Achieving and Maintaining Polio Eradication — New Strategies

New England Journal of Medicine
October 16, 2014 Vol. 371 No. 16

Achieving and Maintaining Polio Eradication — New Strategies
John Modlin, M.D., and Jay Wenger, M.D.
N Engl J Med 2014; 371:1476-1479 October 16, 2014
DOI: 10.1056/NEJMp1407783

It has been nearly 2 years since the last known case of type 3 poliomyelitis occurred in Nigeria, and although it’s still too early to celebrate, the disappearance of the second of the three poliovirus serotypes (type 2 transmission was eliminated in 1999) represents a major milestone and proof of principle that global eradication of paralytic poliomyelitis is achievable.

Poliovirus transmission has been identified in 10 countries this year, but more than 75% of the cases have occurred in Pakistan, where antigovernment militants have denied immunization to more than 300,000 children for more than 2 years. This summer, military activities opened some areas to vaccination teams and provided an opportunity to deliver oral polio vaccine (OPV) with other basic health services to displaced children and families, while also creating a risk of dispersal of poliovirus-infected persons more broadly in the region. Multiple supplemental immunization rounds are targeting the other countries with recent transmission of type 1 poliovirus and additional countries that are at risk for reinfection. Given the substantial progress in Nigeria and the small number of polio cases identified elsewhere in Africa in recent months, it is now possible that the continent will be free of polio by the end of the year.

The past decade has brought new partners to the Global Polio Eradication Initiative (GPEI) consortium, new tools for improving immunization and surveillance, a new sense of urgency about completing eradication, and confidence that such a feat is possible. Several factors are making a difference: improvements in planning for supplementary immunization activities, support for delivering other key health interventions through the polio program, innovations such as global-positioning-system mapping, and strategies including the establishment of immunization stations at transit points and the engagement of government, traditional, and religious leaders at all levels. To further reduce the risk of international exportation of polio from countries where it is endemic — exportation accounted for 60% of all polio cases in 2013 — the World Health Organization (WHO) recently designated polio as a public health emergency of international concern under the International Health Regulations and recommended that travelers leaving any country with active transmission receive additional immunization.

As the areas with sustained polio transmission shrink and the genetic diversity of the remaining type 1 polioviruses narrows, global public health authorities are preparing for a phased transition from the live, attenuated OPV to the inactivated polio vaccine (IPV) originally introduced in 1955. Although it may appear counterintuitive to replace OPV, a cheap vaccine easily administered in two oral drops, with IPV, which is at least 10 times as expensive to produce and is given by injection, discontinuation of OPV has always been a component of polio-eradication plans because of the occurrence of vaccine-associated paralytic poliomyelitis in a very small proportion of OPV recipients (<1 per 750,000 recipients in the United States, for example).

There are two additional challenges that make the switch from OPV to IPV necessary, neither of which was anticipated when the World Health Assembly launched the GPEI in 1988. The first is the magnitude of reduced effectiveness of OPV in locations with a high burden of enteric pathogens and diarrheal disease. This limitation can be striking, with seroconversion rates of less than 20% per dose of trivalent OPV (tOPV) in some locations, which leave many children who have received multiple doses still susceptible to polio. The elimination of naturally occurring type 2 polioviruses allowed for a partial solution to this problem: deployment in supplementary immunization activities of monovalent type 1 vaccine (mOPV1) and bivalent types 1 and 3 vaccine (bOPV), which induced improved immune responses to type 1 and type 3 polioviruses by removing the interfering type 2 OPV viruses from the formulation.

The second problem was uncovered with the development of viral genetic sequencing technology, which revealed that OPV viruses can regain fitness and neurovirulence with continuous person-to-person transmission in areas of low population immunity. Circulating vaccine-derived polioviruses (cVDPVs) were first recognized on Hispaniola in 2000 and have since caused outbreaks and isolated cases of paralytic disease from viruses of all three serotypes in multiple locations. The existence of cVDPVs dictates that all OPV use will need to cease in order to achieve full polio eradication.
A GPEI strategic plan for 2013 through 2018 envisions the complete cessation of circulation of wild-type poliovirus and VDPV followed by coordinated replacement of tOPV with bOPV for an interim period to prevent the generation of new type 2 cVDPVs, which have been responsible for virtually all emergences of VDPV during the past 5 years. The plan calls for the eventual discontinuation of OPV use once eradication of all types is achieved.
However, mathematical models suggest that the global risk of cVDPV reemergence from residual OPV type 2 circulation will be substantial in the first 1 to 3 years after OPV type 2 cessation.1 To mitigate this risk, the WHO Strategic Advisory Group of Experts on immunization has recommended that all countries that use OPV add at least one IPV dose to the routine immunization of infants in advance of the tOPV–bOPV switch, currently planned for 2016. The recommendation is based on affordability, the ability of a single vaccine dose to prime the immune system to respond to another dose administered during an outbreak, and the likelihood that one dose will moderately reduce the risk of disease among vaccinated children in the event of type 2 cVDPV exposure (one-dose seroconversion would be expected in 40 to 50% of recipients). This strategy enhances immunity to types 1 and 3 in two ways: by improving the immunogenicity of OPV with the removal of type 2 vaccine virus and by enhancing immunity in children who are given both bOPV and IPV during routine infant immunization.2
Two recent studies in India have shown that IPV administered to children previously given OPV boosts both humoral neutralizing-antibody levels and intestinal mucosal immunity.3,4 Attention to intestinal immunity has increased because of uncertainty about the extent to which polio may circulate in populations with only IPV-induced immunity. Unlike primary immunization with OPV, primary immunization with IPV provides only marginal intestinal immunity, as measured by poliovirus excretion after OPV challenge.5 Outbreaks of wild-type poliovirus have been adequately contained in the Netherlands and other developed countries that use only IPV for routine childhood immunization. However, recent experience in Israel with prolonged circulation of type 1 polioviruses in sewage effluents has generated substantial concern that IPV-induced intestinal immunity may not prevent silent transmission in developing countries despite high immunization rates and that infection could spread extensively before the first clinical case is detected.
In that event, the only realistic approach to control of the outbreak would be widespread immunization of the at-risk population with OPV or a combination of IPV and OPV. But either option requires creating a risk of downstream cVDPV, threatening final eradication. To better prepare for this possible threat, the Bill and Melinda Gates Foundation is supporting the development and clinical evaluation of new genetically stable OPV strains with reduced ability to genetically revert to cVDPVs.

Although our current optimism must be tempered by the tendency of polio to emerge in areas of armed conflict and humanitarian crisis where routine immunization systems have collapsed and it’s difficult to gain access to susceptible children, more of the world’s population than ever is living in certified polio-free regions, and we are inexorably approaching the end of polio. Key strategic components of the endgame plan, including the tOPV–bOPV switch and introduction of affordable IPV, are focused on the final obstacles to eradication. Development of improved vaccines will provide additional confidence that eradication can be sustained.

Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections

New England Journal of Medicine
October 16, 2014 Vol. 371 No. 16

Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections
WHO Ebola Response Team
N Engl J Med 2014; 371:1481-1495October 16, 2014DOI: 10.1056/NEJMoa1411100
On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a “public health emergency of international concern.”
Full Text of Background…
By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa — Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14.
Full Text of Methods…
The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0 ) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total.
Full Text of Results…
These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

Editorial: Ebola Emergency — Immediate Action, Ongoing Strategy

New England Journal of Medicine
October 16, 2014 Vol. 371 No. 16

The Ebola Emergency — Immediate Action, Ongoing Strategy
Jeremy J. Farrar, M.D., Ph.D., and Peter Piot, M.D., Ph.D.
N Engl J Med 2014; 371:1545-1546 October 16, 2014 DOI: 10.1056/NEJMe1411471
The 25th known outbreak of Ebola virus infection is unlike any of the previous epidemics. It has already killed over 2800 people — more than all previous epidemics combined; it’s affecting virtually the entire territory of three countries, involving rural areas, major urban centers, and capital cities; it has been going on for almost a year; and it is occurring in West Africa, where no Ebola outbreak had previously occurred. Above all, the epidemic seems out of control and has evolved into a major humanitarian crisis that has finally mobilized the world, with responses ranging from an emergency health mission launched by the United Nations Security Council to proposed military-style interventions and the global provision of emergency aid.
The disintegration of the health care systems in the affected countries is already having a profound impact on the populations’ health beyond Ebola, as clinics close or become overwhelmed or nonfunctional. These health system effects will only worsen as the epidemic progresses: West Africa will see much more suffering and many more deaths during childbirth and from malaria, tuberculosis, HIV–AIDS, enteric and respiratory illnesses, diabetes, cancer, cardiovascular disease, and mental health during and after the Ebola epidemic. Indeed, there is a very real danger of a complete breakdown in civic society, as desperate communities understandably lose faith in the established systems.
A report from the Ebola Response Team of the World Health Organization now published in the Journal presents the first comprehensive analysis of epidemiologic surveillance data on the West African epidemic.1 Though the completeness and quality of the data are uncertain — collecting information under such extreme conditions is an enormous challenge, and the remarkable contribution of the data-collection teams in West Africa must be acknowledged — they provide a convincing case that the epidemic is still expanding, with a conservative projection that there will be close to 20,000 cases by early November. Without a more effective, all-out effort, Ebola could become endemic in West Africa, which could, in turn, become a reservoir for the virus’s spread to other parts of Africa and beyond.
Yet despite the vast scale of the current outbreak, the clinical manifestations of Ebola virus disease, the duration of illness, the case fatality rate, and the degree of transmissibility are similar to those in earlier epidemics. It is therefore unlikely that the particularly devastating course of this epidemic can be attributed to biologic characteristics of the virus. It is more likely to be a result of the combination of dysfunctional health systems, international indifference, high population mobility, local customs, densely populated capitals, and lack of trust in authorities after years of armed conflict. Perhaps most important, Ebola has reached the point where it could establish itself as an endemic infection because of a highly inadequate and late global response. Not only did it take more than 3 months to diagnose Ebola as the cause of the epidemic (in contrast to the recent outbreak in the Democratic Republic of Congo, where it took a matter of days), but it was not until 5 months and 1000 deaths later that a public health emergency was declared, and it was nearly another 2 months before a humanitarian response began to be put in place. It is not that the world did not know: Médicins sans Frontières, which has been spearheading the response and care for patients with Ebola, has been advocating for a far greater response for many months. This epidemic, in other words, was an avoidable crisis, and as the Ebola Response Team’s article stresses, a prompt response to an emerging outbreak is critical in order to contain it before it becomes too vast in terms of both numbers of cases and geographic reach.
The current Ebola epidemic highlights three transformations required in our approach to rapidly emerging public health emergencies.
First, in today’s world, it’s important to recognize that if certain conditions are met — biologic shifts in a pathogen, changes in the interactions between humans and our environment, dysfunctional and underresourced health systems, national and international indifference, lack of effective timely response, high population mobility, local customs that can exacerbate morbidity and mortality, spread in densely populated urban centers, and a lack of trust in authorities — what might once have been a limited outbreak can become a massive, nearly uncontrollable epidemic.
Second, classic “outbreak control” efforts are no longer sufficient for an epidemic of this size. Rather, what’s required is a large-scale, coordinated humanitarian, social, public health, and medical response, combining classic public health measures with safe and effective interventions including behavioral changes, therapies, and when possible, vaccination. An appropriate response, moreover, requires an appreciation of the culture of the societies in the affected countries and deployment of interventions with the population’s consent. Development of interventions in collaboration with the affected communities and rebuilding of trust will be essential to their success. And these integrated efforts will need to be accompanied by much better coordination and real-time, open sharing of information across diverse disciplines and with all the players involved, from civil society, national governments, nongovernmental organizations, and academic institutions to regional and international organizations and, when appropriate, the military.
Third, the development of diagnostic tools, therapies, and vaccines (at least up through the acquisition of phase 1 safety data) for these relatively rare but inevitable and potentially devastating epidemic diseases must be prioritized during interepidemic periods, with an accepted, preapproved, and ethical mechanism for accelerating development and testing such interventions when epidemic situations arise. We believe that in this epidemic, we are reaching the limit of what classic containment can achieve.
Meanwhile, the current Ebola epidemic, which is in grave danger of spiraling out of control, must remain the primary focus of our efforts. We are concerned that without a massive increase in the response, way beyond what is being planned in scale and urgency, alongside the complementary deployment of novel interventions (in particular the use of safe and effective vaccines and therapeutics), it will prove impossible to bring this epidemic under control.
But we must also look to the future. There will be more epidemics and outbreaks of Ebola and other new or reemerging infections. Yet our response to such events remains slow, cumbersome, poorly funded, conservative, and ill prepared. We have been very lucky with the severe acute respiratory syndrome (SARS), H5N1 and H1N1 influenza, and possibly the Middle East respiratory syndrome coronavirus (MERS-CoV), but this Ebola epidemic shows what can happen when luck escapes us. With a different pathogen and a different transmission route, a similar crisis could strike in New York, Geneva, and Beijing as easily as this one has in West Africa.
Despite great improvement over the past decade, there is still a need for better surveillance, sharing of data in real time, and rapid action based on the available information. But we cannot think that surveillance alone will bring such events under control. We have become better at picking these things up; we now must also learn to act more effectively.

