Journal of Pediatrics
May 2017 Volume 184, p1-246
http://www.jpeds.com/current

Original Articles
Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study
Stefan Schandelmaier, Yuki Tomonaga, Dirk Bassler, Joerg J. Meerpohl, Erik von Elm, John J. You, Anette Bluemle, Francois Lamontagne, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Mihaela Stegert, Kelechi K. Olu, Kari A.O. Tikkinen, Ignacio Neumann, Alonso Carrasco-Labra, Markus Faulhaber, Sohail M. Mulla, Dominik Mertz, Elie A. Akl, Xin Sun, Jason W. Busse, Ignacio Ferreira-González, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Per O. Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Gordon Guyatt, Heiner C. Bucher, Benjamin Kasenda, Matthias Briel
p209–214.e1
Published online: March 4, 2017
Abstract
Objectives
To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs.
Study design
A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists.
Results
We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants).
Conclusion
Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.

The Lancet
May 06, 2017 Volume 389 Number 10081 p1771-1858
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Research integrity—have we made progress?
The Lancet
Published: 06 May 2017
DOI: http://dx.doi.org/10.1016/S0140-6736(17)31201-1

This month there will be two important anniversaries related to research integrity. The first is the 20 year anniversary of the Committee on Publication Ethics (COPE), celebrated at COPE’s European annual meeting in London, UK, on May 25. The second marks 10 years since the first World Conference on Research Integrity (WCRI) in Lisbon, Portugal, in 2007—to be held at the fifth WCRI in Amsterdam, Netherlands, May 28–31. More than 600 delegates will gather and present research on research integrity and debate current policies and initiatives, progress, and difficulties. The conference theme is transparency and accountability. So what have these initiatives and organisations achieved and what is the current state of research integrity?

Compared with 20 years ago there is undoubtedly more discussion and awareness of research misconduct. There is more research into research integrity and inappropriate research practice. And there is more guidance and support for those researchers, funders, institutions, and journals that want to have good policies, practices, and processes in place. However, there are depressingly familiar examples that show we still have a long way to go to strengthen research integrity and publication ethics. Every day, dubious new journals and conference organisers solicit papers and presentations for a fee. The rise of such predatory journals and conferences is a disappointingly unsavoury by-product of the open access business model.

On April 20, the publisher Springer retracted a record 107 papers from one journal (Tumor Biology) because they had been accepted after fake peer review. These papers were discovered after additional screening as a consequence of an earlier round of retractions, but clearly stronger editorial practices could have detected these fatal flaws before publication. And last week, the investigators of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, originally published in the New England Journal of Medicine in 2014, concluded in a correspondence letter in the journal that after further experiments the findings “arouse concerns regarding study conduct in Russia, and by implication, Georgia”—an example of a multicountry collaboration gone wrong.

Additionally, there are worrying signs that the research environment, which was highlighted at the last WCRI conference in Rio de Janeiro, Brazil, in 2015, as an important factor to promote and ensure responsible research, is becoming more competitive and less resilient. The uncertainty over long-term National Institute of Health funding in the USA sent shock waves through the scientific community. Similar concerns by Canadian scientists have emerged over the past few months where research funding is stagnating and increasingly linked to political priorities. And many researchers in the UK are concerned about European Union funding after Brexit.

So what can be done? A new report by the US National Academies of Sciences, Engineering, and Medicine—Fostering Integrity in Research, released on April 11—produced best practice checklists and issued 11 recommendations. Most of these are obvious and do not cover new ground, such as whistleblower protection and improved education. What the report does add beyond summarising the state of integrity and best practice recommendations is clearer and stronger language. It terms what has previously been called questionable or inappropriate research practices “detrimental practices”, recognising these to be detrimental to the research enterprise. Similarly, the World Association of Medical Editors earlier this year argued that a better name for predatory journals would be pseudo-journals to clearly identify them as destinations that researchers should avoid. And when there are outcries about the so-called reproducibility crisis, it should be understood that reproducibility is used in many different ways, which leads to confusion and disagreement. Steven Goodman concluded in Science Translational Medicine in June, 2016, that “we need to move toward a better understanding of the relationship between reproducibility, cumulative evidence, and the truth of scientific claims”.

The Amsterdam conference theme is a good one. Transparency and accountability are the fundamental principles for research integrity. Transparency in describing all aspects of the research process, from planning, proposing, performing, and reporting, goes a long way towards allowing better selection, scrutiny, and use of research. Such quality assessment needs to be at the heart of academic reward. What we do need also, however, is transparency of policies for all involved in research —institutions, funders, and journals alike—to allow a similar level of assessment and scrutiny by others. Accountability needs to be shared by all

The Lancet
May 06, 2017 Volume 389 Number 10081 p1771-1858
http://www.thelancet.com/journals/lancet/issue/current

Editorial
The next chapter in malaria eradication
The Lancet
Published: 06 May 2017
DOI: http://dx.doi.org/10.1016/S0140-6736(17)31203-5
The narrative around combating malaria has long been equal parts optimism and pessimism. Remarkably, it was only a decade ago that Bill and Melinda Gates made the game-changing call for the eradication of malaria. Previous control efforts to reduce the burden, particularly in low-resource, malaria-endemic countries in sub-Saharan Africa, were limited by poor access to tools such as insecticide-treated nets, and faced rapidly drug-resistant strains of the highly lethal Plasmodium falciparum parasite requiring treatment with costly artemisinin-combination therapies. The proclamation that eradicating malaria was an achievable goal met with stern criticism at the time, but nevertheless spurred massive increases in international funding commitments and served as a lever to shift the then overarching malaria policy towards a common goal of eradication. It also resulted in the introduction of RTS,S, the first candidate malaria vaccine to yield promising safety and efficacy results and to be recommended by both the Strategic Advisory Group of Experts on Immunization and the Malaria Policy Advisory Committee.

Turning a page in the story of malaria, on April 24, 2017, the WHO Regional Office for Africa (WHO/AFRO) announced a pilot implementation programme beginning in 2018. The RTS,S vaccine will be available in three African countries—Ghana, Kenya, and Malawi—chosen for having mature existing immunisation programmes and high coverage of insecticide-treated nets, yet with persistently high malaria burdens. Although the availability and roll out of the RTS,S vaccine is a remarkable achievement, the decision to implement the pilot programme at this stage is not without controversy. Critics have pointed out several serious shortcomings, including the intensive regimen (three injected doses at months 0, 1, and 2, and a booster dose at month 20), which could be unfeasible outside of rigorously controlled clinical trials, as well as waning efficacy over time.

Cautious optimism is understandable, but it must be emphasised that the vaccine is but one additional tool in the current limited armamentarium for making progress against malaria. Adequate support and scrupulous monitoring will determine whether the pilot programme is a success or a cautionary tale.

Lancet Global Health
May 2017 Volume 5 Number 5 e467-e555
http://www.thelancet.com/journals/langlo/issue/current

Comment
Introducing The Lancet Global Health Commission on High-Quality Health Systems in the SDG Era
Margaret E Kruk, Muhammad Pate, Zoë Mullan
The Millennium Development Goals on health have expanded access to basic health interventions to millions of people in low-income and middle-income countries (LMICs). However, access alone will not be sufficient to meet the Sustainable Development Goals (SDGs) if health systems cannot provide high quality care—ie, care that improves health outcomes and provides value to people. Emerging data show that many LMIC health systems struggle to consistently provide good quality of care.1, 2 Yet change is possible. Primary health-care facilities, which tend to reach the poorest segment of populations, are an important plank in the drive towards achieving the SDGs. In Nigeria, supporting primary health-care centres in rural areas with quality assessment, an action plan, and technical assistance in management resulted in significant improvements in adoption of quality practices.3

Health system quality in lower-income countries has been under-defined and under-researched. There is no agreed upon single definition of a high-quality health system or its aims and there is no consensus on metrics. Instead, many countries face a proliferation of definitions and measures across disease areas. The emphasis in quality measurement has been on inputs: equipment, medicines, staff. Yet, this does not paint the full picture of quality—a well-equipped facility may still provide poor care. And patients’ experience of care and patient-reported outcomes, which influence people’s decisions to use or avoid services and provide valuable insights on performance, are rarely measured. There is little information on national and regional levels of quality and its distribution, weak evidence on the factors that drive quality variations, and low effectiveness of current quality improvement approaches. Finally, there is an urgent need to expand the solution space for quality improvement: to move beyond in-service training and other clinic-focused approaches to consider structural solutions, such as service regionalisation, updating medical and nursing education, technological innovation, and strengthening professional and community oversight of care.

To galvanise research and action on quality of care in LMIC health systems, The Lancet Global Health has commissioned a major report: The Lancet Global Health Commission on High-Quality Health Systems in the SDG Era (HQSS Commission). This will be a piece of science-led, multidisciplinary, actionable work with wide-reaching goals and measurable indicators, and will embody the journal’s commitment to “the best science for better lives”. The HQSS Commission will be chaired by Margaret Kruk and Muhammad Pate and brings together 30 academics, policymakers, and health system experts from 18 countries. Guided by the values of originality, rigour, relevance, and respect for local context and actors, the Commission will review current

and improving quality in pursuit of the SDGs. It will produce a single conceptual framework of high-quality health systems to increase the salience of the concept to policymakers, providers, and people. It will build on and inform the work of other ongoing efforts including Countdown to 2030; the Health Data Collaborative; the Quality, Equity, and Dignity Network; and the Primary Health Care Performance Initiative.

The Commission’s specific aims are to (1) define health system quality, (2) describe quality of care and its distribution across tracer SDG conditions, (3) propose practical measures of quality, and (4) identify structural approaches to improve quality. The work will be underpinned by an exploration of the ethical dimensions of quality, including the right to quality health-care and equity. The analysis will be done by four Commission working groups, shown in the panel. The HQSS Commission will hold its first meeting on March 13–15, 2017, in Boston, USA, convening the commissioners and an Advisory Council of experts and global partners.

