International Health
Volume 10, Issue 5, September 2018
http://inthealth.oxfordjournals.org/content/current

EDITORIAL
Eliminating poor quality medicines: ‘Caveat emptor, Caveat venditor’ (buyer beware, seller beware)
Joel G Breman
International Health, Volume 10, Issue 5, 1 September 2018, Pages 321–323, https://doi.org/10.1093/inthealth/ihy051
Extract
Survival is not the case for at least 122,000 African children under 5 y of age who die each year as a result of being treated with fake antimalarial drugs.1 Tens of thousands of others of all ages, with acute malaria and other diseases, are at peril or succumb when the medicines they receive have little or no active pharmaceutical ingredient, contain toxins or are a different compound than indicated on the package.

International Health
Volume 10, Issue 5, September 2018
http://inthealth.oxfordjournals.org/content/current

ORIGINAL ARTICLES
Impact of vaccine stock-outs on infant vaccination coverage: a hospital-based survey from South Africa
Rosemary J Burnett; Gloria Mmoledi; Ntombenhle J Ngcobo; Carine Dochez; L Mapaseka Seheri …
International Health, Volume 10, Issue 5, 1 September 2018, Pages 376–381, https://doi.org/10.1093/inthealth/ihy036

JAMA
August 28, 2018, Vol 320, No. 8, Pages 735-846
http://jama.jamanetwork.com/issue.aspx

Viewpoint
Comparison of 2 Treatment Models – Precision Medicine and Preventive Medicine
Bruce M. Psaty, MD, PhD; Olaf M. Dekkers, MD, PhD; Richard S. Cooper, MD
JAMA. 2018;320(8):751-752. doi:10.1001/jama.2018.8377
This Viewpoint compares the strengths and weaknesses of precision-medicine and preventive-medicine models for treating disease driven by genetics and disease driven by lifestyle and toxic environments.

JAMA
August 28, 2018, Vol 320, No. 8, Pages 735-846
http://jama.jamanetwork.com/issue.aspx

Gaps in the Clinical Management of InfluenzaA Century Since the 1918 Pandemic
Timothy M. Uyeki, MD, MPH, MPP; Robert A. Fowler, MD, MDCM, MSc; William A. Fischer II, MD
JAMA. 2018;320(8):755-756. doi:10.1001/jama.2018.8113
This Viewpoint reviews advances in the surveillance, diagnosis, and treatment of influenza since the 1918 pandemic, and identifies key clinical questions to address in advance of the next outbreak, including optimal treatment for hospitalized and critically ill patients and those with secondary bacterial pneumonia.

Journal of Evidence-Based Medicine
Volume 11, Issue 3  Pages: 131-215  August 2018
https://onlinelibrary.wiley.com/toc/17565391/current

COMMENTARY
Open Access
Meeting public health needs in emergencies–World Health Organization guidelines
Susan L. Norris
Pages: 133-135
First Published: 09 August 2018
Abstract
The World Health Organization (WHO) is a leading source of trustworthy guidelines in public health, including in emergencies. In addition to standard guidelines produced in preparation for emergency response, WHO has processes and methods for issuing guidelines in the context of urgent public health need, including rapid advice guidelines (production time 2 to 3 months) and health emergency interim guidelines (days to weeks). There are numerous challenges to producing guidelines in response to an emergency in addition to the compressed timeline which necessitates truncating or modifying standard processes. There is frequently a lack of scientific data on the disease or situation at hand, especially early in the event timeline. Resources are limited, particularly the availability of WHO staff and external experts, and disease and emergency response experts may lack knowledge and experience in developing guidelines. Finally, the rapid production of new information and the resultant short shelf‐life of recommendations pose a significant challenge to keeping guidelines up to date. In order to better meet end‐users’ needs, WHO must anticipate areas of uncertainty in emergency response and proactively develop relevant guidelines, explore optimal ways of communicating gaps in knowledge in the field to guideline developers, and promote and participate in research on the sources of bias in guideline development within compressed timeframes.

The Lancet
Sep 01, 2018 Volume 392 Number 10149 p711-794
https://www.thelancet.com/journals/lancet/issue/current

Editorial
Measles, war, and health-care reforms in Ukraine
The Lancet
[Excerpt]
Russian-backed attempts to sabotage Ukraine’s economic, political, and health developments have left the country fighting a measles outbreak and continuing a bloody, undeclared war. The situation is emblematic of increasing tension between the ideologies of President Vladimir Putin and countries of the pro-democratic, neoliberal west.

The measles outbreak—affecting other countries including Serbia, Georgia, Greece, and Italy—has hit Ukraine hardest, with the country’s 23 000 cases accounting for more than half the European regional total. Kremlin-supported social media accounts spreading discredited theories about the measles, mumps, rubella (MMR) vaccine, combined with shortages and underfunding, have been blamed for the outbreak. Research published on Aug 23 concluded Russian trolls promoted discord and, masquerading as legitimate users, created a false impression that arguments for and against vaccination were equipoised. The result has been an erosion of public consensus on the value of vaccine programmes. The precipitous fall in vaccination level began after 2008, when 95% of eligible children in Ukraine received their second (and final) recommended dose of the MMR vaccine. By 2016, the rate was 31%, among the lowest in the world. Although now rising again, the latest 85% measles vaccination rate recorded by WHO remains below that needed for herd immunity. Records in 2016 show poor vaccination rates for other diseases: only 19% of children received the third recommended dose of the diphtheria-tetanus-pertussis vaccine and 56% received the third recommended dose of oral polio vaccine. Hepatitis B vaccination was low, with coverage with hepatitis B birth-dose and third-dose vaccines at 37% and 26%, respectively. WHO estimates between 3% and 5% of the Ukraine’s 45 million population has been infected with hepatitis C. Ukraine bears the second largest HIV epidemic in eastern Europe and central Asia…

