Infectious Disease Risk and Vaccination in Northern Syria after 5 Years of Civil War : The MSF Experience February 2 , 2018 ·

This weekly digest targets news, events, announcements, articles and research in the vaccine and global health ethics and policy space and is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage.

and sequenced, can switch into manufacturing mode and produce of the order of 10,000 doses in a matter of weeks as part of localised containment strategy?
2. How to improve and optimise existing manufacturing processes and change the way vaccines are manufactured, stabilised and stored so that costs are reduced, efficiencies increased and existing and new diseases prevented effectively?
Our proposed programme has been developed with LMIC partners as an integrated approach that will bring quick wins to challenge 2 while building on new developments in life sciences, immunology and process systems to bring concepts addressing challenge 1 to fruition.
Examples of strategies for challenge 1 are RNA vaccines. The significant advantage of synthetic RNA vaccines is the ability to rapidly manufacture many thousands of doses within a matter of weeks. This provides a viable business model not applicable to other technologies with much longer lag phases for production (viral vectors, mammalian cell culture), whereby procurement of the vaccine can be made on a needs basis avoiding the associated costs of stockpiling vaccines for rapid deployment, monitoring their on going stability and implementing a cycle of replacement of expired stock. In addition, low infrastructure and equipment costs make it feasible to establish manufacture in low-income settings, where all required equipment has potential to be run from a generator driven electrical supply in the event of power shortage. This fits the concept of a distributed, flexible platform technology, in that once a threat is identified, the specific genetic code can be provided to the manufacturing process and the doses of the specific vaccine can be produced without delay. Additional concepts that we will explore in this category include the rapid production of yeast and bacterially expressed particles that mimic membrane expressed components of pathogenic viruses and bacteria.
Examples of strategies for challenge 2 build on our work on protein stabilisation which has been shown to preserve the function of delicate protein enzymes at temperatures over 100 degrees C. We shall exploit this knowledge to develop new vaccine stabilisation and formulation platforms. These can be used in two ways: (a) to support the last few miles of delivery from centralised cold chains to patients through reformulation and (b) for direct production of thermally stable forms, i.e. vaccines that retain their activity for months despite being not being refrigerated.
We believe that the best way to deliver these step changes in capability and performance is through a team-based approach that applies deep integration in two dimensions: between UK and LMIC partners to ensure that all the LMIC considerations are "baked in" from the start and between different disciplines accounting for the different expertise that will be required to meet the challenges.

Dengvaxia
We continue to monitor developments associated with Dengvaxia. We did not identify any new press releases or statements on the Sanofi website.

'Stop PAO autopsies on suspected Dengvaxia victims'
Ex-DOH chief Esperanza Cabral and other doctors urge the DOJ to stop PAO's autopsies on 14 children who supposedly died due to Dengvaxia February 03, 2018 By Michael Bueza MANILA, Philippines -A group of doctors, including former health secretary Esperanza Cabral, urged the Department of Justice (DOJ) to stop the Public Attorney's Office (PAO) from conducting autopsies on 14 children who supposedly died due to the controversial dengue vaccine Dengvaxia.
In a statement Saturday, February 3, the group Doctors for Public Welfare said it makes "no sense for any more families to be subjected to the torture of having a loved one exhumed and cut up, only to find out that no useful information was derived from the cruel act." "We urge the Department of Justice to order the PAO to stop performing autopsies on these children, and to leave the matter of determining the cause of death to competent forensic pathologists," the doctors said.
The group issued the statement after forensic pathologists from the University of the Philippines-Philippine General Hospital (UP-PGH) presented their diagnosis on these deaths on Friday, February 2…

Kids' vaccination rate down to 60% after Dengvaxia scare -DOH
Health Undersecretary Enrique Domingo appeals to parents to continue getting 'tried and tested' vaccines for their children to avoid diseases like polio, diphtheria, measles, and tetanus February 02, 2018 By Mara Cepeda MANILA, Philippines -The Department of Health (DOH) is alarmed as more and more parents are refusing to avail of the government's various vaccination programs following the Dengvaxia mess.
Health Undersecretary Enrique Domingo said on Friday, February 2, that only about 60% of Filipino children are getting their scheduled vaccines, when the DOH's annual vaccination rate target is around 85%.
"I think we are down to 60% coverage, kasi dati gusto natin diyan mga 85% (because we usually want the figure at 85%). I don't know exactly the exact figures but siguro (maybe) by the end of the year, we'll get a more exact figure. But the local experience right now is the uptake of our vaccination programs is really going down," Domingo in a press conference on Friday.
The health official made the statement on the same day that the DOH and the experts panel from the University of the Philippines-Philippine General Hospital bared the results of the analysis of 14 cases of children who died after getting vaccinated with Sanofi Pasteur's Dengvaxia dengue vaccine.
Three vaccinated children developed and died of dengue, 9 died due to various diseases they got after their vaccination, while the cause of death of the last two cases remain unknown.
Domingo explained that parents have become so scared after Sanofi announced Dengvaxia may lead a person to develop severe dengue if he or she had not been infected by the virus prior to immunization. (READ: TIMELINE: Dengue immunization program for public school students) The parents are now refusing to avail of free government vaccines that could prevent their kids from getting other preventable diseases like polio and measles. Domingo said this explains the recent measles outbreak in Davao. He added parents are even avoiding deworming initiatives from the DOH.
"We really just like to implore all of our parents na kung nagkaroon po tayo ng duda, kung nagkaroon po talaga tayo ng problema dito sa bakunang [Dengvaxia na] ito, hindi po dapat madamay 'yong ibang bakuna (We really just like to implore all of our parents that if you have doubts, if you had problems with the Dengvaxia vaccine, don't let other vaccines be affected by it)," said Domingo.
"[Ito ay] dahil napakarami nating bakuna na magpoprotekta sa anak ninyo, sa polio, sa diphtheria, sa tigdas, sa tetanus. Mga tried and tested po ito at kailangan maibigay ito sa ating mga anak," he added. (This is because we have countless other vaccines that can protect your child from polio, diphtheria, measles, and tetanus. They are tried and tested, and it is vital that your children get them.) Health Secretary Francisco Duque III made the same appeal to parents as soon as he suspended the dengue vaccination program in December 2017…

