EBOLA [to 30 August 2014]

WHO issues roadmap to scale up international response to the Ebola outbreak in West Africa
Statement
28 August 2014
[Full text]
WHO is issuing today a roadmap to guide and coordinate the international response to the outbreak of Ebola virus disease in west Africa.

The aim is to stop ongoing Ebola transmission worldwide within 6–9 months, while rapidly managing the consequences of any further international spread. It also recognizes the need to address, in parallel, the outbreak’s broader socioeconomic impact.

It responds to the urgent need to dramatically scale up the international response. Nearly 40% of the total number of reported cases have occurred within the past three weeks.

The roadmap was informed by comments received from a large number of partners, including health officials in the affected countries, the African Union, development banks, other UN agencies, Médecins Sans Frontières (MSF), and countries providing direct financial support.

It will serve as a framework for updating detailed operational plans. Priority is being given to needs for treatment and management centres, social mobilization, and safe burials. These plans will be based on site-specific data that are being set out in regular situation reports, which will begin this week.

The situation reports map the hotspots and hot zones, present epidemiological data showing how the outbreak is evolving over time, and communicate what is known about the location of treatment facilities and laboratories, together with data needed to support other elements of the roadmap.
The roadmap covers the health dimensions of the international response. These dimensions include key potential bottlenecks requiring international coordination, such as the supply of personal protective equipment, disinfectants, and body bags.
The WHO roadmap will be complemented by the development of a separate UN-wide operational platform that brings in the skills and capacities of other agencies, including assets in the areas of logistics and transportation. The UN-wide platform aims to facilitate the delivery of essential services, such as food and other provisions, water supply and sanitation, and primary health care.

Resource flows to implement the roadmap will be tracked separately, with support from the World Bank.

Ebola response roadmap
WHO
28 August 2014 :: 27 pages pdf: http://apps.who.int/iris/bitstream/10665/131596/1/EbolaResponseRoadmap.pdf?ua=1
[Excerpt from introduction]
GOAL
To stop Ebola transmission in affected countries within 6-9 months and prevent international spread.

CONTEXT
… National authorities in the affected countries have been working with WHO and partners to scale-up control measures. However, the EVD outbreak remains grave and transmission is still increasing in a substantial number of localities, aggravating fragile social, political and economic conditions in the sub-region and posing increasingly serious global health security challenges and risks.

The Ebola response activities to date have generated significant knowledge on the effectiveness and limitations of current approaches, highlighting key areas for course corrections. Clearly, a massively scaled and coordinated international response is needed to support affected and at-risk countries in intensifying response activities and strengthening national capacities. Response activities must be adapted in areas of very intense transmission and particular attention must be given to stopping transmission in capital cities and major ports, thereby facilitating the larger response and relief effort.

This updated and more comprehensive roadmap builds on current, country-specific realities to guide response efforts and align implementation activities across different sectors of government and international partners.

PURPOSE OF DOCUMENT
To assist governments and partners in the revision and resourcing of country-specific operational plans for Ebola response, and the coordination of international support for their full implementation.

OBJECTIVES
1. To achieve full geographic coverage with complementary Ebola response activities in countries with widespread and intense transmission
2. To ensure emergency and immediate application of comprehensive Ebola response interventions in countries with an initial case(s) or with localized transmission
3. To strengthen preparedness of all countries to rapidly detect and respond to an Ebola exposure, especially those sharing land borders with an intense transmission area and those with international transportation hubs

WHO: Global Alert and Response (GAR) – Disease Outbreak News [to 30 August 2014]
http://www.who.int/csr/don/en/
:: Ebola virus disease update – west Africa 28 August 2014
Excerpt
Epidemiology and surveillance
:: The total number of probable and confirmed cases in the current outbreak of Ebola virus disease (EVD) in the four affected countries as reported by the respective Ministries of Health of Guinea, Liberia, Nigeria, and Sierra Leone is 3069, with 1552 deaths.
:: The outbreak continues to accelerate. More than 40% of the total number of cases have occurred within the past 21 days. However, most cases are concentrated in only a few localities.
:: The overall case fatality rate is 52%. It ranges from 42% in Sierra Leone to 66% in Guinea.
:: A separate outbreak of Ebola virus disease, which is not related to the outbreak in West Africa, was laboratory-confirmed on 26 August by the Democratic Republic of Congo (DRC) and is detailed in a separate edition of the Disease Outbreak News.
Health sector response
…WHO does not recommend any travel or trade restrictions be applied except in cases where individuals have been confirmed or are suspected of being infected with EVD or where individuals have had contact with cases of EVD. (Contacts do not include properly-protected health-care workers and laboratory staff.) Temporary recommendations from the Emergency Committee with regard to actions to be taken by countries can be found at:
HR Emergency Committee on Ebola outbreak in west Africa
:: Ebola virus disease – Democratic Republic of Congo 27 August 2014

NIH: Ebola
:: Single animal to human transmission event responsible for 2014 Ebola outbreak
August 29, 2014 — Scientists used advanced genomic sequencing technology to identify a single point of infection from an animal reservoir to a human in the current Ebola outbreak in West Africa. This research has also revealed the dynamics of how the Ebola virus has been transmitted from human to human, and traces how the genetic code of the virus is changing over time to adapt to human hosts. Pardis Sabeti, M.D., Ph.D, a 2009 National Institutes of Health Director’s New Innovator awardee and her team carried out the research…
…Joined by an international team of scientists, Dr. Sabeti used advanced technology to analyze the genetics of the Ebola samples extremely rapidly and with high levels of accuracy. Using this technology, the researchers pinpointed a single late 2013 introduction from an unspecified animal reservoir into humans. Their study showed that the strain responsible for the West African outbreak separated from a closely related strain found in Central Africa as early as 2004, indicating movement from Central to West Africa over the span of a decade. Studying RNA changes occurring over the span of the outbreak suggests that the first human infection of the outbreak was followed by exclusive human to human transmissions….
…While analyzing the genetic makeup of the Ebola samples, Dr. Sabeti and colleagues discovered a number of mutations that arose as the outbreak spread. Some of these mutations, termed nonsynonymous mutations, alter the biological state of the virus and may allow it to continually and rapidly adapt to human immune defenses as the outbreak continues. This feature points to the need for improved methods that will allow for close monitoring of changes in the viral genome and the impact on vaccine targets. Such monitoring, called genomic surveillance, can provide important insights into the biology of how the Ebola virus spreads and evolves. It may also allow scientists to develop improved methods to detect infection, and point the way to new and improved drug and vaccines….
:: NIH to Launch Human Safety Study of Ebola Vaccine Candidate
Trial is First in Series of Accelerated Safety Studies of Ebola Vaccines
August 28, 2014
Initial human testing of an investigational vaccine to prevent Ebola virus disease will begin next week by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The early-stage trial will begin initial human testing of a vaccine co-developed by NIAID and GlaxoSmithKline (GSK) and will evaluate the experimental vaccine’s safety and ability to generate an immune system response in healthy adults. Testing will take place at the NIH Clinical Center in Bethesda, Maryland.

The study is the first of several Phase 1 clinical trials that will examine the investigational NIAID/GSK Ebola vaccine and an experimental Ebola vaccine developed by the Public Health Agency of Canada and licensed to NewLink Genetics Corp. The others are to launch in the fall. These trials are conducted in healthy adults who are not infected with Ebola virus to determine if the vaccine is safe and induces an adequate immune response.

In parallel, NIH has partnered with a British-based international consortium that includes the Wellcome Trust and Britain’s Medical Research Council and Department for International Development to test the NIAID/GSK vaccine candidate among healthy volunteers in the United Kingdom and in the West African countries of Gambia (after approval from the relevant authorities) and Mali.

Additionally, the U.S. Centers for Disease Control and Prevention has initiated discussions with Ministry of Health officials in Nigeria about the prospects for conducting a Phase 1 safety study of the vaccine among healthy adults in that country….

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Ebola vaccine trials fast-tracked by international consortium
Unprecedented international consortium assembled to accelerate collaborative multi-site trials of candidate Ebola vaccine
GSK Media Release
28 August 2014
Excerpt
A candidate Ebola vaccine could be given to healthy volunteers in the UK, The Gambia and Mali as early as September, as part of a series of safety trials of potential vaccines aimed at preventing the disease that has killed more than 1,400 people in the current outbreak in west Africa.

Human trials of this candidate vaccine, being co-developed by the US National Institutes of Health (NIH) and GlaxoSmithKline, are to be accelerated with funding from an international consortium in response to the Ebola epidemic…

A £2.8 million grant from the Wellcome Trust, the Medical Research Council (MRC) and the UK Department for International Development (DFID) will allow a team led by Professor Adrian Hill, of the Jenner Institute at the University of Oxford, to start safety tests of the vaccine alongside similar trials in the USA run by the National Institute of Allergy and Infectious Diseases (NIAID, a part of the NIH).

The phase 1 trials will begin as soon as they receive ethical and regulatory approvals, which will be considered on an expedited basis. If approvals are granted, the UK research teams could start vaccinating volunteers from mid-September.

The consortium’s funding will also enable GSK to begin manufacturing up to around 10,000 additional doses of the vaccine at the same time as the initial clinical trials, so that if the trials are successful stocks could then be made available immediately by GSK to the WHO to create an emergency immunisation programme for high-risk communities.
The candidate vaccine is against the Zaire species of Ebola, which is the one circulating in west Africa, and uses a single Ebola virus protein to generate an immune response. As it does not contain infectious virus material, it cannot cause a person who is vaccinated to become infected with Ebola. Pre-clinical research by the NIH and Okairos, a biotechnology company acquired last year by GSK, has indicated that it provides promising protection in non-human primates exposed to Ebola without significant adverse effects….

Full media release: http://www.gsk.com/en-gb/media/press-releases/2014/ebola-vaccine-trials-fast-tracked-by-international-consortium/

POLIO [to 30 August 2014]
GPEI Update: Polio this week – As of 27 August 2014
Global Polio Eradication Initiative
Editor’s Excerpt and text bolding
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: Continued transmission in Kano: wild poliovirus 1 transmission continues in a geographically limited area of southern Kano state, Nigeria, indicating pockets where vaccination campaigns and social mobilization are still too weak to assure sufficient coverage during campaigns. Kano is the only state in Nigeria reporting cases of wild poliovirus since April.
:: Protecting west Africa: Even as polio programme staff across west Africa support efforts to control the Ebola outbreak affecting the region, preparations are going ahead for large scale multi-country vaccination campaigns in those countries not affected by Ebola, in mid-September.
Afghanistan
:: Vaccination activities have resumed in parts of Helmand Province, Southern Region, where no vaccination had taken place for 5 months.
Nigeria
:: One new case of WPV1 was reported in the past week. This most recent case, which had onset of paralysis in Sumaila Local Government Area (LGA), southern Kano, on 24 July, is the second to be reported in the LGA this year. Nigeria’s total case count for 2014 is now six. Kano is the only state with cases of WPV since April.
:: One new case of type 2 circulating vaccine-derived poliovirus (cVDPV2) was reported in the past week. The total number of cVDPV2 cases for 2014 is 19. The most recent cVDPV2 case had onset of paralysis on 22 June, also in Kano.
Pakistan
:: Two new WPV1 cases were reported in the past week, one from Khyber Agency in the Federally Administered Tribal Areas (FATA) and one from Karachi in Sindh, bringing the total number of WPV1 cases for 2014 to 117. The FATA case is the most recent WPV1 case in the country, with onset of paralysis on 30 July.

