zaher Sahloul, president of the Syrian American Medical Society (SAMS), told Al Jazeera. “The WHO initially underestimated the risk and took the Syrian line.”
Despite the odds, a hugely successful polio campaign has been ongoing in Syria – largely thanks to the Polio Task Force, a coalition of Syrian groups including SAMS, the opposition-linked Assistance and Coordination Unit (ACU) and about half a dozen other groups supported by the Turkish Ministry of Health. Some 8,200 volunteers, including a network of activists and doctors, have completed seven rounds of vaccinations, inoculating about 1.4 million of the estimated 1.5 million children in the area it covers.
But those delivering the vaccinations have faced insurmountable challenges amid the country’s plummeting security situation, including the deaths of more than four volunteers.
“[The volunteers] have faced shelling, explosive barrel bombs and were subjected to sniper fire while working,” Bashir Taj al-Din, a technical coordinator with the ACU, told Al Jazeera.
Doctors running the campaign said they also had to work against rumours that vaccination could cause side effects such as AIDS and impotence, thwarting their efforts to vaccinate as many children as possible against diseases like polio, measles and rubella….

The Atlantic
http://www.theatlantic.com/magazine/
Accessed 29 November 2014
Africa Nears Eradication of Polio
A rigorous vaccination campaign has nearly eliminated the crippling infectious disease from Nigeria and the continent at large, according to a new CDC report.
Nicholas St. Fleur Nov 21 2014, 5:32 PM ET
| 21 November 2014
One month after quelling its deadly Ebola outbreak, Nigeria stands poised to make another public-health triumph—the near-eradication of polio.

Since 2012, when the World Health Organization declared the crippling infectious disease a “global-health emergency,” the West African country (the last center of polio on the continent) has overhauled its strategies for combating the scourge. Now, through rigorous vaccination campaigns, Nigeria is on the verge of eliminating the virus and making Africa polio-free, the CDC reported Thursday.

From January to August of this year, Nigeria only reported six cases of polio—a significant drop from the 49 cases it had during that same period in 2013. And when compared with the 122 polio cases from all of 2012, the recent report reveals the rigor of the nation’s vaccination efforts. For a four-day period every six to eight weeks, health officials from Nigeria’s national polio-eradication program go door-to-door and drop oral immunizations into the mouths of some 10 to 20 million children under the age of five. The campaign especially targets children living in 11 high-risk states located mostly in the northern part of the country.

“The goal is to vaccinate every child in every community that these campaigns hit,” said John Vertefeuille, an epidemiologist and head of the CDC’s polio eradication team for Nigeria. “Every child in that house gets vaccinated, even if they’ve had [the vaccine] 10 times before.”…

Council on Foreign Relations
http://www.cfr.org/
Accessed 29 November 2014
Expert Brief
The Downside of Securitizing the Ebola Virus
Author: Yanzhong Huang, Senior Fellow for Global Health
November 25, 2014
The Ebola outbreak in West Africa, the largest of its kind in history, has been responsible for more than 15,000 cases, including more than 5,400 reported deaths as of late November. Unlike the responses to previous Ebola outbreaks, political and public health leaders have upped the ante by explicitly framing the disease in national and international security terms. Margaret Chan, the director general of the World Health Organization (WHO), spoke of “a threat to national security well beyond the outbreak zones,” and U.S. President Barack Obama described the outbreak as “a growing threat to regional and global security.”…

…To sum up, while securitization might be necessary to address the ongoing Ebola outbreak, it may have negative impacts on socioeconomic stability, civil-military relations, risk management, and long-term health system capacity building. Instead of promoting a securitization approach to handling acute disease outbreaks, a more effective approach would be to frame disease control as a global public good. Under this new approach, countries would be obliged to contribute to an international capacity building fund—administered by the World Health Organization—and to use that fund to strengthen disease surveillance and response capacities in countries that fail to meet the requirements of the revised International Health Regulations. With a more robust health system capacity, these countries will be able to nip a rising pathogen in the bud. And if an outbreak was to evolve into a Public Health Emergency of International Concern as Ebola has, it should trigger an institutionalized (not securitized) arrangement that could lead to a surge of international assistance.

On the domestic front, it would be more responsible and constructive to adopt a risk-based approach that tailors government interventions to the actual risks posed by the disease. The implementation of this approach, when combined with effective international collaboration, would maximize the protection of domestic population health while minimizing the disturbance the virus-spawned fear may cause to the economy and the society.

The Guardian
http://www.guardiannews.com/
Accessed 29 November 2014
Boost Ebola aid to Sierra Leone, Justine Greening told
Open letter calls on international development secretary to increase response to outbreak to avoid ‘catastrophic loss of life’
The Guardian | 27 November 2014
Justine Greening, the international development secretary, has been warned by senior medical professionals that Sierra Leone risks “a public health disaster” worse than Ebola unless UK efforts to contain the virus are significantly stepped up.

In an open letter signed by 53 doctors, charity representatives and a former British diplomat, Greening is told the government needs to quickly review operations in Sierra Leone to avert further crisis.

“Much more needs to be done to avoid further catastrophic loss of life,” says the letter, sent to Greening on Thursday.

The signatories warn that, unless a comprehensive response to the crisis is adopted, “health services will collapse entirely”, resulting in a “public health disaster that will eclipse the Ebola outbreak itself and provide the perfect incubator for further outbreaks”…

The Huffington Post
http://www.huffingtonpost.com/
Accessed 29 November 2014
Ebola Vaccines: Why Clinical Trials Are Just the First Step
Seth Berkley is CEO of Gavi, the Vaccine Alliance
With clinical trials for Ebola vaccines now under way, and with governments and manufacturers stepping up to fund them, there is an almost palpable sense that the panic is over and the problem solved. The reality, however, is that even if a safe and effective vaccine emerges and the epidemic is brought under control, we are still in many ways no better prepared for future outbreaks than we were a year ago.