The Lancet
Sep 01, 2018 Volume 392 Number 10149 p711-794
https://www.thelancet.com/journals/lancet/issue/current

Viewpoint
Prevention of Ebola virus disease through vaccination: where we are in 2018
Yves Lévy, Clifford Lane, Peter Piot, Abdul Habib Beavogui, Mark Kieh, Bailah Leigh, Seydou Doumbia, Eric D’Ortenzio, Claire Lévy-Marchal, Jerome Pierson, Deborah Watson-Jones, Vinh-Kim Nguyen, Heidi Larson, Julia Lysander, Christine Lacabaratz, Rodolphe Thiebaut, Augustin Augier, David Ishola, Stephen Kennedy, Geneviève Chêne, Brian Greenwood, James Neaton, Yazdan Yazdanpanah
[Excerpts]
In 2016, Guinea, Liberia, and Sierra Leone succeeded in interrupting the longest epidemic of Ebola virus disease in global history.

Control of the epidemic was primarily achieved by implementation of effective and coordinated public health measures that involved rapid identification, isolation of cases, contact tracing, and isolation of contacts. However, the risk of re-emergence of Ebola virus disease is real, as shown by the 2017 and 2018 outbreaks in the Democratic Republic of the Congo. Consequently, along with other public health measures, efforts to develop an effective vaccine against Ebola virus disease must continue.

As of June 18, 2018, 36 completed trials, seven active and not recruiting, and seven recruiting Ebola vaccine studies are registered on ClinicalTrials.gov. The only study that has been able to provide data on clinical efficacy is the Ebola Ça Suffit vaccination trial in Guinea…o build on the vaccine research studies that have been done thus far, the outstanding questions on the rapidity and durability of the immune response in adults, safety and immunogenicity in children, and the nature of the responses in immunocompromised and pregnant individuals using different vaccine strategies must be addressed. Improved understanding of humoral and cellular immune responses to Ebola vaccines is needed to identify correlates of protection. Answering these questions will require improvement of global capacity to continue research on Ebola vaccines, and collaborative partnerships are needed to optimise the chances of success. Several Ebola vaccine clinical trials in Africa, North America, and Europe have been done using such partnerships, including the EBOVAC projects, the Ebola Ça Suffit vaccination trial consortium, STRIVE, and PREVAIL…

…Against this backdrop, the Partnership for Research on Ebola Vaccinations (PREVAC) was established as an international consortium, including research and academic institutions (the French Institute for Health and Medical Research [Inserm], London School of Hygiene & Tropical Medicine, the US National Institutes of Health, and the Universities of Bordeaux and Minnesota), health authorities and scientists from four Ebola-affected countries (Guinea, Liberia, Sierra Leone, and Mali), non-governmental organisations (the Alliance for International Medical Action and Leidos) and pharmaceutical companies (MSD, Johnson & Johnson, and Bavarian Nordic). This partnership was built to focus on Ebola research activities to prevent or respond effectively to the next potential Ebola outbreak. This consortium is currently conducting a randomised, double-blind, placebo-controlled trial of three Ebola vaccine strategies in adults and children (aged ≥1 year): (1) rVSV-ZEBOV prime without boost; (2) rVSV-ZEBOV prime followed by a rVSV-ZEBOV boost; and (3) Ad26.ZEBOV prime followed by MVA-BN-Filo boost. As of June, 2018, more than 2350 adults and children have been recruited, and an additional 2500 enrolments are planned to achieve the target enrolment.

In summary, it is important to investigate different scenarios for vaccination strategies and different vaccines to respond more effectively to future outbreaks. These strategies include contact and post-exposure vaccination, targeted preventive vaccination, and widespread preventive vaccination of at-risk populations such as health-care workers and those residing in areas of recurrent outbreaks.

The Lancet
Sep 01, 2018 Volume 392 Number 10149 p711-794
https://www.thelancet.com/journals/lancet/issue/current

Outrageous prices of orphan drugs: a call for collaboration
Lucio Luzzatto, Hanna I Hyry, Arrigo Schieppati, Enrico Costa, Steven Simoens, Franz Schaefer, Jonathan C P Roos, Giampaolo Merlini, Helena Kääriäinen, Silvio Garattini, Carla E Hollak, Giuseppe Remuzzi on behalf of the Second Workshop on Orphan Drugs participants
[Excerpt]
Few instances of a single act of legislation have shifted industrial policy in the pharmaceutical industry like the Orphan Drugs Act did when it was signed in the USA in 1983. The Act was written to facilitate the development of drugs for rare diseases and health conditions, and the incentives provided by the Act, such as 7 year exclusivity, tax credits of up to 50% of research and development costs, and access to research and development grants, resulted in the US Food and Drug Administration (FDA) approving 575 drugs and biological products for rare diseases between 1983 and 2017—a real success. In 2000, the European Commission passed similar legislation for orphan medicinal products (OMPs). As a matter of fact, the diseases, not the drugs, are the orphans because all drugs are very expensive, having marrying this success story (table).