Treatment of Infections in Young Infants in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Frontline Health Worker Diagnosis and Antibiotic Access

PLoS Medicine
(Accessed 18 October2014)

Treatment of Infections in Young Infants in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis of Frontline Health Worker Diagnosis and Antibiotic Access
Anne CC Lee, Aruna Chandran, Hadley K. Herbert, Naoko Kozuki, Perry Markell, Rashed Shah, Harry Campbell, Igor Rudan, Abdullah H. Baqui
Research Article | published 14 Oct 2014 | PLOS Medicine 10.1371/journal.pmed.1001741
Inadequate illness recognition and access to antibiotics contribute to high case fatality from infections in young infants (<2 months) in low- and middle-income countries (LMICs). We aimed to address three questions regarding access to treatment for young infant infections in LMICs: (1) Can frontline health workers accurately diagnose possible bacterial infection (pBI)?; (2) How available and affordable are antibiotics?; (3) How often are antibiotics procured without a prescription?
Methods and Findings
We searched PubMed, Embase, WHO/Health Action International (HAI), databases, service provision assessments (SPAs), Demographic and Health Surveys, Multiple Indicator Cluster Surveys, and grey literature with no date restriction until May 2014. Data were identified from 37 published studies, 46 HAI national surveys, and eight SPAs. For study question 1, meta-analysis showed that clinical sign-based algorithms predicted bacterial infection in young infants with high sensitivity (87%, 95% CI 82%–91%) and lower specificity (62%, 95% CI 48%–75%) (six studies, n = 14,254). Frontline health workers diagnosed pBI in young infants with an average sensitivity of 82% (95% CI 76%–88%) and specificity of 69% (95% CI 54%–83%) (eight studies, n = 11,857) compared to physicians. For question 2, first-line injectable agents (ampicillin, gentamicin, and penicillin) had low variable availability in first-level health facilities in Africa and South Asia. Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions. For question 3, no studies on young infants were identified, however 25% of pediatric antibiotic purchases in LMICs were obtained without a prescription (11 studies, 95% CI 18%–34%), with lower rates among infants <1 year. Study limitations included potential selection bias and lack of neonatal-specific data.
Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity. Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia. Improved data and advocacy are needed to increase the availability and appropriate utilization of antibiotics for young infant infections in LMICs.

Ebola vaccine trials raise ethical issues

17 October 2014 vol 346, issue 6207, pages 277-392

In Depth
Infectious Diseases
Ebola vaccine trials raise ethical issues
Jon Cohen, Kai Kupferschmidt
The Ebola virus keeps spreading in West Africa and some researchers say that a vaccine is necessary to halt the epidemic. The two most advanced candidates have recently entered safety trials, and if they do not cause harm and trigger the immune response scientists hope to see, the World Health Organization (WHO) has recommended jumping straight into what amount to phase III efficacy tests in Liberia, Guinea, and Sierra Leone. But difficult questions are now emerging about how to design clinical trials, who should be the first to get the shots, and when to begin mass production. For instance, at a consultation held by WHO, there was broad support for randomized controlled trials. But some, like Doctors Without Borders, say such a trial, in which some subjects are assigned to a control group that doesn’t receive the actual vaccine, is unethical.

The Vaccination Confidence Scale: A brief measure of parents’ vaccination beliefs

Volume 32, Issue 47, Pages 6177-6324 (29 October 2014)

The Vaccination Confidence Scale: A brief measure of parents’ vaccination beliefs
Original Research Article
Pages 6259-6265
Melissa B. Gilkey, Brooke E. Magnus, Paul L. Reiter, Annie-Laurie McRee, Amanda F. Dempsey, Noel T. Brewer
:: We developed a brief, three-factor scale for measuring confidence about adolescent vaccination.
:: The scale showed good fit both overall (CFI = 0.97) and across demographic subgroups.
:: Using the scale to assess a national sample of parents, we found that confidence was generally high.
:: However, we found lower confidence among subgroups with lower education or of Hispanic ethnicity.

Parental preferences for rotavirus vaccination in young children: A discrete choice experiment

Volume 32, Issue 47, Pages 6177-6324 (29 October 2014)

Parental preferences for rotavirus vaccination in young children: A discrete choice experiment
Original Research Article
Pages 6277-6283
Jorien Veldwijk, Mattijs S. Lambooij, Patricia C.J. Bruijning-Verhagen, Henriette A. Smit, G. Ardine de Wit
This study aimed to identify characteristics that affect parental decisions about rotavirus vaccination, to determine the relative importance of those characteristics and subsequently to estimate vaccination coverage for different implementation strategies.
A Discrete choice experiment (DCE) questionnaire was sent to the parents of 1250 newborns aged 6 weeks (response rate 37.3%). Mixed-logit models were used to estimate the relative importance of the five included rotavirus vaccine and implementation characteristics; vaccine effectiveness, frequency of severe side effects, protection duration, the healthcare facility that administrates vaccination and out-of-pocket costs. Based on the utility functions of the mixed-logit model, the potential vaccination coverage was estimated for different vaccine scenarios and implementation strategies.
All characteristics, except for healthcare facility that administrates vaccination, influenced parental willingness to vaccinate their newborn against rotavirus. Parents were willing to trade 20.2 percentage points vaccine effectiveness for the lowest frequency of severe side effects (i.e., 1 in 1,000,000) or 20.8 percentage points for a higher protection duration. Potential vaccination coverage ranged between 22.7 and 86.2%, depending on vaccine scenario (i.e., vaccine effectiveness and protection duration) and implementation strategy (i.e., out-of-pocket costs and healthcare facility that administrates vaccination).
When deciding about vaccination against rotavirus, parents are mostly driven by the out-of-pocket costs, vaccine effectiveness, protection duration, and frequency of severe side effects. The highest vaccination coverage is expected for a vaccine with high effectiveness and protection duration that is implemented within the current National Immunization Program context. Implementation of the same rotavirus vaccine in the free market will result in lowest coverage.

From Google Scholar+ [to 18 October 2-14]

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

Journal of International Development
October 2014 Volume 26, Issue 7 Pages 939–1096

Research Article
Degnet Abebaw*
Article first published online: 5 NOV 2013
DOI: 10.1002/jid.2975
Using cross section data from rural Ethiopia, this paper investigates the socio-economic determinants of child immunization. Results of a generalized ordered logit model show that child immunization is strongly associated with child’s age, housing quality, presence of health extension worker in a village, proximity to district capital, access to primary school and ethnic diversity. The paper draws both supply-side and demand-side implications to increase full immunization for children in rural Ethiopia.


Assessing Knowledge, Attitudes and Beliefs about Cervical Cancer, Human Papillomavirus and HPV Vaccine among Shipibo-Konibo Women of Peru
Clark, Elizabeth Anne Thesis (Master’s)–University of Washington, 2014
Background: The Shipibo-Konibo ethnic group is one of the largest indigenous populations in the Peruvian Amazon. Due to economic, cultural, and geographical barriers, Shipibo-Konibo women are less likely to access cervical cancer screening and therefore are at higher risk for cervical cancer mortality.
Objective: to learn how cervical cancer is understood from the perspective of Shipibo-Konibo women and to see what factors influence a woman’s decision to vaccinate or not vaccinate her daughter.
Methodology: Thirty in-depth, semi-structured interviews were conducted with Shipibo-Konibo women from a variety of different perspectives: urban, rural, with daughters who had and had not received the vaccine. Interviews were transcribed, coded and analyzed for themes.
Main results: without exception, all women in the study perceived cervical cancer as a dangerous disease and were in favor of their daughter receiving a vaccine that could protect them from cervical cancer. The main difference was: in the rural community, women had more medically accurate beliefs about the etiology of cervical cancer. In both communities, shame and poverty were identified as barriers to seeking preventive care and treatment for cervical cancer.
Conclusions: These results are both encouraging, as the universal acceptability and perceived need of the HPV vaccine is high, and helpful in identifying areas of growth for future health education programs, especially surrounding risk factors for cervical cancer.

Media/Policy Watch: to 18 October 2014 [Ebola/EVD]

Media/Policy Watch: to 18 October 2014 [Ebola/EVD]

Accessed 18 October2014
Cover story: The war on Ebola
The epidemic in West Africa
To win it requires a much larger effort in west Africa than the outside world has so far pledged
Oct 18th 2014
The Ebola crisis
Much worse to come
The Ebola epidemic in west Africa poses a catastrophic threat to the region, and could yet spread further
Oct 18th 2014 |

Financial Times
Accessed 18 October2014
The west’s inadequate response to Ebola
16 October 2014
Nine months after the first cases of Ebola appeared in Guinea, the deadly virus continues to spread across west Africa at an alarming rate. In Europe and the US, much of the media discussion focuses on the handful of cases in developed countries. But the virus will be beaten only if it is checked in the three African states – Guinea, Sierra Leone and Liberia – where it remains rampant. Western governments are beginning to appreciate the scale of the crisis but have yet to make the necessary contributions in terms of money and equipment

Accessed 18 October2014
Ebola Outbreak Shows The Dark Side Of Mother Nature
Guest post written by
Julie Gerberding, MD, MPH,, President of Merck Vaccines, Former Director, Centers for Disease Control & Prevention

The Guardian
Accessed 18 October2014
Texas Ebola hospital mounts PR campaign
Dallas hospital where nurses were infected engages PR firm and takes to social media in face of union criticism

New Yorker
October 20, 2014 Issue
The Fear Equation [Ebola]
By Michael Specter

Wall Street Journal,us&_homepage=/home/us
Accessed 18 October2014
Review & Outlook
The Ebola Twilight of Public Institutions
The WHO and CDC are failing in their core health mission.

Vaccines and Global Health: The Week in Review 11 October 2014

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
pdf version A pdf of the current issue is available here:  Vaccines and Global Health_The Week in Review_11 October 2014

blog edition: comprised of the 35+ entries posted below on 28 September 2014

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…
Editor’s Note on this Edition:
The pace and complexity of the Ebola/EVD crisis and global response continues. We will strive to present a coherent, high-level digest using official sources wherever possible. We will lead with coverage of developments involving candidate vaccines and therapeutic interventions in development and in various trials globally, and include a high level capture of the various UN agencies, NGOs and other organizations that are making a material impact on the crisis. Reading this issue you will encounter significant Ebola/EVD content throughout.


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

University of Maryland School Of Medicine and Malian Ministry of Health Begin Human Trials of Experimental Ebola Vaccine in Mali, West Africa

University of Maryland School Of Medicine and Malian Ministry of Health Begin Human Trials of Experimental Ebola Vaccine in Mali, West Africa
First Study of a Promising Ebola Vaccine Undertaken in West Africa
…The Center for Vaccine Development (CVD) at the University of Maryland School of Medicine announced that, in conjunction with its sister institution, The Center for Vaccine Development of Mali (CVD-Mali) and the Ministry of Health of Mali, initiation of a clinical trial in health care workers (and other front-line workers) to “evaluate a promising experimental Ebola vaccine.”

The trial began on Wednesday, October 8 with the vaccination of the first subject, followed by two additional participants today (October 9), all three being Malian health care workers. In the coming weeks 37 more health care workers will receive the vaccine…

…The vaccine was developed by investigators at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, MD. The clinical trial in Mali brings to fruition two months of work by a consortium dedicated to move the candidate Ebola vaccine (which prior to September had been tested only in animals but not in humans) into clinical studies in West Africa. The consortium, assembled in mid-August at the behest of the World Health Organization (WHO), included, besides WHO, the VRC (which developed the vaccine), the Jenner Institute at the University of Oxford (which carried out clinical trials in UK adults paving the way for the African trial), the CVD-UM SOM and CVD-Mali (carrying out the first clinical trial of the vaccine in West Africa), GlaxoSmithKline (GSK) Biologicals (manufacturer of the vaccine) and the Wellcome Trust, UK (funder of the clinical trials in UK and Mali), with additional funding provided by the Medical Research Council (MRC), UK and the UK Department for International Development (DFID).