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The Weekly Epidemiological Record (WER) 29 August 2014, vol. 89, 35 (pp. 377–388)
Includes:
:: Assessing and mitigating the risks of outbreaks due to wild poliovirus in polio-free African countries, 2013–2014
:: Monthly report on dracunculiasis cases, January– July 2014
http://www.who.int/entity/wer/2014/wer8935.pdf?ua=1

Media Release: Major Milestones for Development of Korea’s First Cholera Vaccine for the World’s Poor
-Global Access Agreement between EuBiologics Co., Ltd. and International Vaccine Institute
– Investments by Global Health Investment Fund I, LLC (GHIF) and domestic investors to EuBiologics
– Milestones pave the way to make an oral cholera vaccine available for developing countries
Excerpt
SEOUL, KOREA – EuBiologics Co., Ltd. (EuBiologics) and the International Vaccine Institute (IVI) announced today that major milestones have been met in their collaborative efforts to develop an oral cholera vaccine (OCV) for use in developing countries. EuBiologics has entered into a Global Access Agreement with IVI to ensure that the cholera vaccine will be made available and accessible at an affordable price for the public sector. Furthermore, Global Health Investment Fund I, LLC (GHIF), a new $108 million USD fund developed by the Bill & Melinda Gates Foundation, Lion’s Head Global Partners and JPMorgan Chase & Co., has committed 2.5 million USD of equity capital and made a 2.5 million USD loan to support EuBiologics in the development and production of the OCV. In addition, Korea-Seoul Life Science Fund (KSLSF) and Korea Investment Global Frontier Fund (KIGFF) have each invested 1.25 million USD of equity capital alongside the GHIF in this financing.

“We are thankful to receive the OCV technology from IVI and are very much delighted to have an opportunity to work with GHIF,” said Mr. Yeong-Ok Baik, CEO of EuBiologics, “We are confident that our vaccine, Euvichol will achieve WHO prequalification with IVI’s support and assistance. We are pleased to supply Euvichol worldwide as per the Global Access Agreement made with IVI, and we are committed to contribute to global efforts to prevent and control cholera in poor communities around the world.”

The OCV was specifically developed for use in developing countries through a public-private partnership led by IVI with support from the Republic of Korea, Sweden, and the Bill & Melinda Gates Foundation. The partnership initially involved Shantha Biotechnics (part of the Sanofi group) in Hyderabad, India; Vabiotech, a state-owned vaccine manufacturer in Hanoi, Vietnam; and the University of Gothenburg in Sweden. IVI transferred the OCV production technology to Shantha, and the vaccine, licensed as Shancholin India, was prequalified by the World Health Organization (WHO) in September 2011.

“Through a phase III clinical trial in Kolkata, India, IVI has shown that the vaccine provides sustained protection against cholera at an efficacy of 65% for at least five years, the longest duration of protection conferred by an oral cholera vaccine to date,” said Dr. Thomas F. Wierzba, Deputy Director General for IVI’s Development and Delivery, “The vaccine is safe and it clearly works. IVI is gratified to be working with a partner like EuBiologics who share IVI’s mission of discovering, developing and delivering safe, effective and affordable vaccines for developing nations.”…

Aeras announced the initiation of a large, multi-country Phase IIb clinical trial to evaluate the ability of a novel vaccine candidate to prevent tuberculosis in adults. Aeras and GSK will jointly conduct the double-blind, randomised, placebo-controlled study (ClinicalTrials.gov Identifier: NCT01755598) to evaluate the efficacy, safety and immunogenicity of GSK’s proprietary vaccine candidate M72/AS01E*. The trial will enroll more than 3500 healthy adults, with latent (asymptomatic) TB infection (LTBI), ages 18-50, in TB-endemic sub-Saharan African countries, starting in South Africa. Subjects will be enrolled in 2014 and 2015, with a 36-month follow-up, yielding study results in 2018.
August 28, 2014 – full press release.

WHO calls for stronger action on climate-related health risks
27 August 2014 — Previously unrecognized health benefits could be realized from fast action to reduce climate change and its consequences. For example, changes in energy and transport policies could save millions of lives annually from diseases caused by high levels of air pollution.

CDC/MMWR Watch [to 30 August 2014]
http://www.cdc.gov/mmwr/mmwr_wk.html

MMWR Weekly – :: August 29, 2014 / Vol. 63 / No. 34
:: National, State, and Selected Local Area Vaccination Coverage Among Children Aged 19–35 Months — United States, 2013
Excerpt
…This report describes national, regional, state, and selected local area vaccination coverage estimates for children born January 2010–May 2012, based on results from the 2013 NIS. In 2013, vaccination coverage achieved the 90% national Healthy People 2020 target* for ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.9%); ≥3 doses of hepatitis B vaccine (HepB) (90.8%); ≥3 doses of poliovirus vaccine (92.7%); and ≥1 dose of varicella vaccine (91.2%).

Coverage was below the Healthy People 2020 targets for ≥4 doses of diphtheria, tetanus, and pertussis vaccine (DTaP) (83.1%; target 90%); ≥4 doses of pneumococcal conjugate vaccine (PCV) (82.0%; target 90%); the full series of Haemophilus influenzae type b vaccine (Hib) (82.0%; target 90%); ≥2 doses of hepatitis A vaccine (HepA) (54.7%; target 85%); rotavirus vaccine (72.6%; target 80%); and the HepB birth dose (74.2%; target 85%).

Coverage remained stable relative to 2012 for all of the vaccinations with Healthy People 2020 objectives except for increases in the HepB birth dose (by 2.6 percentage points) and rotavirus vaccination (by 4.0 percentage points).

The percentage of children who received no vaccinations remained below 1.0% (0.7%). Children living below the federal poverty level had lower vaccination coverage compared with children living at or above the poverty level for many vaccines, with the largest disparities for ≥4 doses of DTaP (by 8.2 percentage points), full series of Hib (by 9.5 percentage points), ≥4 doses of PCV (by 11.6 percentage points), and rotavirus (by 12.6 percentage points). MMR coverage was below 90% for 17 states. Reaching and maintaining high coverage across states and socioeconomic groups is needed to prevent resurgence of vaccine-preventable diseases….

Industry Watch [to 30 August 2014]
Selected media releases and other selected content from industry.
:: Pfizer’s Investigational Vaccine Candidate for Clostridium difficile Receives U.S. Food and Drug Administration Fast Track Designation
August 28, 2014
:: GSK commits to improving access to vaccines – Business Day, Kemi Ajumobi
August 29, 2014
GlaxoSmithKline “…has announced that it will freeze the prices of its vaccines for five years for developing countries that graduate from GAVI Alliance support….”

Harris Poll [U.S.]: Over Three-Fourths of Americans Believe Childhood Vaccinations Should be Mandatory
Younger Americans more likely than their elder counterparts to question vaccine safety
Excerpt from media release
NEW YORK, Aug. 26, 2014 /PRNewswire/ — With incidents on the rise for many diseases once considered dangers of the past, the subject of vaccinations has been a frequent topic of conversation in recent days. In fact, strong majorities of U.S. adults favor childhood vaccinations being mandatory for all children (77%), while seven in ten don’t think unvaccinated children should be allowed to attend either public or private schools (69%). What’s more, nine in ten feel it’s important that children be vaccinated (89%) and believe vaccinations should be provided for free to children whose families cannot afford them (90%).
These are some of the results of The Harris Poll® of 2,306 adults surveyed online between July 16 and 21, 2014…

BMC Public Health
(Accessed 30 August 2014)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
Timely measles vaccination in Tianjin, China: a cross-sectional study of immunization records and mothers
Abram L Wagner, Ying Zhang, JoLynn P Montgomery, Yaxing Ding, Bradley F Carlson and Matthew L Boulton
Author Affiliations
BMC Public Health 2014, 14:888 doi:10.1186/1471-2458-14-888
Published: 29 August 2014
Abstract (provisional)
Background
Measles is a highly infectious disease, and timely administration of two doses of vaccine can ensure adequate protection against measles for all ages in a population. This study aims to estimate the proportion of children aged 8 months to 6 years vaccinated on time with measles-containing vaccines (MCV) and vaccinated during the 2008 and 2010 measles supplementary immunization activities. This study also characterizes differences in mean age at vaccination and vaccination timeliness by demographic characteristics, and describes maternal knowledge of measles vaccination.
Methods
Immunization records were selected from a convenience sample of immunization clinics in Tianjin, China. From the records, overall vaccination coverage and timely vaccination coverage were calculated for different demographic groups. Mothers were also interviewed at these clinics to ascertain their knowledge of measles vaccination.
Results
Within the 329 immunization clinic records, child’s birth year and district of residence were found to be significant predictors of different measures of vaccine timeliness. Children born in 2009 had a lower age at MCV dose 2 administration (17.96 months) than children born in 2005 (22.00 months). Children living in Hebei, a district in the urban center of Tianjin were less likely to be vaccinated late than children living in districts further from the urban core of Tianjin. From the 31 interviews with mothers, most women believed that timely vaccination was very important and more than one dose was very necessary; most did not know whether their child needed another dose.
Conclusions
When reviewing MCV coverage in China, most studies do not consider timeliness. However, this study shows that overall vaccination coverage can greatly overestimate vaccination coverage within certain segments of the population, such as young infants.

BMC Public Health
(Accessed 30 August 2014)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
The prevalence of underweight, overweight, obesity and associated risk factors among school-going adolescents in seven African countries
Taru Manyanga, Hesham El-Sayed, David Teye Doku and Jason R Randall
Author Affiliations
BMC Public Health 2014, 14:887 doi:10.1186/1471-2458-14-887
Published: 28 August 2014
Abstract (provisional)
Background
The burden caused by the coexistence of obesity and underweight in Low and Middle Income Countries is a challenge to public health. While prevalence of underweight among youth has been well documented in these countries, overweight, obesity and their associated risk factors are not well understood unlike in high income countries.
Methods
Cross-sectional data from the Global School-based Student Health Survey (GSHS) conducted in seven African countries were used for this study. The survey used a clustered design to obtain a representative sample (n = 23496) from randomly selected schools. 53.6% of the sample was male, and participants ranged in age from 11-17 years old. Body Mass Index (BMI) was calculated using age and sex adjusted self-reported heights and weights. Classification of weight status was based on the 2007 World Health Organization growth charts (BMI-for-age and sex). Multivariable Logistic Regression reporting Odds Ratios was used to assess potential risk factors on BMI, adjusting for age, sex, and country. Statistical analyses were performed with Stata with an alpha of 0.05 and reporting 95% confidence intervals.
Results
Unadjusted rates of being underweight varied from 12.6% (Egypt) to 31.9% (Djibouti), while being overweight ranged from 8.7% (Ghana) to 31.4% (Egypt). Obesity rates ranged from 0.6% (Benin) to 9.3% (Egypt). Females had a higher overweight prevalence for every age group in five of the countries, exceptions being Egypt and Malawi. Overall, being overweight was more prevalent among younger (<=12) adolescents and decreased with age. Males had a higher prevalence of being underweight than females for every country. There was a tendency for the prevalence of being underweight to increase starting in the early teens and decrease between ages 15 and 16. Most of the potential risk factors captured by the GSHS were not significantly associated with weight status.
Conclusions
The prevalence of both overweight and underweight was relatively high, demonstrating the existence of the double burden of malnutrition among adolescents in developing countries. Several factors were not associated with weight status suggesting the need to explore other potential risk factors for overweight and underweight, including genetic factors and socioeconomic status.

British Medical Journal
23 August 2014(vol 349, issue 7972)
http://www.bmj.com/content/349/7972

Editorials
Including mental health among the new sustainable development goals
BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g5189 (Published 20 August 2014) Cite this as: BMJ 2014;349:g5189
Graham Thornicroft, professor 1, Vikram Patel, professor23
Author affiliations
Excerpt
The United Nations will soon decide what will follow its millennium development goals, which expire in 2015. The case for including mental health among the new sustainable development goals is compelling, both because it cuts across most of the suggested new goals and because of the unmet needs of the 450 million people in the world with mental illness.1

Poorer mental health is a precursor to reduced resilience to conflict. It’s also a barrier to achieving the suggested goal of promoting peaceful and inclusive societies for sustainable development, providing access to justice for all, and building effective, accountable, and inclusive institutions at all levels. In addition, conflict is itself a risk factor for adverse mental health consequences,2 and in the aftermath of conflict the needs of vulnerable groups such as people with mental illness are often accorded the lowest priority (as documented by photojournalist Robin Hammond, http://www.robinhammond.co.uk).