Although we are dealing with rare diseases, the increasing number of new OMPs introduced each year is beginning to threaten the sustainability of health-care systems.
The socioeconomic, ethical, and legal implications of this state of affairs have been analysed extensively. We have previously discussed these implications, and here we concentrate on possible corrective actions. Although the focus here is on OMPs, our recommendations are applicable to other drugs…

Nature 
Volume 560 Issue 7720, 30 August 2018
http://www.nature.com/nature/current_issue.html

Editorial | 29 August 2018
Opening up peer review
A transparent process to publish referees’ reports could benefit science, but not all researchers want their assessments made available.

Nature 
Volume 560 Issue 7720, 30 August 2018
http://www.nature.com/nature/current_issue.html

Comment | 29 August 2018
Publish peer reviews
Jessica K. Polka and colleagues call on journals to sign a pledge to make reviewers’ anonymous comments part of the official scientific record.
Jessica K. Polka, Robert Kiley[…] & Ronald D. Vale

New England Journal of Medicine
August 30, 2018  Vol. 379 No. 9
http://www.nejm.org/toc/nejm/medical-journal

Perspective
Ending Use of Oral Poliovirus Vaccine — A Difficult Move in the Polio Endgame
Mark A. Pallansch, Ph.D.
When the world embarked on a mission of global polio eradication with the adoption of a World Health Assembly resolution in 1988, there was only minimal consideration of what would happen after the eradication of wild poliovirus (WPV) had been certified. Poliovirus eradication efforts have targeted three distinct serotypes, using two vaccines, each containing components against all three types — a live attenuated oral poliovirus vaccine (OPV) used in more than 100 mostly low- and middle-income countries worldwide and an inactivated poliovirus vaccine (IPV) used in most of the developed world. Many experts believed that vaccination against polio either would continue to evolve with strengthening of routine immunization or might be stopped by countries when they no longer had circulating wild-type virus. This view of the posteradication world changed with the first recognition, in 2000, of an outbreak caused by a virus resulting from the genetic reversion of one of the strains in OPV, which was subsequently named “circulating vaccine-derived poliovirus” (cVDPV).1 The detection of this outbreak was aided by the development and implementation of improved molecular diagnostics, which were also used to demonstrate that cVDPV outbreaks had occurred in the past but had been thought to be outbreaks of indigenous WPV strains.

The logical inference from the detection of cVDPV outbreaks was that long-term use of OPV posed an ongoing risk.2 Over the next several years, this finding convinced public health experts that the Global Polio Eradication Initiative (GPEI) needed to include more than certification and WPV containment; OPV vaccination also had to be stopped in order to ensure a polio-free world after eradication.

A more formal process was therefore begun to develop a strategic eradication plan that explicitly included stopping OPV use.3 Since the last case of WPV type 2 (WPV2) had occurred in 1999, the plan for OPV cessation evolved from concurrently stopping the use of all three OPV types to a modified serial plan in which the type 2 component of OPV would be removed first. The Global Commission for the Certification of the Eradication of Poliomyelitis certified WPV2 eradication in September 2015, and in April 2016 there was a coordinated global switch from the trivalent OPV to a bivalent OPV containing only the type 1 and 3 components.

Such synchronized vaccine cessation was unprecedented, and there were therefore many uncertainties. The stage was set for the work described by Blake et al. in this issue of the Journal (pages 834–845). As the authors note, the GPEI has a robust surveillance system for tracking polioviruses globally and has the ability to readily distinguish WPV, cVDPV, and OPV strains. This system allows public health officials to monitor whether, after the switch, all the OPV-related type 2 viruses (OPV2 and VDPV2) will ultimately disappear, as predicted. Because cVDPV type 2 (cVDPV2) outbreaks are sometimes not detected right away, experts predicted that some outbreaks detected after the switch would turn out to have begun before the switch; but newly emergent, postswitch cVDPV outbreaks were also predicted.

Blake et al. focused on analyzing the surveillance data from both acute flaccid paralysis and environmental surveillance systems to characterize the kinetics of OPV2 disappearance and to identify specific instances of events that were not predicted. The authors describe the disappearance of the OPV2-related strains after the switch and the cVDPV2 outbreaks that were newly detected. To date, these outbreaks have occurred in geographic areas where cVDPV and WPV outbreaks had occurred before the switch. These high-risk countries were also the ones where monovalent type 2 OPV (mOPV2) was used in response campaigns. The introduction of mOPV2 into these populations as part of an outbreak response resulted in detection of VDPV2 and OPV2-related viruses and subsequent disappearance of these viruses in the vaccine-coverage areas.

The heterogeneity of experiences at both national and subnational levels allowed analysts to identify specific risk factors for cVDPV2 emergence and variations in the rate of disappearance of OPV2-related strains. One major risk factor for emergence identified by the authors is low population immunity to type 2 virus. This factor not only was associated with virus emergence and circulation, but also had an influence on the rate of disappearance of OPV2-related strains after the use of mOPV2 and accounted for some of the heterogeneity of the rates observed. The critical importance to WPV eradication of population immunity is well understood, and in models, such immunity has a strong influence on the success of cessation of OPV use. The authors provide the first analytic evidence that population immunity is a critical determinant of the successful implementation of the OPV-cessation strategy.