Lancet Global Health
May 2017 Volume 5 Number 5 e467-e555
http://www.thelancet.com/journals/langlo/issue/current

Articles
Pathways between childhood trauma, intimate partner violence, and harsh parenting: findings from the UN Multi-country Study on Men and Violence in Asia and the Pacific
Emma Fulu, Stephanie Miedema, Tim Roselli, Sarah McCook, Ko Ling Chan, Regine Haardörfer, Rachel Jewkes on behalf of the UN Multi-country Study on Men and Violence study team

Articles
Measuring Iran’s success in achieving Millennium Development Goal 4: a systematic analysis of under-5 mortality at national and subnational levels from 1990 to 2015
Younes Mohammadi, Mahboubeh Parsaeian, Parinaz Mehdipour, Ardeshir Khosravi, Bagher Larijani, Ali Sheidaei, Anita Mansouri, Amir Kasaeian, Kamran Yazdani, Maziar Moradi-Lake, Elaheh Kazemi, Saeideh Aghamohammadi, Nazila Rezaei, Maryam Chegini, Rosa Haghshenas, Hamidreza Jamshidi, Farnaz Delavari, Mohsen Asadi-Lari, Farshad Farzadfar

Articles
Progress and inequities in maternal mortality in Afghanistan (RAMOS-II): a retrospective observational study
Linda Bartlett, Amnesty LeFevre, Linnea Zimmerman, Sayed Ataullah Saeedzai, Sabera Torkamani, Weeda Zabih, Hannah Tappis, Stan Becker, Peter Winch, Marge Koblinsky, Ahmed Javed Rahmanzai

Lancet Infectious Diseases
May 2017 Volume 17 Number 5 p461-562 e128-e165
http://www.thelancet.com/journals/laninf/issue/current

Editorial
Is malaria elimination within reach?
The Lancet Infectious Diseases
Published: May 2017
DOI: http://dx.doi.org/10.1016/S1473-3099(17)30197-4

Released on March 24, in ample time for World Malaria Day on April 25, WHO’s A Framework for Malaria Elimination is the first time WHO returns to this significant topic since 2007. Given the launch of this update to the framework it is fitting that the theme for World Malaria Day will ambitiously be “End Malaria for Good”. Within the theme of ending malaria for good there will be particular focus on prevention through the use of insecticide-treated nets and indoor spraying. Prevention has been a significant factor in the reduction of infections and deaths over the past 17 years.

Crucially, WHO has avoided a rigid approach to its framework, acknowledging the need for ongoing revision should new tools and strategies emerge. Pedro Alonso, Director of the Global Malaria Programme, emphasises that the framework does not offer a one size fits all approach; each country is to tailor the interventions to suit local needs. This flexibility is refreshingly pragmatic and stands a greater chance of success.

One tangible gap in the framework is its focus on only two species of the human malaria parasite: Plasmodium falciparum and Plasmodium vivax. The other species (Plasmodium malariae, Plasmodium ovale, and the zoonotic Plasmodium knowlesi) get scant mention. When some species are not factored into the equation it becomes difficult to understand how the ultimate aim of elimination can be achieved. However, taking such a critical view might allow the best to become the enemy of the good. The opening paragraph of the framework lays out why the focus is on P falciparum and P vivax: they pose the greatest threat. And the inclusion of P vivax is a notable advance given this was once considered a neglected parasite.

Nonetheless, the promotion of a strategy that is not comprehensive does risk saving up problems for the future.

To reach the milestones of WHO’s Global Technical Strategy 2016–2030, the pace of progress must be rapidly accelerated. Progress has been particularly difficult in low-income countries. It does not take an inspired leap of imagination to grasp that funding is a limiting factor—in 2015, requirements to support malaria programmes were forecast at US$6·4 billion by 2020, $7·7 billion by 2025, and $8·7 billion by 2030. Thankfully, as noted in the January Editorial in this journal, despite early concerns about the incoming US administration, crucial investment from the USA is likely to be forthcoming, which sends a powerful signal to other partners.

In 2015, when the millennium development goal for malaria was declared met, many stakeholders were at pains to express that this achievement was only the end of the beginning and too soon for any sort of victory celebration. That the framework still focuses on the low-hanging fruit of “areas of low transmission that are progressing to zero” highlights how much there is still to do. Adding to the complexity of the task ahead is the emergence of antimalarial resistance. In this issue, Mallika Imwong and colleagues chronicle the spread of artemisinin-resistant P falciparum in the Greater Mekong subregion. Their worrying conclusion is that elimination of P falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective. Although not part of the new framework, WHO did release a strategy specific to this region in November, 2016.

A section on innovation and research rounds out the framework, providing a very brief outline of ongoing work. Substantial advances have been made. For example, in this issue Mahamadou Sissoko, Sara Healy, and colleagues report for the first time on the safety and efficacy of a P falciparum sporozoite vaccine in the field. Also, progress is being made in the development of new treatments. Recently online in The Lancet Infectious Diseases, James McCarthy and colleagues and Mihály Sulyok and colleagues reported early trials of a new, long-lasting antimalarial, DSM265. Although clearly at an early stage of development, a new treatment offers some hope that it might be possible to keep pace with the emergence of antimalarial resistance.

A notable addition to the framework is the outlining of the requirements for achieving and maintaining malaria elimination. Included among these requirements is a greater emphasis on health systems. If applied with care, this focus on health systems could have broader benefits than on malaria alone. As with any document aimed at policymakers, the aims (ie, elimination) can seem very ambitious; however, as evident from progress so far, ambition is a strategy that has served the malaria community well.

Lancet Infectious Diseases
May 2017 Volume 17 Number 5 p461-562 e128-e165
http://www.thelancet.com/journals/laninf/issue/current

Comment
Cholera vaccination: pregnant women excluded no more
Pedro L Moro, Lakshmi Sukumaran
Summary
Cholera is a serious dehydrating diarrhoeal disease caused by toxigenic serogroups (O1 and O139) of Vibrio cholerae, which is spread by faecal contamination of water and food. It is a disease of poverty and is closely linked to poor sanitation and lack of clean water.1 Cholera affects up to 2·8 million people and kills approximately 91 000 each year.2 Children aged younger than 5 years have the greatest incidence of disease in endemic areas. Among pregnant women, cholera can cause serious complications—namely, fetal loss, with rates varying from 2% to 36%.

Articles
The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study
Mallika Imwong, Kanokon Suwannasin, Chanon Kunasol, Kreepol Sutawong, Mayfong Mayxay, Huy Rekol, Frank M Smithuis, Tin Maung Hlaing, Kyaw M Tun, Rob W van der Pluijm, Rupam Tripura, Olivo Miotto, Didier Menard, Mehul Dhorda, Nicholas P J Day, Nicholas J White, Arjen M Dondorp
Open Access

Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial
Mahamadou S Sissoko, Sara A Healy, Abdoulaye Katile, Freda Omaswa, Irfan Zaidi, Erin E Gabriel, Bourama Kamate, Yacouba Samake, Merepen A Guindo, Amagana Dolo, Amadou Niangaly, Karamoko Niaré, Amatigue Zeguime, Kourane Sissoko, Hama Diallo, Ismaila Thera, Kelly Ding, Michael P Fay, Elise M O’Connell, Thomas B Nutman, Sharon Wong-Madden, Tooba Murshedkar, Adam J Ruben, Minglin Li, Yonas Abebe, Anita Manoj, Anusha Gunasekera, Sumana Chakravarty, B Kim Lee Sim, Peter F Billingsley, Eric R James, Michael Walther, Thomas L Richie, Stephen L Hoffman, Ogobara Doumbo, Patrick E Duffy

Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial
Angela Huttner, Christoph Hatz, Germie van den Dobbelsteen, Darren Abbanat, Alena Hornacek, Rahel Frölich, Anita M Dreyer, Patricia Martin, Todd Davies, Kellen Fae, Ingrid van den Nieuwenhof, Stefan Thoelen, Serge de Vallière, Anette Kuhn, Enos Bernasconi, Volker Viereck, Tilemachos Kavvadias, Kerstin Kling, Gloria Ryu, Tanja Hülder, Sabine Gröger, David Scheiner, Cristina Alaimo, Stephan Harbarth, Jan Poolman, Veronica Gambillara Fonck

Lancet Infectious Diseases
May 2017 Volume 17 Number 5 p461-562 e128-e165
http://www.thelancet.com/journals/laninf/issue/current

Safety of a killed oral cholera vaccine (Shanchol) in pregnant women in Malawi: an observational cohort study
Mohammad Ali, Allyson Nelson, Francisco J Luquero, Andrew S Azman, Amanda K Debes, Maurice Mwesawina M’bang’ombe, Linly Seyama, Evans Kachale, Kingsley Zuze, Desire Malichi, Fatima Zulu, Kelias Phiri Msyamboza, Storn Kabuluzi, David A Sack
Summary
Background
Pregnancy increases the risk of harmful effects from cholera for both mothers and their fetuses. A killed oral cholera vaccine, Shanchol (Shantha Biotechnics, Hydrabad, India), can protect against the disease for up to 5 years. However, cholera vaccination campaigns have often excluded pregnant women because of insufficient safety data for use during pregnancy. We did an observational cohort study to assess the safety of Shanchol during pregnancy.
Methods
This observational cohort study was done in two adjacent districts (Nsanje and Chikwawa) in Malawi. Individuals older than 1 year in Nsanje were offered oral cholera vaccine during a mass vaccination campaign between March 30 and April 30, 2015, but no vaccines were administered in Chikwawa. We enrolled women who were exposed to oral cholera vaccine during pregnancy in Nsanje district, and women who were pregnant in Chikwawa district (and thus not exposed to oral cholera vaccine) during the same period. The primary endpoint of our analysis was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were neonatal deaths and malformations. We evaluated these endpoints using log-binomial regression, adjusting for the imbalanced baseline characteristics between the groups. This study is registered with ClinicalTrials.gov, number NCT02499172.
Findings
We recruited 900 women exposed to oral cholera vaccine and 899 women not exposed to the vaccine between June 16 and Oct 10, 2015, and analysed 835 in each group. 361 women exposed to the vaccine and 327 not exposed to the vaccine were recruited after their pregnancies had ended. The incidence of pregnancy loss was 27·54 (95% CI 18·41–41·23) per 1000 pregnancies among those exposed to the vaccine and 21·56 (13·65–34·04) per 1000 among those not exposed. The adjusted relative risk for pregnancy loss among those exposed to oral cholera vaccine was 1·24 (95% CI 0·64–2·43; p=0·52) compared with those not exposed to the vaccine. The neonatal mortality rate was 11·78 (95% CI 5·92–23·46) per 1000 livebirths for infants whose mothers were exposed to oral cholera vaccine versus 8·91 (4·02–19·77) per 1000 livebirths for infants whose mothers were not exposed to the vaccine (crude relative risk 1·32, 95% CI 0·46–3·84; p=0·60). Only three newborn babies had malformations, two in the vaccine exposure group and one in the no-exposure group, yielding a relative risk of 2·00 (95% CI 0·18–22·04; p=0·57), although this estimate is unreliable because of the small number of outcomes.
Interpretation
Our study provides evidence that fetal exposure to oral cholera vaccine confers no significantly increased risk of pregnancy loss, neonatal mortality, or malformation. These data, along with findings from two retrospective studies, support use of oral cholera vaccine in pregnant women in cholera-affected regions.
Funding
Bill & Melinda Gates Foundation