Philippines: 3 Deaths May Be Linked to Dengue Vaccinations
New York Times | 2 February 2018 MANILA, Philippines -Philippine health officials said Friday that the deaths of three children injected with a Sanofi Pasteur dengue vaccine may have "causal association" to the inoculation, including two who may have died because the vaccine failed.
The Philippine government halted its massive immunization drive last year after Sanofi said a study showed the vaccine may increase the risks of dengue in people vaccinated prior to infection. More than 830,000 children were injected with the Dengvaxia vaccine, health officials said.
"This issue continues to sow fear and confusion, especially to the parents of children who have been injected with Dengvaxia," Health Secretary Francisco Duque III's office said in a statement. "We aim to give clarity on the issues with an honest and objective reporting of the evidence and science." Duque said further study was needed on the vaccine. Investigators found no evidence the rest of the 14 reported child deaths were related to the vaccine.
Dr. Juliet Sio-Aguilar, who led the investigation, told a news conference that only one of the three dead children had developed dengue antibodies, which would have served as a protection against an infection, but still died.
"We really want to know what happened," she said. Sanofi Pasteur officials did not immediately issue any comment. Secretary Duque closed the conference by issuing a set of directives to be immediately pursued and enforced by the entire DOH which will be subject to amendments as the need arises during their implementation.

SECRETARY'S DIRECTIVES
"Considering all the discussions, resolutions, and other outputs of this Joint Executive Committee Meeting and Command Conference on Dengvaxia, I, the Secretary of Health, hereby direct the following: The Dengue Task Force: (a) has approved in principle three interim guidelines to address the issues and concerns as a result of the Dengue vaccination initiative subject to the final review of the Expert Panel: [i] Surveillance -instituting a mechanism of enhanced surveillance over the next five years initially covering admitted cases following immunization, and then expanding to a reporting system covering outpatient settings through health centers, clinics, LGUs, and regional offices.
[ii] Dengue case management and patient referral -emphasizing on the early diagnosis and proper case management of Dengue; and, establishing a network of both public and private hospitals which can provide services to patients.
[iii] Risk communication -giving correct information to allay unfounded fears based on misconceptions; provide basic information on Dengue and the 4S approach to prevent infection; constantly updating the public on DOH's efforts in addressing the concerns of vaccinees; and, designating public health advocates at the regional offices and hospitals who can help patients navigate through the health system so that their health needs are adequately and expeditiously addressed.
These interim guidelines are immediately effective once approved subject to specific period of implementation and revisions as we learn more from our experience.
(b) shall review the policy and processes on the introduction of new antigens in our national immunization program; (c) shall study other proposed guidelines to enhance the delivery of public health vaccination programs; [i] Financing and reimbursement of hospitalized cases of adverse events following immunization using PhilHealth, the Medical Assistance Program, and other possible financing sources. For the regional offices to negotiate with private providers not to charge beyond the PhilHealth case rates.
[ii] Vaccine Injury Compensation; [iii] Autopsy of alleged deaths following Dengvaxia immunization; and, [iv] Laboratory diagnosis and confirmatory test.
(d) shall pursue possible legislative reforms that emerged from this issue by: [i] Strengthening the mandate of RITM to be an independent research arm on infectious diseases, not influenced by the industry; and, [ii] Strengthening the independence of FDA in exercising its mandate to protect the public in regulating health products.
(e) shall be constantly vigilant about possible/emerging concerns that may arise from this issue.
In relation to this, I would also like to reiterate my request to the Expert Panel to give guidance to the DOH on determining the causality of adverse events specifically following Dengue vaccine immunization.
The Regional Directors are to do the following: (a) give a human face to the efforts of the DOH by reaching out to the parents and patients, and to show compassion particularly to the bereaved parents and relatives; (b) document, sustain, and institutionalize best practices that have been developed in the course of addressing the crisis in their respective areas; and, (c) lead the operationalization of policies in their covered provinces/cities and provide feedback.
The Concerned DOH Hospitals are to: [a] extend their utmost service to appropriately manage the health and psychosocial concerns of Dengvaxia vaccinees; [b] raise the level of scientific and administrative discussion among personnel and officials to further enhance the capabilities of their respective units in dealing with such crisis.
For the future directions of the Department on public health programs: [a] The design and implementation of public health programs should consider the universal principles of respect for persons, beneficence, nonmaleficence, and justice.
[b] Exercise of prudence in introducing new health technologies, noting that they should be based on rigorous scientific and economic evaluation, considering other factors when implementing the program in the real world.
I would like to extend my heartfelt gratitude to everyone present today. Your participation and cooperation are vital in addressing these issues on Dengvaxia. I anticipate with optimism the same degree of participation and cooperation in operationalizing these directives in the days to come. With this, I give my full trust and confidence in the decisions you will make as well as the execution of such directives in your own respective offices." consequences of such cutbacks remain the same for vulnerable populations, whose words are often not heard at all. :::::: ::::::

Public Health Emergency of International Concern (PHEIC)
Polio this week as of 31 January 2018 [GPEI] :: New on http://polioeradication.org/: As part of the GPEI's plan to capture and share lessons learnt since its inception, the programme has released detailed best practice guides for active surveillance for polio eradication, monitoring the quality of polio eradication campaign performance, and microplanning. :: Last week, Member states and partners met to discuss polio transition and keeping the world polio-free after eradication at the WHO Executive Board Meeting. :: Chris Maher, a long-time polio eradicator and a central part of the polio programme, has been recognised in the Australia Day honours list named as an Officer of the Order of Australia. His recognition comes for his distinguished service to community and international public health through technical, operational and management roles in the global eradication of poliomyelitis.
:: Weekly country updates as of 31 January 2018 Afghanistan: :: Advance notification has been received of two new cases of wild poliovirus type 1 (WPV1) in Kandahar province. One case occurred in Shawalikot district, with onset on 5 January 2018, and one occurred in Boldak district, with onset on 6 January 2018. These cases will be confirmed in next week's data reporting, raising the number of officially reported WPV1 cases in Afghanistan in 2018 to three. :: Five new WPV1 positive environmental samples were reported this week. One sample was collected in Lashkargah district, Hilmand province on 26 December 2017, and one was collected in Kandahar district, Kandahar province, on 27 December 2017. On 8 January 2018, two samples were collected in Kandahar district, Kandahar province and one sample was collected from Lashkargah district, Hilmand province.… campaign was extended for 2 days in some areas to ensure low performing pockets were covered.
:: According to administrative reports a total of 665 736 children under 5 years were vaccinated with mOPV2, representing 96% of the total estimated target.
:: On 29 January, the Syrian Ministry of Health, World Health Organization and UNICEF met with a communication specialist deployed to support the outbreak response to coordinate on the implementation of communication microplans at lower district and lower levels.
:: Preparations continue for the second vaccination round which will utilize IPV. Global Polio Eradication Initiative (GPEI) partners continue to assist. "An additional dose of diphtheria vaccine is expected to further boost immunity of vulnerable children and help restrict diphtheria. These intense campaigns demonstrate the commendable efforts being made by Bangladesh to protect the health of a vulnerable population," said Dr Bardan Jung Rana, World Health Organization's ai Representative to Bangladesh… :: Weekly Situation Report #11 -29 January 2018