The analysis by Blake et al. covers the first 2 years after the switch, when it was too early to detect any clear trends as a function of time after the last OPV2 use. Since, as the authors note, universal introduction of a single dose of IPV has not resulted in high coverage as originally planned, in part because of a global supply shortage, several countries have seen dramatic decreases in population immunity to type 2 poliovirus among children born after the switch. How this heterogeneity among countries in decreasing immunity will affect the likelihood and severity of future outbreaks, the choices made regarding outbreak responses, the risk of new cVDPV emergence, and the ultimate disappearance of type 2 poliovirus is not clear from this analysis. Answers to these questions not only are important for the completion of the OPV2 switch but also could significantly affect planning for the ultimate cessation of all OPV use.

At this point, the type of virus monitoring and analysis described by Blake et al. will need to continue until all type 2 viruses are no longer detected by the surveillance systems. Since the period covered by their analysis, new cVDPV2 outbreaks have been detected in Somalia and Kenya, the Democratic Republic of Congo, and Nigeria. Responses to these outbreaks have resulted in additional detections of OPV2-related virus. It will be important to monitor whether there are any observable changes over time in the disappearance of OPV2-related virus in these regions where new and past outbreaks have occurred. Each mOPV2 response to a cVDPV2 outbreak carries a risk of seeding new cVDPV2 outbreaks. The unfolding experience following the OPV2 switch will provide lessons that improve our understanding of problems confronting the endgame strategy of OPV cessation.

OPV withdrawal is only one of the elements of the polio endgame, which also includes the goals and challenges of laboratory and vaccine-manufacturing containment of poliovirus and sustaining of polio surveillance in order to detect and identify poliovirus infections. We still need to maintain a stockpile of polio vaccine for outbreak response. The existence of immunodeficient people who chronically excrete VDPV virus also necessitates an effective means of detection and intervention. Many of these issues will require additional research and development, including a better vaccine that produces mucosal immunity without the risk of VDPV, antivirals to treat chronic infections, and better surveillance tools for a world that will quickly forget about polio after eradication is achieved. Clearly, persistence and patience will be needed, not only to complete eradication of WPV, but also for the polio endgame.

New England Journal of Medicine
August 30, 2018  Vol. 379 No. 9
http://www.nejm.org/toc/nejm/medical-journal

Original Articles
Type 2 Poliovirus Detection after Global Withdrawal of Trivalent Oral Vaccine
Isobel M. Blake, Ph.D., Margarita Pons-Salort, Ph.D., Natalie A. Molodecky, Ph.D., Ousmane M. Diop, Ph.D., Paul Chenoweth, N.D., Ananda S. Bandyopadhyay, M.B., B.S., Michel Zaffran, Eng.,
Roland W. Sutter, M.D., and Nicholas C. Grassly, D.Phil.
Background
Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses.
Methods
We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine–derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2…
Conclusions
High population immunity has facilitated the decline in the prevalence of Sabin-2 poliovirus after OPV2 withdrawal and restricted the circulation of VDPV2 to areas known to be at high risk for transmission. The prevention of VDPV2 outbreaks in these known areas before the accumulation of substantial cohorts of children susceptible to type 2 poliovirus remains a high priority. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization.)

PLOS Currents: Disasters
http://currents.plos.org/disasters/
[Accessed 1 Sep 2018]

Earthquakes to Floods: A Scoping Review of Health-related Disaster Research in Low- and Middle-income Countries
Catherine M. Tansey, John Pringle, Anushree Davé, Renaud Boulanger, Matthew Hunt
August 30, 2018 · Review
Introduction: Health-related disaster research is a relatively small; but growing field of inquiry.  A better understanding of the scope and scale of health-related disaster research that has occurred in low- and middle-income countries (LMICs) would be useful to funders, researchers, humanitarian aid organizations, and governments as they strive to identify gaps, disparities, trends, and needs of populations affected by disasters.
Methodology: We performed a scoping review using the process outlined by Arksey & O’Malley to assess the characteristics of peer-reviewed publications of empirical health-related disaster research conducted in LMICs and published in the years 2003-2012.
Results: Five hundred and eighty-two relevant publications were identified.  Earthquakes were by far the most commonly researched events (62% of articles) in the review’s timeframe.  More articles were published about disasters in China & South Asia/South East Asia than all other regions.  Just over half of the articles (51%) were published by research teams in which all the authors’ primary listed affiliations were with an institution located in the same country where the research was conducted.  Most of the articles were classified as either mental health, neurology and stress physiology (35%) or as traumatology, wounds and surgery (19%).  In just over half of the articles (54%), data collection was initiated within 3 months of the disaster, and in 13% research was initiated between 3 and 6 months following the disaster.  The articles in our review were published in 282 different journals.
Discussion: The high number of publications studying consequences of an earthquake may not be surprising, given that earthquakes are devastating sudden onset events in LMICs.  Researchers study topics that require immediate attention following a disaster, such as trauma surgery, as well as health problems that manifest later, such as post-traumatic stress disorder.  One neglected area of study during the review’s timeframe was the impact of disasters on non-communicable and chronic diseases (excluding mental health), and the management of these conditions in the aftermath of disasters. Strengthening disaster research capacity is critical for fostering robust research in the aftermath of disasters, a particular need in LMICs.