In addition, the MRC Unit-The Gambia is expected soon to initiate a second, parallel clinical trial in The Gambia, West Africa. Ordinarily it would take between six to 11 months to obtain all necessary ethical, regulatory agency, technical and administrative approvals needed to transition a vaccine from research in animal models to a clinical trial in a developing country where subjects are at risk of the natural disease. In this instance, with all consortium members working in unison, it took two months…

“This is just the critical first step in a series of additional clinical trials that will have to be carried out.”

WHO Ebola Virus Disease (EVD) – web site [t0 11 August 2014]

WHO Ebola Virus Disease (EVD) – web site

:: Ebola response roadmap – Situation report – 10 October 2014
A total of 8399 confirmed, probable, and suspected cases of Ebola virus disease (EVD) have been reported in seven affected countries (Guinea, Liberia, Nigeria, Senegal, Sierra Leone, Spain, and the United States of America) up to the end of 8 October. There have been 4033 deaths. Following the WHO Ebola Response Roadmap structure1, country reports fall into two categories: 1) those with widespread and intense transmission (Guinea, Liberia, and Sierra Leone); and 2), those with an initial case or cases, or with localized transmission (Nigeria, Senegal, Spain, and the United States of America). An overview of the situation in the
Democratic Republic of the Congo, where a separate, unrelated outbreak of EVD is occurring, is also provided (see Annex 1)….

:: WHO informal consultation on how science can inform our response to Ebola virus disease outbreak 7 October 2014

:: What we know about transmission of the Ebola virus among humans 6 October 2014

UNICEF – Ebola [to 11 August 2104]

UNICEF [to 11 August 2104]

:: Frontline health workers and families in Sierra Leone to receive vital supplies through UNICEF-EU partnership
BRUSSELS/FREETOWN, 10 October 2014 – A cargo plane with nearly 100 metric tons of essential medical supplies left Amsterdam today en route to Sierra Leone as part of UNICEF’s continuing response to the Ebola outbreak ravaging parts of West Africa. Similar flights are planned for Liberia and Guinea, part of a €1 million donation from the European Commission’s Humanitarian Aid and Civil Protection department (ECHO).

FAO – Ebola [to 11 August 2014]

FAO [to 11 August 2014]

:: FAO launches new initiative to tackle growing food security threat (08 October 2014)
8 October 2014, Rome/Dakar – FAO today launched a new programme to urgently assist 90 000 vulnerable households in Guinea, Liberia and Sierra Leone whose food supplies and livelihoods are threatened by the disruptive effect the Ebola epidemic is having on rural economies, agricultural activities and markets.

The Regional Response Programme for West Africa will scale-up the work FAO is currently doing with governments, United Nations partners and local networks of agriculture, veterinary and forestry workers, to help stop the spread of the disease, meet immediate and long-term food and nutrition security needs and build resilience.

FAO is urgently calling for $30 million to support activities linked to the programme over the next 12 months. Programme activities are organized around four key objectives:
– contribute to saving lives by stopping the spread of the disease through social mobilization,
training and awareness raising;
– boost incomes and agricultural production to safeguard livelihoods;
– build resilience of communities to disease threats; and
– strengthen coordination for improved response.

“Our comprehensive response is part of overall United Nations efforts to save lives and protect livelihoods,” said Vincent Martin, Head of FAO’s Dakar-based Subregional Resilience Hub, the office coordinating FAO’s response. “We’re following a twin-track approach to help our United Nations partners halt the tragic loss of life while at the same time protecting incomes, nutrition levels and food security.”

UNDP – Ebola [to 11 October 2014]

UNDP United Nations Development Programme [to 11 October 2014]

10 Oct 2014
:: Ebola crisis could disrupt Guinea’s economy for a decade, UN development officials say
Urgent support is needed to avert an economic meltdown in Guinea, where the Ebola crisis is destroying lives, jobs and essential services, said UN development officials here today. They pointed out that the crisis has already affected every sector of the economy and could be felt ten years after the crisis has ended.
08 Oct 2014

:: Coordination vital to ending Ebola, Guinean President tells UN delegation
Meeting with representatives from the United Nations, including the Head of the new Mission to fight Ebola, Guinean President Alpha Condé welcomed the mission and called for exceptional coordination in the response. Guinea is one of the three West African countries hardest hit by the recent epidemic.

:: Urgent action on Ebola needed to avert regional collapse, say UN development officials
06 Oct 2014
High level visits to affected countries and Ghana to highlight disease’s devastating impact on the most vulnerable

UNMEER (UN Mission for Ebola Emergency Response) [tp 11 Auguts 2014]

UNMEER (UN Mission for Ebola Emergency Response)

External Situation Reports
:: 10 October 2014

Media Releases
:: Secretary-General appoints Marcel Rudasingwa of Rwanda as Ebola Crisis Manager for Guinea, Peter Jan Graaff of the Netherlands as Ebola Crisis Manager for Liberia and Amadu Kamara of the United States as Ebola Crisis Manager for Sierra Leone (09 October 2014)


CDC/MMWR Watch – Ebola [to 11 October 2014]

CDC/MMWR Watch [to 11 October 2014]

: Enhanced Ebola Screening to Start at Five U.S. Airports and New Tracking Program for all People Entering U.S. from Ebola-affected Countries – Press Release
Wednesday, October 8, 2014
New layers of screening at airports that receive more than 94% of West African Travelers.

:: CDC update on first Ebola case diagnosed in the United States and New Ebola Screening Guidelines in U.S. Airports, 10-08-2014
Wednesday, October 8, 2014
Transcript | Audio

:: Questions and Answers on Experimental Treatments and Vaccines for Ebola

MMWR October 10, 2014 / Vol. 63 / No. 40
:: Assessment of Ebola Virus Disease, Health Care Infrastructure, and Preparedness — Four Counties, Southeastern Liberia, August 2014
:: Typhoid Fever surveillance and vaccine use-South-East Asia and Western pacific regions, 2009-2013.

USAID – Ebola [to 11 October 2014]

USAID – Ebola  [to 11 October 2014]

:: USAID Administrator Shah Travels to Liberia, Sierra Leone, Guinea and Senegal
October 10, 2014
U.S. Agency for International Development (USAID) Administrator Rajiv Shah will travel to Liberia, Sierra Leone, Guinea, and Senegal Oct. 13-17, to meet with national and local officials, aid organizations, and staff coordinating the international response to the Ebola outbreak in West Africa. USAID is helping to coordinate an aggressive U.S. Government response to the Ebola outbreak that leverages broad expertise and personnel from several federal departments and agencies, including the Departments of Defense, Health and Human Services, and State, as well as the Centers for Disease Control and Prevention.

:: USAID Announces Grand Challenge to Fight Ebola
October 7, 2014
Call for ideas opens today; focus on solutions in protective gear and frontline tools
U.S. Agency for International Development (USAID) Administrator Rajiv Shah today launched the Fighting Ebola: A Grand Challenge for Development with a call to innovators around the world to submit ideas focused on improving the tools used by frontline healthcare workers in the fight against Ebola in West Africa. The initial focus of the Challenge, as announced by President Obama on Sept. 26, is to generate pioneering solutions to improve the personal protective equipment (PPE) and tools used by healthcare workers battling Ebola. Shah detailed the initiative today at the Grand Challenges Annual Meeting in Seattle, Wash.

World Bank – Ebola [to 11 August 2014]

World Bank – Ebola [to 11 August 2014]

:: Transcript of Remarks at the Event: Impact of the Ebola Crisis: A Perspective from the Countries
The World Bank convened a special event focused on the impact of the Ebola Crisis. This transcript captures comments by World Bank President Jim Kim as host, President CONDÉ of Guinea; President Johnson Sirleaf of Liberia; President Koroma of Sierra Leone, UNSG Ban Ki-moon, and many others including IMF, WHO, CDC, UNICEF, USAID, and leaders from a range of counties providing support.

:: World Bank Group President Calls for New Global Pandemic Emergency Facility
October 10, 2014
WASHINGTON, October 10, 2014—In the wake of a “late, inadequate and slow” global response to the Ebola outbreak, World Bank Group President Jim Yong Kim today called for the creation of a new pandemic emergency facility that would rapidly respond to future outbreaks by delivering money to countries in crisis.
Speaking before the Annual Meetings plenary, a meeting of the governors of the International Monetary Fund and the World Bank Group, Kim said he would like to develop the proposals for a financial instrument with the United Nations, the IMF and regional development banks.
He said even as the focus should now be intensely on doing everything possible to stop Ebola, planning must also begin for the next pandemic, which “could spread much more quickly, kill even more people and potentially devastate the global economy”.
“The world has an IMF to coordinate and work with central banks and ministries to respond to financial crises,” he said. “When it comes to health emergencies, however, our institutional toolbox is empty: There’s no such center of knowledge and skill for response and coordination.”
He said the Bank Group’s financial teams have proposed several solutions, including the pandemic emergency facility. “The device would pre-package a response, establishing contingent funding agreements with donors and receipt mechanisms for possible recipients. So when a global health emergency is declared, financial support would be readily available and flow quickly to support an immediate response”…

:: Ebola: New World Bank Group Study Forecasts Billions in Economic Loss if Epidemic Lasts Longer, Spreads in West Africa
WASHINGTON, October 8, 2014–With the latest death toll from Ebola now at 3,439 in the three worst-affected countries of Guinea, Liberia, and Sierra Leone, a new economic impact assessment from the World Bank Group says that if the epidemic was to significantly infect people in neighboring countries, some of which have much larger economies, the two-year regional financial impact could reach US$32.6 billion by the end of 2015.The new World Bank Group report notes, “as it is far from certain that the epidemic will be fully contained by December 2014 and in light of the considerable uncertainty about its future trajectory, two alternative scenarios are used to estimate the medium-term (2015) impact of the epidemic, extending to the end of calendar year 2015.” A “Low Ebola” scenario corresponds to rapid containment within the three most severely affected countries, while “High Ebola” corresponds to slower containment in the three countries, with broader regional contagion.
October 8, 2014

WHO & Regionals [to 11 October 2014]

WHO & Regionals [to 11 October 2014]
:: WHO Global Alert and Response (GAR) :: Disease Outbreak News (DONs)
Marburg virus disease – Uganda 10 October 2014
Ebola virus disease – Spain 9 October 2014

:: WHO Europe
Risk of Ebola spreading in Europe is very low: statement by Zsuzsanna Jakab, WHO Regional Director for Europe 08-10-2014
Sporadic cases of Ebola virus disease in the WHO European Region are unavoidable. This is
due to travel between Europe and affected countries. Nevertheless, the risk of Ebola
spreading in Europe is avoidable and extremely low. European countries are among the best
prepared in the world to respond to viral haemorrhagic fever, including Ebola.
Spanish nurse diagnosed with Ebola virus disease 07-10-2014
Last night, Spanish authorities notified WHO under the International Health Regulations
(IHR) that an auxiliary nurse in Spain has been diagnosed with Ebola virus disease (EVD)

POLIO [to 11 October 2014]

POLIO [to 11 October 2014]
GPEI Update: Polio this week – As of 8 October 2014
Global Polio Eradication Initiative
Editor’s Excerpt and text bolding
Full report:
:: More than 6 months has passed since a case of wild poliovirus was reported in Syria or Iraq. This is testimony to the dedication of local health workers and the significant efforts of many partners to reach all children with supplementary immunization activities. Over 22 million children have been vaccinated against polio multiple times in the past year, in the midst of active conflict and a humanitarian crisis.
:: National Immunization Days (NIDs) conducted in Pakistan last week reached 34.2 million children across the country, or 95% of all children under the age of five. As case numbers climb steadily during the current ‘high season’ for polio transmission, the success of such campaigns and smaller-scale activities is critical to making the most of the upcoming ‘low season’ for polio transmission in Pakistan.
::: A 6-month Emergency Action Plan has been developed in Somalia following the Outbreak Response Assessment that took place in September. The plan outlines strategies to reach children living in nomadic pastoral communities where population-wide immunity is low.
:: Thirteen new wild poliovirus type 1 (WPV1) cases were reported in the past week in Pakistan. Of these, 9 are from the Federally Administered Tribal Areas (FATA) (2 from Frontier Region Bannu and 7 from Khyber Agency); 2 are from Khyber Pakhtunkhwa province (1 from Bunir and 1 from Mardan district); and 2 cases from Karachi’s Gadap district in Sindh province. This brings the total number of WPV1 cases in 2014 to 187 compared to 39 in 2013 by this date. The most recent case had onset of paralysis on 16 September in Khyber Agency.
:: Immunization activities are continuing with particular focus on known high-risk areas, in particular the newly opened areas of FATA. At exit and entry points, permanent vaccination points are being used to reach internally displaced families as they leave their homes.