The improvement of mental health systems will also have a decisive role in making cities and human settlements inclusive, safe, resilient, and sustainable, and this is especially important given the global trend towards urbanisation with its associated risk factors for mental illness. Moreover, individual adversity—for example, complications of pregnancy, such as miscarriage—is associated with worse mental health.

A third suggested goal is to promote sustained, inclusive, and sustainable economic growth, full and productive employment, and decent …

Cost Effectiveness and Resource Allocation
(Accessed 30 August 2014)
http://www.resource-allocation.com/

Methodology
Guidance on priority setting in health care (GPS-Health): the inclusion of equity criteria not captured by cost-effectiveness analysis
Ole F Norheim, Rob Baltussen, Mira Johri, Dan Chisholm, Erik Nord, DanW Brock, Per Carlsson, Richard Cookson, Norman Daniels, Marion Danis, Marc Fleurbaey, Kjell A Johansson, Lydia Kapiriri, Peter Littlejohns, Thomas Mbeeli, Krishna D Rao, Tessa Tan-Torres Edejer and Dan Wikler
Author Affiliations
Cost Effectiveness and Resource Allocation 2014, 12:18 doi:10.1186/1478-7547-12-18
Published: 29 August 2014
Abstract (provisional)
This Guidance for Priority Setting in Health Care (GPS-Health), initiated by the World Health Organization, offers a comprehensive map of equity criteria that are relevant to health care priority setting and should be considered in addition to cost-effectiveness analysis. The guidance, in the form of a checklist, is especially targeted at decision makers who set priorities at national and sub-national levels, and those who interpret findings from cost-effectiveness analysis. It is also targeted at researchers conducting cost-effectiveness analysis to improve reporting of their results in the light of these other criteria. The guidance was develop through a series of expert consultation meetings and involved three steps: i) methods and normative concepts were identified through a systematic review; ii) the review findings were critically assessed in the expert consultation meetings which resulted in a draft checklist of normative criteria; iii) the checklist was validated though an extensive hearing process with input from a range of relevant stakeholders. The GPS-Health incorporates criteria related to the disease an intervention targets (severity of disease, capacity to benefit, and past health loss); characteristics of social groups an intervention targets (socioeconomic status, area of living, gender; race, ethnicity, religion and sexual orientation); and non-health consequences of an intervention (financial protection, economic productivity, and care for others).

The Lancet
Aug 30, 2014 Volume 384 Number 9945 p715 – 828
http://www.thelancet.com/journals/lancet/issue/current

Comment
Africa’s child demographics and the world’s future
Jeffrey O’Malley, Tessa Wardlaw, Danzhen You, Lucia Hug, David Anthony
Preview
In 1950, only about a tenth of the world’s children lived in Africa.1 Within 50 years, that proportion almost doubled, and it is set to double again by the middle of the 21st century, leaving Africa with nearly a billion children younger than 18 years by 2050—37% of the worldwide total. By the end of the century, based on present trends, almost half of all children will live in Africa.

Global, regional, and national prevalence of overweight and obesity in children and adults during 1980—2013: a systematic analysis for the Global Burden of Disease Study 2013
Marie Ng PhD a, et al
Summary
Background
In 2010, overweight and obesity were estimated to cause 3•4 million deaths, 3•9% of years of life lost, and 3•8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980—2013.
Methods
We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19 244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).
Findings
Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m2 or greater increased between 1980 and 2013 from 28•8% (95% UI 28•4—29•3) to 36•9% (36•3—37•4) in men, and from 29•8% (29•3—30•2) to 38•0% (37•5—38•5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23•8% (22•9—24•7) of boys and 22•6% (21•7—23•6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8•1% (7•7—8•6) to 12•9% (12•3—13•5) in 2013 for boys and from 8•4% (8•1—8•8) to 13•4% (13•0—13•9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down.
Interpretation
Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene.
Funding
Bill & Melinda Gates Foundation.

The Lancet Global Health
Sep 2014 Volume 2 Number 9 e488 – 549
http://www.thelancet.com/journals/langlo/issue/current

Comment
Excess female mortality in infants and children
Shams El Arifeen
Preview |
The sex ratio of mortality in children younger than 5 years (under-5s) has always been regarded as an important indicator for child health and survival, especially in the context of sex preference and discrimination in many cultures such as those in south Asia.1 However, the effective use of this indicator to improve child health and survival has been constrained by the absence of a clear understanding of what the ideal ratio should be.

National, regional, and global sex ratios of infant, child, and under-5 mortality and identification of countries with outlying ratios: a systematic assessment
Leontine Alkema, Fengqing Chao, Danzhen You, Jon Pedersen, Cheryl C Sawyer

Cost-effectiveness of HIV prevention for high-risk groups at scale: an economic evaluation of the Avahan programme in south India
Anna Vassall, Michael Pickles, Sudhashree Chandrashekar, Marie-Claude Boily, Govindraj Shetty, Lorna Guinness, Catherine M Lowndes, Janet Bradley, Stephen Moses, Michel Alary, Charme India Group , Peter Vickerman

Effect of preventive and curative interventions on hepatitis C virus transmission in Egypt (ANRS 1211): a modelling study
Romulus Breban, Naglaa Arafa, Sandrine Leroy, Aya Mostafa, Iman Bakr, Laura Tondeur, Mohamed Abdel-Hamid, Wahid Doss, Gamal Esmat, Mostafa K Mohamed, Arnaud Fontanet

The Lancet Infectious Diseases
Sep 2014 Volume 14 Number 9 p779 – 898
http://www.thelancet.com/journals/laninf/issue/current

Editorial
Ebola in west Africa
The Lancet Infectious Diseases

Comment
Pneumococcal conjugate vaccination: correlates of protection
Angel Vila-Corcoles, Olga Ochoa-Gondar
Preview |
Infections caused by Streptococcus pneumoniae are a major health problem worldwide. Susceptibility to pneumococcal infections varies with age, and is highest in young infants and older adults. Death from pneumococcus is the most common vaccine-preventable illness in infants younger than 5 years, with an estimated 700 000 to 1 million deaths occurring yearly throughout the world in this age group.1

What can rotavirus vaccines teach us about rotavirus?
Jim P Buttery, Carl D Kirkwood
Preview
Suspected and unexpected clinical features of pathogens might only become apparent during clinical trials to test vaccines or after implementation of vaccination programmes. For example, the role of Haemophilus influenzae type b (Hib) in early childhood pneumonia was not evident until findings of a clinical vaccine trial in The Gambia showed that—after 3 years of follow-up—Hib caused more than 20% of radiologically defined pneumonia in infants.1,2 Moreover, the ability of different pneumococcal serotypes, but not meningococcal serogroups, to replace competing strains in nasopharyngeal carriage and invasive disease was only noted after implementation of pneumococcal and group C meningococcal glycoconjugate vaccines.

Islam and polio
Fatima Riaz, Yasir Waheed
Preview
Public health interventions and policies do not have a uniform response worldwide. Medical anthropologists appreciate the role of cultural epidemiology in establishing the community response and, concomitantly, the disease’s fate.1 In the case of polio, which has a viable vaccine, social misconceptions and religious misinterpretations receive the most media attention as the barriers preventing the disease from tipping over into complete eradication.2

Epidemiology of invasive meningococcal disease in the Netherlands, 1960–2012: an analysis of national surveillance data
Merijn W Bijlsma, Vincent Bekker, Matthijs C Brouwer, Lodewijk Spanjaard, Diederik van de Beek, Arie van der Ende

Epidemiology of bacterial meningitis in the USA from 1997 to 2010: a population-based observational study
Rodrigo Lopez Castelblanco, MinJae Lee, Rodrigo Hasbun

Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: a randomised, placebo-controlled, phase 1 study
Jorge E Osorio, Ivan D Velez, Cynthia Thomson, Liliana Lopez, Alejandra Jimenez, Aurelia A Haller, Shawn Silengo, Jaclyn Scott, Karen L Boroughs, Janae L Stovall, Betty E Luy, John Arguello, Mark E Beatty, Joseph Santangelo, Gilad S Gordon, Claire Y-H Huang, Dan T Stinchcomb

Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study
Nick J Andrews, Pauline A Waight, Polly Burbidge, Emma Pearce, Lucy Roalfe, Marta Zancolli, Mary Slack, Shamez N Ladhani, Elizabeth Miller, David Goldblatt

Distribution of rotavirus strains and strain-specific effectiveness of the rotavirus vaccine after its introduction: a systematic review and meta-analysis
Eyal Leshem, Ben Lopman, Roger Glass, Jon Gentsch, Krisztián Bányai, Umesh Parashar, Manish Patel

New England Journal of Medicine
August 28, 2014 Vol. 371 No. 9
http://www.nejm.org/toc/nejm/medical-journal

Perspective
Updating Cost-Effectiveness — The Curious Resilience of the $50,000-per-QALY Threshold
Peter J. Neumann, Sc.D., Joshua T. Cohen, Ph.D., and Milton C. Weinstein, Ph.D.
N Engl J Med 2014; 371:796-797August 28, 2014
DOI: 10.1056/NEJMp1405158

For more than two decades, the ratio of $50,000 per quality-adjusted life-year (QALY) gained by using a given health care intervention has played an important if enigmatic role in health policy circles as a benchmark for the value of care. Researchers have summoned this cost-effectiveness ratio in order to champion or denounce particular investments in medical technologies and health programs. Critics, meanwhile, have argued that the ratio is misunderstood and misused.

The fact that the $50,000-per-QALY yardstick has persisted attests to the medical community’s need for a value threshold and to the advantages enjoyed by incumbents. It has endured even as the United States has legislated against the explicit use of cost-per-QALY thresholds, and it has held its own even though common sense might dictate that it should be updated to reflect inflation and economic growth. Like the 4-minute mile in running, which has withstood threats to its relevance (the current record is 3:43, and the sport long ago switched championship races to 1500 m, the “metric mile”), $50,000-per-QALY retains its place in the imagination. As the United States debates anew how much to spend on medical care — a question that has been highlighted by high-priced drugs for cancer and hepatitis C — it is useful to reexamine what the ratio means, why it persists, and how it might be applied more reasonably to inform resource-prioritization discussions in today’s health care and economic climate.

The $50,000-per-QALY ratio has murky origins. It is often attributed to the U.S. decision to mandate Medicare coverage for patients with end-stage renal disease (ESRD) in the 1970s: because the cost-effectiveness ratio for dialysis at the time was roughly $50,000 per QALY, the government’s decision arguably endorsed that cutoff point implicitly.1 However, the link to dialysis is inexact — and even something of an urban legend, given that the cost-effectiveness ratio for dialysis was probably more like $25,000 to $30,000 per QALY, the ESRD decision was controversial, and even at the time Medicare was covering some treatments costing more than $50,000 per QALY.1
Furthermore, the $50,000-per-QALY standard did not gain widespread use until the mid-1990s, long after the ESRD decision, and seems to stem more from a series of articles that proposed rough ranges ($20,000 to $100,000 per QALY) for defining cost-effective care. The field settled on $50,000 per QALY as an arbitrary but convenient round number, after several prominent cost-effectiveness analyses in the mid-1990s referenced that threshold and helped to congeal it into conventional wisdom.1 Researchers continue to cite the threshold regularly, although in recent years more have been referencing $100,000 per QALY (see table Cost-Effectiveness Thresholds Referenced by Authors of U.S.-Based Cost-Utility Analyses, 1990–2012.).