Lancet Public Health
May 2017 Volume 2 Number 5 e202-e246
http://thelancet.com/journals/lanpub/issue/current

Articles
Progress and prospects for the control of HIV and tuberculosis in South Africa: a dynamical modelling study
Brian G Williams, Somya Gupta, Matthew Wollmers, Reuben Granich
Summary
Background
In September, 2016, South Africa adopted a policy of providing antiretroviral treatment to everyone infected with HIV irrespective of their CD4 cell count. Studies of universal treatment and expanded prevention of HIV differ widely in their projections of effects and the associated costs, so we did this analysis to attempt to find a consensus.
Methods
We used data on HIV from the Joint UN Programme on HIV and AIDS (UNAIDS) from 1988 to 2013 and from data from WHO on tuberculosis from 1980 to to 2013 to fit a dynamical model to time trends in HIV prevalence, antiretroviral therapy (ART) coverage, and tuberculosis notification rates in South Africa. We then used the model to estimate current trends and project future patterns in HIV prevalence and incidence, AIDS-related mortality, and tuberculosis notification rates, and we used data from the South African National AIDS Council to assess current and future costs under different combinations of treatment and prevention approaches. We considered two treatment strategies: the Constant Effort strategy, in which people infected with HIV continue to start treatment at the rate in 2016, and the Expanded Treatment and Prevention (ETP) strategy, in which testing rates are increased, treatment is started immediately after HIV is detected, and prevention programmes are expanded.
Findings
Our estimates show that HIV incidence among adults aged 15 years or older fell from 2·3% per year in 1996 to 0·65% per year in 2016, AIDS-related mortality decreased from 1·4% per year in 2006 to 0·37% per year in 2016, and both continue to fall at a relative rate of 17% per year. Our model shows that maintenance of Constant Effort will have a substantial effect on HIV but will not end AIDS, whereas ETP could end AIDS by 2030, with incidence of HIV and AIDs-related mortality rates both at less than one event per 1000 adults per year. Under ETP the annual cost of health care and prevention will increase from US$2·3 billion in 2016 to $2·9 billion in 2018, then decrease to $1·7 billion in 2030 and $0·9 billion in 2050. Over the next 35 years, the expansion of treatment will avert an additional 3·8 million new infections, save 1·1 million lives, and save $3·2 billion compared with continuing Constant Effort up to 2050. Expansion of prevention, including provision of pre-exposure prophylaxis, condom distribution, and male circumcision, could avert a further 150 000 new infections, save 5000 lives, and cost an additional $5·7 billion compared with Constant Effort.
Interpretation
Our results suggest that South Africa is on track to reduce HIV incidence and AIDS-related mortality substantially by 2030, saving both lives and money. Success will depend on high rates of HIV testing, ART delivery and adherence, good patient monitoring and support, and data to monitor progress.
Funding
None.

Maternal and Child Health Journal
Volume 21, Issue 5, May 2017
http://link.springer.com/journal/10995/21/5/page/1

From the Field
Knowledge, Attitudes and Perceptions About Routine Childhood Vaccinations Among Jewish Ultra-Orthodox Mothers Residing in Communities with Low Vaccination Coverage in the Jerusalem District
Chen Stein Zamir, Avi Israeli
Abstract
Background and aims
Childhood vaccinations are an important component of primary prevention. Maternal and Child Health (MCH) clinics in Israel provide routine vaccinations without charge. Several vaccine-preventable-diseases outbreaks (measles, mumps) emerged in Jerusalem in the past decade. We aimed to study attitudes and knowledge on vaccinations among mothers, in communities with low immunization coverage.
Methods
A qualitative study including focus groups and semi-structured interviews. Results Low immunization coverage was defined below the district’s mean (age 2 years, 2013) for measles-mumps-rubella-varicella 1st dose (MMR1\MMRV1) and diphtheria-tetanus-pertussis 4th dose (DTaP4), 96 and 89%, respectively. Five communities re included, all were Jewish ultra-orthodox. The mothers’ (n=87) median age was 30 years and median number of children 4. Most mothers (94%) rated vaccinations as the main activity in the MCH clinics with overall positive attitudes. Knowledge about vaccines and vaccination schedule was inadequate. Of vaccines scheduled at ages 0–2 years (n=13), the mean number mentioned was 3.9 ± 2.8 (median 4, range 0–9). Vaccines mentioned more often were outbreak-related (measles, mumps, polio) and HBV (given to newborns). Concerns about vaccines were obvious, trust issues and religious beliefs were not. Vaccination delay was very common and timeliness was considered insignificant. Practical difficulties in adhering to the recommended schedule prevailed. The vaccinations visits were associated with pain and stress. Overall, there was a sense of self-responsibility accompanied by inability to influence others.
Conclusion
Investigating maternal knowledge and attitudes on childhood vaccinations provides insights that may assist in planning tailored intervention programs aimed to increase both vaccination coverage and timeliness.

Original Paper
Vaccination Coverage and Timelines Among Children 0–6 Months in Kinshasa, the Democratic Republic of Congo: A Prospective Cohort Study
Paul N. Zivich, Landry Kiketa, Bienvenu Kawende…

Nature Medicine
May 2017, Volume 23 No 5 pp527-643
http://www.nature.com/nm/journal/v23/n5/index.html

Editorial
The curse of uncertainty
doi:10.1038/nm.4342
Proposed US budget cuts and the impending exit of the UK from the European Union have the potential to destabilize the global biomedical-research enterprise. In the meantime, the uncertainty of not knowing just how bad the effects will be will inflict its own damage.

New England Journal of Medicine
May 4, 2017  Vol. 376 No. 18
http://www.nejm.org/toc/nejm/medical-journal

Review Article
The Changing Face of Clinical Trials
Jeffrey M. Drazen, M.D., David P. Harrington, Ph.D., John J.V. McMurray, M.D., James H. Ware, Ph.D., Janet Woodcock, M.D., Editors
Academic, Foundation, and Industry Collaboration in Finding New Therapies
Bonnie W. Ramsey, M.D., Gerald T. Nepom, M.D., Ph.D., and Sagar Lonial, M.D.
N Engl J Med 2017; 376:1762-1769 May 4, 2017 DOI: 10.1056/NEJMra1612575
Breakthroughs in the ability to probe and better understand biologic systems during the past 30 years1-3 have enabled the medical community to develop new therapeutic agents and change the course of many life-shortening diseases.4,5 Despite this success, bridging the gap between promising laboratory observations and the development of effective therapies remains risky and expensive, with fewer than 1 in 10,000 early translational programs successfully achieving Food and Drug Administration (FDA) approval, at a cost of nearly $1 billion.6 Most therapeutic development fails in the preclinical phase, which is sometimes described as the “valley of death.”7

For this reason and because therapies for some conditions will have a limited eventual market value, the pharmaceutical industry has been hesitant to initiate early-stage programs to treat so-called orphan diseases. In recognition of a critical need, federal agencies have developed programs to catalyze innovation and reduce barriers to early development of new therapies.8 In the past two decades, disease-focused foundations also have developed a new approach to bridging this preclinical gap. In a process known as venture philanthropy, such foundations have formed partnerships with industry and federal agencies to share the financial risk of therapeutic development, shorten the early translational pipeline, and advance research with “a focus on human, not financial, return.”9 In addition, foundations and their academic partners have accelerated early development by providing access to patient populations for clinical trials and assistance from disease-specific experts in study design, which has helped in bridging the gap in therapeutic development.

In this review, we will focus on three diseases — cystic fibrosis, multiple myeloma, and type 1 diabetes mellitus — to illustrate how collaborations among academic institutions, foundations, and industry partners have evolved to address the therapeutic challenges of these conditions.

Pediatrics
May 2017, VOLUME 139 / ISSUE 5
http://pediatrics.aappublications.org/content/139/5?current-issue=y

Articles
Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010–2014
Brendan Flannery, Sue B. Reynolds, Lenee Blanton, Tammy A. Santibanez, Alissa O’Halloran, Peng-Jun Lu, Jufu Chen, Ivo M. Foppa, Paul Gargiullo, Joseph Bresee, James A. Singleton, Alicia M. Fry
Pediatrics May 2017, 139 (5) e20164244; DOI: 10.1542/peds.2016-4244

Articles
Effectiveness of Vaccination During Pregnancy to Prevent Infant Pertussis
Roger Baxter, Joan Bartlett, Bruce Fireman, Edwin Lewis, Nicola P. Klein
Pediatrics May 2017, 139 (5) e20164091; DOI: 10.1542/peds.2016-4091

Articles
The Concordance of Parent and Child Immunization
Steve G. Robison, Andrew W. Osborn
Pediatrics May 2017, 139 (5) e20162883; DOI: 10.1542/peds.2016-2883

Pediatrics
May 2017, VOLUME 139 / ISSUE 5
http://pediatrics.aappublications.org/content/139/5?current-issue=y

State-of-the-Art Review Articles
Ethical Conduct of Research in Children: Pediatricians and Their IRB (Part 1 of 2)
Carlos D. Rose
Pediatrics May 2017, 139 (5) e20163648; DOI: 10.1542/peds.2016-3648
Abstract
As human experimentation continues to grow into an ever more complex and sophisticated endeavor, the relevant ethical and regulatory structures become more intricate. When pediatricians and general practitioners are invited by pharmaceutical companies to enroll their offices in a clinical trial or a multicenter observational study or when they develop their own research questions, they frequently find themselves at a loss in the human research environment. The legal and regulatory complexity may have an unintended deterring effect at a time when office-based high quality pediatric research is urgently needed to support evidence-based medicine. Unfortunately, in many instances, unaware practitioners become involved in low-risk research activities without knowing it and become entangled in legal, auditing, and compliance procedures. This paper, written in 2 parts, aims at providing a general guidance on the principles that regulate human research with a focus on pediatrics. Part 1 discusses the history, the legal framework, and the consent process and highlights some practical aspects of initial protocol submission, continued review, and institutional review board determinations with the main focus on multicenter clinical trials (industry-sponsored research). Part 2 focuses on pediatric research regulation, also known as subpart-D, and minimal risk research, which encompasses many research activities aimed at addressing questions that may emerge in pediatricians’ practices (investigator-initiated research).