PLoS Currents: Outbreaks
http://currents.plos.org/outbreaks/
[Accessed 1 Sep 2018]

Information Circulation in times of Ebola: Twitter and the Sexual Transmission of Ebola by Survivors
August 28, 2018 · Research Article
Introduction: The 2013-2015 outbreak of Ebola was by far the largest to date, affecting Guinea, Liberia, Sierra Leone, and secondarily, Nigeria, Senegal and the United States. Such an event raises questions about the circulation of health information across social networks. This article presents an analysis of tweets concerning a specific theme: the sexual transmission of the virus by survivors, at a time when there was a great uncertainty about the duration and even the possibility of such transmission.
Methods: This article combines quantitative and qualitative analysis. From a sample of 50,000 tweets containing the words “Ebola” in French and English, posted between March 15 and November 8, 2014, we created a graphic representation of the number of tweets over time, and identified two peaks: the first between July 27 and August 16, 2014 (633 tweets) and the second between September 28 and November 8, 2014 (2,577 tweets). This sample was divided into two parts, and every accessible publication was analyzed and coded according to the authors’ objectives, feelings expressed and/or publication type.
Results: While the results confirm the significant role played by mainstream media in disseminating information, media did not create the debate around the sexual transmission of Ebola and Twitter does not fully reflect mainstream media contents. Social media rather work like a “filter”: in the case of Ebola, Twitter preceded and amplified the debate with focusing more than the mainstream media on the sexual transmission, as expressed in jokes, questions and criticism.
Discussion: Online debates can of course feed on journalistic or official information, but they also show great autonomy, tinged with emotions or criticisms. Although numerous studies have shown how this can lead to rumors and disinformation, our research suggests that this relative autonomy makes it possible for Twitter users to bring into the public sphere some types of information that have not been widely addressed. Our results encourage further research to understand how this “filter” works during health crises, with the potential to help public health authorities to adjust official communications accordingly. Without a doubt, the health authorities would be well advised to put in place a special watch on the comments circulating on social media (in addition to that used by the health monitoring agencies).

PLoS Medicine
http://www.plosmedicine.org/
(Accessed 1 Sep 2018)

Perspective
Different scientific approaches are needed to generate stronger evidence for population health improvement
Martin White, Jean Adams
| published 28 Aug 2018 PLOS Medicine
https://doi.org/10.1371/journal.pmed.1002639
[Excerpt]
… Broader, more nuanced, and more informative research questions cannot be answered using traditional, more simplistic approaches to evaluation. The present evidence base is significantly limited by a failure to embrace different ways of thinking and working, including addressing questions of context and those related to complex adaptive systems [17,18]. However, a consequence of taking a broader approach to evaluation that embraces complexity will be that it challenges prevailing methodological orthodoxies. Researchers, funders, and journals may all be reluctant to relinquish existing hierarchies of evidence and ‘traditional’ methods of evidence synthesis. With so many intractable global public health challenges associated with NCDs in need of robustly researched solutions, this seems short-sighted. Greater ambition and leadership are needed among researchers, funders, and policymakers to enable smarter approaches to the development and evaluation of low-agency population interventions, including taxes on unhealthy commodities, regulation of marketing, and structural interventions to make active living easier. Ambition and leadership coupled with greater international collaboration to identify opportunities for—and to coordinate efforts to fund, implement, and build capacity for—quasi-natural and natural experimental evaluations of these interventions could more rapidly advance science on NCD prevention.

PLoS One
http://www.plosone.org/
[Accessed 1 Sep 2018]

Research Article
Using geographical analysis to identify child health inequality in sub-Saharan Africa
Jennifer Yourkavitch, Clara Burgert-Brucker, Shireen Assaf, Stephen Delgado
Research Article | published 29 Aug 2018 PLOS ONE
https://doi.org/10.1371/journal.pone.0201870
Abstract
One challenge to achieving Millennium Development Goals was inequitable access to quality health services. In order to achieve the Sustainable Development Goals, interventions need to reach underserved populations. Analyzing health indicators in small geographic units aids the identification of hotspots where coverage lags behind neighboring areas. The purpose of these analyses is to identify areas of low coverage or high need in order to inform effective resource allocation to reduce child health inequity between and within countries. Using data from The Demographic and Health Survey Program surveys conducted in 27 selected African countries between 2010 and 2014, we computed estimates for six child health indicators for subnational regions. We calculated Global Moran’s I statistics and used Local Indicator of Spatial Association analysis to produce a spatial layer showing spatial associations. We created maps to visualize sub-national autocorrelation and spatial clusters. The Global Moran’s I statistic was positive for each indicator (range: 0.41 to 0.68), and statistically significant (p <0.05), suggesting spatial autocorrelation across national borders, and highlighting the need to examine health indicators both across countries and within them. Patterns of substantial differences among contiguous subareas were apparent; the average intra-country difference for each indicator exceeded 20 percentage points. Clusters of cross-border associations were also apparent, facilitating the identification of hotspots and informing the allocation of resources to reduce child health inequity between and within countries. This study exposes differences in health indicators in contiguous geographic areas, indicating that specific regional and subnational, in addition to national, strategies to improve health and reduce health inequalities are warranted
[Article Excerpt]
…Geographic context of child health inequity for six key indicators
…Measles and Diphtheria, pertussis, and tetanus (DPT-3) immunizations.
Although preventable with immunization, measles is still a leading cause of death for children under 5, and is highly contagious [19]. Diphtheria, pertussis, and tetanus are also vaccine-preventable diseases that contribute to substantial global disease burden among children. In addition to measuring coverage of full protection against these diseases, DPT-3 can be a measure of health system strength because it requires individual follow-up on three occasions.
There is high variability of immunization coverage between and within African countries [20]. Identifying geographic areas of low coverage in order to focus immunization efforts was recommended decades ago [21]. Geographic isolation (remoteness) is a key barrier to equitable vaccine coverage for measles and countries with lower coverage have greater inequity [22]. Vaccination rates correlated with distance to a health center in Niger, where distance was affected by geo-temporal conditions hindering access [11]. That spatial analysis pinpointed optimal locations for new health facilities to improve access for hundreds of thousands of people [11] and exemplifies the utility of subnational spatial analysis of immunization and other child health indicators. No research to date has examined the spatial distribution of immunization coverage across and within a large proportion of African countries…