A society’s cost-effectiveness threshold — which indicates its willingness to pay for improvements in health — can also be inferred from its budget for health care expenditures. In theory, if all interventions could be measured in similar terms and ranked by the favorability of their incremental cost-effectiveness ratios, decision makers with a fixed budget could maximize health gains by choosing interventions with the lowest (most favorable) ratios and working their way down the list until the available resources were consumed. The cost-effectiveness of the last (least favorable) technology covered would represent society’s willingness-to-pay threshold — the highest price society is willing to pay for health gains.

In practice, cost-effectiveness information is spotty, and U.S. decision makers do not face rigidly fixed budgets. Instead, thresholds are used as rough guides to help determine whether particular investments constitute reasonable value.1 Referencing a $50,000-per-QALY threshold has in practice implied adding new “favorable” interventions (with ratios below $50,000 per QALY), but without displacing any “unfavorable” interventions (with ratios of $50,000 per QALY or above).

Researchers have attempted in various ways to deduce what constitutes a reasonable threshold on the basis of economic theory or empirical estimates.1 Some economists as well as the World Health Organization have argued, on the basis of plausible assumptions about people’s values and attitudes toward risk, for a threshold of two to three times the per capita annual income, which would imply a U.S. threshold of $110,000 to $160,000 per QALY today (given that the per capita income is roughly $54,000). Others have inferred a threshold of $200,000 to $300,000 per QALY on the basis of increases in health care spending over time and the health gains that have been associated with those increases, surveys that ask people how much they would be willing to pay for health gains, or the trade-offs that people make in the workplace between pay and safety risks.2,3

All this research suggests that $50,000 per QALY is too low, although in truth it is impossible to find a single threshold to represent society’s willingness to pay for QALYs gained, because different approaches yield different values, each of which is based on different assumptions, inferences, and contexts. Searching for a single benchmark is at best a quixotic exercise because there is no threshold that is appropriate in all decision contexts.4 In principle, the threshold should depend on the budget available to a decision maker and the costs and benefits of alternative uses of that budget. In the United States, no single decision maker knows the opportunity costs of alternative health investments and issues health care decisions under a single budget.4 Moreover, U.S. policymakers, who are already averse to explicit rationing, would balk at such a rigid exercise.

Still, we face a powerful need to assess comparative value. The effective but costly hepatitis C drug sofosbuvir (Sovaldi, Gilead Sciences) is only the most recent example to remind us that society cannot avoid difficult trade-offs in choosing among health-improving technologies. Despite its problems, the threshold is a useful tool for organizing evidence and informing decisions. It should, however, be used with greater thoughtfulness and consistency. For example, it is useful to know that sofosbuvir may in fact be cost-effective in certain populations according to traditional cost-per-QALY thresholds, but its widespread use at its current price raises critical questions about its affordability and about what services will not be provided in order to pay for it.

Rather than settling on a single threshold, we believe it would be preferable to use multiple thresholds, ideally ones based on the available resources for the relevant decision maker and possible alternative uses of those resources. For example, decision makers in resource-poor settings would have a more stringent (lower) ceiling.
Given the evidence suggesting that $50,000 per QALY is too low in the United States, it might best be thought of as an implied lower boundary.4 Instead, we would recommend that analysts use $50,000, $100,000, and $200,000 per QALY. If one had to select a single threshold outside the context of an explicit resource constraint or opportunity cost, we suggest using either $100,000 or $150,000.

Invoking thresholds, however, means acknowledging limits — and thus in some cases displacing currently provided interventions that have cost-effectiveness ratios exceeding the threshold. It also suggests that more of our spending should focus on underutilized interventions with ratios below the threshold; substituting more cost-effective interventions for less cost-effective ones could improve health outcomes and save money.5 Finally, much more work is needed to elucidate the comparative effectiveness and cost-effectiveness of existing care and to establish systemwide incentives to encourage cost-conscious decisions.

PLoS One
[Accessed 30 August 2014]
http://www.plosone.org/

Research Article
The Immune System in Children with Malnutrition—A Systematic Review
Maren Johanne Heilskov Rytter, Lilian Kolte, André Briend, Henrik Friis, Vibeke Brix Christensen
Published: August 25, 2014
DOI: 10.1371/journal.pone.0105017
Abstract
Background
Malnourished children have increased risk of dying, with most deaths caused by infectious diseases. One mechanism behind this may be impaired immune function. However, this immune deficiency of malnutrition has not previously been systematically reviewed.
Objectives
To review the scientific literature about immune function in children with malnutrition.
Methods
A systematic literature search was done in PubMed, and additional articles identified in reference lists and by correspondence with experts in the field. The inclusion criteria were studies investigating immune parameters in children aged 1–60 months, in relation to malnutrition, defined as wasting, underweight, stunting, or oedematous malnutrition.
Results
The literature search yielded 3402 articles, of which 245 met the inclusion criteria. Most were published between 1970 and 1990, and only 33 after 2003. Malnutrition is associated with impaired gut-barrier function, reduced exocrine secretion of protective substances, and low levels of plasma complement. Lymphatic tissue, particularly the thymus, undergoes atrophy, and delayed-type hypersensitivity responses are reduced. Levels of antibodies produced after vaccination are reduced in severely malnourished children, but intact in moderate malnutrition. Cytokine patterns are skewed towards a Th2-response. Other immune parameters seem intact or elevated: leukocyte and lymphocyte counts are unaffected, and levels of immunoglobulins, particularly immunoglobulin A, are high. The acute phase response appears intact, and sometimes present in the absence of clinical infection. Limitations to the studies include their observational and often cross-sectional design and frequent confounding by infections in the children studied.
Conclusion
The immunological alterations associated with malnutrition in children may contribute to increased mortality. However, the underlying mechanisms are still inadequately understood, as well as why different types of malnutrition are associated with different immunological alterations. Better designed prospective studies are needed, based on current understanding of immunology and with state-of-the-art methods.

Risk Analysis
August 2014 Volume 34, Issue 8 Pages 1359–1579
http://onlinelibrary.wiley.com/doi/10.1111/risa.2014.34.issue-8/issuetoc

Original Research Article
A Scenario-Based Evaluation of the Middle East Respiratory Syndrome Coronavirus and the Hajj
Lauren M. Gardner1,2,*, David Rey1, Anita E. Heywood3, Renin Toms3, James Wood3, S. Travis Waller1,2 andC. Raina MacIntyre3
Article first published online: 14 JUL 2014
DOI: 10.1111/risa.12253
Abstract
Between April 2012 and June 2014, 820 laboratory-confirmed cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported in the Arabian Peninsula, Europe, North Africa, Southeast Asia, the Middle East, and the United States. The observed epidemiology is different to SARS, which showed a classic epidemic curve and was over in eight months. The much longer persistence of MERS-CoV in the population, with a lower reproductive number, some evidence of human-to-human transmission but an otherwise sporadic pattern, is difficult to explain. Using available epidemiological data, we implemented mathematical models to explore the transmission dynamics of MERS-CoV in the context of mass gatherings such as the Hajj pilgrimage, and found a discrepancy between the observed and expected epidemiology. The fact that no epidemic occurred in returning Hajj pilgrims in either 2012 or 2013 contradicts the long persistence of the virus in human populations. The explanations for this discrepancy include an ongoing, repeated nonhuman/sporadic source, a large proportion of undetected or unreported human-to-human cases, or a combination of the two. Furthermore, MERS-CoV is occurring in a region that is a major global transport hub and hosts significant mass gatherings, making it imperative to understand the source and means of the yet unexplained and puzzling ongoing persistence of the virus in the human population.

Vaccine
Volume 32, Issue 41, Pages 5259-5370 (15 September 2014)
http://www.sciencedirect.com/science/journal/0264410X/32/41

Global vaccine supply. The increasing role of manufacturers from middle income countries
Pages 5259-5265
Donald P. Francis, Yu-Ping Du, Alexander R. Precioso
Abstract
Hallmarks in the remarkable evolution of vaccines and their application include the eradication of smallpox, the development and delivery of the early childhood vaccines and the emergence of recombinant vaccines initiated by the hepatitis B vaccine. Now we enter a most exciting era as vaccines are increasingly produced and delivered in less developed countries. The results are dramatic decreases in childhood morbidity and mortality around the world.

Vaccine
Volume 32, Issue 41, Pages 5259-5370 (15 September 2014)
http://www.sciencedirect.com/science/journal/0264410X/32/41

Experiences with provider and parental attitudes and practices regarding the administration of multiple injections during infant vaccination visits: Lessons for vaccine introduction
Original Research Article
Pages 5301-5310
Aaron S. Wallace, Carsten Mantel, Gill Mayers, Osman Mansoor, Jacqueline S. Gindler, Terri B. Hyde
Abstract
Introduction
An increasing proportion of childhood immunization visits include administration of multiple injections. Future introduction of vaccines to protect against multiple diseases will further increase the number of injections at routine immunization childhood visits, particularly in developing countries that are still scaling up introductions. Parental and healthcare provider attitudes toward multiple injections may affect acceptance of recommended vaccines, and understanding these attitudes may help to inform critical decisions about vaccine introduction.
Methods
We conducted a systematic review of the literature to examine factors underlying reported parental and healthcare provider concerns and practices related to administration of multiple injections during childhood vaccination visits.
Results
Forty-four articles were identified; 42 (95%) were from high income countries, including 27 (61%) from the USA. Providers and parents report concerns about multiple injections, which tend to increase with increasing numbers of injections. Common parental and provider concerns included apprehension about the pain experienced by the child, worry about potential side effects, and uncertainty about vaccine effectiveness. Multiple studies reported that a positive provider recommendation to the parent and a high level of concern about the severity of the target disease were significantly associated with parental acceptance of all injections. Providers often significantly overestimated parental concerns about multiple injections.
Discussion
Providers may play a critical role in the decision for a child to receive all recommended injections. Their overestimation of parental concerns may lead them to postpone recommended vaccinations, which may result in extra visits and delayed vaccination. More research is needed on interventions to overcome provider and parental concern about multiple injections, particularly in developing countries.

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

Epidemiology and Infection
Volume 142 – Issue 10 – October 2014
http://journals.cambridge.org/action/displayIssue?jid=HYG&tab=currentissue
FirstView Articles Published online: 22 August 2014
A probability model for evaluating the bias and precision of influenza vaccine effectiveness estimates from case-control studies.
M. HABER, Q. AN, I. M. FOPPA, D. K. SHAY, J. M. FERDINANDS and W. A. ORENSTEIN
DOI: http://dx.doi.org/10.1017/S0950268814002179
SUMMARY
As influenza vaccination is now widely recommended, randomized clinical trials are no longer ethical in many populations. Therefore, observational studies on patients seeking medical care for acute respiratory illnesses (ARIs) are a popular option for estimating influenza vaccine effectiveness (VE). We developed a probability model for evaluating and comparing bias and precision of estimates of VE against symptomatic influenza from two commonly used case-control study designs: the test-negative design and the traditional case-control design. We show that when vaccination does not affect the probability of developing non-influenza ARI then VE estimates from test-negative design studies are unbiased even if vaccinees and non-vaccinees have different probabilities of seeking medical care against ARI, as long as the ratio of these probabilities is the same for illnesses resulting from influenza and non-influenza infections. Our numerical results suggest that in general, estimates from the test-negative design have smaller bias compared to estimates from the traditional case-control design as long as the probability of non-influenza ARI is similar among vaccinated and unvaccinated individuals. We did not find consistent differences between the standard errors of the estimates from the two study designs.