WHO & Regional Offices [to 3 February 2018]
Latest news High levels of antibiotic resistance found worldwide, new data shows 29 January 2018 -WHO's first release of surveillance data on antibiotic resistance reveals high levels of resistance to a number of serious bacterial infections in both high-and lowincome countries.

Cervical cancer prevention and control is saving lives in the Republic of Korea
2 February 2018 -The Republic of Korea is demonstrating how it is possible, through investment and expanded universal health coverage, to reduce illness and death through cervical cancer prevention and control, also a key focus of World Cancer Day on 4 February

Proposed members announced for WHO Independent Commission on NCDs
January 2018 -Leaders in health, politics and development have accepted to participate in the first-ever WHO Independent Global High-level Commission on Noncommunicable diseases (NCDs), which aims to identify and propose bold and practical ways to curb the world's leading causes of death and illness.

Kiribati Butiraoi ferry disaster
January 2018 -WHO and UNICEF send their deepest condolences to the people of Kiribati following the recent Butiraoi ferry disaster. This is a tragic event for the country of Kiribati, and we extend our thoughts to those affected families and communities. WHO and UNICEF are closely coordinating with the Government of Kiribati to support the emergency response.

$46 billion in productivity lost to cancer in major emerging economies
January 2018 -A new study published today in the journal Cancer Epidemiology evaluates for the first time the cost of productivity lost due to premature cancer deaths in several major emerging economies.

First online consultation of the Nurturing Care Framework for Early Childhood Development
January 2018 -In the first of two online consultations, WHO is seeking feedback from stakeholders on a global framework for early childhood development. This process will guide policy, programme, and budget support focused on early childhood development and the first 1000 days after conception, at country level.

WHO South-East Asia Region SEARO
:: 'Big 6' countries of WHO South-East Asia Region meet to close measles' immunity gap, accelerate elimination efforts SEAR/PR/1679 New Delhi, 31 January 2018 -With nearly 4.8 million children in WHO South-East Asia Region missing measles vaccination every year, the 'big six' countries of the Region today shared their immunization challenges and lessons learnt for accelerating efforts to eliminate measles and control rubella by the year 2020.
"Eliminating measles would avert half a million deaths, while controlling rubella and Congenital Rubella Syndrome would promote health of pregnant woman and the infants they give life to," said Dr Poonam Khetrapal Singh, Regional Director for WHO South-East Asia.
Two of the Region's countries -Bhutan and Maldives -eliminated measles in 2017 while the others are carrying out large-scale immunization drives to achieve the same.
Nearly 500 million children in the Region are planned to be reached with measles and rubella containing vaccines through routine immunization and supplementary immunization campaigns in the next two years. Sharing challenges and lessons learnt from various recent achievements and initiatives will help member countries address their unique problems to close the immunity gap against measles, rubella and CRS, she said… :: Over 350,000 children to get additional dose of diphtheria vaccine in Cox's Bazar 28 January 2018,

CEPI announces new permanent board Media release, , London -Coalition for Epidemic Preparedness Innovations
Today, CEPI, the coalition launched one year ago to finance and coordinate the development of new vaccines to prevent and contain epidemics, announces the establishment of its new permanent Board.
The Board includes global leaders who have made extraordinary contributions to protecting and improving health, and who bring a wealth of expertise to CEPI as it moves into the next phase of its development.
CEPI's new Board will have twelve members. Eight seats will be held by independent members, while four seats have been reserved for investors. The independent members are: : The four investor seats will be named by CEPI's newly formed Investors Council. It is anticipated that three seats will be held by sovereign investors and one by a philanthropic investor.
Dr Richard Hatchett, CEO of CEPI, said: "I'm delighted to welcome these eminent experts to our Board. This is a seminal moment in CEPI's development as we invest in developing the vaccines and capabilities that the world currently lacks to prepare against future epidemics. CEPI is fortunate to have a Board of this calibre to advise us as we deliver our mission to make the world safer through new vaccines." D. announced at the White House today a formal agreement aimed at making the oversight of food more efficient and effective by bolstering coordination between the two agencies. The formal agreement outlines efforts to increase interagency collaboration, efficiency and effectiveness on produce safety and biotechnology activities, while providing clarity to manufacturers.

EDCTP
"Today, Commissioner Gottlieb and I signed a formal agreement to promote coordination and the streamlining of capacities and obligations on shared concerns and jurisdiction," said Secretary Perdue. "Congress passed the Food Safety Modernization Act and assigned responsibilities to the USDA and the FDA. The USDA has the knowledge and expertise to support the FDA's work related to farming. We at the USDA have a motto: Do Right, and Feed Everyone. We believe this joint effort will help us move one step closer to that goal."… OUAGADOUGOU -Burkina Faso and the Global Fund strengthened their partnership by launching four new grants that move toward ending epidemics of HIV, tuberculosis, malaria and strengthen health systems with a focus on community health systems and data quality.
The new investments will support efforts to scale up HIV programs to achieve the 90-90-90 targets by enrolling more than 93,000 people on antiretroviral treatment by 2020, and expanding HIV services, including access to prevention and treatment for key populations. The new grants also aim to strengthen the country's supply-chain management, improve TB case detection, and procure 12 million mosquito nets for the 2019 mass distribution campaign.
…The four grants, worth a total of EUR130 million for the 2018-2020 implementation period, bring the total amount of Global Fund grants allocated to Burkina Faso to EUR427 million. The grants will be managed by le Programme d'Appui au Développement Sanitaire, le Comité National de Lutte contre le Sida -and l'Initiative Privée pour la lutte contre le SIDA/IPC…

Tanzania and Global Fund Sign New Grants to Accelerate End of Epidemics 30 January 2018
The Global Fund and health partners in Tanzania yesterday signed grant agreements to work toward ending the epidemics of HIV, tuberculosis and malaria.