Science         
31 August 2018  Vol 361, Issue 6405
http://www.sciencemag.org/current.dtl
Special Issue: Technologies Transforming Biology

Editorial
Revolutionary technologies
By Jeremy Berg
Science31 Aug 2018 : 827
Summary
In this issue of Science, we present reviews of four technologies whose power and rapid growth across biological research communities make them revolutionary (see page 864). New technology is one of the most powerful drivers of scientific progress. For example, the earliest microscopes magnified images only 50-fold at most. When the Dutch fabric merchant and amateur scientist Antonie van Leeuwenhoek developed microscopes with more than 200-fold magnifications (likely to examine cloth), he used them to study many items, including pond water and plaque from teeth. His observations of “animalcules” led to fundamental discoveries in microbiology and cell biology, and spurred the elaboration of improved microscopes. Today, various light microscopes remain prime tools in modern biology. This example embodies two characteristics of a revolutionary technology: a capability for addressing questions better than extant technologies, and the possibility of being utilized and adapted by many other investigators

Science         
31 August 2018  Vol 361, Issue 6405
http://www.sciencemag.org/current.dtl
Special Issue: Technologies Transforming Biology

CRISPR-Cas guides the future of genetic engineering
By Gavin J. Knott, Jennifer A. Doudna
Science31 Aug 2018 : 866-869
Abstract
The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.

Science Translational Medicine
29 August 2018  Vol 10, Issue 456
http://stm.sciencemag.org/

Perspective
Glycoconjugate vaccines: Principles and mechanisms
By Rino Rappuoli
Science Translational Medicine29 Aug 2018 Restricted Access
Insight into the mechanisms of glycoconjugate vaccines can improve their efficacy and impact in the future.
Abstract
Bacterial conjugate vaccines are used in infants, adolescents, and the elderly, and they are among the safest and most successful vaccines developed during the last 40 years. Conjugation of polysaccharides to proteins provides T cell epitopes that are necessary in the germinal centers for the affinity maturation of polysaccharide-specific B cells. Collective analysis of data from animal experiments and clinical trials, reviewed with current knowledge of immunology, revealed possible mechanistic explanations that may improve our understanding of conjugate vaccines. Key conclusions are that naïve infants respond differently from adolescents and adults and that most of recommended schedules generate only 10 to 35% of the maximal antibody titer that the vaccine can induce, indicating that the full potential of glycoconjugate vaccines has not yet been reached.

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36

Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan
Research article 
Personalized vaccinology: A review
G.A. Poland, I.G. Ovsyannikova, R.B. Kennedy
Pages 5350-5357
Abstract
At the current time, the field of vaccinology remains empirical in many respects. Vaccine development, vaccine immunogenicity, and vaccine efficacy have, for the most part, historically been driven by an empiric “isolate-inactivate-inject” paradigm. In turn, a population-level public health paradigm of “the same dose for everyone for every disease” model has been the normative thinking in regard to prevention of vaccine-preventable infectious diseases. In addition, up until recently, no vaccines had been designed specifically to overcome the immunosenescence of aging, consistent with a post-WWII mentality of developing vaccines and vaccine programs for children. It is now recognized that the current lack of knowledge concerning how immune responses to vaccines are generated is a critical barrier to understanding poor vaccine responses in the elderly and in immunoimmaturity, discovery of new correlates of vaccine immunogenicity (vaccine response biomarkers), and a directed approach to new vaccine development.

The new fields of vaccinomics and adversomics provide models that permit global profiling of the innate, humoral, and cellular immune responses integrated at a systems biology level. This has advanced the science beyond that of reductionist scientific approaches by revealing novel interactions between and within the immune system and other biological systems (beyond transcriptional level), which are critical to developing “downstream” adaptive humoral and cellular responses to infectious pathogens and vaccines. Others have applied systems level approaches to the study of antibody responses (a.k.a. “systems serology”), [1] high-dimensional cell subset immunophenotyping through CyTOF, [2,3] and vaccine induced metabolic changes [4]. In turn, this knowledge is being utilized to better understand the following: identifying who is at risk for which infections; the level of risk that exists regarding poor immunogenicity and/or serious adverse events; and the type or dose of vaccine needed to fully protect an individual. In toto, such approaches allow for a personalized approach to the practice of vaccinology, analogous to the substantial inroads that individualized medicine is playing in other fields of human health and medicine. Herein we briefly review the field of vaccinomics, adversomics, and personalized vaccinology.