Gavi retains high ranking in leading transparency index

GAVI Watch [to 11 October 2014]

:: Gavi retains high ranking in leading transparency index
Geneva 8 October 2014 – A leading aid transparency group has for the second year running ranked Gavi, the Vaccine Alliance as a leading organisation for openness and accountability.
Publish What You Fund’s 2014 Aid Transparency Index (ATI) placed Gavi 4th out of 68 organisations, including UN agencies and donor governments, working on international development. Gavi’s ranking puts it in the top category of transparent organisations alongside the United Nations Development Programme (UNDP), which top-scored with 91%, and the UK Department for International Development (DFID) and the Millennium Challenge Corporation (MCC) who both, like Gavi, scored above 85%…

Bill & Melinda Gates Foundation and Grand Challenge Partners Commit to Innovation with New Investments in Breakthrough Science

Bill & Melinda Gates Foundation and Grand Challenge Partners Commit to Innovation with New Investments in Breakthrough Science

A consortium of partners including Brazil, Canada, India, Norway, South Africa, the United Kingdom and the United States will fund a new phase of Grand Challenge initiatives

SEATTLE (October 7, 2014) – At an event in Seattle commemorating the tenth anniversary of Grand Challenges, a group of international partners today announced three new initiatives aimed at creating breakthroughs in science.

This anniversary event, attended by scientists and researchers from around the world, celebrates a decade of progress since the Bill & Melinda Gates Foundation’s launch of the initial Grand Challenges in Global Health initiative. This original US$450 million research initiative was created to catalyze scientific and technological innovation to achieve major breakthroughs in global health.

The three new initiatives being announced today are:
:: All Children Thriving – focusing on developing new tools and holistic approaches to help mothers and children thrive in the developing world by ensuring a healthy birth for both mother and child and setting children on a path to healthy physical growth and cognitive development. All Children Thriving includes new initiatives and commitments from Grand Challenges Canada (Saving Brains); the Saving Lives at Birth partnership (including the US Agency for International Development, the Government of Norway, the Bill & Melinda Gates Foundation, Grand Challenges Canada and the UK Department for International Development); the Governments of Brazil, India, and South Africa; and the Bill & Melinda Gates Foundation.
:: Putting Women and Girls at the Center of Development – focusing on a rigorous understanding of women’s and girls’ needs and preferences and gender inequalities and supporting new approaches to promote women’s and girls’ empowerment that will enhance the ability to achieve multiple health and development goals.
:: Creating New Interventions for Global Health – focusing on accelerating the translation of original and innovative concepts for vaccines, drugs and diagnostics into safe, effective, affordable and widely used interventions for diseases in the developing world…

American Journal of Public Health – November 2014

American Journal of Public Health
Volume 104, Issue 11 (November 2014)

Nonmedical Exemptions From School Immunization Requirements: A Systematic Review
Eileen Wang, Jessica Clymer, BA, BSN, Cecilia Davis-Hayes, BA, and Alison Buttenheim, PhD, MBA
We summarized studies describing the prevalence of, trends in, and correlates of nonmedical exemptions from school vaccination mandates and the association of these policies with the incidence of vaccine-preventable disease.
We searched 4 electronic databases for empirical studies published from 1997 to 2013 to capture exemption dynamics and qualitatively abstracted and synthesized the results. Findings from 42 studies suggest that exemption rates are increasing and occur in clusters; most exemptors questioned vaccine safety, although some exempted out of convenience. Easier state-level exemption procedures increase exemption rates and both individual and community disease risk.
State laws influence exemption rates, but policy implementation, exemptors’ vaccination status, and underlying mechanisms of geographical clustering need to be examined further to tailor specific interventions.

Improving Global Access to New Vaccines: Intellectual Property, Technology Transfer, and Regulatory Pathways
Sara Eve Crager, MD
The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

The Convention on the Rights of Persons With Disabilities: A Foundation for Ethical Disability and Health Research in Developing Countries
Jo Durham, PhD, Claire E. Brolan, MA, and Bryan Mukandi, MD
The United Nations Convention on the Rights of Persons with Disabilities (CRPD) has foregrounded disability as a human rights and equity issue, elevating it to a priority global research area.
Academics from Western universities are likely to play an increasing role in disability health research in developing countries. In such contexts, there is a need to bridge the gap between procedural ethics and the realities of disability research in cross-cultural contexts.
We provide guidance on engaging in ethical disability health research that intersects with and upholds the CRPD. We highlight challenges and tensions in doing so, underscoring the need to be sensitive to the sociocultural and political context of disability that determines how ethical research should proceed. We conclude with 5 recommendations.

Mandatory Influenza Vaccination for Health Care Workers as the New Standard of Care: A Matter of Patient Safety and Nonmaleficent Practice
Nicolas Cortes-Penfield, MD
A growing body of literature defends the efficacy of seasonal influenza vaccination for health care workers in reducing the mortality of hospitalized patients. I review the evidence concerning influenza vaccination, concluding that universal vaccination of health care workers against influenza should be considered standard patient care and that nonvaccination represents maleficent care. I further argue that the ethical responsibility to ensure universal vaccination of staff against seasonal influenza lies not only with individual health care providers but with each individual health care institution.

The Role of Applied Epidemiology Methods in the Disaster Management Cycle
Josephine Malilay, PhD, MPH, Michael Heumann, MPH, MA, Dennis Perrotta, PhD, Amy F. Wolkin, DrPH, MSPH, Amy H. Schnall, MPH, Michelle N. Podgornik, MPH, Miguel A. Cruz, MPH, Jennifer A. Horney, PhD, MPH, CPH, David Zane, MS, Rachel Roisman, MD, MPH, Joel R. Greenspan, MD, MPH, Doug Thoroughman, PhD, MS, Henry A. Anderson, MD, Eden V. Wells, MD, MPH, and Erin F. Simms, MPH
Disaster epidemiology (i.e., applied epidemiology in disaster settings) presents a source of reliable and actionable information for decision-makers and stakeholders in the disaster management cycle. However, epidemiological methods have yet to be routinely integrated into disaster response and fully communicated to response leaders. We present a framework consisting of rapid needs assessments, health surveillance, tracking and registries, and epidemiological investigations, including risk factor and health outcome studies and evaluation of interventions, which can be practiced throughout the cycle. Applying each method can result in actionable information for planners and decision-makers responsible for preparedness, response, and recovery. Disaster epidemiology, once integrated into the disaster management cycle, can provide the evidence base to inform and enhance response capability within the public health infrastructure.

Teaching seven principles for public health ethics: towards a curriculum for a short course on ethics in public health programmes

BMC Medical Ethics
(Accessed 11 October 2014)

Teaching seven principles for public health ethics: towards a curriculum for a short course on ethics in public health programmes
Peter Schröder-Bäck12*, Peter Duncan3, William Sherlaw4, Caroline Brall1 and Katarzyna Czabanowska15
Author Affiliations
BMC Medical Ethics 2014, 15:73 doi:10.1186/1472-6939-15-73
Published: 7 October 2014
Teaching ethics in public health programmes is not routine everywhere – at least not in most schools of public health in the European region. Yet empirical evidence shows that schools of public health are more and more interested in the integration of ethics in their curricula, since public health professionals often have to face difficult ethical decisions.
The authors have developed and practiced an approach to how ethics can be taught even in crowded curricula, requiring five to eight hours of teaching and learning contact time. In this way, if programme curricula do not allow more time for ethics, students of public health can at least be sensitised to ethics and ethical argumentation. This approach – focusing on the application of seven mid-level principles to cases (non-maleficence, beneficence, health maximisation, efficiency, respect for autonomy, justice, proportionality) – is presented in this paper. Easy to use ‘tools’ applying ethics to public health are presented.
The crowded nature of the public health curriculum, and the nature of students participating in it, required us to devise and develop a short course, and to use techniques that were likely to provide a relatively efficient introduction to the processes, content and methods involved in the field of ethics.

Individual- and Regional-level determinants of Human Papillomavirus (HPV) vaccine refusal: the Ontario grade 8 HPV vaccine cohort study

BMC Public Health
(Accessed 11 October 2014)

Individual- and Regional-level determinants of Human Papillomavirus (HPV) vaccine refusal: the Ontario grade 8 HPV vaccine cohort study
Olivia Remes, Leah M Smith, Beatriz E Alvarado-Llano, Lindsey Colley and Linda E Lévesque
Author Affiliations
BMC Public Health 2014, 14:1047 doi:10.1186/1471-2458-14-1047
Published: 8 October 2014
Abstract (provisional)
Studies on the determinants of human papillomavirus (HPV) vaccine use have generally focused on individual-level characteristics, despite the potentially important influence of regional-level characteristics. Therefore, we undertook a population-based, retrospective cohort study to identify individual- and regional-level determinants of HPV vaccine non-receipt (refusal) in Ontario’s (Canada) Grade 8 HPV Immunization Program.
Ontario administrative health and immunization databases were used to identify girls eligible for free HPV vaccination in 2007-2011 and to ascertain individual-level characteristics of cohort members (socio-demographics, vaccination history, health care utilization, medical history). The social and material characteristics of the girl’s region (health unit) were derived from the 2006 Canadian Census. Generalized estimating equations (binomial distribution, logit link) were used to estimate the population-average effects of individual- and regional-level characteristics on HPV vaccine refusal.
Our cohort consisted of 144,047 girls, 49.3% of whom refused HPV vaccination. Factors associated with refusal included a previous diagnosis of Down’s syndrome (OR = 1.37, 95% CI 1.16-1.63) or autism (OR = 1.60, 95% CI 1.34-1.90), few physician visits (OR = 1.45, 95% CI 1.35-1.55), and previous refusal of mandatory (OR = 2.23, 95% CI 2.07-2.40) and optional (OR = 3.96, 95% CI 3.87-4.05) vaccines. Refusal was highest among the lowest and highest income levels. Finally, a previous diagnosis of obesity and living in an area of high deprivation were associated with lower refusal (OR = 0.87, 95% CI 0.83-0.92 and OR = 0.82 95%, CI 0.79-0.86, respectively).
Studies on HPV vaccine determinants should consider regional-level factors. Efforts to increase HPV vaccine acceptance should include vulnerable populations (such as girls of low income) and girls with limited contact with the healthcare system.

Clinical Infectious Diseases (CID) – November 1, 2014

Clinical Infectious Diseases (CID)
Volume 59 Issue 9 November 1, 2014

Editorial Commentary: Fifteen Years of Protection by Meningococcal C Conjugate Vaccines: Lessons From Disease Surveillance
Martin C. J. Maiden and Jenny M. MacLennan
Author Affiliations
Department of Zoology, University of Oxford, United Kingdom
(See the Major Articles by Sadarangani et al on pages 1208–15, and Bijlsma et al on pages 1216–21.)
Despite the extensive advances that have been made in biomedical sciences in the past few decades, the development and implementation of novel vaccines remains a highly pragmatic and uncertain endeavor. Although the concept of vaccination is >200 years old and was formalized by Pasteur >100 years ago, progress in the development of vaccines remains comparatively slow and has not accelerated in the way seen in virtually all other areas of technology. The many reasons for this include safety concerns arising from the administration of vaccinations to otherwise healthy individuals, often infants or children, and our inability to predict reliably the behavior of a novel human vaccine at the population level from data gathered in laboratory experiments or even during phase I or phase II trials of human subjects [1]. Although large placebo-controlled double-blind phase III trials can provide useful information in both regards, these are very expensive, prohibitively so if the disease is rare, and even very large studies may be insufficiently powered to detect population effects [1].