The Human Genome Project is awarded the Thai 2017 Prince Mahidol Award for the field of medicine
February 1, 2018 -The award will be received on behalf of the project by NHGRI Director Dr. Eric Green.

NIH launches partnership to improve success of clinical trials for patients with Parkinson's disease
January 30, 2018 -Effort is part of the Accelerating Medicines Partnership to speed development of disease-altering treatments.

Roadmap to guide progress toward replacing animal use in toxicity testing
January 30, 2018 -Framework aims to provide more human relevant toxicology data. "As a PATH board member, Dave has applied his private-sector experience to the biggest health challenges facing our world," said Steve Davis, PATH's president and CEO. "He is a brilliant business leader who is deeply committed to health equity, and we are delighted that he is now our board chair." Mr. King succeeds Dean Allen, who recently completed a three-year term as board chair… Press release | January 31, 2018

DRC government steps up commitment to eliminating sleeping sickness by 2020
International partners support government in innovative approach to fight devastating disease Announcement | January 30, 2018

New research consortium to evaluate evidence for single-dose HPV vaccination
Leading health and research institutions come together to evaluate the evidence for potential single-dose HPV vaccination schedule.
The Single-Dose HPV Vaccine Evaluation Consortium, coordinated by PATH and encompassing nine leading research institutions, has begun work to collate and synthesize existing evidence and evaluate new data on the potential for single-dose human papillomavirus (HPV) vaccine delivery.
While 80 countries and territories have introduced HPV vaccines on a two-or three-dose schedule into their national immunization schedules, rollout in low-and lower-middle-income countries has lagged. If demonstrated to be effective, single-dose HPV vaccination could significantly accelerate national vaccine introduction by simplifying programs and lowering procurement and delivery costs.
Funded by the Bill & Melinda Gates Foundation, the consortium will review existing evidence and evaluate new information available from trials and other observational studies on the effectiveness of a single-dose schedule in order to inform global policy discussions and guidance around HPV vaccination. A group of modeling experts within the consortium will also analyze data, identify critical data gaps, and conduct exploratory what-if scenarios to estimate the impact and cost-effectiveness of a single-dose schedule versus non-vaccination or two-dose schedules to inform decision-making. On 27 January, the African Commission on Human and Peoples' Rights (the African Commission) launched a groundbreaking report, HIV, the law and human rights in the African human rights system: key challenges and opportunities for rights-based responses.
The report addresses the key human rights challenges in the response to HIV, including inequality and discrimination towards people living with HIV, access to treatment and restrictive intellectual property regimes, conflict and migration, coercive HIV testing and counselling, restrictions on civil society and the criminalization of people living with HIV and key populations.
While noting the progress made in the response to HIV in Africa, the report expresses concerns about the populations left behind-young women and girls, prisoners, sex workers, men who have sex with men, transgender people and people who use drugs.
As well as the challenges, the report also highlights good practices from across the continent for responding to them, including law and policy reform, progressive court decisions and programmes to advance human rights protection and access to HIV and health services. The development of the report is the result of three years of work involving inputs from various stakeholders, including people living with and affected by HIV, civil society and members of key populations.

UNICEF [to 3 February 2018]
https://www.unicef.org/media/ 31 January 2018 3 in 10 young people in conflict or disaster-stricken countries are illiterate -UNICEF NEW YORK, 31 January 2018 -Nearly 3 in 10 young people aged between 15 and 24 years old -59 million -living in countries affected by conflict or disaster are illiterate, triple the global rate, UNICEF said today. UNICEF seeks $3.6 billion in emergency assistance for 48 million children caught up in catastrophic humanitarian crises NEW YORK/GENEVA, 30 January 2018 -UNICEF appealed today for $3.6 billion to provide lifesaving humanitarian assistance to 48 million children living through conflict, natural disasters and other emergencies in 51 countries in 2018.
The increasing complexities of the recommended immunization schedule and vaccine products available make it almost impossible for even the best informed and intentioned practitioners and staff to get it perfect. Mistakes are "costly," leaving some children suboptimally protected from vaccine-targeted diseases (and in some scenarios requiring extra doses), while other children may be over-immunized. In this volume of The Journal, Rodgers et al report a study of the frequency and cost of vaccinations administered outside minimum and maximum recommended ages despite using what currently is likely to be one of the "smartest" electronic systems that aims to prevent these errors. Data included examination and analysis of de-identified information throughout 2014 from 6 Centers for Disease Control and Prevention Sentinel Sites of Immunization Information Systems in 6 states, representing approximately 10% of the US population <19 years of age. The system possesses advanced functionality available at the point of clinical care.
In most regards, the findings are reassuring. Among roughly 3.4 million doses of vaccines with maximum age recommendations, only 0.3% of doses were given after the maximum age. Among roughly 7.5 million doses of vaccines with minimum age recommendations, only 0.1% of doses were administered before the minimum age. Monetary costs could accrue when an unnecessary dose was given after a maximum age (eg, Prevnar given after the fifth birthday) or an inadequate dose given required re-vaccination (eg, a 0.25 mL dose of Fluzone Quadrivalent given after the third birthday when a dose of 0.5 mL is recommended). The most costly errors of administration before a minimum recommended age are those requiring re-vaccination. This report identified approximately $291 000 in direct and indirect re-vaccination costs that would have been incurred in 1 year in this sample population if each error identified was corrected. An estimated annual cost on a national level would be 10-fold, ie, almost 3 million dollars.
Immunizations are a critical pillar of our children's health, and a precious resource. Until an impossibly smart computer program can be brought to bear at the point of care to integrate each patient's unique immunization record and need, and to preclude misuse, we will have to strive to be advocates for as well as best protectors of the precious resource.