Pediatrics
May 2017, VOLUME 139 / ISSUE 5
http://pediatrics.aappublications.org/content/139/5?current-issue=y

Special Articles
The Next 7 Great Achievements in Pediatric Research
Tina L. Cheng, Clifford W. Bogue, George J. Dover
Pediatrics May 2017, 139 (5) e20163803; DOI: 10.1542/peds.2016-3803
Abstract
The “7 Great Achievements in Pediatric Research” campaign noted discoveries in the past 40 years that have improved child and adult health in the United States and around the globe. This article predicts the next 7 great pediatric research advancements, including new immunizations, cancer immunotherapy, genomic discoveries, identification of early antecedents of adult health, impact of specific social–environmental influences on biology and health, quality improvement science, and implementation and dissemination research to reduce global poverty. It is an extraordinary time of new research tools that include electronic health records, technological ability to manage big data and measure “omics,” and new functional and structural imaging modalities. These tools will discern mechanisms leading to health and disease with new prevention targets and cures. This article further discusses the challenges and opportunities to accelerate these exciting pediatric research discoveries to improve the lives of children and the adults they will become.

Pediatrics
May 2017, VOLUME 139 / ISSUE 5
http://pediatrics.aappublications.org/content/139/5?current-issue=y

Improving Recruitment and Retention Rates in a Randomized Controlled Trial
Hadley S. Sauers-Ford, Jennifer M. Gold, Angela M. Statile, Heather L. Tubbs-Cooley, Jeffrey M. Simmons, Samir S. Shah, Kathleen Bell, Cory Pfefferman, Margo J. Moore, Katherine A. Auger, on behalf of the H2O Study Group
Pediatrics May 2017, 139 (5) e20162770; DOI: 10.1542/peds.2016-2770
Abstract
High recruitment and retention rates in randomized controlled trials are essential to ensure validity and broad generalizability. We used quality improvement methods, including run charts and intervention cycles, to achieve and sustain high recruitment and retention rates during the Hospital-To-Home Outcomes randomized controlled trial. This study is examining the effects of a single nurse–led home health care visit after discharge for an acute pediatric hospitalization. A total of 1500 participants were enrolled in the 15-month study period. For study recruitment, we assessed the percentage of patients who enrolled in the study among those randomly selected to approach (goal ≥50%) and the percentage of patients who refused to enroll from those randomly selected to approach (goal ≤30%). For intervention completion, we examined the percentage of patients who completed the home visit intervention among those randomized to receive the intervention (goal ≥95%) were examined. Follow-up rates were tracked as the percentage of patients who completed the 14-day follow-up telephone survey (goal ≥95%). The study goals for 2 of the 4 metrics were met and sustained, with statistically significant improvements over time in 3 metrics. The median enrollment rate increased from 50% to 59%, and the median refusal rate decreased from 37% to 32%. The median intervention completion rate remained unchanged at 88%. The 14-day follow-up completion median rate increased from 94% to 96%. These results indicate that quality improvement methods can be used within the scope of a large research study to achieve and sustain high recruitment and retention rates.

PharmacoEconomics
Volume 35, Issue 5, May 2017
http://link.springer.com/journal/40273/35/5/page/1

Original Research Article
The Potential Cost Effectiveness of Different Dengue Vaccination Programmes in Malaysia: A Value-Based Pricing Assessment Using Dynamic Transmission Mathematical Modelling
Asrul Akmal Shafie, Hui Yee Yeo, Laurent Coudeville, Lucas Steinberg…
Abstract
Background
Dengue disease poses a great economic burden in Malaysia.
Methods
This study evaluated the cost effectiveness and impact of dengue vaccination in Malaysia from both provider and societal perspectives using a dynamic transmission mathematical model. The model incorporated sensitivity analyses, Malaysia-specific data, evidence from recent phase III studies and pooled efficacy and long-term safety data to refine the estimates from previous published studies. Unit costs were valued in $US, year 2013 values.
Results
Six vaccination programmes employing a three-dose schedule were identified as the most likely programmes to be implemented. In all programmes, vaccination produced positive benefits expressed as reductions in dengue cases, dengue-related deaths, life-years lost, disability-adjusted life-years and dengue treatment costs. Instead of incremental cost-effectiveness ratios (ICERs), we evaluated the cost effectiveness of the programmes by calculating the threshold prices for a highly cost-effective strategy [ICER  Conclusion
Routine vaccination for a population aged 13 years with a catch-up cohort aged 14–30 years in targeted hotspot areas appears to be the best-value strategy among those investigated. Dengue vaccination is a potentially good investment if the purchaser can negotiate a price at or below the cost-effective threshold price.

PLOS Currents: Disasters
http://currents.plos.org/disasters/
[Accessed 6 May 2017]

Risk Criteria in Hospital Site Selection: A Systematic Review
May 1, 2017 · Review
Introduction: Hospitals should be safe and remain functional in emergencies and disasters as it is mentioned in the Sendai Framework. Proper selection of a hospital location has a direct effect on survival of affected population in disasters as well as cost and benefit of the hospital in non-emergency situation. Different studies applied different criteria for Hospital Site Selection (HSS). The present study through a systematic review aimed to find out a categorized criteria list that have been used for (HSS) in the literature.
Methods: In accordance with the PRISMA statement, “PubMed”, “ScienceDirect”, “Google Scholar”, and “Scopus” were searched up to end of 2015. All English Articles that were published in peer-reviewed journals and had discussed site selection criteria for hospitals were included. Out of 41 articles, 15 met the inclusion criteria in which 39 general criteria for HSS were applied. These criteria were categorized in six main groups including cost, demand, environmental, administrative, disaster risk, and “other” concerns through a focus group discussion.
Results: Accordingly, the application percentage of cost, demand, environmental, administrative, disaster risk, and “other” concerns in the articles was 100, 93.3, 53.3, 33.3, 20.0, and 13.3 respectively. The least devoted attention was to disaster risk issues.
Discussion: Few researchers applied risk related criteria for HSS. Further consideration of “risk of hazards” and “burden of diseases” in comprehensive studies, is recommended for HSS to guide the decision makers for building more resilient hospitals.

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
[Accessed 6 May 2017]

No Evidence of On-farm Circulation of Avian Influenza H5 Subtype in Ca Mau Province, Southern Vietnam, March 2016 – January 2017
May 5, 2017 · Research Article
Background: Subtype H5N1 avian influenza viruses, both high pathogenicity and low pathogenicity, have been enzootic in Vietnam since 2001.  The viruses are readily identified at live bird markets, but virus prevalence on smallholder poultry is typically zero or very low.  If the true direction of the viral transmission chain is farm to market, it is unknown why farm prevalence should be low when market prevalence is moderate to high.
Methods: We established a cohort of 50 smallholder poultry farms in Ca Mau province in the Mekong Delta regions of Vietnam.  From March 2016 to January 2017, we collected naso-pharyngeal and cloacal samples from 156 ducks and 96 chickens.  In addition, 126 environmental samples were collected.  Samples were assayed for H5 subtype influenza by real-time RT-PCR.
Results/Discussion: None of the 378 collected samples were positive for H5 influenza.  This is likely to mean that circulation of subtype H5 influenza viruses was low in Ca Mau in 2016.  Detection of avian influenza on smallholder poultry farms is necessary to determine the directionality and association between farm prevalence and market prevalence of avian influenza viruses.  Larger farm-level studies should be planned as these will be critical for determining the presence and strength of this association.

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
[Accessed 6 May 2017]

Rapid Assessment Zika Virus Knowledge Among Clinical Specialists in Singapore: A Cross-sectional Survey
May 3, 2017 · Research Article
Introduction: We report the results of a rapid assessment of Zika virus awareness among key clinical specialties in Singapore.
Methods: Between June 6 and June 19, 2016 we conducted an online survey of doctors working in obstetrics and gynaecology, neonatology and paediatrics in Singapore. The survey included 15 multiple choice questions to measure respondents’ knowledge of Zika virus in four domains covering clinical and public health.
Results: A total of 110 survey responses (15% response rate) were obtained, 82% of respondents worked in the public sector. Overall, the median respondent score was 9.4 (Max score=15), with substantial variation (range: 3.5 – 14.7). Microcephaly and Guillain-Barré syndrome were recognised as causal complications of Zika virus infection by 99% and 50% of respondents respectively.  Clinical features which could help differentiate Zika from Dengue were less well understood with 50% and 68% correctly identifying conjunctivitis and low grade fever respectively. Worryingly, 14% favoured non-steroidal anti-inflammatory drugs as part of treatment, without first excluding dengue as a diagnosis. Also, only 36% of respondents were aware of the current recommendation for preventing sexual transmission of Zika virus. Fewer than 50% were aware of the need for ophthalmological evaluation as part of congenital Zika virus infection.
Discussion: Our assessment demonstrates that there is good awareness of the clinical manifestation of Zika virus disease among key specialty doctors, but confusion with Dengue disease remains. It also highlights knowledge gaps in the prevention of sexually-transmitted Zika virus infection and the clinical management of congenital Zika virus infection in newborns. Our study identified strategic areas to improve communication to front-line doctors during public health response to the Zika epidemic.