Epidemics
Available online 27 August 2014
Seven challenges in Modelling Vaccine Preventable Diseases
C.J.E. Metcalfa, O.N. Bjørnstadc, K. Eamesd, W.J. Edmundsd, S. Funkd, T.D. Hollingsworthe, f, J. Lesslerg, C. Viboudh, B.T. Grenfella, h
Highlights
:: Mathematical models have informed vaccination from the underlying science to program design.
:: This is an exciting time as novel challenges are emerging from changing biology and advancing vaccine technology.
:: Population scale challenges range from modeling immune heterogeneity to dynamics near elimination.
:: Within host challenges include modeling immune memory, evolution of escape, and new vaccine biology.
Abstract
Vaccination has been one of the most successful public health measures since the introduction of basic sanitation. Substantial mortality and morbidity reductions have been achieved via vaccination against many infections, and the list of diseases that are potentially controllable by vaccines is growing steadily. We introduce key challenges for modeling in shaping our understanding and guiding policy decisions related to vaccine preventable diseases.

Clinical Infectious Diseases
Volume 59, Issue suppl 2 Pp. S80-S84
Ending the Global HIV/AIDS Pandemic: The Critical Role of an HIV Vaccine
Anthony S. Fauci, Gregory K. Folkers, and Hilary D. Marston
Author Affiliations
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
Abstract
While the human immunodeficiency virus (HIV)/AIDS pandemic continues, the incidence of HIV infections has fallen because of the deployment of antiretroviral drugs and multiple prevention modalities. To achieve a durable end to the pandemic, a vaccine remains essential. Recent advances in vaccinology offer new promise for an effective HIV vaccine.

Current Gene Therapy
Volume 14, No. 2, 2014
http://benthamscience.com/journal/contents.php?journalID=cgt&issueID=124005
Editorial (Thematic Issue: The Coming of Age of DNA Vaccines)
ANikolai Petrovsky
Affiliation: Director, Department of Diabetes and Endocrinology, Flinders Medical Centre, Adelaide, SA 5042 Australia.
Abstract
Conventional immunization approaches utilize live attenuated pathogens, inactivated organisms, recombinant proteins or polysaccharide antigens to induce protective immunity. Twenty years ago in a major breakthrough it was shown that immune responses could instead be elicited by injecting plasmid DNA encoding relevant vaccine antigens [1-3]. This heralded the start of DNA vaccination. DNA vaccines offer many potential advantages; including speed and simplicity of manufacture. Despite early hype, this technology has yet to yield approved human products although there are already a number of approved veterinary DNA vaccines suggesting human applications are only a matter of time [4]. It should be remembered that monoclonal antibodies took over 2 decades from initial discovery to final successful human application. By these standards DNA vaccine technology is still in its relatively infancy. Hence this special edition on DNA vaccines is timely to examine the state of the art in DNA vaccine technology. It is hoped this collections of papers will help address the perennial question asked on all long journeys, “are we there yet?” These papers convey a sense of the tremendous distance that DNA vaccine technology has come over the 20 years since its initial discovery. In particular, issues of DNA vaccine safety have by and large been satisfactorily addressed, leaving vaccine efficacy as the only real remaining challenge [5]. Despite the passage of time there is still a sense of excitement that surrounds the DNA vaccine field. These papers convey a willingness of those in the field to press on to solve the remaining challenges to bring DNA vaccines to the human market. This augurs well for the eventual success of DNA vaccine technology. A variety of key topics are covered by this collection. The excellent review by Jim Williams describes the state of the art in DNA plasmid design. It highlights just how far plasmid design has been advanced and explores how plasmids can be fine-tuned for maximal protein expression. Kwilas et al., describe a novel delivery approach that uses a jet injector device to deliver the plasmid intramuscularly without the need for a needle. Interestingly this form of administration appears to also enhance plasmid expression and vaccine immunogenicity. Another area where there have been major advances is the area of DNA vaccine adjuvants. Capitani et al. demonstrate that plasmids encoding aggregation-promoting domains act as DNA vaccine adjuvants by triggering frustrated autophagy leading to caspase activation and apoptotic cell death. The induction of cell death is common to traditional vaccine adjuvants including alum and squalene oil emulsions [6], but poses safety risks as excess cell death may trigger unwanted side effects and even autoimmunity in susceptible individuals [7, 8]. No discussion of DNA vaccines would be complete without including electroporation as a method of enhancing plasmid expression. Davtyan et al. describe studies on electroporation settings to maximize delivery of an Alzheimer’s disease DNA vaccine encoding a β-amyloid epitope. Electroporation remains a potent tool for maximizing DNA delivery but with the downsides of inconvenience, cost and discomfort. Finally, Lucyna Cova examines the history of hepatitis B DNA vaccine development, describing the many challenges encountered along the way. This is a story that could easily be repeated for the many other DNA vaccines under development. I trust this collection of papers on current DNA vaccine research will convince the reader that the field of DNA vaccines is not dead, and in fact under the surface vigorous research and development efforts continue towards a key milestone which will be approval of the first human DNA vaccine. Considering the more than 20 years that monoclonal antibody technology had to spend in the wilderness before all their problems were solved and they became the pharmaceutical industry’s biggest success story, DNA vaccines may yet have their time in the sun.

Vaccines and Global Health: The Week in Review is a service of the Center for Vaccines Ethics and Policy (CVEP) which is solely responsible for its content. Support for this service is provided by its governing institutions – Department of Medical Ethics, NYU Medical School; The Wistar Institute Vaccine Center and the Children’s Hospital of Philadelphia Vaccine Education Center. Additional support is provided by the PATH Vaccine Development Program; the International Vaccine Institute (IVI); the Bill & Melinda Gates Foundation; industry resource members Janssen, Pfizer, and Sanofi Pasteur U.S. (list in formation), and the Developing Countries Vaccine Manufacturers Network (DCVMN). Support is also provided by a growing list of individuals who use this membership service to support their roles in public health, clinical practice, government, NGOs and other international institutions, academia and research organizations, and industry.

WHO: Global Alert and Response (GAR) – Disease Outbreak News [to 23 August 2014]
http://www.who.int/csr/don/en/
:: Ebola virus disease update – west Africa 22 August 2014
Epidemiology and surveillance
Between 19 and 20 August 2014, a total of 142 new cases of Ebola virus disease (laboratory-confirmed, probable, and suspect cases) as well as 77 deaths were reported from Guinea, Liberia, Nigeria, and Sierra Leone.

Health sector response
Questions have been received in WHO Headquarters about the original proposed budget for the response and the new draft budget, which is being reviewed by partners. The increase in needed resources is based on improved data and understanding of the situation on the ground in the affected countries. The new estimation of costs is derived using a unit-cost model, built for the most intense transmission areas and reflects the average operational costs based on the current situation in the affected countries. The major assumptions for the cost estimates will be announced towards the end of next week.

WHO continues to receive reports of rumoured or suspected cases from countries around the world and systematic verification of these cases is ongoing. Countries are encouraged to continue engaging in active surveillance and preparedness activities. As of today, no new cases have been confirmed outside of Guinea, Liberia, Nigeria, or Sierra Leone.

WHO does not recommend any travel or trade restrictions be applied except in cases where individuals have been confirmed or are suspected of being infected with EVD or where individuals have had contact with cases of EVD. (Contacts do not include properly-protected health-care workers and laboratory staff.) Temporary recommendations from the Emergency Committee with regard to actions to be taken by countries can be found at:
IHR Emergency Committee on Ebola outbreak in west Africa

:: WHO Director-General briefs Geneva UN missions on the Ebola outbreak – 12 August 2014

:: Statement on travel and transport in relation to Ebola virus disease (EVD) outbreak – 18 August 2014

.

Ethical considerations for use of unregistered interventions for Ebola virus disease
Report of an advisory panel to WHO
2014 :: 10 pages :: WHO reference number: WHO/HIS/KER/GHE/14.1
Overview
West Africa is experiencing the largest, most severe, most complex outbreak of Ebola virus disease in history. On 11 August 2014, WHO convened a consultation to consider and assess the ethical implications for clinical decision-¬making of use of unregistered interventions that have shown promising results in the laboratory and in animal models but that have not yet been evaluated for safety and efficacy in humans.

Conclusion [full text from report p.7]
In the particular context of the current Ebola outbreak in West Africa, it is ethically acceptable to offer unproven interventions that have shown promising results in the laboratory and in animal models but have not yet been evaluated for safety and efficacy in humans as potential treatment or prevention.

Ethical, scientific and pragmatic criteria must guide the provision of such interventions. The ethical criteria include transparency about all aspects of care, so that the maximum information is obtained about the effects of the interventions, fairness, promotion of cosmopolitan solidarity, informed consent, freedom of choice, confidentiality, respect for the person, preservation of dignity, involvement of the community and risk–benefit assessment.

If and when unproven interventions that have not yet been evaluated for safety and efficacy in humans but have shown promising results in the laboratory and in animal models are used to treat patients, those involved have a moral obligation to collect and share all the scientifically relevant data generated, including from treatments provided for “compassionate use”.

Researchers have a moral duty to evaluate these interventions (for treatment or prevention) in clinical trials that are of the best possible design in the current exceptional circumstances of the West African Ebola outbreak, in order to establish the safety and efficacy of the interventions or to provide evidence to stop their use. Continuous evaluation should guide future interventions.

POLIO [to 23 August 2014]

GPEI Update: Polio this week – As of 20 August 2014
Global Polio Eradication Initiative
Editor’s Excerpt and text bolding
Full report: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
:: The Horn of Africa Technical Advisory Group (TAG) met last week to review the current epidemiological situation, the impact of outbreak response and to determine additional strategies needed to rapidly interrupt residual transmission in the region. Plans were developed to increase access to mobile populations, to improve community surveillance and to strengthen campaign quality. Read more in the Horn of Africa section below.
:: China, India and Australia have joined Saudi Arabia in requiring proof of polio vaccination for visa applications for travellers coming from polio endemic and outbreak countries to mitigate the risk of international spread of polio.
:: In Cameroon, genetic sequencing of the recently-reported cases confirms continued wild poliovirus circulation, gaps in surveillance resulting in undetected transmission and geographic expansion to new areas of the country. See ‘central Africa’ section below for further information.
Pakistan
:: Seven new WPV1 cases were reported in the past week, all from Federally Administered Tribal Areas (FATA), from North Waziristan, South Waziristan and Khyber, bringing the total number of WPV1 cases for 2014 to 115. One of the newly-reported cases from North Waziristan is the most recent WPV1 case in the country, with onset of paralysis on 27 July.
Horn of Africa
:: The Horn of Africa TAG met from 12-14 August to review the current epidemiological situation and the impact of the outbreak response and to determine additional strategies needed to rapidly interrupt residual transmission in the region.
:: Strategies were proposed to improve operations and strengthen surveillance including targeted tactics for reaching mobile populations in Somalia and Ethiopia, considering new communication channels and opportunities to reach these groups. The need to sustain the sense of urgency until the outbreak is stopped was highlighted
Middle East
:: In the Middle East, the second phase of the comprehensive outbreak response is being implemented across the region.
:: WHO and UNICEF are committed to working with all organizations and agencies providing humanitarian assistance to Syrians affected by the conflict. This includes vaccination of all children no matter where they are, whether in government or contested areas of the country, or outside Syria.
:: SNIDs will start on 31 August in high-risk governorates of Syria where over the past several SIAs coverage has been lower than in other areas. Technical support is being maximized to these areas.
:: On 6-7 September, there will be a review of the Phase 2 outbreak response in the Middle East so far.
West Africa
:: Polio staff across West Africa are supporting efforts to control the Ebola outbreak affecting the region. The Ebola outbreak will impact the planned multi-country polio campaigns in September in the Ebola affected countries with campaigns in Liberia, Sierra Leone, and Guinea being postponed until the Ebola outbreak is brought under control. Preparations for large scale multi-country campaigns in countries across the rest of West Africa in mid-September are proceeding as planned.