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36
Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan

Research article  Open access
Focusing on the implementation of 21st century vaccines for adults
Paolo Bonanni, Guglielmo Bonaccorsi, Chiara Lorini, Francesca Santomauro, … Angela Bechini
Pages 5358-5365
Abstract
Adult immunization is a priority for public health, particularly in countries where an aging population has become increasingly more numerous. Protection against diseases which typically affect adults (like flu, pneumococcal diseases and Herpes zoster), the shift of age of infections which originally affected children (like measles), the decreasing protection with time for infections which need periodical booster doses of vaccines (Tdap), the availability of vaccines which can also impact on adult health (HPV) are only some examples of the importance of implementing targeted vaccination strategies.
The possibility to reach high coverage with immunizations that can guarantee a fundamental improvement of health for adults and the elderly can only be achieved through a coordinated effort where all stakeholders, under the coordination of public health, contribute to issue recommendations; create a functioning database for vaccine coverage registration; promote formative courses for healthcare workers and continuous information for the public; increase vaccines uptake among healthcare workers, who need to give the first testimony on the relevance of immunization.

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36
Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan

Research article
The crucial role of maternal care providers as vaccinators for pregnant women
Luz Maria Vilca, Susanna Esposito
Pages 5379-5384

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36
Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan

Research article
Vaccination in newly arrived immigrants to the European Union
Roman Prymula, Jana Shaw, Roman Chlibek, Ingrid Urbancikova, Karolina Prymulova
Pages 5385-5390

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36
Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan

Research article 
Progress in prophylactic human papillomavirus (HPV) vaccination in 2016: A literature review
Polona J. Maver, Mario Poljak
Pages 5416-5423

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36
Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan

Research article
Global polio eradication: Where are we in Europe and what next?
Lucia Pastore Celentano, Paloma Carrillo-Santisteve, Patrick O’Connor, Niklas Danielsson, … Donato Greco
Pages 5449-5453

Vaccine
Volume 36, Issue 36, Pages 5349-5494 (28 August 2018)
https://www.sciencedirect.com/journal/vaccine/vol/36/issue/36
Progress in Vaccines
Research grant and educational unconditioned grant received from GSK, Novartis, Pfizer, Sanofi MSD — Edited by Mario Poljak, Susanna Esposito, Litjan Tan

Research article
Vaccines against Ebola virus
Navin Venkatraman, Daniel Silman, Pedro M. Folegatti, Adrian V.S. Hill
Pages 5454-5459

Vaccines — Open Access Journal
http://www.mdpi.com/journal/vaccines
(Accessed 1 Sep 2018)

Open Access  Review
The Future of Influenza Vaccines: A Historical and Clinical Perspective
by Nicole M. Bouvier
Vaccines 2018, 6(3), 58; https://doi.org/10.3390/vaccines6030058 – 30 August 2018
Abstract
For centuries, the development of vaccines to prevent infectious disease was an empirical process. From smallpox variolation in Song dynasty China, through the polysaccharide capsule vaccines developed in the 1970s, vaccines were made either from the pathogen itself, treated in some way to render it attenuated or non-infectious, or from a closely related non-pathogenic strain. In recent decades, new scientific knowledge and technologies have enabled rational vaccine design in a way that was unimaginable before. However, vaccines optimal against some infectious diseases, influenza among them, have remained elusive. This review will highlight the challenges that influenza viruses pose for rational vaccine design. In particular, it will consider the clinically beneficial endpoints, beyond complete sterilizing immunity, that have been achieved with vaccines against other infectious diseases, as well as the barriers to achieving similar success against influenza

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

Reviews in Medical Virology
First published: 29 August 2018  https://doi.org/10.1002/rmv.2003
Review
Rotavirus: Genetics, pathogenesis and vaccine advances
A Sadiq, N Bostan, KC Yinda, S Naseem, S Sattar – 2018
Summary
Since its discovery 40 years ago, rotavirus (RV) is considered to be a major cause of infant and childhood morbidity and mortality particularly in developing countries. Nearly every child in the world under 5 years of age is at the risk of RV infection. It is estimated that 90% of RV‐associated mortalities occur in developing countries of Africa and Asia. Two live oral vaccines, RotaTeq (RV5, Merck) and Rotarix (RV1, GlaxoSmithKline) have been successfully deployed to scale down the disease burden in Europe and America, but they are less effective in Africa and Asia. In April 2009, the World Health Organization recommended the inclusion of RV vaccination in national immunization programs of all countries with great emphasis in developing countries. To date, 86 countries have included RV vaccines into their national immunization programs including 41 Global Alliance for Vaccines and Immunization eligible countries. The predominant RV genotypes circulating all over the world are G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8], while G12[P6] and G12[P8] are emerging genotypes. On account of the segmented genome, RV shows an enormous genetic diversity that leads to the evolution of new genotypes that can influence the efficacy of current vaccines. The current need is for a global RV surveillance program to monitor the prevalence and antigenic variability of new genotypes to formulate future vaccine development planning. In this review, we will summarize the previous and recent insights into RV structure, classification, and epidemiology and current status of RV vaccination around the globe and will also cover the status of RV research and vaccine policy in Pakistan.

Public Health
Volume 164, November 2018, Pages 16-25
Original Research
What is causing high polio vaccine dropout among Pakistani children?
W Imran, F Abbas, SA Javed – Public Health, 2018
Highlights
:: In almost three decades, there is about 58 percentage point reduction in polio dropout across Pakistan.
:: Rural Pakistani child is highly likely to be dropout of polio vaccination relative to his/her urban counterparts.
:: Significant likelihood of increase in never-vaccinated children in Baluchistan, KPK, and Sindh during 2012–13 is alarming.
:: Children of female-headed household are less likely to be dropouts.

