PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 7 January 2017)

Viewpoints
Zika Virus: Promoting Male Involvement in the Health of Women and Families
Pauline E. Osamor, Christine Grady
| published 29 Dec 2016 PLOS Neglected Tropical Diseases
http://dx.doi.org/10.1371/journal.pntd.0005127

PLoS One
http://www.plosone.org/
[Accessed 7 January 2017]

Research Article
Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis
Gerhard Falkenhorst, Cornelius Remschmidt, Thomas Harder, Eva Hummers-Pradier, Ole Wichmann, Christian Bogdan
Research Article | published 06 Jan 2017 PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0169368

Research Article
Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An Observational Study
Eric D. McCollum, Bejoy Nambiar, Rashid Deula, Beatiwel Zadutsa, Austin Bondo, Carina King, James Beard, Harry Liyaya, Limangeni Mankhambo, Marzia Lazzerini, Charles Makwenda, Gibson Masache, Naor Bar-Zeev, Peter N. Kazembe, Charles Mwansambo, Norman Lufesi, Anthony Costello, Ben Armstrong, Tim Colbourn
Research Article | published 04 Jan 2017 PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0168209

Research Article
Potential Cost-Effectiveness of an Influenza Vaccination Program Offering Microneedle Patch for Vaccine Delivery in Children
Carlos Wong, Minghuan Jiang, Joyce H. S. You
Research Article | published 22 Dec 2016 PLOS ONE
http://dx.doi.org/10.1371/journal.pone.0169030

PLoS Pathogens
http://journals.plos.org/plospathogens/

Research Article
Detection of Viral RNA in Tissues following Plasma Clearance from an Ebola Virus Infected Patient
Mirella Biava, Claudia Caglioti , Licia Bordi, Concetta Castilletti, Francesca Colavita, Serena Quartu, Emanuele Nicastri, Francesco Nicola Lauria, Nicola Petrosillo, Simone Lanini, Thomas Hoenen, Gary Kobinger, Alimuddin Zumla,  [ … ], Eleonora Lalle
Published: January 5, 2017
http://dx.doi.org/10.1371/journal.ppat.1006065
Abstract
An unprecedented Ebola virus (EBOV) epidemic occurred in 2013–2016 in West Africa. Over this time the epidemic exponentially grew and moved to Europe and North America, with several imported cases and many Health Care Workers (HCW) infected. Better understanding of EBOV infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. We have longitudinally explored the persistence of EBOV-specific negative sense genomic RNA (neg-RNA) and the presence of positive sense RNA (pos-RNA), including both replication intermediate (antigenomic-RNA) and messenger RNA (mRNA) molecules, in the upper and lower respiratory tract, as compared to plasma, in a HCW infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), Rome, Italy. We observed persistence of pos-RNA and neg-RNAs in longitudinally collected specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The purpose of the present study is to enhance the knowledge on the biological features of EBOV that can contribute to the human-to-human transmissibility and to develop effective intervention strategies. However, further investigation is needed in order to better understand the clinical meaning of viral replication and shedding in the respiratory tract.
Author Summary
An unprecedented Ebola outbreak occurred in 2013–2016 in West Africa. In order to better understand EBOV infection patterns in different body compartments, we have longitudinally explored the presence of already assessed markers of ongoing EBOV replication (negative sense genomic RNA and positive sense RNA) in the upper and lower respiratory tract, as compared to plasma and other body compartments, in a Health Care Worker infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), Rome, Italy. The presence of total EBOV RNA and replication markers was observed in specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. Our results contribute to the knowledge on the biological features of EBOV and shed light on the potential role of respiratory compartment in human-to-human transmissibility.

Research Matters
The Importance of International Collaborations to Advance Research Endeavors
Alfredo G. Torres
| published 05 Jan 2017 PLOS Pathogens
http://dx.doi.org/10.1371/journal.ppat.1006047

Public Health Reports
Volume 132, Issue 1, January/February 2017
http://phr.sagepub.com/content/current

Commentary
Fifty Years of Global Immunization at CDC, 1966-2015
First Published December 19, 2016; pp. 18–26
Eric E. Mast, Stephen L. Cochi, Olen M. Kew, K. Lisa Cairns, Peter B. Bloland, Rebecca Martin

Public Health Reports
Volume 132, Issue 1, January/February 2017
http://phr.sagepub.com/content/current

Research
Infectious Disease Hospitalizations Among American Indian/Alaska Native and Non–American Indian/Alaska Native Persons in Alaska, 2010-2011
First Published December 9, 2016; pp. 65–75
Prabhu P. Gounder, Robert C. Holman, Sara M. Seeman, Alice J. Rarig, Mary McEwen, Claudia A. Steiner, Michael L. Bartholomew, Thomas W. Hennessy
Abstract
Objective:
Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska.
Methods:
We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis.
Results:
ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001).
Conclusions:
A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons.

Science Translational Medicine
04 January 2017 Vol 9, Issue 371
http://stm.sciencemag.org/

Research Article
Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects
By James G. Kublin, Sebastian A. Mikolajczak, Brandon K. Sack, Matt E. Fishbaugher, Annette Seilie, Lisa Shelton, Tracie VonGoedert, Melike Firat, Sara Magee, Emma Fritzen, Will Betz, Heather S. Kain, Dorender A. Dankwa, Ryan W. J. Steel, Ashley M. Vaughan, D. Noah Sather, Sean C. Murphy, Stefan H. I. Kappe
Science Translational Medicine04 Jan 2017 Restricted Access
A triple punch knocks out the malaria parasite
Vaccination with weakened infectious forms of the malaria parasite is the most promising approach to protect against malaria infection. However, creating genetically defined and weakened parasite strains that are safe for vaccination remains challenging. In a new study, Kublin et al. show that genetic engineering of the malaria parasite by the precise removal of three genes creates a parasite strain that infects humans and is well tolerated but cannot cause malaria. These genetically attenuated parasites thus appear safe for vaccination and stimulate the human immune system to generate responses that have the potential to block infection.
Abstract
Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52−/p36−/sap1−). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers. Pf GAP3KO sporozoites were delivered to 10 volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage–negative and developed inhibitory antibodies to sporozoites. GAP3KO rodent malaria parasites engendered complete, protracted immunity against infectious sporozoite challenge in mice. The results warrant further clinical testing of Pf GAP3KO and its potential development into a vaccine strain.