So how is it that we can spend billions of dollars every year keeping fleets of nuclear-armed submarines permanently patrolling our oceans, to protect us from a threat that will almost certainly never happen, and yet invest virtually nothing into the prevention of something as tangible and evolutionarily certain as virulent infectious disease?

Even now, with more than 5,000 people dead and 14,000 confirmed cases of Ebola in eight countries, it is still not clear who will pay if, or when, a vaccine becomes available. Millions of doses will be needed, and not just to help end the current epidemic but also, crucially, as a stockpile to prevent future outbreaks from getting out of control.

What is now clear though is that West Africa needs a vaccine, and needs one now. Modeling carried out by the London School of Hygiene and Tropical Medicine, on behalf of the World Health Organization, suggests that even if the outbreak was already in decline by the time a viable vaccine becomes available, it could still help prevent tens of thousands of deaths between now and the end of 2015. And in the worst-case scenario, if the virus were to continue to spread and become endemic, this figure could rise well into the millions.

The problem is that there is no market. It’s one thing developing and approving a vaccine, and quite another getting it out to the people who need it the most. Just ask the 15 million predominantly poor children who still don’t receive any of the basic vaccines that you and I take for granted.

It can take a billion dollars to bring a vaccine to market. Yet with diseases like Ebola, which kills ferociously but occurs sporadically, usually with only a few hundred cases every few years, and in poor African countries that can ill-afford to pay top dollar, manufacturers would be unlikely to see a return on that investment. Even now, with the virus having reached the Western world, the financial incentives are just not there.

So with no market, even if one of these candidate Ebola vaccines receives clinical approval, we’ll still be left with a significant funding gap standing between the vaccine and the people in West Africa who desperately need it. Not just in terms of who pays for the doses, but also the significant costs involved in scaling-up to commercial production, the costs involved in delivery and deployment and for stockpiling to ensure we are prepared for the next outbreak. That means making funds available to not only improve on the first wave of vaccines so that they include more than one strain of Ebola and are easier to store and use, but also to develop vaccines for other virulent diseases, such as Marburg, which also have the same devastating potential but for whom there is also no market.
Such market failures are nothing new in global health, and one of the reasons why in 2000 Gavi, the Vaccine Alliance, was created; to find innovative solutions to help poor countries pay for existing vaccines for infectious diseases, and to incentivise manufacturers to develop new ones. This has led to the development of new approaches to funding which have already proved extremely effective when dealing with vaccines for more common – and in terms of headcount far more deadly – infectious diseases, such as measles, hepatitis B, pneumonia and diarrhoea.

So in the case of Ebola, one approach we are currently considering has the potential to plug the funding gap that exists in the scaling-up of vaccine production, which would be necessary both for mass vaccination programmes and stockpiling. This could take the form of an advanced purchase commitment, where donor funds are committed to guarantee manufacturers an agreed price once the vaccine has been developed. This sort of pull mechanism could involve frontloaded incentives to make it attractive for industry to make the necessary investments to scale-up production.

Similarly it may be possible to plug the future procurement gap by using long-term flexible guaranteed funding, like the International Finance Facility for Immunisation (IFFIm), to pay for doses to be stockpiled. IFFIm currently works by using long-term government donor pledges, from a range of governments, to sell “vaccine bonds” in capital markets, making large volumes of long-term funds available immediately for vaccine programs at the point in time when funds are required.

So in theory we could have a flexible standing fund available to scale-up production, pay for vaccines, assist countries with rollout and the restocking of a stockpile when they are needed. But there is a catch. For it to work we need to change our attitude towards infectious disease. We need to stop waiting for evidence of a disease becoming a global threat before we treat it like one. If we want to prevent major outbreaks of diseases like Ebola then we need to invest in vaccine stockpiles and start viewing them as though they were nuclear submarines; willing to pay for them and at the same time praying we never have to use them.

New Yorker
http://www.newyorker.com/
Accessed 29 November 2014
Currency
November 25, 2014
The Race for an Ebola Vaccine
By Vauhini Vara

New York Times
http://www.nytimes.com/
Accessed 29 November 2014
Sierra Leone to Eclipse Liberia in Ebola Cases
RICK GLADSTONE NOV. 26, 2014
Sierra Leone will soon displace Liberia as the worst-hit of the West African countries ravaged by Ebola, the World Health Organization said Wednesday.
More than 600 new cases of Ebola were reported in the three countries most affected — Sierra Leone, Liberia and Guinea — in the week that ended Sunday, and more than half were in Sierra Leone, according to figures in an updated summary of cases and deaths on the W.H.O. website.

The W.H.O. update suggested that taken together, all three countries would miss the Dec. 1 target date for achieving important progress benchmarks — 70 percent isolation of patients and 70 percent of burials performed safely. Corpses of Ebola patients are extremely infectious and are an acute source of contagion.

While Guinea has met or exceeded the benchmarks, the W.H.O. said, progress has been slower in Liberia and Sierra Leone, and that “at a national level, both countries are apparently unable to isolate 70 percent of patients.” The updated data showed a total of 15,935 confirmed, probable and suspected cases of Ebola, nearly all of them in the three worst-hit countries, and 5,689 reported deaths…