PLoS Medicine
http://www.plosmedicine.org/
(Accessed 6 May 2017)

Perspective
Towards control of the global HIV epidemic: Addressing the middle-90 challenge in the UNAIDS 90–90–90 target
Collins Iwuji, Marie-Louise Newell
| published 02 May 2017 PLOS Medicine
https://doi.org/10.1371/journal.pmed.1002293

In 2016, just over 2 million people worldwide acquired HIV infection, mostly via heterosexual transmission and mostly in sub-Saharan Africa [1]. Antiretroviral treatment (ART) aims to suppress viral load to very low, or undetectable, levels, delaying HIV disease progression [2,3] and reducing the risk of onward transmission [4]. Following the 2015 WHO guidelines recommending ART for all HIV-positive people regardless of CD4 count, WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued the 90–90–90 target, aiming by 2020 to have 90% of infected people knowing their HIV status, 90% of HIV-positive people initiated on ART, and 90% of people treated with ART virally suppressed [5], so as to achieve containment of the HIV epidemic.

We commend Richard Hayes and colleagues for their success in navigating the complex logistic challenges in implementing a large-scale universal testing and treatment (UTT) intervention in sub-Saharan Africa, as described in their accompanying research article in PLOS Medicine [6]. They report how close they were able to come to reaching the first two stages of the 90–90–90 target in four communities in Zambia after one year of implementing their PopART intervention (comprising home-based HIV testing by Community HIV care Providers [CHiPs] with support for linkage to care, adherence, and retention). Among those consenting to the intervention, 6,197 HIV-positive individuals not on ART (most of whom had never been in care) were referred to care, 42% of whom initiated ART within six months and 53% by 12 months. Extrapolating to the entire population, the estimated percentage of HIV-positive adults who knew their status increased from 52% to 78% (men) and from 56% to 87% (women); percentages of known HIV-positive people on ART increased from 54% to 74% (men) and from 53% to 73% (women). The overall estimated percentage of HIV-positive adults on ART was 61% after 1 y of intervention implementation, compared to the WHO/UNAIDS target of 81% (90% of 90%). We note that many process indicators in the study were based on self-report and, apparently, data from the CHiPs electronic capture system were not verified with clinic data. Further, in this setting, in which nearly 50% of all HIV-positive individuals were ART-naive because they were newly diagnosed, it is likely that most of the 20% of people who migrated out of the area never linked to care or commenced ART. This 20% of people, no longer resident in the PopART communities, was not included in the denominator for the post-CHiPs evaluation at 12 months on linkage to care and ART initiation, which could have resulted in an overestimate of the change observed following the CHiPs intervention.

Hayes and colleagues’ findings thus confirm the high acceptability of home-based HIV testing, and a less-than-optimal linkage to care, with initiation of ART rates suggesting that those who do link to care are willing to start ART; there is a substantial proportion of people identified as HIV positive who do not (yet) link to care, can therefore not be initiated on ART, and who may continue to transmit HIV. The Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) 12249 Treatment as Prevention (TasP) trial, also evaluating a UTT intervention in rural South Africa, recently reported that 92% of HIV-positive individuals knew their status, 49% of those people initiated ART, and 93% achieved virological suppression on ART [7]. Higher rates of ART initiation were reported from Uganda and Kenya in the Sustainable East Africa Research in Community Health (SEARCH) trial, another UTT intervention study, with 97% of HIV-positive individuals knowing their status, 93% on ART, and 90% virologically suppressed at the end of year two [8]. Similarly, estimates from the Botswana Combination Prevention Project (BCPP) trial, a UTT intervention implemented in Botswana, reported that, overall, 70% of all HIV-positive individuals were virologically suppressed, close to the UNAIDS target of 73% (90% of 90% of 90%), with 83% of HIV-positive individuals diagnosed and 87% on ART, of whom 97% achieved virological suppression [9]. The different approaches to the estimation of percentages in the HIV care cascade in these trials hinder direct comparison of results; hence, we agree with Hayes and colleagues that approaches for estimating proportions of people at different stages in the HIV cascade need to be harmonised.

Hayes and colleagues report that it was challenging to find young men at home, again in line with experience elsewhere [10]. Slow linkage to care suggests that people will only attend facilities once they prioritise doing so, and this is especially pertinent before they are driven to do so by the development of HIV symptoms and signs. An earlier study in rural KwaZulu-Natal highlighted that linkage to care was significantly less likely in those who had never been in HIV care, students in education, and those further away from the clinic, while those who had positive experience of ART in friends or family were more likely to access the trial clinic [11]. Hayes and colleagues will address progress towards the third 90% target later in their trial, but evidence from other studies suggests that once people engage with ART care, they are likely to adhere, at least in the short term [7], and that early linkage to ART care is the main hurdle in the HIV care cascade.

The big question remains whether, in the global heterosexually-driven HIV epidemic, UTT will ultimately reduce HIV incidence to levels sufficient for containment. Findings from the ANRS 12249 TasP trial in South Africa showed little impact on HIV incidence [7], likely due to the slow linkage to care. Hayes and colleagues, although suggesting success of UTT in the first round of trial implementation, do not provide information about sustainability of either HIV test offer uptake or ART adherence, issues which may be especially important in settings with high migration movements.

Overall, these results would suggest that it is unlikely that the rather optimistic forecasts, based on statistical modelling [12], of an imminent end to the global HIV epidemic will be fulfilled. The current gloomy political environment, with uncertainty about the global will to continue to support the large-scale implementation of HIV treatment and care programmes worldwide [13], further adds to the already considerable challenges faced by public health programmes in many settings with a high HIV burden. Health care system requirements for a successful UTT programme are not negligible, even if a UTT approach is found to be cost-effective [14]. Substantial resources are needed to further scale up ART for all HIV-positive adults, and allocation of limited resources will need to be optimised on the basis of evidence of efficacy.

Given extensive resource constraints, there may come a time to consider whether public programmes will need to focus on providing optimal health care and support for those people who engage with care at public facilities and who have thus indicated that they have prioritised access to health care in their lives.

PLoS Neglected Tropical Diseases
http://www.plosntds.org/
(Accessed 6 May 2017)

Research Article
Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults
David J. Diemert, Janaína Freire, Vanderson Valente, Carlos Geraldo Fraga, Frederico Talles, Shannon Grahek, Doreen Campbell, Amar Jariwala, Maria Victoria Periago, Martin Enk, Maria Flávia Gazzinelli, Maria Elena Bottazzi, Robert Hamilton, Jill Brelsford, Anna Yakovleva, Guangzhao Li, Jin Peng, Rodrigo Correa-Oliveira, Peter Hotez, Jeffrey Bethony
Research Article | published 02 May 2017 PLOS Neglected Tropical Diseases
https://doi.org/10.1371/journal.pntd.0005574

External quality assessment study for ebolavirus PCR-diagnostic promotes international preparedness during the 2014 – 2016 Ebola outbreak in West Africa
Heinz Ellerbrok, Sonja Jacobsen, Pranav Patel, Toni Rieger, Markus Eickmann, Stephan Becker, Stephan Günther, Dhamari Naidoo, Livia Schrick, Kathrin Keeren, Angelina Targosz, Anette Teichmann, Pierre Formenty, Matthias Niedrig
Research Article | published 01 May 2017 PLOS Neglected Tropical Diseases
https://doi.org/10.1371/journal.pntd.0005570

PLoS One
http://www.plosone.org/
[Accessed 6 May 2017]

Research Article
Neutralizing misinformation through inoculation: Exposing misleading argumentation techniques reduces their influence
John Cook, Stephan Lewandowsky, Ullrich K. H. Ecker
Research Article | published 05 May 2017 PLOS ONE
https://doi.org/10.1371/journal.pone.0175799
Abstract
Misinformation can undermine a well-functioning democracy. For example, public misconceptions about climate change can lead to lowered acceptance of the reality of climate change and lowered support for mitigation policies. This study experimentally explored the impact of misinformation about climate change and tested several pre-emptive interventions designed to reduce the influence of misinformation. We found that false-balance media coverage (giving contrarian views equal voice with climate scientists) lowered perceived consensus overall, although the effect was greater among free-market supporters. Likewise, misinformation that confuses people about the level of scientific agreement regarding anthropogenic global warming (AGW) had a polarizing effect, with free-market supporters reducing their acceptance of AGW and those with low free-market support increasing their acceptance of AGW. However, we found that inoculating messages that (1) explain the flawed argumentation technique used in the misinformation or that (2) highlight the scientific consensus on climate change were effective in neutralizing those adverse effects of misinformation. We recommend that climate communication messages should take into account ways in which scientific content can be distorted, and include pre-emptive inoculation messages.

Cost-effectiveness of alternate strategies for childhood immunization against meningococcal disease with monovalent and quadrivalent conjugate vaccines in Canada
Thomas E. Delea, Derek Weycker, Mark Atwood, Dion Neame, Fabián P. Alvarez, Evelyn Forget, Joanne M. Langley, Ayman Chit
Research Article | published 04 May 2017 PLOS ONE
https://doi.org/10.1371/journal.pone.0175721

Preventive Medicine
Volume 98, Pages 1-44 (May 2017)
http://www.sciencedirect.com/science/journal/00917435/98
Special Issue: Emerging Paradigms in Cervical Cancer Screening
Edited by Mark Schiffman

Cervical cancer screening in women vaccinated against human papillomavirus infection: Recommendations from a consensus conference
Original Research Article
Pages 21-30
Paolo Giorgi Rossi, Francesca Carozzi, Antonio Federici, Guglielmo Ronco, Marco Zappa, Silvia Franceschi, The Italian Screening in HPV vaccinated girls Consensus Conference group
Abstract
In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age (25 years) for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by “one size fits all” protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5 years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept

Preventive Medicine
Volume 98, Pages 1-44 (May 2017)
http://www.sciencedirect.com/science/journal/00917435/98
Special Issue: Emerging Paradigms in Cervical Cancer Screening
Edited by Mark Schiffman

Considerations for HPV primary screening in lower-middle income countries
Original Research Article
Pages 39-41
Mauricio Maza, Julia C. Gage
Abstract
The accumulated scientific evidence now provides ample support for HPV primary screening as a superior method for detecting cervical precancer and preventing cervical cancer. Approximately half of the global burden of cervical cancer could be reduced in lower-middle income countries where attempts to implement traditional cytology-based programs have not experienced successes. In these countries screening programs have struggled with poor screening and diagnostic test sensitivity, difficulties maintaining quality control and adequate population coverage. HPV testing is not only more accurate and reliable, but also requires less training, quality assurance and expensive personnel. Because these countries are especially vulnerable to economic, political and societal instabilities, HPV tests must become more affordable and accessible in order to enable Ministries of Health to make long-term resource commitments.