Social Science & Medicine
Volume 171, Pages 1-102 (December 2016)
http://www.sciencedirect.com/science/journal/02779536/170

Regular articles
Standardizing psycho-medical torture during the War on Terror: Why it happened, how it happened, and why it didn’t work
Original Research Article
Pages 1-8
Myles Balfe
Abstract
After 9/11/2001 the United States launched a global War on Terror. As part of this War, terrorism suspects were detained by the U.S. military and by the C.I.A. It is now widely recognized that the United States tortured a number of these detainees in the context of its ‘enhanced interrogation’ programme. This article examines how and why U.S. organizations developed standards that allowed healthcare professionals to become involved in torture; why the standards developed by U.S. security institutions failed to control the actions of enhanced interrogation personnel on the ground; and what the role of standards were in stopping the enhanced interrogation initiative. The article concludes by discussing the general lessons that the enhanced interrogation programme has for social science research on standards, namely that individuals can experience ambivalence when caught between competing organizational and professional standards and that it might be inherently difficult to successfully enact certain protocols when these relate to deviant or destructive acts.

Tropical Medicine & International Health
January 2017 Volume 22, Issue 1 Pages 1–121
http://onlinelibrary.wiley.com/doi/10.1111/tmi.2017.22.issue-1/issuetoc

Original Research Papers
Household experience and costs of seeking measles vaccination in rural Guinea-Bissau (pages 12–20)
S. Byberg, A. B. Fisker, A. Rodrigues, I. Balde, U. Enemark, P. Aaby, C. S. Benn and U. K. Griffiths
Version of Record online: 28 OCT 2016 | DOI: 10.1111/tmi.12793

Tropical Medicine & International Health
January 2017 Volume 22, Issue 1 Pages 1–121
http://onlinelibrary.wiley.com/doi/10.1111/tmi.2017.22.issue-1/issuetoc

Original Research Papers
Human papillomavirus (HPV) awareness and vaccine receptivity among Senegalese adolescents (pages 113–121)
Philip M. Massey, Ruth K. Boansi, Jessica D. Gipson, Rachel M. Adams, Helene Riess, Thierno Dieng, Michael L. Prelip and Deborah C. Glik
Version of Record online: 14 NOV 2016 | DOI: 10.1111/tmi.12798

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

A general measles vaccination campaign in urban Guinea-Bissau: Comparing child mortality among participants and non-participants
Original Research Article
Pages 33-39
S. Byberg, S.M. Thysen, A. Rodrigues, C. Martins, C. Cabral, M. Careme, P. Aaby, C.S. Benn, A.B. Fisker
Abstract
Background
Measles vaccination campaigns targeting children aged 9–59 months are conducted every three years in Guinea-Bissau. Studies have demonstrated beneficial non-specific effects of measles vaccine. We compared mortality one year after the December 2012 measles vaccination campaign in Bissau city for children who received campaign measles vaccine with children who did not receive campaign measles vaccine.
Methods
Field workers from Bandim Health Project registered all children living in the Bandim Health Project’s study area who received measles vaccination at the campaign posts. Children not seen during the campaign were visited at home and campaign participation status was assessed. We compared mortality rates of participants vs. non-participants in Cox regression models.
Results
5633 children aged 9–59 months (85%) received campaign measles vaccination and 1006 (15%) did not. During the subsequent year 16 children died. Adjusted for background factors, the hazard ratio (HR) comparing measles vaccinated versus unvaccinated was 0.28 (95% CI: 0.10–0.77). The benefit was larger for girls (HR: 0.17 (0.05–0.59)) and for children who had received routine measles vaccine before the campaign (HR: 0.15 (0.04–0.63)).
Conclusions
We found indications of strong beneficial non-specific effects of receiving measles vaccine during the 2012 campaign, especially for girls and children with previous routine measles vaccination. Measles vaccination campaigns may be an effective way of improving child survival.

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

Country specific predictions of the cost-effectiveness of malaria vaccine RTS,S/AS01 in endemic Africa
Original Research Article
Pages 53-60
Katya Galactionova, Fabrizio Tediosi, Flavia Camponovo, Thomas A. Smith, Peter W. Gething, Melissa A. Penny
Abstract
Background
RTS,S/AS01 is a safe and moderately efficacious vaccine considered for implementation in endemic Africa. Model predictions of impact and cost-effectiveness of this new intervention could aid in country adoption decisions.
Methods
The impact of RTS,S was assessed in 43 countries using an ensemble of models of Plasmodium falciparum epidemiology. Informed by the 32 months follow-up data from the phase 3 trial, vaccine effectiveness was evaluated at country levels of malaria parasite prevalence, coverage of control interventions and immunization. Benefits and costs of the program incremental to routine malaria control were evaluated for a four dose schedule: first dose administered at six months, second and third – before 9 months, and fourth dose at 27 months of age. Sensitivity analyses around vaccine properties, transmission, and economic inputs were conducted.
Results
If implemented in all 43 countries the vaccine has the potential to avert 123 (117; 129) million malaria episodes over the first 10 years. Burden averted averages 18,413 (range of country median estimates 156–40,054) DALYs per 100,000 fully vaccinated children with much variation across settings primarily driven by differences in transmission intensity. At a price of $5 per dose program costs average $39.8 per fully vaccinated child with a median cost-effectiveness ratio of $188 (range $78–$22,448) per DALY averted; the ratio is lower by one third – $136 (range $116–$220) – in settings where parasite prevalence in children aged 2–10 years is at or above 10%.
Conclusion
RTS,S/AS01 has the potential to substantially reduce malaria burden in children across Africa. Conditional on assumptions on price, coverage, and vaccine properties, adding RTS,S to routine malaria control interventions would be highly cost-effective. Implementation decisions will need to further consider feasibility of scaling up existing control programs, and operational constraints in reaching children at risk with the schedule.