Treating and Preventing HIV with Generic Drugs -Barriers in the United States
Erika G. Martin, Ph.D., M.P.H., and Bruce R. Schackman, Ph.D.
Combination antiretroviral therapy (ART) has dramatically improved survival rates among people with HIV and is a mainstay of HIV prevention; evidence shows that durable viral suppression prevents the transmission of infection. In addition, preexposure prophylaxis (PrEP) is an emerging approach to preventing HIV acquisition for certain high-risk groups. Generic ART medications offer the potential for treating and preventing HIV with fewer resources. Generic versions of lamivudine, abacavir, and efavirenz became available in the United States within the past 6 years at prices lower than their brand-name counterparts, a generic version of PrEP (emtricitabine and tenofovir disoproxil fumarate) was approved in 2016, and generic versions of tenofovir disoproxil are expected later in 2018. Yet most of the discussion about the availability of generic HIV drugs focuses on low-and middle-income countries…

The cost-effectiveness of alternative vaccination strategies for polyvalent meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study
The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. In light of the increasing refusal of some parents to vaccinate children, public health strategies have focused on increasing knowledge and awareness based on a "knowledge-deficit" approach. However, decisions about vaccination are based on more than mere knowledge of risks, costs, and benefits. Individual decision making about vaccinating involves many other factors including those related to emotion, culture, religion, and socio-political context. In this paper, we use a nationally representative internet survey in the U.S. to investigate sociopolitical characteristics to assess attitudes about vaccination. In particular, we consider how political ideology and trust affect opinions about vaccinations for flu, pertussis, and measles. Our findings demonstrate that ideology has a direct effect on vaccine attitudes. In particular, conservative respondents are less likely to express pro-vaccination beliefs than other individuals. Furthermore, ideology also has an indirect effect on immunization propensity. The ideology variable predicts an indicator capturing trust in government medical experts, which in turn helps to explain individual-level variation with regards to attitudes about vaccine choice. Offering HPV vaccine in settings beyond the traditional medical home holds promise for increasing the currently low levels of coverage. As adolescents frequently visit dentists, dental practices may be one such alternative vaccination setting. This study assessed parent attitudes about the roles dental providers could play in HPV prevention, including vaccine provision. Development of an HIV vaccine might be essential to ending the HIV/AIDS pandemic. However, vaccines can result in the emergence and spread of vaccine-resistant strains. Indeed, analyses of breakthrough infections in the HIV phase 3 vaccine trial RV144 identified HIV genotypes with differential rates of transmission in vaccine and placebo recipients. We hypothesized that, for HIV vaccination programs based on partially effective vaccines similar to RV144, HIV adaptation will rapidly diminish the expected vaccine impact.

Reports/Research/Analysis/Commentary/Conferences/Meetings/Book Watch/Tenders
Vaccines and Global Health: The Week in Review has expanded its coverage of new reports, books, research and analysis published independent of the journal channel covered in Journal Watch below. Our interests span immunization and vaccines, as well as global public health, health governance, and associated themes. If you would like to suggest content to be included in this service, please contact David Curry at: david.r.curry@centerforvaccineethicsandpolicy.org The event is open to Geneva-based delegations to WHO, WIPO and WTO, representatives of international and philanthropic organizations, experts on intellectual property and trade, civil society organizations and interested individuals and organizations. The provisional programme of the event is available here. Further details about the Symposium can be accessed here.

Background
The post-2015 Agenda for Sustainable Development sets out an ambitious plan for action: to reach and empower the most vulnerable and take action in areas of critical importance for humanity and the planet. The Sustainable Development Goals usher in a new era of global development that seeks to leave no one behind. Achievement of the SDGs will require a delicate choreography of interplay between all stakeholders.
Access to, and innovation in, health technologies is a requisite element for ensuring progress toward universal health coverage and achievement of the SDGs, namely SDG 3 Ensure healthy lives and promote well-being for all at all ages. Scientific progress, advances in health technologies and improved trade have contributed to unprecedented improvements in health outcomes. However, gains in life expectancy and quality of life are unequally distributed between low-, middle-, and high-income countries. Troubling inequalities in the burden of disease are, in part, attributed to the disparate access to health technologies. As a fundamental human right, the right of everyone to enjoy the highest attainable standard of physical and mental health obliges governments to ensure appropriate access to essential medicines.
The seventh technical symposium organized by WHO, WIPO, WTO will discuss challenges and opportunities for the international community to ensure that innovative technologies are developed and reach patients in order to realize the right to health and the health-related SDGs. The Symposium will offer a forum for an evidence-based exchange of views and experiences of the various stakeholders and representatives of the relevant sectors. Innovative, inclusive, and multi-stakeholder initiatives and partnerships that research, develop and facilitate access to novel, needs-based health technologies will be highlighted. The exchange will provide the basis for discussion and allow participants to achieve a better understanding of the benefits, drawbacks, and impact of the various available options.
The joint technical symposia convened by WHO, WIPO and WTO build on the collaborative work undertaken by the three agencies to enhance capacity, including the trilateral study "Promoting Access to Medical Technologies and Innovation." Background Fake news and alternative facts have become commonplace in these so-called "post-factual times." What about medical research -are scientific facts fake as well? Many recent disclosures have fueled the claim that scientific facts are suspect and that science is in crisis. Scientists appear to engage in facting interests instead of revealing interesting facts. This can be observed in terms of what has been called polarised research, where some researchers continuously publish positive results while others publish negative results on the same issueeven when based on the same data. In order to identify and address this challenge, the objective of this study is to investigate how polarised research produce "polarised facts." Mammography screening for breast cancer is applied as an example BMC Medicine http://www.biomedcentral.com/bmcmed/content (Accessed 27 January 2018)

Rotavirus vaccine impact and socioeconomic deprivation: an interrupted time-series analysis of gastrointestinal disease outcomes across primary and secondary care in the UK
Rotavirus causes severe gastroenteritis in infants and young children worldwide. The UK introduced the monovalent rotavirus vaccine (Rotarix®) in July 2013. Vaccination is free of charge to parents, with two d...

Objective
To describe the implementation and feasibility of an innovative mass vaccination strategybased on single-dose oral cholera vaccine -to curb a cholera epidemic in a large urban setting. Method In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Findings Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign -2.31 United States dollars (US$) per dose -included the relatively low cost of local delivery -US$ 0.41 per dose.