Preventive Medicine
Volume 98, Pages 1-44 (May 2017)
http://www.sciencedirect.com/science/journal/00917435/98
Special Issue: Emerging Paradigms in Cervical Cancer Screening
Edited by Mark Schiffman

The time is now to implement HPV testing for primary screening in low resource settings
Original Research Article
Pages 42-44
Louise Kuhn, Lynette Denny
Abstract
Unacceptable disparities in cervical cancer between richer and poorer countries persist and serve as reminders of gross disparities in access to and quality of screening services. HPV testing is well-suited to address some of the barriers to implementing adequate screening programs in low resource settings. HPV testing has considerably better sensitivity than cytology providing the same extent of safety with fewer rounds of screening. New robust HPV testing platforms require little to no skill by laboratory workers and some can be used at the point-of-care. This allows for a round of screening to be accomplished in one or two visits, reducing costs and the inevitable attrition that occurs when women need to be recalled to obtain their results. HPV testing is ideal for incorporating into the new “screen-and-treat” approaches designed to overcome limitations of conventional, multi-visit, colposcopy-based approaches to screening. Visual inspection with acetic acid (VIA) is the screening test that has been used most widely in screen-and-treat programs to date but the performance characteristics of this test are poor. HPV-based screen-and-treat is more effective in reducing disease in the population and reduces over-treatment intrinsic to this approach. HPV testing can be adapted or combined with other molecular tests to improve treatment algorithms. Infrastructure established to support VIA-based screen-and-treat can effectively incorporate HPV testing. We are poised at a critical juncture in public health history to implement HPV testing as part of primary screening and thereby improve women’s health in low resource settings

Public Health Ethics
Volume 10, Issue 1   April 2017
http://phe.oxfordjournals.org/content/current

Original Articles
Research Ethics Governance in Times of Ebola
Doris Schopper; Raffaella Ravinetto; Lisa Schwartz; Eunice Kamaara; Sunita Sheel …
Abstract
The Médecins Sans Frontières (MSF) ethics review board (ERB) has been solicited in an unprecedented way to provide advice and review research protocols in an ‘emergency’ mode during the recent Ebola epidemic. Twenty-seven Ebola-related study protocols were reviewed between March 2014 and August 2015, ranging from epidemiological research, to behavioural research, infectivity studies and clinical trials with investigational products at (very) early development stages. This article examines the MSF ERB’s experience addressing issues related to both the process of review and substantive ethical issues in this context. These topics include lack of policies regarding blood sample collection and use, and engaging communities regarding their storage and future use; exclusion of pregnant women from clinical and vaccine trials; and the difficulty of implementing timely and high-quality qualitative/anthropological research to consider potential upfront harms. Having noticed different standards across ethics committees (ECs), we propose that when multiple ethics reviews of clinical and vaccine trials are carried out during a public health emergency they should be accompanied by transparent communication between the ECs involved. The MSF ERB experience should trigger a broader discussion on the ‘optimal’ ethics review in an emergency outbreak and what enduring structural changes are needed to improve the ethics review process.

Public Health Reports
Volume 132, Issue 3, May/June 2017
http://phr.sagepub.com/content/current

Reports and Recommendations
Overcoming Barriers and Identifying Opportunities for Developing Maternal Immunizations: Recommendations From the National Vaccine Advisory Committee
Approved by the National Vaccine Advisory Committee on September 20, 2016
First Published April 5, 2017; pp. 271–284

Research
Voluntarily Reported Immunization Registry Data: Reliability and Feasibility to Predict Immunization Rates, San Diego, California, 2013
Zachary J. Madewell, Robert B. Wester, Wendy W. Wang, Tyler C. Smith, K. Michael Peddecord, Jessica Morris, Heidi DeGuzman, Mark H. Sawyer, Eric C. McDonald
First Published April 5, 2017; pp. 357–365

Science        
05 May 2017 Vol 356, Issue 6337
http://www.sciencemag.org/current.dtl

Editorial
Moving forward after the march
Rush D. Holt
Science  05 May 2017: Vol. 356, Issue 6337, pp. 467 DOI: 10.1126/science.aan5596
Summary
On 22 April, many thousands of people took part in demonstrations, teach-ins, museum open houses, and science festivals in hundreds of places around the world—an unparalleled show of support for science. Some journalists have tried to portray the march as yet another political demonstration against President Trump and Congress. Yet, neither appeared to be the target for most marchers—not in the United States and even less so around the world. That the March for Science saw the scientific community and the wider public come together in unprecedented numbers signaled that the day was not just a protest by scientists with concerns about their funding or job security. The multitude of T-shirt slogans, placards, and impassioned remarks by marchers and speakers of all ages, backgrounds, and professions spoke volumes—something serious was going on.

Science        
05 May 2017 Vol 356, Issue 6337
http://www.sciencemag.org/current.dtl

In Depth
Congress trumps president in backing science
By Jeffrey Mervis, Science News Staff
Science05 May 2017 : 470-471 Restricted Access
Legislators ignore Trump’s call for cuts and give NIH, NASA research big increases
Summary
A new U.S. budget deal makes it clear that scientists have enough friends in Congress to counter the chill from the White House—at least for now. This week, lawmakers were expected to approve a spending plan for the 2017 fiscal year, which ends on 30 September. The deal they voted on contains a lot more good news than the two budget requests that President Donald Trump so far has sent to Congress. The National Institutes of Health (NIH) and NASA’s science programs are the biggest winners in a 1665-page document that closes a tumultuous budget year and staves off a government shutdown. NIH was in line for a 6.2% boost, to $34 billion, whereas NASA’s science missions received a hike of 3.1%, to $5.76 billion. The rest of the big four federal research programs—the Office of Science at the Department of Energy and the National Science Foundation—trail those leaders but still grow modestly.

Science Translational Medicine
03 May 2017   Vol 9, Issue 388
http://stm.sciencemag.org/

Research Articles
A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants
By Qing Zhu, Jason S. McLellan, Nicole L. Kallewaard, Nancy D. Ulbrandt, Susan Palaszynski, Jing Zhang, Brian Moldt, Anis Khan, Catherine Svabek, Josephine M. McAuliffe, Daniel Wrapp, Nita K. Patel, Kimberly E. Cook, Bettina W. M. Richter, Patricia C. Ryan, Andy Q. Yuan, JoAnn A. Suzich
Science Translational Medicine03 May 2017 Full Access
Development of a highly potent anti-RSV monoclonal antibody with extended half-life intended to be used as RSV prophylaxis for all infants.
Pan-RSV prophylaxis
The common respiratory syncytial virus (RSV) can progress to a very dangerous lower respiratory infection in some infants. A protective monoclonal antibody is available but is not recommended for general use. Zhu et al. describe the selection and optimization of a human monoclonal antibody able to neutralize a wide array of RSV A and B viruses and protect cotton rats at lower doses than the currently approved antibody. The antibody was optimized to persist in circulation, and data indicate that infants could be given a single dose and be protected for the entirety of the RSV season. If administered widely, this antibody could potentially prevent the hospitalization of thousands of children each year.

Tropical Medicine & International Health
May 2017 Volume 22, Issue 5  Pages 513–654
http://onlinelibrary.wiley.com/doi/10.1111/tmi.2017.22.issue-5/issuetoc

Editorial
Can infant vaccination prevent pneumococcal meningitis outbreaks in sub-Saharan Africa? (pages 514–515)
James M. Stuart
Version of Record online: 29 MAR 2017 | DOI: 10.1111/tmi.12860
The WHO Strategic Advisory Group of Experts is reviewing the technical evidence to inform policy on optimal use of infant pneumococcal conjugate vaccines (PCV) [1]. Since 2010, multivalent vaccines (PCV-10, PCV-13) have been successfully introduced with the support of Gavi, the Vaccine Alliance into infant immunisation programmes across the developing world [2]. One recommended schedule consists of three doses under the age of 6 months (3 + 0), with the aim of providing maximum protection to infants, the age group at highest risk of pneumococcal disease [3]. An alternative schedule consists of two vaccine doses under the age of 6 months with a booster at 9–15 months (2 + 1). This schedule may have more impact on reducing carriage and transmission of vaccine serotypes to unvaccinated individuals, leading to indirect or herd protection. The question around the most cost-effective policy to achieve both direct and indirect protection has particular importance for the meningitis belt of sub-Saharan Africa.

The launch of mass campaigns with a serogroup A conjugate vaccine (MenAfriVacR) across the meningitis belt in 2010 saw a dramatic fall in the incidence of meningitis due to serogroup A, while meningitis due to other meningococcal serogroups and Streptococcus pneumoniae has become more prominent [4]. Recent publications from the meningitis belt emphasise the continuing burden of pneumococcal meningitis among older children and adults in this region. In Ghana, a large outbreak occurred in 2016 with close to 900 suspected cases and 104 cases confirmed as due to S. pneumoniae, mainly serotype 1, with a median age of 20 years, in part of the country adjoining the meningitis belt [5]. In Burkina Faso from 2011 to 13, 1528 (53%) of 2858 cases of laboratory confirmed bacterial meningitis was due to S. pneumoniae, also mainly serotype 1 [6]. The proportion of cases aged over 5 years was 95% in Ghana and 69% in Burkina Faso. PCV programmes that started in 2013 in Ghana likely protected young children in the 2016 outbreak, whereas the Burkina Faso data were taken from the years preceding PCV vaccination.

Bacterial meningitis due to S. pneumoniae has a remarkably high case fatality ratios in sub-Saharan Africa [7] and causes much disability in survivors [8]. A systematic review of paediatric meningitis in children in Africa found among cases of confirmed pneumococcal meningitis that the median in-hospital case fatality ratio was 35% and that 25% of survivors had in-hospital sequelae, these figures being 9× and 4× higher respectively than those for meningococcal meningitis [8]. Incidence of pneumococcal meningitis is particularly high in the meningitis belt, with a similar seasonality to meningococcal meningitis, consistent with similar predisposing environmental factors [7, 9]. Reducing the burden of pneumococcal meningitis in these countries should be given high public health priority.