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

Vaccination against hepatitis B virus among people who inject drugs – A 20 year experience from a Swedish needle exchange program
Original Research Article
Pages 84-90
M. Alanko Blomé, P. Björkman, L. Flamholc, H. Jacobsson, A. Widell
Abstract
Background
People who inject drugs (PWID) are at particular risk of hepatitis B virus (HBV) acquisition, but often have poor access or adherence to HBV vaccination. Vaccination against HBV has been offered at a major Swedish needle exchange program (NEP) since 1994. The aim of this study was to evaluate vaccine completion and response rates, and the effect of sequential booster doses to non-responders to the standard vaccination schedule.
Methods
PWID enrolled in the NEP 1994–2013, without serological markers for HBV at baseline (negative for HBsAg/anti-HBc/anti-HBs), were offered a three-dose standard intramuscular vaccination schedule (Engerix®-B, GSK, 20 μg/mL, intended to be received at months 0, 1 and 6). Vaccination response was defined as protective levels of anti-HBs (⩾10 mIU/mL). Up to three booster doses were then offered for non-responders, each followed by anti-HBs testing.
Results
HBV data was available for 2352 identifiable individuals at NEP enrolment, of whom 1516 (64.5%) had no markers for previous HBV exposure or vaccination. Vaccination was initiated for 1142 (75.3%) individuals and 898 (59.2%) completed the standard vaccination schedule. Post-vaccination anti-HBs levels were available from 800 individuals, with 598 (74.8%) responding to the basic vaccination schedule. After up to three booster doses a total of 676 (84.5%) individuals achieved protective anti-HBs levels. Non-response to vaccination was associated with higher age and anti-HCV positivity (p < 0.001). Eighteen incident cases of HBV infection were observed among vaccine non-responders, as well as 30 cases among those who had not completed vaccination.
Conclusion
We demonstrate the feasibility of including HBV vaccination in the services offered by a NEP, with completion of vaccination in a majority of HBV-susceptible PWID. The response to HBV vaccination among PWID was relatively low; however, the addition of up to three booster doses improved the response rate from 74.8 to 84.5%.

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

Improving adolescent HPV vaccination in a randomized controlled cluster trial using the 4 Pillars™ practice Transformation Program
Original Research Article
Pages 109-117
Richard K. Zimmerman, Krissy K. Moehling, Chyongchiou J. Lin, Song Zhang, Jonathan M. Raviotta, Evelyn C. Reis, Sharon G. Humiston, Mary Patricia Nowalk
Abstract
Objective
Uptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices.
Methods
Practices with at least 50 patients 11–17 years old with estimated vaccination rates less than national goals, were assigned to intervention (n = 11) and control (n = 11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods were 7/1/2013–6/30/2014 and 7/1/2014–3/31/2015, respectively. Vaccination and demographic data for patients who had a visit in both study periods were derived from de-identified EMR extractions. Primary outcomes were vaccination rates and percentage point (PP) changes. Data were analyzed in 2015–16.
Results
Among the cohort of 10,861 adolescent patients, 38% were 11–13 years old; 50% were female; 18% were non-white; and 64% were commercially insured. Average baseline HPV initiation rates were 52.5% for intervention and 61.8% for control groups. After 9 months, the intervention sites increased HPV initiation 10.2 PP compared with 7.3 PP in control sites (P < 0.001); HPV series completion rates did not differ between groups. Implementation of >10 strategies to improve rates significantly increased the likelihood of HPV series initiation (OR = 2.06, 95% CI = 1.43, 2.96).
Conclusions
Using >10 strategies from the 4 Pillars™ Practice Transformation Program is effective for increasing HPV series initiation among adolescents.
Clinical trial registry number: NCT02165722.

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

Clinician knowledge, clinician barriers, and perceived parental barriers regarding human papillomavirus vaccination: Association with initiation and completion rates
Original Research Article
Pages 164-169
Lila J. Finney Rutten, Jennifer L. St. Sauver, Timothy J. Beebe, Patrick M. Wilson, Debra J. Jacobson, Chun Fan, Carmen Radecki Breitkopf, Susan T. Vadaparampil, Robert M. Jacobson
Abstract
Purpose
We tested the hypothesis that clinician knowledge, clinician barriers, and perceived parental barriers relevant to the human papillomavirus (HPV) vaccination account for the variation in vaccine delivery at the practice-site level.
Methods
We conducted a survey from October 2015 through January 2016 among primary care clinicians (n = 280) in a 27-county geographic region to assess clinician knowledge, clinician barriers, and perceived parental barriers regarding HPV vaccination. Primary care clinicians included family medicine physicians, general pediatricians, and family and pediatric nurse-practitioners. We also used the Rochester Epidemiology Project to measure HPV vaccination delivery. Specifically we used administrative data to measure receipt of at least one valid HPV vaccine dose (initiation) and receipt of three valid HPV vaccine doses (completion) among 9–18 year old patients residing in the same 27-county geographic region. We assessed associations of clinician survey data with variation in vaccine delivery at the clinical site using administrative data on patients aged 9–18 years (n = 68,272).
Results
Consistent with our hypothesis, we found that greater knowledge of HPV and the HPV vaccination was associated with higher rates of HPV vaccination initiation (Incidence rate ratio [IRR] = 1.05) and completion of three doses (IRR = 1.28). We also found support for the hypothesis that greater perceived parental barriers to the HPV vaccination were associated with lower rates of initiation (IRR = 0.94) and completion (IRR = 0.90). These IRRs were statistically significant even after adjustment for site-level characteristics including percent white, percent female, percent ages 9–13, and percent with government insurance or self-pay at each site.
Conclusions
Clinician knowledge and their report of the frequency of experiencing parental barriers are associated with HPV vaccine delivery rates—initiation and completion. Higher measures of knowledge correlated with higher rates. Fewer perceived occurrences of parental barriers correlated with lower rates. These data can guide efforts to improve HPV vaccine delivery in clinical settings.