Conclusion
We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Methods
In November 2015, we conducted a systematic search of the following online databases and sources: PubMed®, Embase®, Global Health, Scopus, World Health Organization (WHO) Global Index Medicus, WHO Bulletin on IHR Implementation and the International Society for Disease Surveillance. We included identified studies and reports summarizing national experience in implementing any of the IHR (2005) core capacities or their components. We excluded studies that were theoretical or referred to IHR (1969). Qualitative systematic review methodology, including meta-ethnography, was used for qualitative synthesis. Findings We analysed 51 articles from 77 countries representing all WHO Regions. The meta-syntheses identified a total of 44 lessons learnt across the eight core capacities of IHR (2005). Major themes included the need to mobilize and sustain political commitment; to adapt global requirements based on local sociocultural, epidemiological, health system and economic contexts; and to conduct baseline and follow-up assessments to monitor the status of IHR (2005) implementation. Conclusion Although experiences of IHR (2005) implementation covered a wide global range, more documentation from Africa and Eastern Europe is needed. We did not find specific areas of weakness in monitoring IHR (2005); sustained monitoring of all core capacities is required to ensure effective systems. These lessons learnt could be adapted by countries in the process of meeting IHR (2005)  There is an unmet need for greater investment in preparedness against major epidemics and pandemics. The arguments in favour of such investment have been largely based on estimates of the losses in national incomes that might occur as the result of a major epidemic or pandemic. Recently, we extended the estimate to include the valuation of the lives lost as a result of pandemic-related increases in mortality. This produced markedly higher estimates of the full value of loss that might occur as the result of a future pandemic. We parametrized an exceedance probability function for a global influenza pandemic and estimated that the expected number of influenza-pandemic-related deaths is about 720,000 per year. We calculated that the expected annual losses from pandemic risk to be about 500 billion United States dollars -or 0.6% of global income -per year. This estimate falls within -but towards the lower end of -the Intergovernmental Panel on Climate Change's estimates of the value of the losses from global warming, which range from 0.2% to 2% of global income. The estimated percentage of annual national income represented by the expected value of losses varied by country income grouping: from a little over 0.3% in high-income countries to 1.6% in lowermiddle-income countries. Most of the losses from influenza pandemics come from rare, severe events.

The Lancet
Jan 27, 2018 Volume 391 Number 10118 p281-400 e2-e4 http://www.thelancet.com/journals/lancet/issue/current Editorial Yellow fever: a major threat to public health The Lancet | 3 February 2018 The world's largest fractional-dose vaccination campaign for yellow fever started on Jan 25 in Brazil, with the support of WHO. The campaign attempts to avoid the urban transmission cycle, not seen in the country since 1942. 33 people have died due to yellow fever between Jan 14 and 23, while the number of confirmed cases in the country has reached more than 130.
Although more cases of yellow fever were recorded in Brazil in 2016-17, the recent outbreak has extended into a much larger area, including highly populated cities, making it more threatening to public health. These large cities are infested by Aedes aegypti, the urban yellow fever vector, which can transmit the disease from person to person. The number of people at risk is also increasing in other tropical regions, such as South America and Africa.
Due to a global shortage of the vaccine, in outbreak emergencies WHO recommends fractional dosing to protect more people by using less antigen in each dose. Whereas studies have shown that a fifth of the standard dose can provide the same immunity as the standard full dose for at least 12 months, it is not clear how long the immunity ultimately lasts.
For routine immunisation, the standard full dose, recommended by WHO since 2013, is thought to confer lifelong protection, although supporting evidence for this view is not strong. Some Brazilian experts believe that a booster vaccine 10 years after the primary vaccination should be administered to guarantee lifetime protection.
As a zoonotic disease, with a reservoir in non-human primates, it is unlikely that yellow fever will be eradicated. However, epidemics can be prevented if populations are protected by routine immunisation and if mass vaccination campaigns are implemented quickly in response to an outbreak. A coalition of partners led by WHO, UNICEF, and Gavi, the Vaccine Alliance, aims to eliminate yellow fever epidemics worldwide by 2026. To achieve this goal, there is an urgent need for research to clarify the duration of protective levels of immunity provided by fractionated and full-dose yellow fever vaccines to support development of effective vaccination programmes. Suk, Onno C P van Schayck, Gautam N Yadama, Kandeh Yumkella, Ma Zhong Pollution is the largest environmental cause of disease and premature death in the world today. Diseases caused by pollution were responsible for an estimated 9 million premature deaths in 2015-16% of all deaths worldwide-three times more deaths than from AIDS, tuberculosis, and malaria combined and 15 times more than from all wars and other forms of violence. In the most severely affected countries, pollution-related disease is responsible for more than one death in four.

Lancet Global Health
Feb 2018 Volume 6 Number 2 e121-e228 http://www.thelancet.com/journals/langlo/issue/current Articles Monitoring universal health coverage within the Sustainable Development Goals: development and baseline data for an index of essential health services Daniel R Hogan, Gretchen A Stevens, Ahmad Reza Hosseinpoor, Ties Boerma Summary Background Achieving universal health coverage, including quality essential service coverage and financial protection for all, is target 3.8 of the Sustainable Development Goals (SDG). As a result, an index of essential health service coverage indicators was selected by the UN as SDG indicator 3.8.1. We have developed an index for measuring SDG 3.8.1, describe methods for compiling the index, and report baseline results for 2015. Methods 16 tracer indicators were selected for the index, which included four from within each of the categories of reproductive, maternal, newborn, and child health; infectious disease; noncommunicable diseases; and service capacity and access. Indicator data for 183 countries were taken from UN agency estimates or databases, supplemented with submissions from national focal points during a WHO country consultation. The index was computed using geometric means, and a subset of tracer indicators were used to summarise inequalities. Findings On average, countries had primary data since 2010 for 72% of the final set of indicators. The median national value for the service coverage index was 65 out of 100 (range 22-86). The index was highly correlated with other summary measures of health, and after controlling for gross national income and mean years of adult education, was associated with 21 additional years of life expectancy over the observed range of country values. Across 52 countries with sufficient data, coverage was 1% to 66% lower among the poorest quintile as compared with the national population. Sensitivity analyses suggested ranks implied by the index are fairly stable across alternative calculation methods. Interpretation Service coverage within universal health coverage can be measured with an index of tracer indicators. Our universal health coverage service coverage index is simple to compute by use of available country data and can be refined to incorporate relevant indicators as they become available through SDG monitoring. Funding Ministry of Health, Japan, and the Rockefeller Foundation.