It is often the case, therefore, that vaccines are introduced without full knowledge of their likely impact, particularly without knowledge of how population effects might be best exploited in vaccination schedules. Consequently, it is important to ensure that enhanced disease surveillance is in place before, during, and after any vaccine introduction to evaluate vaccine impact post hoc and enable immunization schedules to be modified as necessary. Two articles in this issue [2, 3], describing the effectiveness of meningococcal serogroup C conjugate (MCC) vaccines during a 15-year period in the Netherlands and Canada, demonstrate the lasting value of such surveillance data in understanding how a vaccine

The Impact of the Meningococcal Serogroup C Conjugate Vaccine in Canada Between 2002 and 2012
Clin Infect Dis. (2014) 59 (9): 1208-1215 doi:10.1093/cid/ciu597
Manish Sadarangani, David W. Scheifele, Scott A. Halperin, Wendy Vaudry, Nicole Le Saux,
Raymond Tsang, and Julie A. Bettinger
For the investigators of the Canadian Immunization Monitoring Program, ACTive (IMPACT)
The meningococcal serogroup C conjugate vaccine has significantly reduced serogroup C meningococcal disease in Canada, despite different immunization schedules used in different provinces. Direct and indirect protection was achieved with the largest reduction in the 15–24 year age group.

A Decade of Herd Protection After Introduction of Meningococcal Serogroup C Conjugate Vaccination
Clin Infect Dis. (2014) 59 (9): 1216-1221 doi:10.1093/cid/ciu601
Merijn W. Bijlsma, Matthijs C. Brouwer, Lodewijk Spanjaard, Diederik van de Beek, and Arie van der Ende
Nationwide laboratory surveillance data from the Netherlands (1998–2012) shows a decline of >93% in meningococcal serogroup C (MenC) invasive disease. Herd protection is responsible for >36% of MenC conjugate vaccine impact and lasts for ≥10 years.

Rotavirus Vaccines in Routine Use
Clin Infect Dis. (2014) 59 (9): 1291-1301 doi:10.1093/cid/ciu564
Jacqueline E. Tate and Umesh D. Parashar
Rotavirus vaccines have had substantial impact on diarrhea and rotavirus hospitalizations and on diarrhea mortality in children. The risk-benefit analysis of rotavirus vaccine is extremely favorable, but other strategies to improve vaccine effectiveness, particularly in low-income settings, should be considered.

Bulletin of the World Health Organization – October 2014

Bulletin of the World Health Organization
Volume 92, Number 10, October 2014, 697-772

Sustainable health: the need for new developmental models
Iris Borowy a
a. Institute for the History, Theory and Ethics of Medicine, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany.
Bulletin of the World Health Organization 2014;92:699. doi:
In 2015, the eight Millennium Development Goals (MDGs) will probably be replaced by 17 Sustainable Development Goals (SDGs). Although only one SDG names health directly, it has been assumed that health involves a broad range of social determinants covered by the other SDGs and that sustainable health requires a sustainable world….

Estimation of maternal and child mortality one year after user-fee elimination: an impact evaluation and modelling study in Burkina Faso
Mira Johri, Valéry Ridde, Rolf Heinmüller & Slim Haddad
To estimate the impact on maternal and child mortality after eliminating user fees for pregnant women and for children less than five years of age in Burkina Faso.
Two health districts in the Sahel region eliminated user fees for facility deliveries and curative consultations for children in September 2008. To compare health-care coverage before and after this change, we used interrupted time series, propensity scores and three independent data sources. Coverage changes were assessed for four variables: women giving birth at a health facility, and children aged 1 to 59 months receiving oral rehydration salts for diarrhoea, antibiotics for pneumonia and artemesinin for malaria. We modelled the mortality impact of coverage changes in the Lives Saved Tool using several scenarios.
Coverage increased for all variables, however, the increase was not statistically significant for antibiotics for pneumonia. For estimated mortality impact, the intervention saved approximately 593 (estimate range 168–1060) children’s lives in both districts during the first year. This lowered the estimated under-five mortality rate from 235 deaths per 1000 live births in 2008 to 210 (estimate range 189–228) in 2009. If a similar intervention were to be introduced nationwide, 14 000 to 19 000 (estimate range 4000–28 000) children’s lives could be saved annually. Maternal mortality showed a modest decrease in all scenarios.
In this setting, eliminating user fees increased use of health services and may have contributed to reduced child mortality.

Eurosurveillance – 09 October 2014 :: Ebola/EVD

Volume 19, Issue 40, 09 October 2014

Preparedness is crucial for safe care of Ebola patients and to prevent onward transmission in Europe – outbreak control measures are needed at its roots in West Africa
by MJ Sprenger, D Coulombier

Rapid communications
Describing readmissions to an Ebola case management centre (CMC), Sierra Leone, 2014
by G Fitzpatrick, F Vogt, OB Moi Gbabai, B Black, M Santantonio, E Folkesson, T Decroo, M Van Herp

Transmission dynamics and control of Ebola virus disease outbreak in Nigeria, July to September 2014
by FO Fasina, A Shittu, D Lazarus, O Tomori, L Simonsen, C Viboud, G Chowell

Data protection and epidemiological research: a new EU regulation is in the pipeline

International Journal of Epidemiology
Volume 43 Issue 5 October 2014

Data protection and epidemiological research: a new EU regulation is in the pipeline
Jørn Olsen
Author Affiliations
Department of Public Health-Epidemiology, University of Aarhus, Bartholins Alle 2 – Building 1260, DK-8000 Aarhus C, Denmark.
Since the days of the Helsinki Declaration (, informed consent has been a cornerstone in all medical research. That is probably how it should be if you do experimental research on humans that carries a risk for the participants or collect new data, but in non-experimental research based on existing data it is not so clear cut. The Helsinki Declaration states that ‘the health of my patient will be my first consideration’ and ‘while the goal of the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects’. Most will agree on these general principles. However, if the principle of informed consent is required when using existing data, where the only risk is related to unwanted disclosure of personal data, they go too far and the term ‘research subject’ is misleading. If we are using data that already exist and the research can be done with no risk for the people under study, there may well more ethical problems in not doing the research than in doing it. We lack an ethics committee for important missed research opportunities!
Using the Helsinki Declaration uncritically to fit all types of research has not been without problems, including ethical problems. Important data collections have been destroyed because no informed consent had been given at the time of data collection. Useful information has not been used to benefit the public, sometimes because the data could have revealed unpleasant facts for those in charge of health service and medical treatment…

JAMA – October 8, 2014

October 8, 2014, Vol 312, No. 14

Expanding the Options for Confronting Pandemic Influenza
John J. Treanor, MD1
[+] Author Affiliations
JAMA. 2014;312(14):1401-1402. doi:10.1001/jama.2014.12558.
The majority of physicians and public health practitioners are familiar with the concept that the vast reservoir of influenza A viruses found in migratory waterfowl represent an ongoing threat to emerge in humans and cause widespread disease. Although these avian influenza A viruses, which include all of the known hemagglutinin (H1-H16) and neuraminidase (N1-N9) subtypes, are generally restricted in their ability to replicate in humans, recent work has shown that a minimal number of mutations can result in viruses likely to transmit efficiently from person to person.1,2 The resulting global epidemic or pandemic of influenza would spread rapidly and almost certainly would have massive public health implications. Among the many hemagglutinin subtypes, viruses of the H5 and more recently H7 subtypes are of particular concern because of their demonstrated ability to cause severe disease in humans.3,4 …


Contemporary Challenges to Human Health: Infectious Disease Theme Issue
Preeti N. Malani, MD, MSJ

Original Investigation
Serological Responses to an Avian Influenza A/H7N9 Vaccine Mixed at the Point-of-Use With MF59 Adjuvant: A Randomized Clinical Trial
Mark J. Mulligan, MD; David I. Bernstein, MD, MA; Patricia Winokur, MD; Richard Rupp, MD; Evan Anderson, MD; Nadine Rouphael, MD; Michelle Dickey, MS, CRNP; Jack T. Stapleton, MD; Srilatha Edupuganti, MD; Paul Spearman, MD; Dilek Ince, MD; Diana L. Noah, PhD; Heather Hill, MS; Abbie R. Bellamy, PhD; for the DMID 13-0032 H7N9 Vaccine Study Group
Includes: Supplemental Content

Immunogenicity of Avian Influenza A/Anhui/01/2005(H5N1) Vaccine With MF59 Adjuvant: A Randomized Clinical Trial
Robert B. Belshe, MD; Sharon E. Frey, MD; Irene L. Graham, MD; Edwin L. Anderson, MD; Lisa A. Jackson, MD; Paul Spearman, MD; Srilatha Edupuganti, MD; Mark J. Mulligan, MD; Nadine Rouphael, MD; Patricia Winokur, MD; Rowena J. Dolor, MD; Christopher W. Woods, MD; Emmanuel B. Walter, MD; Wilbur H. Chen, MD; Christine Turley, MD; Kathryn M. Edwards, MD; C. Buddy Creech, MD; Heather Hill, MS; Abbie R. Bellamy, PhD; for the National Institute of Allergy and Infectious Diseases–Funded Vaccine and Treatment Evaluation Units
Includes: Supplemental Content

Global Tuberculosis: Perspectives, Prospects, and Priorities

October 8, 2014, Vol 312, No. 14

Viewpoint | October 8, 2014
Global Tuberculosis: Perspectives, Prospects, and Priorities
Thomas R. Frieden, MD, MPH1; Karen F. Brudney, MD2; Anthony D. Harries, MD, FRCP3,4
Author Affiliations
JAMA. 2014;312(14):1393-1394. doi:10.1001/jama.2014.11450.
This Viewpoint discusses the importance of innovation and persistence in tuburculosis control programs.
Despite being nearly 100% curable, tuberculosis remains a major public health problem, representing the second leading cause of death from infectious diseases globally, with drug-resistant tuberculosis increasingly common. In 2012, an estimated 8.6 million people developed tuberculosis worldwide—a global incidence rate of 122 persons per 100 000 population—and 1.3 million people died. Incidence rates vary from high in southern Africa (550/100 000 population in Mozambique and Zimbabwe and 1000/100 000 population in South Africa) to fewer than 10/100 000 population in the United States, Canada, and most of Western Europe.1 Although the global prevalence of multidrug-resistant tuberculosis was estimated at 3.6% of newly diagnosed and 20.2% of previously treated patients, these rates were 20% to 35% for newly diagnosed cases and 50% to 69% for retreatment cases in the Russian Federation and some other former Soviet republics….


Current status of rabies and prospects for elimination

The Lancet
Oct 11, 2014 Volume 384 Number 9951 p1321 – 1400 e49 – 51

Current status of rabies and prospects for elimination
Prof Anthony R Fooks PhD a b c d, Ashley C Banyard PhD a b, Daniel L Horton PhD a b, Nicholas Johnson PhD a b, Lorraine M McElhinney PhD a b d, Prof Alan C Jackson MD e
Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60 000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-effective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial

The Lancet
Oct 11, 2014 Volume 384 Number 9951 p1321 – 1400 e49 – 51

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial
Maria Rosario Capeding MD a, Prof Ngoc Huu Tran MD b, Prof Sri Rezeki S Hadinegoro MD c, Hussain Imam HJ Muhammad Ismail FRCPCH d, Tawee Chotpitayasunondh MD e, Mary Noreen Chua MD f, Chan Quang Luong MD b, Prof Kusnandi Rusmil PhD g, Prof Dewa Nyoman Wirawan MD h, Revathy Nallusamy MBBS i, Punnee Pitisuttithum MD j, Prof Usa Thisyakorn MD k, In-Kyu Yoon MD l, Dr Diane van der Vliet MD m, Edith Langevin MSc m, Thelma Laot MD n, Yanee Hutagalung MD o, Carina Frago MD o, Mark Boaz PhD p, T Anh Wartel MD o, Nadia G Tornieporth MD m, Melanie Saville MBBS q, Alain Bouckenooghe MD o, the CYD14 Study Group
An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children.
We did an observer-masked, randomised controlled, multicentre, phase 3 trial in five countries in the Asia-Pacific region. Between June 3, and Dec 1, 2011, healthy children aged 2—14 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratified by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective efficacy against symptomatic, virologically confirmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine efficacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with, number NCT01373281.
We randomly assigned 10 275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confirmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 56•5% (95% CI 43•8—66•4) efficacy. We recorded 647 serious adverse events (402 [62%] in the vaccine group and 245 [38%] in the control group). 54 (1%) children in the vaccine group and 33 (1%) of those in the control group had serious adverse events that happened within 28 days of vaccination. Serious adverse events were consistent with medical disorders in this age group and were mainly infections and injuries.
Our findings show that dengue vaccine is efficacious when given as three injections at months 0, 6, and 12 to children aged 2—14 years in endemic areas in Asia, and has a good safety profile. Vaccination could reduce the incidence of symptomatic infection and hospital admission and has the potential to provide an important public health benefit.
Sanofi Pasteur.

Dengue vaccines: dawning at last?