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

Age-specific effectiveness following each dose of acellular pertussis vaccine among infants and children in New Zealand
Original Research Article
Pages 177-183
Sarah Radke, Helen Petousis-Harris, Donna Watson, Dudley Gentles, Nikki Turner
Abstract
Background
Though it is believed the switch from whole cell to acellular pertussis vaccine has contributed to the resurgence of pertussis disease, few studies have evaluated vaccine effectiveness (VE) and duration of protection provided by an acellular vaccine schedule including three primary doses but no toddler-age dose. We assessed this schedule in New Zealand (NZ), a setting with historically high rates of pertussis disease, and low but recently improved immunisation coverage. We further evaluated protection following the preschool-age booster dose.
Methods
We performed a nested case-control study using national-level healthcare data. Hospitalised and non-hospitalised pertussis was detected among children 6 weeks to 7 years of age between January 2006 and December 2013. The NZ National Immunisation Register provided vaccination status for cases and controls. Conditional logistic regression was used to calculate dose-specific VE with duration of immunity examined by stratifying VE into ages aligned with the immunisation schedule.
Results
VE against pertussis hospitalisation was 93% (95% confidence interval [CI]: 87, 96) following three doses among infants aged 5–11 months who received three compared to zero doses. This protection was sustained through children’s fourth birthdays (VE ⩾ 91%). VE against non-hospitalised pertussis was also sustained after three doses, from 86% (95% CI: 80, 90) among 5–11 month olds to 84% (95% CI: 80, 88) among 3-year-olds. Following the first booster dose at 4 years of age, the protective VE of 93% (95% CI: 90, 95) among 4-year-olds continued through 7 years of age (VE ⩾ 91%).
Conclusions
We found a high level of protection with no reduction in VE following both the primary course and the first booster dose. These findings support a 3-dose primary course of acellular vaccine with no booster dose until 4 years of age.

Vaccine
Volume 35, Issue 1, Pages 1-200 (3 January 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/1

Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design
Original Research Article
Pages 184-190
Lauren M. Schwartz, M. Elizabeth Halloran, Ali Rowhani-Rahbar, Kathleen M. Neuzil, John C. Victor
Abstract
Background
The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness.
Methods
This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed.
Results
TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea.
Conclusions
This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings

Vaccines — Open Access Journal
http://www.mdpi.com/journal/vaccines
(Accessed 7 January 2017)
Latest Articles
Young Hungarian Students’ Knowledge about HPV and Their Attitude Toward HPV Vaccination
by Bettina Claudia Balla, András Terebessy, Emese Tóth and Péter Balázs
Vaccines 2017, 5(1), 1; doi:10.3390/vaccines5010001 – 29 December 2016
Abstract
(1) Background: Hungarys’s estimated cervical cancer mortality was 6.9/100,000 in 2012, above the average of the EU27 countries (3.7/100,000) in the same year. Since 2014, the bivalent HPV vaccine has been offered to schoolgirls aged 12–13.
(2) Methods: We conducted a cross-sectional study among 1022 high school seniors (492 girls, 530 boys) in 19 randomly selected schools in Budapest. Our anonymous questionnaire contained 54 items: basic socio-demographic data, knowledge about HPV infection/cervical cancer and HPV vaccination.
(3) Results: 54.9% knew that HPV caused cervical cancer, and 52.1% identified HPV as an STD. Knowledge of risk factors such as promiscuity (46.9%) and early sexual activity (15.6%) was low, but higher than that of further HPV-induced diseases: genital warts (in females 9.9%, in males 9%), anal cancer (in females 2.2%, in males 1.9%), penile cancer (9.4%), and vulvar cancer (7.8%). A percentage of 14.6% feared getting infected, and 35.7% supported compulsory HPV vaccination. A percentage of 51.2% would have their future children vaccinated—significantly more girls than boys.
(4) Conclusion: Our results support the findings of previous studies about young adults’ HPV-related knowledge, which was poor, especially regarding pathologies in men. Despite the low level of awareness, the students’ attitude was mostly positive when asked about vaccinating their future children.