Summary
Background Development of vaccines that are effective against all four dengue virus serotypes (DENV-1-4) in all age groups is important. Here, we present 18-month interim data from an ongoing study undertaken to assess the immunogenicity and safety of Takeda's tetravalent dengue vaccine (TDV) candidate over 48 months in children living in dengue-endemic countries. Methods We undertook a phase 2, multicentre, randomised, double-blind, placebo-controlled study at three sites in the Dominican Republic, Panama, and the Philippines. We randomly assigned children aged 2-17 years to receive either two TDV doses 3 months apart (group 1), one TDV dose (group 2), one TDV dose and a booster dose 1 year later (group 3), or placebo (group 4). We did the randomisation (1:2:5:1) using an interactive web response system stratified by age. The primary endpoint of this 18-month interim analysis was DENV serotype-specific antibody geometric mean titres (GMTs) in the per-protocol immunogenicity subset on days 1, 28, 91, 180, 365, 393, and 540. Secondary safety endpoints were the proportions of participants with serious adverse events and with virologically confirmed dengue in the safety set, and solicited and unsolicited adverse events in the immunogenicity subset. This trial is registered with ClinicalTrials.gov, number NCT02302066. Findings Between Dec 5, 2014, andFeb 13, 2015, 1800 children were randomly assigned to group 1 (n=201), group 2 (n=398), group 3 (n=1002), and group 4 (n=199). 1794 participants received at least one dose of TDV or placebo (safety set), of whom 562 participated in the immunogenicity subset and 509 were included in the per-protocol set. Antibody titres remained elevated 18 months after vaccination in all TDV groups. At day 540, in groups 1, 2, 3, and 4, respectively, DENV-1 GMTs were 476 (95% CI 286-791), 461 (329-647), 1056 (804-1388), and 92 (49-173); DENV-2 GMTs were 1212 (842-1744), 1242 (947-1628), 1457 (1182-1796), and 177 (93-337); DENV-3 GMTs were 286 (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Limited differences in GMTs were observed between groups 1 and 2 (in which participants received one and two doses of TDV, respectively). In baseline-seronegative participants, a 1year booster clearly increased GMTs. Vaccine-related unsolicited adverse events occurred in 14 (2%) of 562 participants, but no vaccine-related serious adverse events arose. Symptomatic, virologically confirmed dengue was recorded in 21 (1·3%) of 1596 participants vaccinated with TDV compared with nine (4·5%) of 198 placebo recipients. Interpretation TDV was well tolerated and immunogenic against all four dengue serotypes, irrespective of baseline dengue serostatus. These data provide proof of concept for TDV and support the ongoing phase 3 efficacy assessment of two doses 3 months apart. Funding Takeda Vaccines. Antimicrobial resistance is an important threat to international health. Therapeutic guidelines for empirical treatment of common life-threatening infections depend on available information regarding microbial aetiology and antimicrobial susceptibility, but sub-Saharan Africa lacks diagnostic capacity and antimicrobial resistance surveillance. We systematically reviewed studies of antimicrobial resistance among children in sub-Saharan Africa since 2005. 18 of 1075 articles reviewed met inclusion criteria, providing data from 67,451 invasive bacterial isolates from inconsistently defined populations in predominantly urban tertiary settings. Among neonates, Gram-negative organisms were the predominant cause of early-onset neonatal sepsis, with a high prevalence of extended-spectrum β-lactamase-producing organisms. Gram-positive bacteria were responsible for a high proportion of infections among children beyond the neon atal period, with high reported prevalence of non-susceptibility to treatment advocated by the WHO therapeutic guidelines. There are few up-to-date or representative studies given the

Results
The participants reviewed findings of research supported by TDR and others. Surveillance and early outbreak warning. Systematic reviews and country studies identify the critical characteristics that an alert system should have to document trends reliably and trigger timely responses (i.e., early enough to prevent the epidemic spread of the virus) to dengue outbreaks. A range of variables that, according to the literature, either indicate risk of forthcoming dengue transmission or predict dengue outbreaks were tested and some of them could be successfully applied in an Early Warning and Response System (EWARS). Entomological surveillance and vector management. A summary of the published literature shows that controlling Aedes vectors requires complex interventions and points to the need for more rigorous, standardised study designs, with disease reduction as the primary outcome to be measured. House screening and targeted vector interventions are promising vector management approaches. Sampling vector populations, both for surveillance purposes and evaluation of control activities, is usually conducted in an unsystematic way, limiting the potentials of entomological surveillance for outbreak prediction. Combining outbreak alert and improved approaches of vector management will help to overcome the present uncertainties about major risk groups or areas where outbreak response should be initiated and where resources for vector management should be allocated during the interepidemic period.

Conclusions
The Forum concluded that the evidence collected can inform policy decisions, but also that important research gaps have yet to be filled. The international spread of poliovirus has been declared a Public Health Emergency of International Concern by the World Health Organization, and Pakistan is one of only three countries that have never stopped poliovirus circulation. We analyzed polio incidence and polio vaccination data from 32 districts of northwest Pakistan and constructed a measure of insecurity based on journalistic reports of deaths and injuries resulting from conflict-related security incidents. Insecurity was associated with reduced vaccinator access, reduced polio vaccination, and increased polio incidence. These findings provide strong scientific evidence that insecurity is an important obstacle to global polio eradication.

Abstract
Pakistan is one of three countries in which endemic transmission of poliovirus has never been stopped. Insecurity is often cited but poorly studied as a barrier to eradicating polio. We analyzed routinely collected health data from 32 districts of northwest Pakistan and constructed an index of insecurity based on journalistic reports of the monthly number of deaths and injuries resulting from conflict-related security incidents. The primary outcomes were the monthly incidence of paralytic polio cases within each district between 2007 and 2014 and the polio vaccination percentage from 666 district-level vaccination campaigns between 2007 and 2009, targeting ∼5.7 million children. Multilevel Poisson regression controlling for time and district fixed effects was used to model the association between insecurity, vaccinator access, vaccination rates, and polio incidence. The number of children inaccessible to vaccinators was 19.7% greater (95% CI: 19.2-20.2%), and vaccination rates were 5.3% lower (95% CI: 5.2-5.3%) in "high-insecurity" campaigns compared with "secure" campaigns. The unadjusted mean vaccination rate was 96.3% (SD=8.6) in secure campaigns and 88.3% (SD=19.2) in highinsecurity campaigns. Polio incidence was 73.0% greater (95% CI: 30-131%) during highinsecurity months (unadjusted mean = 0.13 cases per million people, SD=0.71) compared with secure months (unadjusted mean=1.23 cases per million people, SD=4.28). Thus, insecurity was associated with reduced vaccinator access, reduced polio vaccination, and increased polio incidence in northwest Pakistan. These findings demonstrate that insecurity is an important obstacle to global polio eradication.