For outbreak control, pneumococcal vaccines could potentially be given to children and adults in reactive mass campaigns, a similar strategy to that using meningococcal vaccines for controlling outbreaks of meningococcal meningitis [10]. However, reactive vaccination for meningococcal meningitis is resource intensive and relatively ineffective unless undertaken promptly [11, 12], and effectiveness of such a policy in controlling outbreaks of pneumococcal meningitis is not known [13]. Preventive vaccination offers more hope. Even though serotype 1 is rarely found in carriage isolates, evidence of indirect protection against serotype 1 was found in South Africa after introduction of a 2 + 1 PCV-13 infant vaccination schedule [14].

How best can we achieve indirect protection of older age groups at high risk of pneumococcal meningitis in the meningitis belt? Inclusion of a booster dose may be more important for some serotypes, including serotype 1 [15], and extended vaccination among children up to the age of 5 years, in whom carriage prevalence is highest in sub-Saharan Africa [16], may increase effectiveness [2, 17]. A 3 + 0 schedule supplemented by a catch-up campaign to the age of 5 years in Kenya reduced carriage of vaccine serotypes in vaccinated and unvaccinated age groups [18]. In contrast, a study from the Gambia showed no evidence as yet of a reduction in serotype 1 disease in persons aged >5 years after introducing a 3 + 0 PCV-13 schedule without catch-up in 2011 [19], and the pneumococcal meningitis outbreak this year in Ghana occurred despite the prior introduction of a 3 + 0 schedule with high coverage in the two previous years. Most countries of the meningitis belt have introduced a 3 + 0 schedule. Switching to a 2 + 1 schedule with a single dose catch-up in children up to 5 years of age could extend individual protection, lead to a higher level of indirect protection and lower the risk of outbreaks from this devastating disease.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Reviews
Coverage and determinants of childhood immunization in Nigeria: A systematic review and meta-analysis
Review Article
Pages 2871-2881
Davies Adeloye, Wura Jacobs, Ann O. Amuta, Oluwatomisin Ogundipe, Oluwaseun Mosaku, Muktar A. Gadanya, Gbolahan Oni
Abstract
Introduction
The proportion of fully immunized children in Nigeria is reportedly low. There are concerns over national immunization data quality, with this possibly limiting country-wide response. We reviewed publicly available evidence on routine immunization across Nigeria to estimate national and zonal coverage of childhood immunization and associated determinants.
Methods
A systematic search of Medline, EMBASE, Global Health and African Journals Online (AJOL) was conducted. We included population-based studies on childhood immunization in Nigeria. A random effects meta-analysis was conducted on extracted crude rates to arrive at national and zonal pooled estimates for the country.
Results
Our search returned 646 hits. 21 studies covering 25 sites and 26,960 children were selected. The estimated proportion of fully immunized children in Nigeria was 34.4% (95% confidence interval [CI]: 27.0–41.9), with South-south zone having the highest at 51.5% (95% CI: 20.5–82.6), and North-west the lowest at 9.5% (95% CI: 4.6–14.4). Mother’s social engagements (OR = 4.0, 95% CI: 1.9–8.1) and vaccines unavailability (OR = 3.9, 95% CI: 1.2–12.3) were mostly reported for low coverage. Other leading determinants were vaccine safety concerns (OR = 3.0, 95% CI: 0.9–9.4), mother’s low education (OR = 2.5, 95% CI: 1.8–3.6) and poor information (OR = 2.0, 95% CI: 0.8–4.7).
Conclusion
Our study suggests a low coverage of childhood immunization in Nigeria. Due to the paucity of data in the Northern states, we are still uncertain of the quality of evidence presented. It is hoped that this study will prompt the needed research, public health and policy changes toward increased evenly-spread coverage of childhood immunization in the country.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Review Article
Indirect (herd) protection, following pneumococcal conjugated vaccines introduction: A systematic review of the literature
Pages 2882-2891
Gal Tsaban, Shalom Ben-Shimol
Abstract
Background
Pneumococcal diseases are major causes of morbidity among adults, especially those over 50 years of age. While pneumococcal conjugated vaccines (PCV’s) impact on pneumococcal disease rates among children is well established, the extent of its impact on adult pneumococcal related illness remains unclear. The aim of this systematic literature review was to describe the impact of PCV introduction to childhood national immunization programs worldwide on PCV-naive adult population.
Methods
A systematic literature search was performed using the PubMed database. The search was limited to articles written in English and published between January 2000 and February 2016. Studies evaluating pneumococcal disease rates in individuals over 5 years of age were included. Independent extraction of articles was performed by the two authors. Search terms included: Pneumococcal conjugated vaccine, herd, indirect, adults, and pneumonia.
Results
Forty-nine articles meeting the selection criteria were identified, 39 regarding invasive pneumococcal disease (IPD, one on meningitis only), 8 regarding pneumonia, and 2 on both IPD and pneumonia. The majority of reports were from the US, UK and Canada. Considerable variability in the data sources, quality and completeness was observed. While most studies reported either statistically significant reduction or insignificant changes in IPD and pneumonia disease rates in adults following PCV nationwide implementation, few studies reported statistically significant increase in pneumococcal disease rates, these were mainly from countries with low PCV coverage rates and/or inadequate surveillance.
Conclusion
Invasive pneumococcal diseases and pneumonia rates among the adult population decreased in most countries following PCV introduction into the NIP. This indirect effect on older population seems to be dependent on PCV coverage rates and time from PCV nationwide implementation. Adults >65 years old seem to benefit the most from PCV introduction.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Two-dose schedules for human papillomavirus vaccine: Systematic review and meta-analysis
Review Article
Pages 2892-2901
Maddalena D’Addario, Shelagh Redmond, Pippa Scott, Dianne Egli-Gany, A. Ximena Riveros-Balta, Ana Maria Henao Restrepo, Nicola Low
Abstract
Simpler schedules for human papillomavirus (HPV) vaccine delivery could improve vaccine coverage and the effectiveness of cervical cancer prevention. The objective of this study was to systematically review evidence about the effects of two-dose compared with three-dose schedules for human papillomavirus (HPV) vaccine and to describe the uptake of two-dose HPV vaccination schedules globally. We searched PubMed, the Cochrane Central Registry of Controlled Trials, trials registers, and manufacturers’ databases from their earliest date to February 2016. We selected randomised controlled trials and controlled clinical trials that directly compared HPV vaccine schedules with two or three doses. We extracted data on immunological and clinical outcomes and used meta-analysis where appropriate. We also described the use of two-dose HPV vaccine schedules globally. We screened 1464 items and included seven eligible noninferiority trials in 11 countries. In randomised comparisons amongst adolescent girls (three trials), geometric mean concentrations (GMC) of antibodies against HPV16 and HPV18 were non-inferior or inconclusive, up to 24 months after a two-dose compared with a three-dose schedule. One trial with a clinical outcome found no persistent HPV infections occurred after either two or three doses. In non-randomised comparisons, GMC were non-inferior or superior in adolescent girls receiving the two-dose schedule compared with women receiving the three-dose schedule for at least 21 months after vaccination. By February 2017, 23 low and middle income and 25 high income countries had adopted a two-dose HPV vaccination schedule. A two-dose HPV vaccine schedule provides satisfactory immunological outcomes in adolescent girls, but uptake globally is limited, particularly in countries with the highest burden of cervical cancer.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Original papers
Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness
Original Research Article
Pages 2908-2915
Sarah Moberley, Paul V. Licciardi, Anne Balloch, Ross Andrews, Amanda J. Leach, Marie Kirkwood, Paula Binks, Kim Mulholland, Jonathan Carapetis, Mimi L.K. Tang, Sue Skull
Abstract
Background
Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults.
Methods
Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3 μg/ml but 4.0 μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose.
Results
All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (−27%, 95% CI: −43% to −11%; p=0.01) and 90% (−38%, 95% CI: −60% to −16%; p=0.006) of serotypes with a positive response.
Conclusion
Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Health workers’ attitudes, perceptions and knowledge of influenza immunization in Lima, Peru: A mixed methods study
Original Research Article
Pages 2930-2936
Magdalena Bazán, Erika Villacorta, Gisella Barbagelatta, M. Michelle Jimenez, Cecilia Goya, Rosario M. Bartolini, Mary E. Penny
Abstract
Background
Vaccination against seasonal influenza in health workers is recommended but coverage is variable. This study aimed to determine coverage of influenza vaccination among health workers in Lima, Peru in 2010; explore barriers and enabling elements for vaccination; and suggest strategies to improve coverage.
Methods
Qualitative interviews informed the development of a survey instrument that consisted of open and close-ended questions. Sub-analyses were done by occupational group and results were calculated as percentages for each possible response with confidence intervals of 95%.
Results
Coverage of the influenza vaccination was 77.2%. Vaccinated staff were less likely to have permanent contracts (p = 0.0150) and vaccination coverage was lower in physicians (p = 0.0001). Over 90% cited protection of themselves, families and patients as reasons for vaccination and 48% mentioned peer encouragement. Fear of adverse events (47%) and organizational barriers (>30%) were reasons for non-vaccination. To improve coverage, highest priority was given to strategies providing more information.
Conclusions
Key factors in driving health worker vaccination include desire for protection and peer encouragement. Perceptual barriers based on a misunderstanding of the epidemiology of influenza and vaccination could be overcome by targeted education and information. Organizational barriers require attention to how vaccination is implemented within health facilities.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Vaccine hesitancy among parents in a multi-ethnic country, Malaysia
Original Research Article
Pages 2955-2961
Fatin Shaheera Mohd Azizi, Yueting Kew, Foong Ming Moy
Abstract
Background
Vaccine hesitancy is a threat in combating vaccine-preventable diseases. It has been studied extensively in the Western countries but not so among Asian countries.
Objectives
To assess the test-retest reliability of the Parent Attitudes about Childhood Vaccines (PACV) questionnaire in Malay language; to determine the prevalence of vaccine hesitancy among parents and its associations with parents’ socio-demographic characteristics.
Methods
Forward and backward translation of PACV in Malay language was carried out. The reliability of the Malay-PACV questionnaire was tested among parents with children. The same questionnaire was used to study vaccine hesitancy among parents in a tertiary hospital in Kuala Lumpur. Information pertaining to socio-demographic characteristics, sources of information regarding vaccination and vaccine hesitancy were collected. Associations between vaccine hesitancy with socio-demographic factors were tested using Multivariable Logistic Regression.
Results
The Spearman correlation coefficient and Cronbach alpha for total PACV was 0.79 (p < 0.001) and 0.79 respectively. The intra-class correlation coefficients of the subscales ranged from 0.54 to 0.90 demonstrating fair to excellent reliability. A total of 63 (11.6%) parents were noted to be vaccine hesitant. In the univariate analyses, vaccine hesitancy was associated with unemployed parents, parents who were younger, had fewer children and non-Muslim. In the multivariate model, pregnant mothers expecting their first child were four times more likely to be vaccine hesitant compared to those who already had one or more children (aOR: 3.91, 95% CI: 1.74–8.79) and unemployed parents were also more likely to be vaccine hesitant (aOR: 1.97, 95% CI: 1.08–3.59). The internet (65.6%) was the main source of information on vaccination followed by brochures (56.9%).
Conclusion
The Malay-PACV questionnaire is reliable to be used. The prevalence of vaccine hesitancy among the multi-ethnic Malaysians was comparable with other populations. Pregnant mothers expecting their first child and unemployed parents were found to be more vaccine hesitant.