* * * *

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

PLOS Currents Outbreaks
December 29, 2016 · Research Article
Exploring the Continuum of Vaccine Hesitancy Between African American and White Adults: Results of a Qualitative Study
S Quinn, A Jamison, D Musa, K Hilyard, V Freimuth -, 2016
Abstract
Vaccine delay and refusal present very real threats to public health. Since even a slight reduction in vaccination rates could produce major consequences as herd immunity is eroded, it is imperative to understand the factors that contribute to decision-making about vaccines. Recent scholarship on the concept of “vaccine hesitancy” emphasizes that vaccine behaviors and beliefs tend fall along a continuum from refusal to acceptance. Most research on hesitancy has focused on parental decision-making about childhood vaccines, but could be extended to explore decision-making related to adult immunization against seasonal influenza. In particular, vaccine hesitancy could be a useful approach to understand the persistence of racial/ethnic disparities between African American and White adults. This study relied on a thematic content analysis of qualitative data, including 12 semi-structured interviews, 9 focus groups (N=90), and 16 in-depth interviews, for a total sample of 118 (N=118) African American and White adults. All data were transcribed and analyzed with Atlas.ti. A coding scheme combining both inductive and deductive codes was utilized to identify themes related to vaccine hesitancy. The study found a continuum of vaccine behavior from never-takers, sometimes-takers, and always-takers, with significant differences between African Americans and Whites.  We compared our findings to the Three Cs: Complacency, Convenience, and Confidence framework. Complacency contributed to low vaccine acceptance with both races.  Among sometimes-takers and always-takers, convenience was often cited as a reason for their behavior, while never-takers of both races were more likely to describe other reasons for non-vaccination, with convenience only a secondary explanation.  However, for African Americans, cost was a barrier.  There were racial differences in trust and confidence that impacted the decision-making process. The framework, though not a natural fit for the data, does provide some insight into the differential sources of hesitancy between these two populations. Complacency and confidence clearly impact vaccine behavior, often more profoundly than convenience, which can contribute either negatively or positively to vaccine acceptance. The Three Cs framework is a useful, but limited tool to understanding racial disparities. Understanding the distinctions in those cultural factors that drive lower vaccine confidence and greater hesitancy among African Americans could lead to more effective communication strategies as well as changes in the delivery of vaccines to increase convenience and passive acceptance.
Funding Statement
This research was supported by the Research Center of Excellence in Race, Ethnicity and Health Disparities Research (NIH-NIMHD: P20MD006737; PIs, Quinn and Thomas). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

* * * *

Media/Policy Watch [to 7 January 2017]
This watch section is intended to alert readers to substantive news, analysis and opinion from the general media and selected think tanks and similar organizations on vaccines, immunization, global public health and related themes. Media Watch is not intended to be exhaustive, but indicative of themes and issues CVEP is actively tracking. This section will grow from an initial base of newspapers, magazines and blog sources, and is segregated from Journal Watch above which scans the peer-reviewed journal ecology.

We acknowledge the Western/Northern bias in this initial selection of titles and invite suggestions for expanded coverage. We are conservative in our outlook in adding news sources which largely report on primary content we are already covering above. Many electronic media sources have tiered, fee-based subscription models for access. We will provide full-text where content is published without restriction, but most publications require registration and some subscription level.

Forbes
http://www.forbes.com/
Accessed 7 January 2017
Cleveland Clinic Doctor Goes Full Anti-Vaccine
7 Jan 2017 Tara Haelle, Contributor
The Cleveland Clinic has allowed anti-vaccine advocates to infiltrate its highest ranks.

The Guardian
http://www.guardiannews.com/
Accessed 7 January 2017
Bill Gates: world faces decade at risk from antibiotic-resistant bugs
30 December 2016
Philanthropist says he believes ‘better medical tools’ will come, but until then the world is vulnerable to a pandemic
People across the world, particularly those in developing countries, face a decade at risk from pandemics spread by antibiotic-resistant bugs, the billionaire Bill Gates has warned..

New York Times
http://www.nytimes.com/
Accessed 7 January 2017
China Jails Former Drug Regulatory Official for Taking Bribes: State Media
SHANGHAI — A former official with the China Food and Drug Administration has been jailed for taking bribes from vaccine manufacturers who wanted help with gaining approval for their drugs, the state-owned Legal Evening News
January 04, 2017 – By REUTERS

Philippine FDA Orders Sanofi to Take Down Dengue Vaccine Ads
MANILA, Philippines — The Philippine Food and Drug Administration said Tuesday that it has ordered pharmaceutical giant Sanofi Pasteur Inc. to stop airing television and radio advertisements for its dengue vaccine in violation of a ban on promoting prescription or ethical drugs in mass media.
January 03, 2017 – By THE ASSOCIATED PRESS –

Vaccines and Global Health: The Week in Review

Ebola Vaccines Update
23 December 2016
Center for Vaccine Ethics & Policy (CVEP)

Editor’s Note:
    This is a special update on Ebola vaccine development and trials results as published in The Lancet – Online First on 22 December 2016, led with a 23 December 2016 news release by WHO.
    Vaccines and Global Health: The Week in Review will resume regular publication on 7 January 2017 following the end-of-year holiday period.

::::::
::::::

WHO: Final trial results confirm Ebola vaccine provides high protection against disease
News release
23 December 2016 | GENEVA – An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea, according to results published today in The Lancet. The vaccine is the first to prevent infection from one of the most lethal known pathogens, and the findings add weight to early trial results published last year.

The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11 841 people in Guinea during 2015. Among the 5837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine.

The trial was led by WHO, together with Guinea’s Ministry of Health, Medecins sans Frontieres and the Norwegian Institute of Public Health, in collaboration with other international partners.
“While these compelling results come too late for those who lost their lives during West Africa’s Ebola epidemic, they show that when the next Ebola outbreak hits, we will not be defenceless,” said Dr Marie-Paule Kieny, WHO’s Assistant Director-General for Health Systems and Innovation, and the study’s lead author.

The vaccine’s manufacturer, Merck, Sharpe & Dohme, this year received Breakthrough Therapy Designation from the United States Food and Drug Administration and PRIME status from the European Medicines Agency, enabling faster regulatory review of the vaccine once it is submitted.

Since Ebola virus was first identified in 1976, sporadic outbreaks have been reported in Africa. But the 2013–2016 West African Ebola outbreak, which resulted in more than 11 300 deaths, highlighted the need for a vaccine.

The trial took place in the coastal region of Basse-Guinée, the area of Guinea still experiencing new Ebola cases when the trial started in 2015. The trial used an innovative design, a so-called “ring vaccination” approach – the same method used to eradicate small pox.

When a new Ebola case was diagnosed, the research team traced all people who may have been in contact with that case within the previous 3 weeks, such as people who lived in the same household, were visited by the patient, or were in close contact with the patient, their clothes or linen, as well as certain “contacts of contacts”. A total of 117 clusters (or “rings”) were identified, each made up of an average of 80 people.