Eradication of spontaneous malignancy by local immunotherapy
By Idit Sagiv-Barfi, Debra K. Czerwinski, Shoshana Levy, Israt S. Alam, Aaron T. Mayer, Sanjiv S. Gambhir, Ronald Levy Science Translational Medicine31 Jan 2018 Full Access In situ vaccination with low doses of TLR ligands and anti-OX40 antibodies can cure widespread cancers in preclinical models.

Abstract
Deliver locally, act globally Mobilizing endogenous T cells to fight tumors is the goal of many immunotherapies. Sagiv-Barfi et al. investigated a combination therapy in multiple types of mouse cancer models that could provide sustainable antitumor immunity. Specifically, they combined intratumoral delivery of a TLR9 ligand with OX40 activation to ramp up T cell responses. This dual immunotherapy led to shrinkage of distant tumors and long-term survival of the animals, even in a stringent spontaneous tumor model. Both of these stimuli are in clinical trials as single agents and could likely be combined at great benefit for cancer patients. Abstract It has recently become apparent that the immune system can cure cancer. In some of these strategies, the antigen targets are preidentified and therapies are custom-made against these targets. In others, antibodies are used to remove the brakes of the immune system, allowing preexisting T cells to attack cancer cells. We have used another noncustomized approach called in situ vaccination. Immunoenhancing agents are injected locally into one site of tumor, thereby triggering a T cell immune response locally that then attacks cancer throughout the body. We have used a screening strategy in which the same syngeneic tumor is implanted at two separate sites in the body. One tumor is then injected with the test agents, and the resulting immune response is detected by the regression of the distant, untreated tumor. Using this assay, the combination of unmethylated CG-enriched oligodeoxynucleotide (CpG)-a Toll-like receptor 9 (TLR9) ligand-and anti-OX40 antibody provided the most impressive results. TLRs are components of the innate immune system that recognize molecular patterns on pathogens. Low doses of CpG injected into a tumor induce the expression of OX40 on CD4+ T cells in the microenvironment in mouse or human tumors. An agonistic anti-OX40 antibody can then trigger a T cell immune response, which is specific to the antigens of the injected tumor. Remarkably, this combination of a TLR ligand and an anti-OX40 antibody can cure multiple types of cancer and prevent spontaneous genetically driven cancers. To understand factors that influence sustained adoption of water, sanitation and hygiene (WASH) technologies or behaviours. Methods Systematic review of the current literature. Articles were gathered from databases of peerreviewed articles and grey literature, and screened for relevance. After exclusion, we created a descriptive map of 148 articles and analysed in-depth 44 articles that had an explicit focus on promoting or evaluating sustained adoption or programme sustainability. Twenty-two of these articles met our definition of measuring sustained adoption.

Results
Definitions of sustained adoption varied widely and were often inadequate, making comparison of sustained adoption across studies difficult. The time frame for measurements of sustained adoption is frequently inadequate for examination of longer-term behaviour change. Conclusions Ideally, an evaluation should specify the project period and describe the context surrounding adoption, make measurements at multiple time points, diversify measurement methods and describe and measure a range of factors affecting sustained adoption. Additional consideration needs to be given to developing behaviour change models that emphasise factors related to sustained adoption, and how they differ from those related to initial adoption.

Introduction
The SAGE Working Group on Vaccine Hesitancy developed a vaccine hesitancy measure, the Vaccine Hesitancy Scale (VHS). This scale has the potential to aid in the advancement of research and immunization policy but has not yet been psychometrically evaluated. Methods Using a cross-sectional design, we collected self-reported survey data from a large national sample of Canadian parents from August to September 2016. An online questionnaire was completed in English or French. We used exploratory and confirmatory factor analysis to identify latent constructs underlying parents' responses to 10 VHS items (response scale 1-5, with higher scores indicating greater hesitancy). In addition to the VHS, measures included sociodemographics items, vaccine attitudes, parents' human papillomavirus (HPV) vaccine decisionmaking stage, and vaccine refusal. Results A total of 3779 Canadian parents completed the survey in English (74.1%) or French (25.9%). Exploratory and confirmatory factor analysis revealed a two-factor structure best explained the data, consisting of 'lack of confidence' (M = 1.98, SD = 0.72) and 'risks' (M = 3.07, SD = 0.95). Significant Pearson correlations were found between the scales and related vaccine attitudes. ANOVA analyses found significant differences in the VHS sub-scales by parents' vaccine decision-making stages (p < .001). Independent samples t-tests found that the VHS sub-scales were associated with HPV vaccine refusal and refusing another vaccine (p < .001). Sociodemographic differences in the VHS were found; however, effect sizes were small (η2 < 0.02).

Conclusions
The VHS was found to have two factors that have construct and criterion validity in identifying vaccine hesitant parents. A limitation of the VHS was few items that loaded on the 'risks' component and a lack of positively and negatively worded items for both components. Based on these results, we suggest modifying the wording of some items and adding items on risk perceptions. The emerging combination of radiation therapy with vaccines is a promising new treatment plan in the fight against cancer. While many cancer vaccines such as MUC1, p53 CpG oligodeoxynucleotide, and SOX2 may be great candidates for antitumor vaccination, there still remain many investigations to be done into possible vaccine combinations. One fruitful partnership that has emerged are anti-tumor vaccines in combination with radiation. Radiation therapy was previously thought to be only a tool for directly or indirectly damaging DNA and therefore causing cancer cell death. Now, with much preclinical and clinical data, radiation has taken on the role of an in situ vaccine. With both cancer vaccines and radiation at our disposal, more and more studies are looking to combining vaccine types such as toll-like receptors, viral components, dendritic-cell-based, and subunit vaccines with radiation. While the outcomes of these combinatory efforts are promising, there is still much work to be covered. This review sheds light on the current state of affairs in cancer vaccines and how radiation will bring its story into the future Open Access Review Abstract Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions To those not familiar with this situation, this generally comes as a big surprise because drugs, diagnostics and a vaccine are available as control measures. Currently, means of interventions, however, are insufficient and better ones are urgently needed for early detection, successful treatment and efficacious prevention.