The Lancet
Oct 11, 2014 Volume 384 Number 9951 p1321 – 1400 e49 – 51

Dengue vaccines: dawning at last?
Annelies Wilder-Smith
Preview |
The need for a dengue vaccine is more pressing than ever. Dengue—a mosquito-borne viral infection caused by any of the four dengue virus serotypes—is regarded as the most important arboviral disease globally, because more than 50% of the world’s population live in regions at risk of the disease, and evidence points towards further geographical and numerical expansion.1 The results of Maria Capeding and colleagues’ multicentre phase 3, randomised, observer-masked, placebo-controlled efficacy trial2 for a recombinant, chimeric, live attenuated tetravalent dengue vaccine (CYD-TDV), in The Lancet, have been awaited with great anticipation paired with some trepidation, on the basis of the disappointing results from a previous single-centre trial with the same vaccine in Thailand.


The Lancet – Oct 11, 2014 Ebola/EVD Editorials/Analysis

The Lancet
Oct 11, 2014 Volume 384 Number 9951 p1321 – 1400 e49 – 51

Ebola: what lessons for the International Health Regulations?
The Lancet
With more than 3000 deaths since the first case was confirmed in March, 2014, and after months of slow, fragmented responses, the international community has recognised Ebola as a public health emergency of international concern and a clear threat to global health security. It is the subject of a high-level UN Security Council resolution, and has triggered the creation of a UN Mission for Ebola Emergency Response. Despite these efforts, Ebola is staying ahead of efforts to contain it. In such a situation, although it is understandable to focus on urgent actions, it would be a mistake not to reflect on how we arrived at this situation and what we need to do to prevent it from happening again.

The International Health Regulations (IHR) represent the system designed to prevent national public health emergencies from becoming international crises. WHO’s historic responsibility has been to control the spread of disease. The IHR were adopted in 1969 (IHR 1969) and focused on smallpox, plague, cholera, and yellow fever. In 1995, in the wake of plague in India and Ebola in DR Congo, a resolution was passed in the World Health Assembly (WHA) to revise and update the IHR. In the late 1990s a new way of working within WHO was created to detect and respond to infectious disease outbreaks using sources of information other than countries as prescribed under the IHR, and creating a network of over 120 partners to respond—called the Global Outbreak Alert and Response Network. The severe acute respiratory syndrome epidemic in 2003 gave great impetus to the revision process. In 2005, a revised IHR (IHR 2005) was adopted by the WHA, to come into force in 2007. The IHR 2005 are not limited to any specific diseases and they oblige countries to notify WHO of “events that may constitute a public health emergency of international concern” and to develop “core public health capacities”. They also offered flexibility to countries to develop core capacities by 2012, with a possible 2-year extension. Although all WHO member states have agreed to the IHR principles, countries were left to self-report their progress on core capacity development, such as surveillance, diagnostic, and containment demands.

With no additional financing in place and no proper accountability mechanism to ensure independent monitoring, this laudable vision has become a huge missed opportunity. Today, every person newly infected with Ebola reminds us of this lost opportunity. Whereas most developed countries certainly have the capacities to implement such a framework, many low-income and middle-income countries, and especially fragile states, do not. It was only on Aug 8, after a meeting of the International Health Regulations Emergency Committee, that WHO declared the outbreak a “public health emergency of international concern”. Such delays have probably enabled the outbreak to spread rapidly.

Several commentators have questioned the capability of WHO to address international threats, such as Ebola. Acknowledging gaps in global governance, and with its distinctive interest in global security, the USA has taken the lead and launched its Global Health Security Agenda earlier this year “to accelerate progress toward a world safe and secure from infectious disease threats and to promote global health security as an international security priority”. On Sept 26, a meeting took place in the White House to discuss the implementation of this new security agenda, together with the delivery of commitments to assist west Africa.

In view of the seriousness of the crisis, US leadership should be welcomed. However, the US Government is not a multilateral health agency. The final responsibility to prevent the international spread of disease rests with WHO and its IHR. But WHO has been poorly served by its member states and governing bodies. Member states have failed to invest in WHO to ensure the agency has full capacity to address its global mandate. And WHO’s Executive Board and WHA failed utterly to keep the promise they made in 2005 to scale-up attention and investment in crucial surveillance and reporting systems so necessary to prevent the kind of epidemic that is Ebola today.

Two priorities stand out. First, an urgent donor conference must be convened to discuss the implications of the Ebola epidemic and the international community’s failure to invest in the IHR. That conference must end with substantial financial commitments to strengthen delivery of core IHR public health capacities. Second, a robust mechanism must be put in place to guarantee independent monitoring and review of country implementation of the IHR. Self-reporting is an unreliable way to protect the world’s peoples from new and dangerous epidemics.

Ebola: a crisis in global health leadership
Lawrence O Gostin, Eric A Friedman
Preview |
The Ebola epidemic will take hundreds of thousands of lives if the current trajectory is not reversed.1 Fear has gripped the most affected countries: Sierra Leone instituted a national lockdown,2 Liberia cordoned off swathes of territory,3 and in Guinea, panicked residents in one village killed a team that had come to raise awareness about the disease.4 WHO, with its budget and capacity to respond diminished, has largely been sidelined in the response to Ebola. In a leadership vacuum, high-income countries sent in military assets, the UN Security Council declared Ebola a threat to international peace and security, and UN Secretary-General Ban Ki-moon created a special UN mission.


Ebola: towards an International Health Systems Fund
Lawrence O Gostin
Preview |
The international response to the current outbreak of Ebola virus in west Africa, which is projected to infect about 20 000 people with a case fatality rate of more than 50%,1,2 has been fractured and delayed. The index case (a 2-year-old boy from Guinea) died in December, 2013, followed by confirmed Ebola clusters on March 22, 2014, which quickly spread to Liberia and then Sierra Leone. The disease jumped to Nigeria through air travel, and, recently, to Senegal. Yet WHO did not declare a Public Health Emergency of International Concern (PHEIC) until Aug 8, 2014, and only released an Ebola response roadmap on Aug 28—5 months after international spread.


Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Nature Medicine
October 2014, Volume 20 No 10 pp1079-1217

Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge – pp1126 – 1129
Daphne A Stanley, Anna N Honko, Clement Asiedu, John C Trefry, Annie W Lau-Kilby, Joshua C Johnson, Lisa Hensley, Virginia Ammendola, Adele Abbate, Fabiana Grazioli, Kathryn E Foulds, Cheng Cheng, Lingshu Wang, Mitzi M Donaldson, Stefano Colloca, Antonella Folgori, Mario Roederer, Gary J Nabel, John Mascola, Alfredo Nicosia, Riccardo Cortese, Richard A Koup & Nancy J Sullivan
Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge…

New England Journal of Medicine October 9, 2014 – Ebola/EVD Editorials/Analysis

New England Journal of Medicine
October 9, 2014 Vol. 371 No. 15

Ebola — A Growing Threat?
H. Feldmann

Brief Report
Emergence of Zaire Ebola Virus Disease in Guinea
Sylvain Baize, Ph.D., Delphine Pannetier, Ph.D., Pharm.D., Lisa Oestereich, M.Sc., Toni Rieger, Ph.D., Lamine Koivogui, Ph.D., N’Faly Magassouba, Ph.D., Barrè Soropogui, M.Sc., Mamadou Saliou Sow, M.D., Sakoba Keïta, M.D., Hilde De Clerck, M.D., Amanda Tiffany, M.P.H., Gemma Dominguez, B.Sc., Mathieu Loua, M.D., Alexis Traoré, M.D., Moussa Kolié, M.D., Emmanuel Roland Malano, M.D., Emmanuel Heleze, M.D., Anne Bocquin, M.Sc., Stephane Mély, M.Sc., Hervé Raoul, Ph.D., Valérie Caro, Ph.D., Dániel Cadar, D.V.M., Ph.D., Martin Gabriel, M.D., Meike Pahlmann, Ph.D., Dennis Tappe, M.D., Jonas Schmidt-Chanasit, M.D., Benido Impouma, M.D., Abdoul Karim Diallo, M.D., Pierre Formenty, D.V.M., M.P.H., Michel Van Herp, M.D., M.P.H., and Stephan Günther, M.D.
N Engl J Med 2014; 371:1418-1425 October 9, 2014 DOI: 10.1056/NEJMoa1404505
In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea.

Ebola — An Ongoing Crisis
Lindsey R. Baden, M.D., Rupa Kanapathipillai, M.B., B.S., M.P.H., D.T.M.&H., Edward W. Campion, M.D., Stephen Morrissey, Ph.D., Eric J. Rubin, M.D., Ph.D., and Jeffrey M. Drazen, M.D.
N Engl J Med 2014; 371:1458-1459 October 9, 2014 DOI: 10.1056/NEJMe1411378
In March 2014, an outbreak of a febrile illness associated with a high case fatality rate was identified in the Guéckédou region of Guinea–Conakry, a remote part of West Africa. An international field investigation was initiated. On April 16, the Journal published a preliminary report identifying the outbreak as due to Ebola virus.1 The initial sequence data showed that the outbreak strain was Zaire ebolavirus, but a strain distinct from those identified in prior outbreaks, such as those in the Democratic Republic of Congo (DRC) and Gabon. In Guinea there appeared to be ongoing human-to-human transmission. Over the next 4 to 8 weeks, the outbreak seemed to be resolving, as over 20 previous outbreaks have, with a substantial decline in new cases. We and many others thought it would soon be over.2

We were wrong. Cases started to appear over the summer, and the number increased exponentially as this viral infection spread more widely in Guinea–Conakry and in Liberia and Sierra Leone.3 Cases associated with travel have been identified in Senegal and Nigeria, and there is evidence of ongoing transmission in Nigeria.4 Recently, Ebola transmission has been identified in the DRC, although molecular data suggest that this event is unrelated to the ongoing West African outbreak.5,6 These molecular data provide the information we need to define important aspects of ongoing transmission dynamics and to guide control strategies. Currently, there is no effective treatment, but human vaccine trials have been initiated.7

As of September 18, 2014, there were 5335 identified cases of Ebola virus disease, with more than 2622 associated deaths, which is more than in all previous Ebola outbreaks combined.4 These numbers are nonetheless likely to be underestimates, given the limitations of case identification, and the fraction of deaths probably underestimates the case fatality rate, because the interval between case identification and death has been just over 2 weeks. Although clinical data remain sparse, it seems likely that effective basic supportive care may make the difference between life and death for an infected patient. Unfortunately, health care workers have been disproportionately affected owing to the tremendous demands of patient care and the difficulty of implementing the infection-control measures required to prevent transmission.8 The Ebola outbreak is having serious adverse effects on travel, commerce, and routine health care, such as care for malaria, which threaten to further disrupt the already precarious conditions in which millions of people in the region live.9

The fear associated with a virulent and potentially deadly contagious infectious disease, which respects neither borders nor social status, has captured the attention of the world. The responders, both local and international, have been dedicated and brave. But far more is needed. It is critical that all members of the global health community — health care workers, scientists, regulators, funders, governments, and local communities — collaborate in responding as rapidly as possible if we are to control this enlarging outbreak. For example, the move by regulators to allow vaccine trials to proceed quickly shows flexibility and good judgment.

We, as a global health care community, must move decisively to bring this dangerous epidemic under control and then to improve the health care systems in the affected region.10 This will require more resources and more health care workers on the front lines (see the Ebola Outbreak page at for volunteer opportunities). It will also require communication and teamwork to win the trust of those in the affected communities. The Journal will continue to report on this unprecedented outbreak with updates on the efforts to control it, the biomedical findings emerging from it, and the difficult stories of those who are suffering through it.

Nature | Editorial – Out of Africa

Volume 514 Number 7521 pp139-266 9 October 2014

Nature | Editorial
Out of Africa
The Ebola outbreak in West Africa must be shut down now, or the disease will continue to spread.
07 October 2014
…The world is fiddling as West Africa burns, and unless it acts much faster, the outbreak risks spreading to surrounding regions. Sparks from it could lead to exports to more far-flung places, perhaps even to major cities that lack decent public-health infrastructure. But countries and the public must also realize that although action is needed urgently, the commitments must be sustained until the outbreak has been stamped out, which could take many months. The relatively low threat to developed countries must not distract or detract from the pressing need to tackle the outbreak at its source.