Initially, rings were randomised to receive the vaccine either immediately or after a 3-week delay, and only adults over 18 years were offered the vaccine. After interim results were published showing the vaccine’s efficacy, all rings were offered the vaccine immediately and the trial was also opened to children older than 6 years.

In addition to showing high efficacy among those vaccinated, the trial also shows that unvaccinated people in the rings were indirectly protected from Ebola virus through the ring vaccination approach (so called “herd immunity”). However, the authors note that the trial was not designed to measure this effect, so more research will be needed.

“Ebola left a devastating legacy in our country. We are proud that we have been able to contribute to developing a vaccine that will prevent other nations from enduring what we endured,” said Dr KeÏta Sakoba, Coordinator of the Ebola Response and Director of the National Agency for Health Security in Guinea.

To assess safety, people who received the vaccine were observed for 30 minutes after vaccination, and at repeated home visits up to 12 weeks later. Approximately half reported mild symptoms soon after vaccination, including headache, fatigue and muscle pain but recovered within days without long-term effects. Two serious adverse events were judged to be related to vaccination (a febrile reaction and one anaphylaxis) and one was judged to be possibly related (influenza-like illness). All three recovered without any long term effects.

It was not possible to collect biological samples from people who received the vaccine in order to analyse their immune response. Other studies are looking at the immune response to the vaccine including one conducted in parallel to the ring trial among frontline Ebola workers in Guinea.

“This both historical and innovative trial was made possible thanks to exemplary international collaboration and coordination, the contribution of many experts worldwide, and strong local involvement,” said Dr John-Arne Røttingen, specialist director at the Norwegian Institute of Public Health, and the chairman of the study steering group.

In January, GAVI, the Vaccine Alliance provided US$5 million to Merck towards the future procurement of the vaccine once it is approved, prequalified and recommended by WHO. As part of this agreement, Merck committed to ensure that 300 000 doses of the vaccine are available for emergency use in the interim, and to submit the vaccine for licensure by the end of 2017. Merck has also submitted the vaccine to WHO’s Emergency Use and Assessment Listing procedure, a mechanism through which experimental vaccines, medicines and diagnostics can be made available for use prior to formal licensure.

Additional studies are ongoing to provide more data on the safety of the vaccine in children and other vulnerable populations such as people with HIV. In case of Ebola flare-ups prior to approval, access to the vaccine is being made available through a procedure called “compassionate use” that enables use of the vaccine after informed consent. Merck and WHO’s partners are working to compile data to support license applications.

The rapid development of rVSV-EBOV contributed to the development of WHO’s R&D Blueprint, a global strategy to fast-track the development of effective tests, vaccines and medicines during epidemics…

::::::
::::::

The Lancet
Online First
22 December 2016

Articles
Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!)
Ana Maria Henao-Restrepo, Anton Camacho, Ira M Longini, Conall H Watson, W John Edmunds, Matthias Egger, Miles W Carroll, Natalie E Dean, Ibrahima Diatta, Moussa Doumbia, Bertrand Draguez, Sophie Duraffour, Godwin Enwere, Rebecca Grais, Stephan Gunther, Pierre-Stéphane Gsell, Stefanie Hossmann, Sara Viksmoen Watle, Mandy Kader Kondé, Sakoba Kéïta, Souleymane Kone, Eewa Kuisma, Myron M Levine, Sema Mandal, Thomas Mauget, Gunnstein Norheim, Ximena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S Vicari, John-Arne Røttingen, Marie-Paule Kieny
Open Access
PDF: http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)32621-6.pdf
PPT Images: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32621-6/ppt
Summary
Background
rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
Methods
We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.
Findings
In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae.
Interpretation
The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters.
Funding
WHO, UK Wellcome Trust, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway’s GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development).

::::::

Comment
First Ebola virus vaccine to protect human beings?
Thomas W Geisbert
Since the discovery of Ebola virus in 1976, researchers have attempted to develop effective vaccines. Early efforts were largely stalled as a result of the small global market for a vaccine for Ebola virus disease because of an absence of financial incentives for pharmaceutical companies. After the attacks in the USA on Sept 11, 2001, several governments invested in Ebola virus because they had concerns that it could be used as a biological weapon. These investments laid the groundwork for several candidate vaccines for Ebola virus disease that showed promise in preclinical studies in animals.1 Among the most promising vaccines showing protection in the gold standard non-human primate models of Ebola virus disease was a vaccine based on a recombinant vesicular stomatitis virus expressing the Ebola virus glycoprotein (rVSV-ZEBOV).2 Findings from preclinical studies in non-human primates jointly financed by the Public Health Agency of Canada and the US Defense Threat Reduction Agency showed that the rVSV-ZEBOV vaccine could completely protect non-human primates as a preventive vaccine against all medically relevant species of Ebola virus when given as a single-injection vaccine;2, 3 protect 50% of non-human primates against Ebola virus disease when given shortly after exposure;4 and seemed to be safe in non-human primates as evidenced by an absence of serious adverse events in severely immunocompromised animals5 and no evidence of neurovirulence in non-human primates.6