Journal of Preventive Medicine and Public Health (JPMPH)
2018 Jul; 51(4): 173–180.  Published online 2018 May 25.
Original Article
Factors Influencing Vaccination in Korea: Findings From Focus Group Interviews
Bomi Park,1 Eun Jeong Choi,1 Bohyun Park,1 Hyejin Han,1 Su Jin Cho,2 Hee Jung Choi,3 Seonhwa Lee,1 and Hyesook Park1
Abstract
Objectives
Immunization is considered one of the most successful and cost-effective public health interventions protecting communities from preventable infectious diseases. The Korean government set up a dedicated workforce for national immunization in 2003, and since then has made strides in improving vaccination coverage across the nation. However, some groups remain relatively vulnerable and require intervention, and it is necessary to address unmet needs to prevent outbreaks of communicable diseases. This study was conducted to characterize persistent challenges to vaccination.
Methods
The study adopted a qualitative method in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist. Three focus group interviews were conducted with 15 professionals in charge of vaccination-related duties. The interviews were conducted according to a semi-structured guideline, and thematic analysis was carried out. Data saturation was confirmed when the researchers agreed that no more new codes could be found.
Results
A total of 4 main topics and 11 subtopics were introduced regarding barriers to vaccination. The main topics were vaccine hesitancy, personal circumstances, lack of information, and misclassification. Among them, vaccine hesitancy was confirmed to be the most significant factor impeding vaccination. It was also found that the factors hindering vaccination had changed over time and disproportionately affected certain groups.
Conclusions
The study identified ongoing unmet needs and barriers to vaccination despite the accomplishments of the National Immunization Program. The results have implications for establishing tailored interventions that target context- and group-specific barriers to improve timely and complete vaccination coverage.

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.
 
 
The Atlantic
http://www.theatlantic.com/magazine/
Accessed 1 Sep 2018
[No new, unique, relevant content]
 
BBC
http://www.bbc.co.uk/
Accessed 1 Sep 2018
[No new, unique, relevant content]
 
The Economist
http://www.economist.com/
Accessed 1 Sep 2018
Battling Ebola in a war zone in Congo – A deadly virus in an already dangerous place…
Health workers are finding it hard to outrun a deadly virus
30 August 2018
 
Financial Times
http://www.ft.com/home/uk
Accessed 1 Sep 2018
[No new, unique, relevant content]
 
Forbes
http://www.forbes.com/
Accessed 1 Sep 2018
Aug 30, 2018
Meet The Forgotten Scientist Who Invented The Measles Vaccine
Kiona N. Smith, Contributor
Jonas Salk gained worldwide fame for his polio vaccine; Louis Pasteur is remembered, among other things, for developing a vaccine against rabies, and Edward Jenner’s name is forever connected to vaccination against smallpox. But history barely remembers the microbiologist who, arguably, saved more lives than any other doctor or medical researcher of the 20th century (and who continues to save millions every year despite having been dead since 2005).         His name is Maurice R. Hilleman, and during his 40-year career, he developed over 40 human and animal vaccines (that’s roughly a vaccine per year, for those of you playing at home), including the ones for chickenpox, hepatitis A and B, measles, meningitis, mumps, rubella, and several strains of the flu virus. The measles vaccine alone prevents an estimated 1 million deaths from the once-common disease every year…

Foreign Affairs
http://www.foreignaffairs.com/
Accessed 1 Sep 2018
[No new, unique, relevant content]

Foreign Policy
http://foreignpolicy.com/
Accessed 1 Sep 2018
[No new, unique, relevant content]

The Guardian
http://www.guardiannews.com/
Accessed 1 Sep 2018
[No new, unique, relevant content]
 
New Yorker
http://www.newyorker.com/
Accessed 1 Sep 2018
[No new, unique, relevant content]
 
New York Times
http://www.nytimes.com/
Accessed 1 Sep 2018
Sept. 1, 2018
Africa
Ebola Control Measures Seem to Be Working in Congo, WHO Says
Efforts to halt an outbreak of the deadly Ebola virus in Democratic Republic of Congo appear to be working, but substantial risks remain, the World Health Organization said on Friday.

Aug. 30, 2018
Middle East
UN Says 120,000 Suspected Cases of Cholera in Yemen
The United Nations says nearly 120,000 suspected cases of cholera were reported in conflict-wracked Yemen between January and mid-August and the pace has been increasing.

Wall Street Journal
http://online.wsj.com/home-page?_wsjregion=na,us&_homepage=/home/us
Accessed 1 Sep 2018
[No new, unique, relevant content]

Washington Post
http://www.washingtonpost.com/
Accessed 1 Sep 2018
[No new, unique, relevant content]

Think Tanks et al
 
Brookings
http://www.brookings.edu/
Accessed 1 Sep 2018
[No new relevant content]

Center for Global Development  
http://www.cgdev.org/page/press-center
Accessed 1 Sep 2018
[No new relevant content]

CSIS
https://www.csis.org/
Accessed 1 Sep 2018
[No new relevant content]

Council on Foreign Relations
http://www.cfr.org/
Accessed 1 Sep 2018
[No new relevant content]