More Evidence on the Impact of India’s Conditional Cash Transfer Program, Janani Suraksha Yojana: Quasi-Experimental Evaluation of the Effects on Childhood Immunization and Other Reproductive and Child Health Outcomes

PLoS One
[Accessed 11 October 2014]

Research Article
More Evidence on the Impact of India’s Conditional Cash Transfer Program, Janani Suraksha Yojana: Quasi-Experimental Evaluation of the Effects on Childhood Immunization and Other Reproductive and Child Health Outcomes
Natalie Carvalho mail, Naveen Thacker, Subodh S. Gupta, Joshua A. Salomon
Published: October 10, 2014
DOI: 10.1371/journal.pone.0109311
In 2005, India established a conditional cash transfer program called Janani Suraksha Yojana (JSY), to increase institutional delivery and encourage the use of reproductive and child health-related services.
To assess the effect of maternal receipt of financial assistance from JSY on childhood immunizations, post-partum care, breastfeeding practices, and care-seeking behaviors.
We use data from the latest district-level household survey (2007–2008) to conduct a propensity score matching analysis with logistic regression. We conduct the analyses at the national level as well as separately across groups of states classified as high-focus and non-high-focus. We carry out several sensitivity analyses including a subgroup analysis stratified by possession of an immunization card.
Receipt of financial assistance from JSY led to an increase in immunization rates ranging from 3.1 (95%CI 2.2–4.0) percentage points for one dose of polio vaccine to 9.1 (95%CI 7.5–10.7) percentage points in the proportion of fully vaccinated children. Our findings also indicate JSY led to increased post-partum check-up rates and healthy early breastfeeding practices around the time of childbirth. No effect of JSY was found on exclusive breastfeeding practices and care-seeking behaviors. Effect sizes were consistently larger in states identified as being a key focus for the program. In an analysis stratified by possession of an immunization card, there was little to no effect of JSY among those with vaccination cards, while the effect size was much larger than the base case results for those missing vaccination cards, across nearly all immunization outcomes.
Early results suggest the JSY program led to a significant increase in childhood immunization rates and some healthy reproductive health behaviors, but the structuring of financial incentives to pregnant women and health workers warrants further review. Causal interpretation of our results relies on the assumption that propensity scores balance unobservable characteristics.

Determinants of Acceptance and Subsequent Uptake of the HPV Vaccine in a Cohort in Eldoret, Kenya
Heleen Vermandere, Violet Naanyu, Hillary Mabeya, Davy Vanden Broeck, Kristien Michielsen, Olivier Degomme
Research Article | published 09 Oct 2014 | PLOS ONE 10.1371/journal.pone.0109353

Global Financing and Long-Term Technical Assistance for Multidrug-Resistant Tuberculosis: Scaling Up Access to Treatment

PLoS Medicine
(Accessed 11 October 2014)

Open Access
Policy Forum
Global Financing and Long-Term Technical Assistance for Multidrug-Resistant Tuberculosis: Scaling Up Access to Treatment
Thomas J. Hwang, Salmaan Keshavjee mail
Published: September 30, 2014
DOI: 10.1371/journal.pmed.1001738
Summary Points
:: Multidrug-resistant tuberculosis (MDR-TB) is a leading public health concern, particularly in low- and middle-income countries, necessitating coordinated international action to prevent its spread and effectively treat the infected.
: The cost of treatment for MDR-TB is over 200 times the comparable cost for a drug-susceptible tuberculosis (TB) patient. Data show that prices for three of the currently most expensive drugs have increased dramatically since 2001, outpacing inflation.
:: Many of the high MDR-TB burden countries were ranked by WHO as being in the bottom 50% of health systems worldwide. Without sufficient technical, human, and organizational resources, weak health systems can pose a significant barrier to access to treatment.
:: In order to achieve the goal of eradicating MDR-TB, policymakers should implement a two-pronged intervention that pools donor resources for the coupling of market-oriented solutions to MDR-TB drug prices and targeted investments in health systems strengthening and innovative care delivery models. Innovative policy mechanisms piloted for other infectious diseases, such as pneumococcal vaccine, may offer lessons for the MDR-TB context.

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries

PNAS – Proceedings of the National Academy of Sciences of the United States
of America
(Accessed 11 October 2014)

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries
Gwenan M. Knighta, Ulla K. Griffithsb, Tom Sumnera, Yoko V. Laurenceb, Adrian Gheorgheb,
Anna Vassallb, Philippe Glaziouc, and Richard G. Whitea,1
Author Affiliations
To aid in prioritizing the development of tuberculosis (TB) vaccines most likely to reach the 2050 TB elimination goal, we estimated the impact and cost-effectiveness of a range of vaccine profiles in low- and middle-income countries. Using mathematical modeling, we show that vaccines targeted at adolescents/adults could have a much greater impact on the TB burden over a 2024–2050 time horizon than those vaccines targeted at infants. Such vaccines could also be cost-effective, even with relatively high vaccine prices. Our results suggest that to achieve the 2050 elimination goals, future TB vaccine development should focus on vaccines targeted at adolescents/adults, even if only relatively low efficacies and short durations of protection are technically feasible.
To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40–80% efficacy, and to be targeted at “infants” or “adolescents/adults.” Vaccine prices were tiered by income group (US $1.50–$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024–2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11–24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42–1.58) million TB cases could be prevented at $1,692 ($634–$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle–, and upper-middle–income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.

Provider knowledge of trivalent inactivated and high-dose influenza vaccines

Volume 32, Issue 46, Pages 6025-6176 (21 October 2014)

Provider knowledge of trivalent inactivated and high-dose influenza vaccines
Pages 6025-6028
Chad Tewell, Patty W. Wright, H. Keipp Talbot
The objective of this study was to assess provider knowledge about trivalent inactivated and high dose influenza vaccines. Hence, a 20-item survey was distributed to providers within the Internal Medicine department at an urban academic medical center.
Two hundred and eighty-one (24.5%) providers responded. The correct response rate was 63.2%. The highest performing subspecialties were infectious diseases (80.5%), endocrinology (69.2%), and pulmonary (68%). Those who received an influenza vaccine during the most recent season scored significantly higher than those who did not (63.6% vs. 43.6%, p = .001). Areas where respondents did poorly included questions pertaining to contraindications to immunizations (27.4%), common adverse events after immunization (29.2%), target antigen (73.5%), number of strains in the trivalent inactivated vaccine (62.9%), and time to immunity (61.4%). High dose vaccine knowledge was poor, with 37% of providers unaware of its existence.
Significant gaps in provider knowledge exist regarding both trivalent inactivated and high dose influenza vaccine

Prioritization of the introduction of new vaccines to the national immunization program in the Republic of Korea

Volume 32, Issue 46, Pages 6025-6176 (21 October 2014)

Prioritization of the introduction of new vaccines to the national immunization program in the Republic of Korea
Original Research Article
Pages 6049-6053
Young June Choe, Ok Pil Han, Heeyeon Cho, Geun-Ryang Bae, Byung-Chul Chun, Jong-Hyun Kim, Kyung-Hyo Kim, Hoan Jong Lee, Eun Hwa Choi
This study was performed to determine the priority of vaccine introduction for five vaccine-preventable diseases (VPDs) caused by Haemophilus influenzae type b (Hib), pneumococcus (Spn), hepatitis A virus (HepA), rotavirus (RV), and human papillomavirus (HPV) to the future Korean National Immunization Program (NIP) and to suggest framework programs to assist decision makers on implementation of the NIP.
Following analysis of the disease burden and economics of the five VPDs by the core team and Korean Advisory Committee on Immunization Practices sub-committee members, a Delphi survey was administered to 94 Korean experts using structured questionnaires that provided the reference data. The two evaluation frameworks for NIP prioritization were (1) a disease-related framework and (2) a vaccine-related framework. After analyzing the responses, a meeting of experts was held to build a consensus for determining how to prioritize NIP implementation.
The average scores for relative importance were 63.29 for the disease-related framework and 36.71 for the vaccine-related framework. Within the disease-related framework, the mortality and case fatality rate was the highest scored factor (8.97), whereas within the vaccine-related framework, efficacy of the vaccine was considered the most important factor (9.56). On average, Spn, Hib, and HepA had the highest priority scores.
The Korean experts suggested that the main factors influencing the decision to adopt new vaccines in the Korean NIP should be disease mortality, case fatality, and the efficacy and effectiveness of the vaccine. Among the five selected VPDs, Spn, Hib, and HepA were considered to be of higher priority than RV and HPV.

Parental acceptance of inactivated polio vaccine in Southeast Nigeria: A qualitative cross-sectional interventional study

Volume 32, Issue 46, Pages 6025-6176 (21 October 2014)

Parental acceptance of inactivated polio vaccine in Southeast Nigeria: A qualitative cross-sectional interventional study
Original Research Article
Pages 6157-6162
Beckie Nnenna Tagbo, Maduka Donatus Ughasoro, Dorothy Omono Esangbedo
The introduction of inactivated polio vaccines (IPV) is imminent. In view of the Polio Eradication and Endgame Strategic Plan 2013–2018, parental acceptance of IPV will be important for achieving universal coverage. In view of the imminent introduction of IPV, it is only reasonable to assess the awareness and acceptance of IPV, so that necessary socio-anthropological measures would be put in place. This study is aimed at determining the level of awareness and acceptance of IPV by parents.
A cross-sectional study involving 408 parents that brought their children for immunization. Structured-questionnaire was to collect data on the parent’s demographic characteristics, awareness and acceptance of IPV. The independent factors that may affect parental acceptability of IPV were evaluated using linear regression analysis.
About 53% of the parents had no knowledge of vaccine content and 84.1% had not heard of IPV, and 40.2% were willing to accept IPV. However, with post-intervention (IPV) health education, the level of acceptance of IPV increased to 95.6% and the difference was statistically significant (p = 0.0001). 35.3% expressed fear for IPV, and 61.8% cited fear for pain (61.8%). In the rating scale of 1 to 5, doctors (4.7), Nurses (4.0) and staff of the Ministry of Health (4.0) were rated high as reliable media to inform them about a new vaccine. The logistic regression revealed only educational level of mothers (p-value = 0.048) was the only significant factor associated with acceptability of IPV.
The parents’ knowledge on vaccine was poor, as well as IPV acceptability (pre health education). But the acceptability was improved with provision of extra information. Although most still preferred OPV, and with improvement in pain management, acceptability of IPV can be improved further. Clear policies and strategies should be immediately developed and implementation of pre-introduction awareness/sensitization on IPV should be commenced.

Parent perceptions important for HPV vaccine initiation among low income adolescent girls

Volume 32, Issue 46, Pages 6025-6176 (21 October 2014)

Parent perceptions important for HPV vaccine initiation among low income adolescent girls
Original Research Article
Pages 6163-6169
Stephanie A.S. Staras, Susan T. Vadaparampil, Roshni P. Patel, Elizabeth A. Shenkman
The study aims were to assess the influence of provider recommendations on parental vaccine perceptions and identify the most potent parent vaccine perceptions for HPV vaccine series initiation considering provider recommendation strength.
We administered a questionnaire and assessed HPV vaccine claims among a stratified-random sample of parents of 9–17 year old girls enrolled in Florida’s Medicaid and the Children’s Health Insurance Program. Using multivariate analyses, we evaluated the associations between: (1) parent vaccine perceptions and provider recommendation strength, and (2) parent vaccine perceptions and HPV vaccine series initiation (≥1 vaccine claim or positive parental report) controlling for provider recommendation strength.
The majority of the 2422 participating parents agreed that the HPV vaccine was safe (61%), would not make girls more likely to have sex (69%), and prevented cervical cancer (71%). About half (44%) reported receiving a strong provider recommendation. Compared to parents without recommendations, parents with strong recommendations had 2 to 7 times higher odds of agreeing that: vaccines are safe, the HPV vaccine is safe, not concerned about side effects, and the vaccine prevents cervical cancer. Even when considering provider recommendation strength, HPV vaccine series initiation was more likely among girls of parents who agreed rather than disagreed that the HPV vaccine was safe [odds ratio (OR) = 5.8, 95% confidence interval (CI) = 3.1, 11.1], does not cause sex (OR = 2.0, 95% CI = 1.2, 3.4), prevents cervical cancer (OR = 2.0, 95% CI = 1.0, 3.4), and prevents HPV infections (OR = 1.8, 95% CI = 1.0, 3.0).
Parent concerns about HPV vaccine are similar to their concerns about other vaccines. Providers should focus HPV vaccine discussions with parents on vaccine safety and illness prevention.