Outbreaks of Ebola virus disease have occurred sporadically, mostly in central Africa since 1976. These outbreaks have been small in size and generally well contained until December, 2013, when the largest recorded outbreak of Ebola virus disease began in the west African country of Guinea and quickly spread to surrounding countries with cases also being exported to Europe and the USA. As the outbreak grew in magnitude and appeared to be uncontained, efforts to use medical counter-measures to intervene intensified. In an Article published in The Lancet, Ana Maria Henao-Restrepo and colleagues follow-up their interim results7 and present the final results of their ring vaccination cluster-randomised trial in Guinea in 2015 to assess the efficacy of a single intramuscular dose of the rVSV-ZEBOV vaccine in the prevention of laboratory confirmed Ebola virus disease.8 The study involved vaccinating a ring of all contacts and contacts of contacts of confirmed cases of Ebola virus disease, either immediately or delayed to 21 days after randomisation. Briefly, 2119 contacts and contacts of contacts in 51 clusters randomly allocated, and 1677 contacts and contacts of contacts in 19 non-randomised clusters were immediately vaccinated, and 2041 contacts and contacts of contacts in 47 randomised clusters received a delayed vaccination 21 days after randomisation. Importantly, no cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters compared with 16 cases in those in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045). Vaccine efficacy was also 100% in the non-randomised clusters (95% CI 79·3–100·0, p=0·0033). These data strongly suggest that the rVSV-ZEBOV vaccine was effective in protecting against Ebola virus infection and probably contributed to controlling the 2013–16 outbreak of Ebola virus disease in Guinea.

Protective efficacy is clearly the strength of the study by Henao-Restrepo and colleagues. There have been concerns in the past regarding the safety profile of rVSV-ZEBOV because it is a replication-competent vaccine. In this study, the investigators identified 80 serious adverse events, of which only two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness), with all three cases recovering without sequelae. Conflicting safety results have been reported from phase I clinical trials of the rVSV-ZEBOV vaccine with oligoarthritis being reported in 13 of 51 low-dose vaccines in one study.9 No significant adverse events have been reported in other phase 1 studies.10 Although rVSV-ZEBOV seems to be highly efficacious and safe in the context of an outbreak, some questions remain. One question that has not been adequately addressed, even in non-clinical studies with any Ebola virus vaccine, is with regard to durability—is the vaccine long-lasting? Is it still protective, for example, 2–3 years after the vaccination? Another question is in regard to improvements in safety: clearly, the VSV-based Ebola virus vaccines appear to be the lead candidates for use in human beings, but can they be further attenuated to reduce the number of adverse events noted in phase 1 trials without reducing efficacy? Results of preclinical studies in non-human primates suggest that this attenuation might be possible.11

After 40 years we appear to now have an effective vaccine for Ebola virus disease to build upon. This success has been achieved by leveraging findings from published preclinical studies to justify the use of the rVSV-ZEBOV vaccine during an outbreak without the need for time-consuming and costly good laboratory practices (GLP) or GLP-like preclinical studies required by regulatory policies such as the US FDA Animal Rule,12 that although well intentioned, are impractical and inefficient in the context of the few high containment biosafety level 4 laboratories that exist worldwide (ie, laboratories that use the highest level of biosafety precautions and where, in most cases, workers wear positive pressure suits to work the with most hazardous viruses such as Ebola virus).

I have five US patents in the fields of filovirus and antiviral vaccines, including Ebola virus disease, and two provisional US patents: number 7635485, entitled “Method of accelerated vaccination against Ebola viruses” issued to G Nabel, N Sullivan, P Jahrling, and TW Geisbert on Dec 22, 2009, issued to the US government; number 7838658, entitled “siRNA silencing of filovirus gene expression” issued to I MacLachlan, V Sood, LE Hensley, E Kagan, and TW Geisbert on Nov 23, 2010, issued to Tekmira Pharmaceuticals and the US government; number 8017130 entitled “Method of accelerated vaccination against Ebola viruses” issued to G Nabel, N Sullivan, P Jahrling, and TW Geisbert on Sept 13, 2011, issued to US Government; number 8716464, entitled “Compositions and methods for silencing Ebola virus gene expression” issued to TW Geisbert, ACH Lee, M Robbins, V Sood, A Judge, LE Hensley, and I MacLachlan, on May 6, 2014, issued to Tekmira Pharmaceuticals and US Government; and number 8796013 entitled “Pre- or post-exposure treatment for filovirus or arenavirus infection” issued to TW Geisbert on Aug 5, 2014, issued to Boston University and Profectus Biosciences. I also have two patent provisional US patents: 61/014669 filed Feb 8, 2008, by TW Geisbert pending to Boston University, entitled “Compositions and methods for treating Ebola virus infection”, and 61/070748 filed March 25, 2008, by TW Geisbert, JH Connor, and H Ebihara pending to Boston University, entitled “Multivalent vaccine vector for the treatment and inhibition of viral infection.

References: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32618-6/fulltext

::::::

Comment
Safety and immunogenicity of a recombinant adenovirus vector-based Ebola vaccine
Martin P Grobusch, Abraham Goorhuis
Summary
The 2013–16 epidemic of Ebola virus disease in west Africa was a game changer—not only in terms of the location and dimension of the outbreak and with regards to many painful lessons learnt about the epidemiology, features, and management of the disease, but also in terms of furthering the development of monoclonal antibody treatments1,2 and, most importantly, vaccines. Besides the replicative vector-based rVSV-ZEBOV vaccine,3,4 which has yielded high efficacy in an interim analysis of an open-label, cluster-randomised ring vaccination trial in Guinea,5 a range of other candidate vaccines have progressed into clinical development.

::::::

Articles
Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial
Feng-Cai Zhu, Alie H Wurie, Li-Hua Hou, Qi Liang, Yu-Hua Li, James B W Russell, Shi-Po Wu, Jing-Xin Li, Yue-Mei Hu, Qiang Guo, Wen-Bo Xu, Abdul R Wurie, Wen-Juan Wang, Zhe Zhang, Wen-Jiao Yin, Manal Ghazzawi, Xu Zhang, Lei Duan, Jun-Zhi Wang, Wei Chen
Summary
Background
A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose.
Methods
We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone–China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18–50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 1011 viral particles), low-dose vaccine (8·0 × 1010 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed.
Findings
During Oct 10–28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 [26%] in high-dose group and 31 [25%] in low-dose group) than in those receiving placebo (17 [14%]; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 [95% CI 976·6–1602·5] in low-dose group and 1728·4 [1459·4–2047·0] in high-dose group) and peaked at day 28 (1471·8 [1151·0–1881·8] and 2043·1 [1762·4–2368·4]), but declined quickly in the following months (223·3 [148·2–336·4] and 254·2 [185·0–349·5] at day 168). Geometric mean titres in the placebo group remained around 6·0–6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine.
Interpretation
The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 1010 viral particles was the optimal dose.
Funding
Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

* * * *
* * * *

Vaccines and Global Health: The Week in Review is a service of the Center for Vaccines Ethics and Policy (CVEP) which is solely responsible for its content, and is an open access publication, subject to the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/). Copyright is retained by CVEP.