UNICEF Watch [to 23 August 2014]
http://www.unicef.org/media/media_71724.html
Mass Polio Vaccination Campaign Supported by WHO and UNICEF Kicks Off in Iraq
ERBIL/AMMMAN, 11 August 2014 – Iraq has launched a polio immunization campaign aiming to protect over four million children under the age of 5 throughout the country against the crippling disease.

The Weekly Epidemiological Record (WER) 22 August 2014, vol. 89, 34 (pp. 369–376) includes:
:: Summary analysis of 2014 survey of National Influenza Centres in the WHO Global Influenza Surveillance and Response System
http://www.who.int/entity/wer/2014/wer8934.pdf?ua=1

WHO: Humanitarian Health Action [to 23 August 2014]
:: Kuwaiti aid to WHO improves health for Syrians affected by conflict
21 August 2014, Geneva — A US$45 million donation to the World Health Organization from Kuwait has saved the lives and addressed the health needs of millions of people affected by the conflict in Syria, a new WHO report says.

The much needed funds have been used to provide essential health care in both government- and opposition-controlled areas within Syria, as well as in neighbouring countries struggling to cope with 2.9 million Syrians who have taken refuge in Egypt, Iraq, Jordan and Lebanon, Turkey.

In a final report to the Government of Kuwait on the use of its donation, WHO says it has served to provide several million people with critical medicines to treat life-threatening chronic conditions, such as renal failure, epilepsy, asthma and diabetes, and over 5 million of the sick or injured with medicines, anaesthetics and surgical supplies…

CDC/MMWR Watch [to 23 August 2014]
http://www.cdc.gov/mmwr/mmwr_wk.html

:: Two U.S. Patients Recover from Ebola, Discharged from Hospital – Media Statement
August 21, 2014
“CDC is heartened to learn that the two U.S. citizens treated at Emory University Hospital for Ebola have been discharged from the hospital and can rejoin their families and communities.”

MMWR Weekly – August 22, 2014 / Vol. 63 / No. 33
:: Vaccine-Associated Paralytic Poliomyelitis and BCG-osis in an Immigrant Child with Severe Combined Immunodeficiency Syndrome — Texas, 2013
:: Update on Recommendations for Use of Herpes Zoster Vaccine

Industry Watch [to 23 August 2014]
Selected media releases and other selected content from industry.
:: Pfizer Announces FDA Acceptance Of And Priority Review Designation For Biologics License Application For Investigational Meningococcal B Vaccine August 14, 2014

:: Merck Statement regarding Role of PNEUMOVAX® 23 (Pneumococcal Vaccine Polyvalent) in Updated ACIP Recommendations for Pneumococcal Vaccination in Adults – August 13, 2014

:: Advisory Committee on Immunization Practices Votes to Recommend Pfizer’s Prevnar 13® Vaccine in Adults Aged 65 Years and Older – August 13, 2014

Let’s Not Talk About Sex
By PAUL A. OFFIT
The New York Times
The Opinion Pages | Op-Ed Contributor
AUG. 19, 2014
PHILADELPHIA — EVERY year in the United States thousands of men and women die from cancers that can be prevented with a simple vaccine. Sadly, uptake of this cancer-preventing vaccine is abysmal. One reason: Doctors don’t want to talk about sex. The good news is, they don’t have to.

In the past decade, the Centers for Disease Control and Prevention, in concert with the American Academy of Pediatrics, has recommended three vaccines for adolescents. One to prevent meningococcus, which causes bloodstream infections and meningitis; another, given in a three-in-one shot called Tdap, to prevent tetanus, diphtheria and pertussis (whooping cough); and a third to prevent human papillomavirus (HPV), which causes several types of cancer.

In July, the C.D.C. announced the most recent results of its teenage immunization survey. Around 80 percent of adolescents now receive the meningococcal and Tdap vaccines. The HPV vaccine, however, is a different story. Only 57 percent of girls had started the three-dose series; 38 percent had finished it. In boys, for whom the vaccine was recommended a few years ago, 35 percent had started and 14 percent had finished the series.
“It’s frustrating to report almost the same HPV vaccination coverage levels among girls for another year,” said Dr. Anne Schuchat, director of the National Center for Immunization and Respiratory Diseases at the C.D.C., in a statement.

Why are adolescents and their parents embracing meningococcal and Tdap vaccines but not the HPV vaccine? One possible explanation is a clash between perception and reality, People just don’t understand how serious an infection HPV can be. In a typical year in the United States about 150 people die from meningococcus, four from tetanus, none from diphtheria, 20 from pertussis, and roughly 4,000 from cancers caused by HPV. People are more than 20 times more likely to die from HPV than from the other four diseases combined.

About 79 million people in the United States have been infected with HPV, and 14 million new infections occur every year. As a consequence, 18,000 women and 8,000 men suffer preventable cancers of the cervix, anus, penis and throat; it’s the most common, and except for H.I.V., the most fatal sexually transmitted disease.

Another common misperception is that the HPV vaccine is ineffective and immunity is short-lived. But the truth is that the HPV vaccine is virtually 100 percent effective at preventing the precancerous lesions caused by the types of HPV contained in the vaccine, which would most likely prevent most cervical cancers. Regarding how long immunity will last, the HPV vaccine is made in the same manner as the hepatitis B vaccine, for which immunity lasts at least 30 years. Immunity provided by the HPV vaccine is likely to be no different.

Further, some high-profile — and highly irresponsible — claims have been made that the vaccine is unsafe. The HPV vaccine has now been studied in more than a million women to determine whether it causes any serious side effects. It doesn’t. There is no scientific support for the suggestion by the onetime presidential hopeful Michele Bachmann that the HPV vaccine could cause “mental retardation,” or for Katie Couric’s giving voice to the notion that it may have caused illnesses and death.

Finally, some fear that the HPV vaccine may increase sexual promiscuity. A study of 1,243 young women and girls between the ages of 15 and 24 alleviated this concern. Those who received the HPV vaccine were not more likely to engage in risky sexual behavior. Nor did it make sense that they would. The HPV vaccine doesn’t prevent other sexually transmitted diseases, like chlamydia, gonorrhea, herpes and syphilis. Indeed, the HPV vaccine doesn’t even prevent all types of HPV, just the majority of those most likely to cause cancer. This argument would be analogous to the claim that people who received a tetanus vaccine could run across a bed of rusty nails with impunity.

When the C.D.C.’s Dr. Schuchat stood in front of the media in July and analyzed the woeful rates of HPV vaccination, she didn’t mention any of these misperceptions. Rather, she offered something else. Adolescents weren’t getting the HPV vaccine because doctors weren’t recommending it strongly enough. In fact, one of the top reasons parents gave for not vaccinating was the lack of a recommendation from their health care providers. A likely reason: Doctors are uncomfortable talking about sex with 11-year-olds. So, what to do? How do we separate “the sex talk” from the first dose of HPV vaccine?

Amy B. Middleman, chief of adolescent medicine at the University of Oklahoma College of Medicine offers one solution in the coming NOVA television special “Vaccines — Calling the Shots”: Don’t talk about sex. “The sex part,” says Dr. Middleman, “the way in which you get the target disease, is irrelevant. We don’t talk about diphtheria, and how you can get diphtheria, before we give the Tdap vaccine.” In other words, it’s not about sex. It’s about cancer.

The fact remains that millions of adolescents aren’t getting a vaccine to prevent a known cause of cancer. It takes about 20 years for an HPV infection to progress to cancer. That’s when the bill is due. Given current rates of immunization, somewhere around 2,000 adults every year whose parents had chosen not to give them the HPV vaccine will probably die from a preventable cancer. It’s unconscionable. And doctors will have only themselves to blame.

Paul A. Offit is a professor of pediatrics in the division of infectious diseases, and director of the Vaccine Education Center, at the Children’s Hospital of Philadelphia.

The Cost of Inaction for Young Children Globally – Workshop Summary
IOM
August 20, 2014
The Forum on Investing in Young Children Globally, which has now launched, went through a yearlong planning process with initial planning grants by the Bernard Van Leer Foundation and the Doris Duke Charitable Foundation. The first planning meeting took place in March 2013 and the second one in June 2013. Out of those two meetings and discussions with multiple leaders in the field, most of whom are here today, came the vision, objectives, and goals for the Forum on Investing in Young Children Globally.
The Board on Children, Youth, and Families of the Institute of Medicine (IOM) and the National Research Council (NRC), in collaboration with the IOM Board on Global Health launched the Forum on Investing in Young Children Globally in January 2014. At this meeting the participants agreed to focus on creating and sustaining, over 3 years, an evidence-driven community of stakeholders across northern and southern countries that aims to explore existing, new, and innovative science and research from around the world and translate this evidence into sound and strategic investments in policies and practices that will make a difference in the lives of children and their caregivers. Forum activities will highlight the science and economics of integrated investments in young children living in low-resourced regions of the world across the areas of health, nutrition, education, and social protection. As a result the forum will explore a holistic view of children and caregivers by integrating analyses and disciplines that span from neurons to neighborhoods and discuss the science from the microbiome to culture. Moreover, the forum will support an integrative vision to strengthen human capital. This work will be done through the forum and will engage in a series of stakeholder consultative sessions or public workshops, each focusing on specific aspects of science integration, bridging equity gaps, and implementing and scaling evidence-informed efforts.
Report pdf:
https://download.nap.edu/login.php?record_id=18845&page=%2Fdownload.php%3Frecord_id%3D18845

BMC Infectious Diseases
(Accessed 23 August 2014)
http://www.biomedcentral.com/bmcinfectdis/content

Research article
An epidemiological analysis of acute flaccid paralysis and its surveillance system in Iraq, 1997-2011
Jagar A Jasem, Kawa Marof, Adnan Nawar, Yosra Khalaf, Faisal Al-Hamdani, Sagvan Ali, Andre C Kalil and KM Monirul Islam
Author Affiliations
BMC Infectious Diseases 2014, 14:448 doi:10.1186/1471-2334-14-448
Published: 20 August 2014
Abstract (provisional)
Background
Acute flaccid paralysis surveillance (AFP) is an essential strategy of the WHO’s Polio Eradication Initiative. This is the first study conducted to estimate the incidence, etiology, distribution, and surveillance performance of AFP in Iraq.
Methods
Surveillance data about the AFP cases under the age of 15 years reported from Iraq during January 1997 to December 2011 were depended in the current study.
Results
A total of 4974 cases of AFP were reported from Iraq during the study period, with an annual incidence of 2.5/100,000 population. Guillain-Barre syndrome represented more than half of the reported cases (N = 2611, 52.5%), followed by traumatic neuritis (N = 715, 14.4%), and other CNS infections (N = 292, 5.9%). Poliomyelitis accounted for 166 (3.3%) of cases, the last reported case being in January 2000. Surveillance performance showed that all, but two, indicators were below the required WHO recommended levels.
Conclusions
AFP surveillance remains the gold standard method for poliomyelitis detection. It witnessed dramatic changes over the last two decades. This has raised people’s and clinicians’ awareness to the importance of promptness in notifying suspected cases and timely transportation of stool specimens to the National Poliovirus Laboratory in Baghdad, or alternatively having more than one laboratory for poliovirus detection in the country, all of which are very useful measures to increase the surveillance performance in the country.