Vaccine
Volume 35, Issue 22, Pages 2871-3006 (19 May 2017)
http://www.sciencedirect.com/science/journal/0264410X/35/22

Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule
Original Research Article
Pages 2993-2998
Abhijeet Anand, Natalie A. Molodecky, Mark A. Pallansch, Roland W. Sutter
Abstract
Introduction
The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries.
Methods
We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV.
Results
Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19–42% (median: 37%, p < 0.001) and relative increase of 53–125% (median: 82%), and antibody titer to type 2 increasing by 2–32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity.
Discussion
Overall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14 weeks has been endorsed by technical oversight committees and has been introduced in some affected countries

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

International Journal of Health Policy and Management
ePublished: 8 April 2017
Original Article
How Are New Vaccines Prioritized in Low-Income Countries? A Case Study of Human Papilloma Virus Vaccine and Pneumococcal Conjugate Vaccine in Uganda
Lauren Wallace1, Lydia Kapiriri2*
Abstract
Background: To date, research on priority-setting for new vaccines has not adequately explored the influence of the global, national and sub-national levels of decision-making or contextual issues such as political pressure and stakeholder influence and power. Using Kapiriri and Martin’s conceptual framework, this paper evaluates priority setting for new vaccines in Uganda at national and sub-national levels, and considers how global priorities can influence country priorities. This study focuses on 2 specific vaccines, the human papilloma virus (HPV) vaccine and the pneumococcal conjugate vaccine (PCV).
Methods: This was a qualitative study that involved reviewing relevant Ugandan policy documents and media reports, as well as 54 key informant interviews at the global level and national and sub-national levels in Uganda. Kapiriri and Martin’s conceptual framework was used to evaluate the prioritization process.
Results: Priority setting for PCV and HPV was conducted by the Ministry of Health (MoH), which is considered to be a legitimate institution. While respondents described the priority setting process for PCV process as transparent, participatory, and guided by explicit relevant criteria and evidence, the prioritization of HPV was thought to have been less transparent and less participatory. Respondents reported that neither process was based on an explicit priority setting framework nor did it involve adequate representation from the districts (program implementers) or publicity. The priority setting process for both PCV and HPV was negatively affected by the larger political and economic context, which contributed to weak institutional capacity as well as power imbalances between development assistance partners and the MoH.
Conclusion: Priority setting in Uganda would be improved by strengthening institutional capacity and leadership and ensuring a transparent and participatory processes in which key stakeholders such as program implementers (the districts) and beneficiaries (the public) are involved. Kapiriri and Martin’s framework has the potential to guide priority setting evaluation efforts, however, evaluation should be built into the priority setting process a priori such that information on priority setting is gathered throughout the implementation cycle.

Journal of Health Communication
Published online: 27 Apr 2017
Original Articles
Explanations for Not Receiving the Seasonal Influenza Vaccine: An Ontario Canada Based Survey
SB Meyer, R Lum
Abstract
Despite evidence of the importance of the seasonal influenza vaccine for both individual and population health, only a third of the Ontario population received the vaccine in 2013/2014. The objective of this study was to identify why Ontarians are not getting the seasonal influenza vaccine. Written responses to the question “Why didn’t you get the seasonal flu vaccine in the last flu season?” were deductively analyzed using the Conceptual Model of Vaccine Hesitancy. Inductive coding was also conducted to identify explanations that fall outside of the present model and may be unique to the seasonal influenza vaccine. Data were collected between August and early September, 2014 through a survey in the Region of Waterloo, Ontario. Overall, 91.4% of responses could be explained using the conceptual model and specifically relate to perceived importance of vaccination (46.8%), moral convictions (19.4%), and past experiences with vaccinations services (14.5%). Notably, explanations related to healthcare professional attitudes, risk perceptions and trust, and subjective norms were identified to a much lesser extent than those discussed above. The remaining 8.6% of responses cannot be explained by the model because they do not relate to hesitancy. Our data contribute to the minimal body of Canadian research investigating low uptake of the seasonal flu vaccine, adding to an evidence-base upon which to inform promotional campaigns. Our data also highlight the utility of the Conceptual Model of Vaccine Hesitancy for the design and analysis of research investigating seasonal flu vaccine refusal or delay.

Media/Policy Watch

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.

Economic Times
http://economictimes.indiatimes.com/
Accessed 6 May 2017
Modi government advances immunisation programme deadline to 2018 
1 May 2017
…The Prime Minister’s Office has advanced the deadline for the Centre’s immunisation programme, Mission Indradhanush, by more than a year and asked the health ministry to strive to complete it by December 2018…

Forbes
http://www.forbes.com/
Accessed 6 May 2017
A New Hope: Vaccine Supply Chains Get More Attention
1 May 2017
Bruce Y. Lee Contributor
…Now, with a just-published special issue of the journal Vaccine entitled “Building Next-Generation Immunization Supply Chains,” vaccine supply chains are finally getting more deserved time in the limelight…
 

The Guardian
http://www.guardiannews.com/
Accessed 6 May 2017
Nigeria battles to beat polio and Boko Haram
Northern Nigeria is the frontline in two wars: the disease and the brutal rebels who reject the west’s influence
Tracy McVeigh
Saturday 6 May 2017 19.03 EDT
…This is the “flag-off” in Ungogo, Kano state. The party marks the first of four days of intense work by an army of volunteers, mostly young mothers, who will go door to door across Nigeria. Some will pass through thousands of twisting warrens of slums fanning out into the red-orange, mud-built hamlets and reed-thatched huts. Others will visit the crumbling concrete city blocks, slipping drops of polio vaccine into as many of the 30 million Nigerian children under five as they can find.
Their capes bear the slogan: “Lafiyar al’ummarmu hakkin kowa da kowa ne” – “The health of the child is the responsibilty of all.” The lunchboxes are filled with ice and polio vaccine. They have marker pens to dab on the finger of each treated child and chalk to mark every house wall they visit, marking which child was vaccinated and when. No one is to be missed out…

New York Times
http://www.nytimes.com/
Accessed 6 May 2017
Minnesota Sees Largest Outbreak of Measles in Almost 30 Years
Health officials are grappling with the largest outbreak of measles in Minnesota in almost 30 years, which is mainly sickening young children of Somali immigrants who fell under the sway of anti-vaccination activists.
The state has reported 44 confirmed cases of measles since April 11, and the outbreak is the largest this year in the United States, which had essentially eradicated the disease in 2000 before discredited research stoked fears of a link between vaccines and autism.
As of Thursday, 11 patients have been hospitalized, Doug Schultz, a spokesman for the Minnesota Department of Health, said on Friday. It is the largest outbreak in the state since 1990, when 460 cases were reported. All of the patients, with the exception of an adult health care worker, were children younger than 10. Most were under 5, he said.
May 05, 2017 – By CHRISTOPHER MELE

Julius Youngner, Polio Vaccine Pioneer, Dies at 96
[See Milestones/Perspectives above for full text]

The Opinion Pages | Editorial
1 May 2017
Populism, Politics and Measles
[See Milestones/Perspectives above for full text]

Think Tanks et al

Council on Foreign Relations
http://www.cfr.org/
Accessed 6 May 2017
Article
Can Drug Importation Address High Generic Drug Prices?
by Thomas J. Bollyky, Aaron S. Kesselheim May 5, 2017
…we propose a sustainable strategy to address price spikes among U.S. generic drugs and improve patients’ access to safe medicines. We begin by outlining the important role of generic medicines in the U.S. health system and the market failures that have contributed to recent price hikes and shortages. Next, we consider the various strategies that have been proposed to address those market failures and the reasons that those strategies are likely to fall short in fixing the problem. Third, we propose a three-pronged approach for increasing competition in the U.S. generic drug market, while minimizing any attendant risks to patient safety or undermining the institutional role of the FDA. This proposal centers on the use of reciprocal drug approval and draws on previous precedents and the existing platforms for regulatory cooperation in the pharmaceutical sector. Last, we apply our proposal to show how it might affect international competition among a cohort of U.S. drugs currently eligible for generic competition, but lacking sufficient competition to achieve substantial price reductions…

CSIS
https://www.csis.org/
Accessed 6 May 2017
New Partnerships Needed After Ebola’s Hard Lessons:
Program Manager and Research Associate Chris Millard and I published a new commentary exploring the vital importance of vaccines in both preventing and mitigating the effects of the next pandemic. We argue that three lessons came from the Ebola experience: 1) not having a vaccine at the ready when an outbreak strikes creates huge vulnerabilities and imposes tremendous costs; 2) scrambling to accelerate vaccine development in the middle of an outbreak is expensive and no way to conduct business; and 3) a new approach is needed to create durable partnerships, innovate and act early, and get ahead of the curve in vaccine development against dangerous pathogens. The piece was published by the Thomson Reuters Foundation