CVEP is a program of the GE2P2 Global Foundation – whose purpose and mission is to advance ethical and scientific rigor in research and evidence generation for governance, policy and practice in health, human rights action, humanitarian response, heritage stewardship, education and sustainable development – serving governments, international agencies, INGOs, civil society organizations (CSOs), commercial entities, consortia and alliances. CVEP maintains an academic affiliation with the Division of Medical Ethics, NYU School of Medicine, and an operating affiliation with the Vaccine Education Center of Children’s Hospital of Philadelphia [CHOP].

Support for this service is provided by the Bill & Melinda Gates Foundation; Aeras; PATH; the International Vaccine Institute (IVI); and industry resource members Crucell/Janssen/J&J, Pfizer, PRA Health Sciences, Sanofi Pasteur U.S.,Takeda, Valera (list in formation), and the Developing Countries Vaccine Manufacturers Network (DCVMN).

Support is also provided by a growing list of individuals who use this membership service to support their roles in public health, clinical practice, government, NGOs and other international institutions, academia and research organizations, and industry.

* * * *
* * * *

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

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

– pdf version:  A pdf of the current issue is available here: vaccines-and-global-health_the-week-in-review_17-december-2016

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

– 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 this knowledge-sharing service: Your financial support helps us cover our costs and to address a current shortfall in our annual operating budget. Click here to donate and thank you in advance for your contribution.

Editor’s Note:
Vaccines and Global Health: The Week in Review will resume publication on 7 January 2017 following the end-of-year holiday period.

.
David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy

African Union [to 17 December 2016]
http://www.au.int/en/
November 30, 2016   Press Releases
Dr. John Nkengasong named first director of Africa CDC
Addis Ababa, Ethiopia – The Governing Board of the Africa Centers for Diseases Control and Prevention (Africa CDC) is pleased to announce that Dr. John Nkengasong, PhD, MSc, a seasoned virologist, has been named as the first Director of the Africa CDC effective January 1, 2017.

Dr. Nkengasong brings a wealth of public and global health experience to his new role. He currently serves as the Acting Deputy Principal Director for the Center for Global Health (CGH) at the United States Centers for Disease Control and Prevention (CDC) in Atlanta, GA. He joined CDC more than 20 years ago and has directed the laboratory programs for the Division of Global HIV and TB, and the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) to support diverse programs in partner’s countries in several countries in Africa, South East Asia, Central America, and the Caribbean.

“The Africa CDC offers a monumental opportunity to strengthen public health capacity on the continent to respond to the threats we face. The institution will provide strategic direction and promote public health practices within Member States through capacity building, promotion of continuous quality improvement in the delivery of public health services as well in the prevention of public health emergencies and threats”, said Professor Isaac Adewole, Minister of Health of the Federal Republic of Nigeria, who serves as the vice chair of the Governing Board…

:::::::
:::::::

CEPI Joint Coordination Group – First Meeting Report
Coalition for Epidemic Preparedness Innovations (CEPI)
The first meeting of the CEPI Joint Coordination Group was held in Geneva November 18, 2016 where members of the JCG and invited observers participated. The attending organizations contributed with expertise and experiences in furtherance of fulfilling the CEPI mission by discussing alignment of activities, and making recommendations for how CEPI can best coordinate vaccine development for EID along the ‘end-to-end’ spectrum.
:: Agenda
:: Summary of proceedings
High Level Summary
Purpose
Inform about the first JCG meeting, which intended to; clarify and discuss roles and responsibilities of the JCG, update stakeholders on CEPIs work and progress, get feedback on how CEPI should proceed and what considerations to take when working in the end-to-end spectrum.

Key considerations
:: More clarity on the regulatory pathway is sought, as fast approval during outbreak is crucial. CEPI should support and facilitate a regulatory harmonization, but not take on a normative or direct coordinating role. Others should fulfil the latter.
:: Funding and shared risks/rewards: Need guarantee for industry that no loss will incur by
engaging. Some point at the necessity for allowing a small profit margin, in particular to ensure
sustainability for smaller biotech companies, even if it might impede accessibility. Others
disagree. Value-based pricing is discussed.
:: To securing a diverse preclinical pipeline, CEPI should focus on what others are not. Focus on
platform technologies and lead head-to head comparisons. Benchmarking is important in several aspects, and standardization and reference labs should therefore be considered.
:: CEPI will play an important role in aligning investments and actors for clinical development and trials. Pull mechanisms, the use of prices and milestone payments should also be considered.
:: In preparedness phase, CEPI could create clinical trial centers of excellence and a network of
investigator sites to build capacity and preparedness in LMIC. Consider doing efficacy trials
outside of outbreaks.
:: Strong national level and community engagement necessary in countries when outbreaks occur. Ethical standards to be upheld.
:: Secure stockpiles for emergency use and containment of outbreak: aligning interest with
procurement agencies will be important. Transparency is necessary for more accurate forecasting of stockpile needs. Consider mechanisms for reserved manufacturing capabilities.
:: Strong appetite for setting up working groups. No objections to reconstituting the JCG into a
smaller and more technical group, possibly also extending with additional meetings.

:::::::
:::::::