Vaccines and Global Health: The Week in Review 4 October 2014

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
pdf version A pdf of the current issue is available here:  Vaccines and Global Health_The Week in Review_4 October 2014

blog edition: comprised of the 35+ entries posted below on 28 September 2014

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…
Editor’s Note on this Edition:
The pace and complexity of the Ebola/EVD crisis continues. We will strive to present a coherent, high-level digest of the situation using official sources wherever possible, with a special focus on vaccines and other interventions now in development and various trials globally. Reading this issue you will encounter significant Ebola content throughout.

We note that UNMEER (UN Mission for Ebola Emergency Response) – the new UN coordinating mission established by and reporting to the UN Secretary General –
began operations and launched its own website with daily “external situation reports” updates and other content as below.

We lead this edition with the full text of a report from a WHO consultation on the status of and milestones ahead for candidate Ebola/EVD vaccines.


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

WHO: Experimental Ebola vaccines – 1 October 2014

WHO: Experimental Ebola vaccines 1 October 2014
WHO consultation on Ebola vaccines
[Full text with milestones summary at bottom]

From 29–30 September, WHO organized an expert consultation to assess the status of work to test and eventually license two candidate Ebola vaccines. More than 70 experts, including many from affected and neighbouring countries in West Africa, attended the event.

The expertise represented among participants ranged from the virology of emerging infections, to regulatory requirements that must be met, to medical ethics, public health, and infectious diseases. Heads of clinical research and other executives from the pharmaceutical industry also presented their views.

Some participants came with more than 3 decades of experience working in Africa on other infectious diseases.

Experts on the use of innovative, cutting-edge trial designs also shared their most recent work.

The overarching objective was to take stock of the many efforts currently under way to rapidly evaluate Ebola vaccines for safety and efficacy. The next step is to make these vaccines available as soon as possible – and in sufficient quantities – to protect critical frontline workers and to make a difference in the epidemic’s future evolution.
All agreed on the ultimate goal: to have a fully tested and licensed product that can be scaled up for use in mass vaccination campaigns.

Two promising candidate vaccines
Given the public health need for safe and effective Ebola interventions, WHO regards the expedited evaluation of all Ebola vaccines with clinical grade material as a high priority.

Two candidate vaccines have clinical-grade vials available for phase 1 pre-licensure clinical trials.

One (cAd3-ZEBOV) has been developed by GlaxoSmithKline in collaboration with the US National Institute of Allergy and Infectious Diseases. It uses a chimpanzee-derived adenovirus vector with an Ebola virus gene inserted.

The second (rVSV-ZEBOV) was developed by the Public Health Agency of Canada in Winnipeg. The license for commercialization of the Canadian vaccine is held by an American company, the NewLink Genetics company, located in Ames, Iowa. The vaccine uses an attenuated or weakened vesicular stomatitis virus, a pathogen found in livestock; one of its genes has been replaced by an Ebola virus gene.

Phase 1 clinical trials
WHO and other partners have helped facilitate expedited evaluation of these two vaccines in order to generate phase 1 safety and immunogenicity data for decision-making. A series of coordinated phase 1 trials is currently under way or will soon be initiated with international consortia at more than 10 sites in Africa, Europe and North America.
These studies aim to ensure good communication and harmonization of key design elements to allow for merging of data from different trials of the same candidate products.

The trials, which are being conducted in healthy human volunteers, are designed to test safety and immunogenicity and select the appropriate dose. Two phase 1 trials of the cAd3-ZEBOV started in September 2014 in USA and UK, and the first Phase 1 trial of VSV-ZEBOV is due to start early in October in USA.

The government of Canada has donated 800 vials of rVSV-ZEBOV to WHO. Once data on dosing from phase 1 trials become available, this donation could translate into about 1500 to 2000 doses of vaccine.

Both companies are working to augment their manufacturing capacity. The goal is a very significant increase in scale during the first half of 2015.

No delays
One shared mindset was readily apparent during the two-day discussions. Nothing must be allowed to slow down the goal of making vaccines accessible to people in affected West African countries. The phrase, “Nothing can be allowed to delay this work”, was heard over and over again.

The ambition: to accomplish, within a matter of months, work that normally takes from two to four years, without compromising international standards for safety and efficacy.
In other words: to give the African people and their health authorities the best product that the world’s scientists, working collectively, have to offer.

What the experts considered
Against this background, the meeting looked specifically at the objectives and key design elements for moving in an expedited manner to conduct additional clinical trials (phase 2 trial designs) that will generate additional safety data and evidence that the vaccine confers protection.

Parallel pathways for emergency use of experimental candidate vaccines with data collection, among frontline health care workers and other critical personnel, were also explored.

Apart from the great sense of urgency, the overall spirit of the discussions was characterized by a strong sense of solidarity with the people of West Africa, their governments, and their medical, scientific, and public health communities.

Equally strong was the insistence on ensuring that evidence on safety, immunogenicity, and efficacy of the vaccines is collected properly.

Multiple challenges
Multiple potential challenges and uncertainties were put forward and assessed. Issues ranging from barriers to rapid implementation of R&D, to the design of trials and their use to guide eventual widespread vaccination, were discussed together with proposed ways to overcome them.

Some of the practical issues discussed included how to address communities’ perceptions regarding vaccines in general, and vaccine studies more specifically, public expectations for vaccine availability for widespread use, and whether there is an adequate infrastructure in place to rapidly and safely evaluate and distribute vaccines.
One important technical challenge is the fact that the candidate vaccines must be stored at a temperature of -80°C.

Further issues that need to be urgently addressed include identifying staff who can conduct trials meeting international standards, logistical issues (such as cold chain needs for the vaccines), and the resources needed to start the studies quickly.

Some of the scientific challenges include how to conduct studies as safely and rapidly as possible to inform decisions about mass production of vaccines and their administration.

Key questions
Discussions focused on the main questions that studies should help address, which part of the research should be conducted in non-affected areas and which part in affected areas, and how such decisions could either help expedite or delay the availability of robust evidence.

One overarching conclusion was that the international community, joining the affected countries as a whole, has a responsibility and a role to play in accelerating the evaluation, licensing, and availability of the candidate vaccines – if proven safe and effective.

For all these reasons, the actions emerging from the consultation clearly identify a role for each of the main stakeholders.

Randomized controlled trials
Regarding the issue of how to accelerate the assessment and licensure of the vaccines, experts reiterated that, if feasible, randomized controlled trials are the design of choice because they provide the most robust data, in the shortest amount of time, to judge whether a vaccine is safe and induces protection.

Trials must be expedited, while preserving ethical and safety standards. Efficacy data of high quality must be gathered. Trials need to be carefully designed so that they concomitantly address the most important questions regarding safety, immunogenicity, and efficacy.

While individually randomized controlled trials provide the most robust data, alternative designs should be considered when these trials are not judged feasible. These include cluster-randomized and stepped-wedge designs. As long as the amount of vaccine remains limited, units – such as health or treatment facilities – can be randomized. Regardless of the design chosen, trials should move forward as quickly as possible.

Alternative study designs
Alternative study designs will not delay deployment of vaccine to those who need it. Instead, they will influence the choice of people who receive the vaccine. For some months to come, the critical limiting factor is extremely restricted vaccine supply, and not the need to conduct studies using alternative designs.

Descriptions of the so-called “randomized stepped wedge” design attracted lively interest and much discussion. In this design, a “wedge” (like a slice of a pie or a cake) of the study population is selected for step-wise inclusion in the trials.

As each “wedge” receives the vaccine, all lessons learned or needed to adjust the study design are then applied to the next group to be included in the study. The selection of study populations can be randomized by units, as described above; the entire study population eventually receives the vaccine if trials demonstrate sufficient efficacy.

Such a design makes it possible to roll out vaccinations and evaluate efficacy at the same time. It further has features that meet the explicit objective of fairness.
Other designs will be more relevant when large numbers of vaccine doses are available.

Involving countries
Decisions on study designs and target populations must be made with the active participation of experts from the three hardest-hit countries. Consultations with frontline health workers should be undertaken as a matter of urgency to identify the most feasible approaches to evaluate vaccine efficacy and identify factors influencing acceptability of randomized trials.

The experts discussed the importance of making sure that the trials are appropriately designed to inform the use of these vaccines in all populations, including children, pregnant women, and immunocompromised populations, including people who are HIV positive.

The group also discussed how best to use the doses of experimental vaccine donated by Canada and additional doses that may be available later this year and in 2015.
If vaccine doses are used in the short term, vaccines should be deployed to consenting frontline health workers.

The decision to initiate such deployment should be informed by data emerging from the phase 1 studies, and will occur with data collection on the deployment itself.

Equity is important and therefore vaccine should be made available in an equitable and consensual manner to the affected countries. Maximizing the information gained from the use of these vaccines during this phase is critical.

Information sharing
A cross-cutting issue is the need for data sharing – in real time – among the research, medical, and public health communities, coordinated by WHO. This was considered of paramount importance to inform decisions on future studies and scaling up the production of those experimental vaccines that look most promising.

Vaccine development normally takes a long time and is notoriously costly. Even under the best conditions and with the massive efforts of many partners, a significant number of doses will not be available until late in the first quarter of 2015.

One important factor for the completion of all the above steps is to secure the funding to ensure the production of the vaccine and to support priority studies. Major international funding partners should promptly pledge or commit the necessary funding so that this critical research is completed without further delay.

The African perspective
The presence of West African researchers, scientists, clinicians, and health officials vastly enriched the discussions, especially concerning the practical dimensions of trial design.

These experts further underscored the importance of communicating with communities and engaging their views, and called for qualitative studies to begin immediately. For example, some cultures are deeply distrustful of “Western” medicine and foreign medical staff in general, and of vaccines in particular.

Interventions from the three hardest-hit countries, Guinea, Liberia, and Sierra Leone, clearly stated that international assistance is both greatly needed and fully welcomed.
Families and entire villages have been shattered. Some communities are on the verge of hopelessness and helplessness. Many do not comprehend what hit them and why, especially as this is the first time that the Ebola virus and Ebola virus disease have been seen in West Africa.

Governments are on board. Clinicians are on board. Researchers and their institutes are on board.

Statements made by West Africans reminded all participants of what life is really like in these countries. Children do not play in school yards, play pens, fenced back yards, or terraced gardens. They play in the bush.

These realities of daily African life need to be kept in mind when high-risk exposures are considered and defined.

Health workers
Participants were further reminded that the definition of “health care workers” in these African countries includes doctors, nurses, and laboratory technicians but also hospital cleaners, ambulance drivers, burial teams, mortuary attendants, and in some instances, traditional healers.

As hospitals in many areas are overflowing or closed, the number of treatment beds in all three countries is woefully inadequate, and people frequently do not trust the health care system, more and more patients are being cared for by their loved ones in homes or within the community.

These people are also at very high risk of infection and should be considered when priorities for support – in all its forms – are being set. The importance of community engagement cannot be overstated.

Operational changes made since the unprecedented resolutions on Ebola virus disease were adopted by an emergency session of the UN Security Council (on 18 September) and by a UN General Assembly high-level session on Ebola (on 25 September) involve a vast ground-swell scaling-up of international support to affected countries. This support includes a much larger number of medical staff working in countries, thanks to generous support from the governments of China, Cuba, and many others.

Lessons learned
Participants also drew heavily on lessons learned, in the African setting, during trials for candidate malaria, HIV/AIDS, cholera, epidemic meningitis, hepatitis B, and other vaccines.

As some experts noted, never again can the international community allow what boils down to “market failure” to create such catastrophic suffering for humanity in any country, in any region of the world.

The sense of urgency and need for speed, without compromising the integrity of studies or the quality of their data, are fully justified by the dire situation in affected countries and the risk that other countries may soon experience their first imported cases.

The Ebola outbreak currently ravaging parts of West Africa is the most severe acute public health emergency in modern times. Never before in recent history has a biosafety level 4 pathogen infected so many people so quickly, over such a wide geographical area, for so long.

Key expected milestones
:: October 2014 – Mechanisms for evaluating and sharing data in real time must be prepared
and agreed upon and the remainder of the phase 1 trials must be started
:: October–November 2014 – Agreed common protocols (including for phase 2 studies) across
different sites must be developed
:: October–November 2014 – Preparation of sites in affected countries for phase 2 b should
start as soon as possible
:: November–December 2014 – Initial safety data from phase 1 trials will be available
:: January 2015 – GMP (Good Manufacturing Practices) grade vaccine doses will be available for
phase 2 as soon as possible
:: January–February 2015 – Phase 2 studies to be approved and initiated in affected and non-
affected countries (as appropriate)
:: As soon as possible after data on efficacy become available – Planning for large-scale
vaccination, including systems for vaccine financing, allocation, and use.