BMC Public Health
(Accessed 23 August 2014)
http://www.biomedcentral.com/bmcpublichealth/content

Research article
HPV catch-up vaccination of young women: a systematic review and meta-analysis
Elisabeth Couto, Ingvil Sæterdal, Lene Kristine Juvet and Marianne Klemp
Author Affiliations
BMC Public Health 2014, 14:867 doi:10.1186/1471-2458-14-867
Published: 23 August 2014
Abstract (provisional)
Background
While prophylactic human papilloma virus (HPV) vaccination is considered effective in young girls, it is unclear whether a catch-up vaccination of older girls would be beneficial. We, therefore, aimed to examine the potential health impact of a HPV catch-up vaccination of girls who were too old at the time of vaccine introduction, hence aged 16 and older.
Methods
We systematically searched the literature for randomized clinical trials (RCTs) that examined the effect of HPV vaccines on overall mortality, cancer mortality and incidence, high-grade cervical intraepithelial neoplasia grade 2 and higher (CIN2+), vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) grade 2 and higher lesions (VIN2+ and VaIN2+, respectively) genital warts (condyloma). We considered all lesions and those associated with HPV type(s) included in the vaccines. RCTs reporting on serious adverse events were also eligible. Selected publications were assessed for potential risk of bias, and we ascertained the overall quality of the evidence for each outcome using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were performed, assuming both random and fixed effects, to estimate risk ratios (RR) and corresponding 95% confidence intervals (CI), using intention-to-treat and per-protocol populations.
Results
We included 46 publications reporting on 13 RCTs. Most of the RCTs had a maximum follow-up period of four years. We identified no RCT reporting on the effect of HPV catch vaccination on overall and cancer related mortality, and on cervical cancer incidence. We found a borderline protective effect of a HPV catch-up vaccination on all CIN2+, with a pooled RR of 0.80 (95% CI: 0.62-1.02) for a follow-up period of 4 years. A HPV catch-up vaccination was associated with a reduction in VIN2+ and VaIN2+ lesions, and condyloma. No difference in risk of serious adverse events was seen in vaccinated participants versus unvaccinated women (pooled RR of 0.99 (0.91-1.08)).
Conclusions
This systematic review indicates that a HPV catch-up vaccination could be beneficial, however the long-term effect of such a vaccination, and its effect on cervical cancer incidence and mortality is still unclear.

Research article
Preparing for human papillomavirus vaccine introduction in Kenya: implications from focus-group and interview discussions with caregivers and opinion leaders in Western Kenya
Allison L Friedman, Kelvin O Oruko, Melissa A Habel, Jessie Ford, Jennine Kinsey, Frank Odhiambo, Penelope A Phillips-Howard, Susan A Wang, Tabu Collins, Kayla F Laserson and Eileen F Dunne
Author Affiliations
BMC Public Health 2014, 14:855 doi:10.1186/1471-2458-14-855
Published: 16 August 2014
Abstract (provisional)
Background
Cervical cancer claims the lives of 275,000 women each year; most of these deaths occur in low-or middle-income countries. In Kenya, cervical cancer is the leading cause of cancer-related mortality among women of reproductive age. Kenya’s Ministry of Public Health and Sanitation has developed a comprehensive strategy to prevent cervical cancer, which includes plans for vaccinating preteen girls against human papillomavirus (HPV) by 2015. To identify HPV vaccine communication and mobilization needs, this research sought to understand HPV vaccine-related perceptions and concerns of male and female caregivers and community leaders in four rural communities of western Kenya.
Methods
We conducted five focus groups with caregivers (n = 56) and 12 key-informant interviews with opinion leaders to explore cervical cancer-related knowledge, attitudes and beliefs, as well as acceptability of HPV vaccination for 9-12 year-old girls. Four researchers independently reviewed the data and developed codes based on questions in interview guides and topics that emerged organically, before comparing and reconciling results through a group consensus process.
Results
Cervical cancer was not commonly recognized, though it was understood generally in terms of its symptoms. By association with cancer and genital/reproductive organs, cervical cancer was feared and stigmatized. Overall acceptability of a vaccine that prevents cervical cancer was high, so long as it was endorsed by trusted agencies and communities were sensitized first. Some concerns emerged related to vaccine safety (e.g., impact on fertility), program intent, and health equity.
Conclusion
For successful vaccine introduction in Kenya, there is a need for communication and mobilization efforts to raise cervical cancer awareness; prompt demand for vaccination; address health equity concerns and stigma; and minimize potential resistance. Visible endorsement by government leaders and community influencers can provide reassurance of the vaccine’s safety, efficacy and benefits for girls and communities. Involvement of community leadership, parents and champions may also be critical for combatting stigma and making cervical cancer relevant to Kenyan communities. These findings underscore the need for adequate planning and resources for information, education and communication prior to vaccine introduction. Specific recommendations for communication and social-marketing strategies are made.

Bulletin of the World Health Organization
Volume 92, Number 8, August 2014, 545-620
http://www.who.int/bulletin/volumes/92/8/en/

Editorial
Family planning and the post-2015 development agenda
Tricia Petruney, Lucy C Wilson, John Stanback & Willard Cates
doi: 10.2471/BLT.14.142893

Varicella and herpes zoster hospitalizations before and after implementation of one-dose varicella vaccination in Australia: an ecological study
Anita E Heywood, Han Wang, Kristine K Macartney & Peter McIntyre
Abstract
Objective
To examine trends in varicella and herpes zoster (HZ) hospitalization following the availability and subsequent National Immunization Programme funding of one-dose varicella vaccination in Australia.
Methods
Varicella vaccination coverage for children born between 2001 and 2009 was obtained from the Australian Childhood Immunization Register. Principal or any coded varicella or HZ hospitalizations were retrieved from the national hospital morbidity database from 1998 to 2010. Trends in hospitalization rates in different age groups and indigenous status were assessed. Incidence rate ratios (IRR) were calculated between periods before and after implementation of immunization programme funding.
Findings
In the first year of the funded immunization programme, varicella vaccine coverage reached 75% in children aged 24 months and more than 80% in children aged 60 months. Compared with the pre-vaccine period, varicella hospitalization rates during the funded programme were significantly lower for age groups younger than 40 years; with the greatest reduction in children aged 18–59 months (IRR: 0.25; 95% confidence interval, CI: 0.22–0.29). Indigenous children had a higher varicella hospitalization rate compared with non-indigenous children before vaccine implementation (IRR: 1.9; 95% CI: 1.4–2.7), but afterwards reached equivalence (IRR: 1.1; 95% CI: 0.7–1.6). The age-standardized HZ hospitalization rate declined between the periods (IRR: 0.95; 95% CI: 0.92–0.97).
Conclusion
Rapid attainment of high coverage reduced varicella hospitalizations in the targeted age group, particularly for indigenous children, but also in non-targeted age groups, with no increase in HZ hospitalizations. This suggests high one-dose varicella vaccine coverage can have a substantial impact on severe disease.

A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries
Sarah Saleem, Elizabeth M McClure, Shivaprasad S Goudar, Archana Patel, Fabian Esamai, Ana Garces, Elwyn Chomba, Fernando Althabe, Janet Moore, Bhalachandra Kodkany, Omrana Pasha, Jose Belizan, Albert Mayansyan, Richard J Derman, Patricia L Hibberd, Edward A Liechty, Nancy F Krebs, K Michael Hambidge, Pierre Buekens, Waldemar A Carlo, Linda L Wright, Marion Koso-Thomas, Alan H Jobe, Robert L Goldenberg & on behalf of the Global Network Maternal Newborn Health Registry Study Investigators
Abstract
Objective
To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths.
Methods
A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum.
Findings
Between 2010 and 2012, 214 070 of 220 235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100 000 live births, ranging from 69 per 100 000 in Argentina to 316 per 100 000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97–11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26–5.67) and 7-day (RR: 3.94; 95% CI: 2.74–5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54–9.77).
Conclusion
Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality.

Clinical Infectious Diseases (CID)
Volume 59 Issue 5 September 1, 2014
http://cid.oxfordjournals.org/content/current

Risk of Pneumococcal Disease in Children With Chronic Medical Conditions in the Era of Pneumococcal Conjugate Vaccine
Clin Infect Dis. (2014) 59 (5): 615-623 doi:10.1093/cid/ciu348
Stephen I. Pelton, Derek Weycker, Raymond A. Farkouh, David R. Strutton, Kimberly M. Shea,
and John Edelsberg
Abstract
Children with previously identified at-risk/high-risk conditions remain at elevated risk of pneumococcal disease in the era of widespread use of pneumococcal conjugate vaccine. Children with multiple at-risk conditions or moderate/severe asthma also are at elevated risk and warrant consideration for immunoprophylaxis

Global Health: Science and Practice (GHSP)
August 2014 | Volume 2 | Issue 3
http://www.ghspjournal.org/content/current

Evidence-based public health: not only whether it works, but how it can be made to work practicably at scale
James D Shelton
Glob Health Sci Pract 2014;2(3):253-258.
http://dx.doi.org/10.9745/GHSP-D-14-00066
Because public health must operate at scale in widely diverse, complex situations, randomized controlled trials (RCTs) have limited utility for public health. Other methodologies are needed. A key conceptual backbone is a detailed “theory of change” to apply appropriate evidence for each operational component. Synthesizing patterns of findings across multiple methodologies provides key insights. Programs operating successfully across a variety of settings can provide some of the best evidence. Challenges include judging the quality of such evidence and assisting programs to apply it. WHO and others should shift emphasis from RCTs to more relevant evidence when assessing public health issues.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
August 2014 Volume 10, Issue 8
http://www.landesbioscience.com/journals/vaccines/toc/volume/10/issue/8/

Do current cost-effectiveness analyses reflect the full value of childhood vaccination in Europe?: A rotavirus case study
Bernd Brüggenjürgen, Mathie Lorrot, Fiona R Sheppard and Vanessa Rémy
Abstract
Economic evaluation of vaccination programs can be challenging and does not always fully capture the benefits provided. Reasons for this include the difficulties incurred in accurately capturing the health and economic impact of infectious diseases and how different diseases may interact with each other. Rotavirus infection, for example, peaks at a similar time than other infectious diseases, such as RSV and influenza, which can cause hospital overcrowding and disruption, and may pose a risk to more vulnerable children due to limited availability of isolation facilities. Another challenge, specific to evaluating childhood vaccination, is that QoL cannot be accurately measured in children due to a lack of validated instruments. Childhood diseases also incur a care giver burden, due to the need for parents to take time off work, and this is important to consider. Finally, for diseases such as RVGE, cost-effectiveness analyses in which longer time horizons are considered may not reflect the short-term benefits of vaccination. Further quantification of the economic impact of childhood diseases is thus required to fully highlight the true benefits of childhood vaccination that may be realized. Herein we explore the limitations of existing economic evaluations for childhood vaccination, and how economic analyses could be better adapted in future.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
August 2014 Volume 10, Issue 8
http://www.landesbioscience.com/journals/vaccines/toc/volume/10/issue/8/

Short Report
Inequalities in vaccination coverage for young females whose parents are informal caregivers
Tabatha N Offutt-Powell, Rohit P Ojha, Tara M Brinkman, Joseph E Tota, Bradford E Jackson, Karan P Singh and Jennifer S Smith
Abstract
The effects of caregiver strain and stress on preventive health service utilization among adult family members are well-established, but the effects of informal caregiving on children of caregivers are unknown. We aimed to assess whether inequalities in vaccination coverage (specifically human papillomavirus [HPV] and influenza) exist for females aged 9 to 17 years whose parents are informal caregivers (i.e., care providers for family members or others who are not functionally independent) compared with females whose parents are not informal caregivers. Data from the 2009 Behavioral Risk Factor Surveillance System were analyzed using Poisson regression with robust variance to estimate overall and subgroup-specific HPV and influenza vaccination prevalence ratios (PRs) and corresponding 95% confidence limits (CL) comparing females whose parents were informal caregivers with females whose parents were not informal caregivers. Our unweighted study populations comprised 1645 and 1279 females aged 9 to 17 years for the HPV and influenza vaccination analyses, respectively. Overall, both HPV and influenza vaccination coverage were lower among females whose parents were informal caregivers (HPV: PR = 0.72, 95% CL: 0.53, 0.97; Influenza: PR = 0.89, 95% CL: 0.66, 1.2). Our results suggest consistently lower HPV and influenza vaccination coverage for young females whose parents are informal caregivers. Our study provides new evidence about the potential implications of caregiving on the utilization of preventive health services among children of caregivers.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
August 2014 Volume 10, Issue 8
http://www.landesbioscience.com/journals/vaccines/toc/volume/10/issue/8/

Research Paper
Safety and immunogenicity of pentavalent rotavirus vaccine in a randomized, double-blind, placebo-controlled study in healthy elderly subjects
Jody Lawrence, Su He, Jason Martin, Florian Schödel, Max Ciarlet and Alexander V Murray
Abstract
Rotavirus may be an important causative agent of acute gastroenteritis (AGE) in the elderly, a population that is particularly vulnerable due to waning immunity. It is estimated that rotavirus may account for 2–5% of adult gastroenteritis hospitalizations in the United States. This is the first study to assess the safety and immunogenicity of the live pentavalent rotavirus vaccine (RV5) in an elderly population. In this study, healthy, independently living adults aged 65–80 years were randomized in a 2:1 ratio to receive three 2-mL oral doses of RV5 or placebo administered 28–42 days apart. All subjects were followed for safety for 42 days post any vaccination and up to 180 days after the final vaccination for clinical adverse events. Immunogenicity of RV5 was measured by serum anti-rotavirus IgA enzyme immunoassay and serum neutralizing antibody responses to human rotavirus serotypes prior to and after each dose. Results of this study demonstrated that RV5 was generally safe and well tolerated in healthy elderly adults, where 9% of placebo and 27% of RV5 recipients experienced a vaccine-related adverse event of mild or moderate intensity. Immune responses (serum anti-rotavirus immunoglobulin A [IgA] and serum neutralizing antibodies against human rotavirus serotypes in the vaccine) were augmented in this population after a single dose of RV5, despite the factors of older age and preexisting antibodies to the virus. Therefore, if vaccination in the elderly is needed, further evaluation of RV5 as a candidate vaccine in this age group may be warranted.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
August 2014 Volume 10, Issue 8
http://www.landesbioscience.com/journals/vaccines/toc/volume/10/issue/8/

Research Paper
Knowledge of and attitudes to influenza in unvaccinated primary care physicians and nurses: A cross-sectional study
Angela Domínguez, Pere Godoy, Jesús Castilla Catalán, José María Mayoral, Núria Soldevila, Nuria Torner, Diana Toledo, Jenaro Astray, Sonia Tamames, Susana García-Gutiérrez, Fernando González-Candelas, Vicente Martín, José Díaz, the CIBERESP Working Group and for the Survey on Influenza Vaccination in Primary Health Care Workers
Abstract
Primary healthcare workers, especially nurses, are exposed to the vast majority of patients with influenza and play an important role in vaccinating patients. Healthcare workers’ misconceptions about influenza and influenza vaccination have been reported as possible factors associated with lack of vaccination. The objective of this study was to compare the characteristics of unvaccinated physicians and unvaccinated nurses in the 2011–2012 influenza season. We performed an anonymous web survey of Spanish primary healthcare workers in 2012. Information was collected on vaccination and knowledge of and attitudes to the influenza vaccine. Multivariate analysis was performed using unconditional logistic regression. We included 461 unvaccinated physicians and 402 unvaccinated nurses. Compared with unvaccinated nurses, unvaccinated physicians had more frequently received seasonal influenza vaccination in the preceding seasons (aOR 1.58; 95% CI 1.11–2.25), and more frequently believed that vaccination of high risk individuals is effective in reducing complications (aOR 2.53; 95% CI 1.30–4.95) and that influenza can be a serious illness (aOR 1.65; 95% CI 1.17–2.32). In contrast, unvaccinated physicians were less concerned about infecting patients (aOR 0.62; 95% CI 0.40–0.96). Unvaccinated nurses had more misconceptions than physicians about influenza and the influenza vaccine and more doubts about the severity of annual influenza epidemics in patients with high risk conditions and the prevention of complications by means of the influenza vaccination. For unvaccinated physicians, strategies to improve vaccination coverage should stress the importance of physicians as a possible source of infection of their patients. The effectiveness of influenza vaccination of high risk persons should be emphasized in nurses.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
August 2014 Volume 10, Issue 8
http://www.landesbioscience.com/journals/vaccines/toc/volume/10/issue/8/

Research Paper
Cost-effectiveness of hepatitis A vaccination in Indonesia
Auliya A Suwantika, Philippe Beutels and Maarten J Postma
Abstract
Objective
This study aims to assess the cost-effectiveness of hepatitis A immunization in Indonesia, including an explicit comparison between one-dose and two-dose vaccines.
Methods
An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involved a 70-year time horizon with 1-month cycles for children less than 2-years-old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination.
Results
Vaccination would save US$ 3 795 148 and US$ 2 892 920 from the societal perspective, for the two-dose and one-dose vaccine schedules, respectively, in the context of hepatitis A treatment. It also would save 8917 and 6614 discounted quality-adjusted-life-years (QALYs), respectively. With the vaccine price of US$ 3.21 per dose, the implementation of single dose vaccine would yield an incremental cost-effectiveness ratio (ICER) of US$ 4933 per QALY gained versus no vaccination, whereas the two-dose versus one-dose schedule would cost US$ 14 568 per QALY gained. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules in isolation, but two-dose vaccination would no longer be cost-effective if one-dose vaccination is a feasible option. Vaccination would be 100% affordable at budgets of US$ 71 408 000 and US$ 37 690 000 for the implementation of the two-dose and one-dose vaccine schedules, respectively.
Conclusions
The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine price. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The vaccine price, mortality rate and discount rate were the most influential parameters impacting the ICERs.

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
August 2014 Volume 10, Issue 8
http://www.landesbioscience.com/journals/vaccines/toc/volume/10/issue/8/

Research Paper
Parents’ attitude toward multiple vaccinations at a single visit with alternative delivery methods
Patricia Kaaijk, Deborah E Kleijne, Mirjam J Knol, Irene A Harmsen, Olga JAE Ophorst and Nynke Y Rots
Abstract
Last decades, the number of routine childhood vaccinations has increased considerably, which consequently has led to multiple vaccine injections per consultation. Implementation of additional vaccines will probably lead to more than 2 vaccine injections per consult, which might be a barrier for parents to vaccinate their child. A decrease in vaccination coverage, however, increases the risk of disease outbreaks. Less stressful alternative methods for vaccine delivery might lead to an increased acceptance of multiple childhood vaccinations by parents. The present questionnaire study was set up to explore the maximum number of vaccine injections per visit that is acceptable for parents, as well as to gauge parents’ attitude toward alternative needle-free methods for vaccine delivery. For this purpose, the parents’ opinion toward a jet injector, a patch, a microneedle system, and nasal spray device as methods for vaccine delivery was assessed. The majority of the 1154 participating parents indicated that 3 vaccine injections per visit was perceived as too much. Most participants had a positive attitude with respect to the jet injector and the patch as alternative vaccine delivery method, whereas the microneedle device and an intranasal spray device were not perceived as better than the conventional syringe by the parents. Parents indicated that both the jet injector and the patch might increase their acceptance of giving their children more than 2 vaccinations at the same time. This should encourage vaccine developers and manufacturers to put efforts in developing these delivery methods for their vaccines.

JAMA
August 20, 2014, Vol 312, No. 7
http://jama.jamanetwork.com/issue.aspx

Editorial | August 13, 2014
Meta-analysis as Evidence Building a Better Pyramid
Jesse A. Berlin, ScD1; Robert M. Golub, MD2
JAMA. 2014;312(6):603-605. doi:10.1001/jama.2014.8167.
Initial text
In following the practice of evidence-based medicine, when faced with a question about prevention or treatment the clinician should seek out the best evidence that addresses the question. If quality of evidence is considered a pyramid, what category should be placed at the peak? One dogma argues that it is the best-conducted randomized clinical trial (RCT) comprising patients similar to those seen by the clinician, reasoning that a well-done RCT mimics pure experimental conditions better than any other study design, hence minimizing the likelihood of confounding. A counterargument is that the best evidence is a systematic review with meta-analysis, because this approach can integrate all of the relevant evidence and provide a more reliable answer than a single study, however well conducted….

Journal of Infectious Diseases
Volume 210 Issue 6 September 15, 2014
http://jid.oxfordjournals.org/content/current

Prevalence of Human Papillomavirus Infection in Adolescent Girls Before Reported Sexual Debut
Jennifer S. Smith
Author Affiliations
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, and Cervical Cancer Free Coalition, Chapel Hill
(See the major article by Houlihan et al on pages 837–45.)
Houlihan et al present data on the prevalence of human papillomavirus (HPV) infection among 474 adolescent girls aged 15–16 years in Tanzania who reported no previous sexual intercourse. Despite no reported history of sex, a nonnegligible fraction of girls (8.4%) tested positive for HPV infection, using a highly sensitive polymerase chain reaction assay from nurse-assisted, self-administered cervicovaginal specimens.

Global data on the prevalence of HPV infection among adolescents worldwide are extremely limited [1]. Therefore, these data from Tanzania are important because they are among the first to examine HPV infection prevalence among female adolescents and are from sub-Saharan Africa, which has one of the highest incidence rates of invasive cervical cancer in the world [2].

As cited by the authors, the laboratory-confirmed prevalence of HPV infection was relatively higher than that previously observed in studies from Europe, Australia, and the United States, which found extremely low or no HPV detection among female participants reporting no previous sexual intercourse. The 2010 Tanzania Demographic and Health Survey (TDHS) documented a self-reported median age at first intercourse of 17.4 years…

Journal of Infectious Diseases
Volume 210 Issue 6 September 15, 2014
http://jid.oxfordjournals.org/content/current

Influence of Enteric Infections on Response to Oral Poliovirus Vaccine: A Systematic Review and Meta-analysis
Edward P. K. Parker1, Beate Kampmann2,3, Gagandeep Kang4 and Nicholas C. Grassly1
Author Affiliations
1Department of Infectious Disease Epidemiology
2Department of Paediatrics, St Mary’s Campus, Imperial College London, United Kingdom
3MRC Unit, The Gambia, Fajara
4Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India
Presented in part: Seventh International Conference on Vaccines for Enteric Diseases (VED 2013), Bangkok, Thailand, 6–8 November 2013.
Abstract
Background. The impaired immunogenicity of oral poliovirus vaccine (OPV) in low-income countries has been apparent since the early field trials of this vaccine. Infection with enteropathogens at the time of vaccination may contribute to this phenomenon. However, the relative influence of these infections on OPV performance remains uncertain.
Methods. We conducted a systematic review to examine the impact of concurrent enteric infections on OPV response. Using random-effects models, we assessed the effects of nonpolio enteroviruses (NPEVs) and diarrhea on the odds of seroconversion and/or vaccine virus shedding.
Results. We identified 25 trials in which OPV outcomes were compared according to the presence or absence of enteric infections, the majority of which (n = 17) reported only on NPEVs. Concurrent NPEVs significantly reduced the odds of per-dose seroconversion for type 1 poliovirus (odds ratio [OR] 0.44, 95% confidence interval 0.23−0.84), but not type 2 (OR 0.53 [0.19−1.46]) or type 3 (OR 0.56 [0.27−1.12]). A similar reduction, significant for type 1 poliovirus (OR 0.50 [0.28−0.89]), was observed in the odds of vaccine virus shedding among NPEV-infected individuals. Concurrent diarrhea significantly inhibited per-dose seroconversion overall (OR 0.61 [0.38−0.87]).
Conclusions. Our findings are consistent with an inhibitory effect of concurrent enteric infections on OPV response.

Journal of Medical Ethics
September 2014, Volume 40, Issue 9
http://jme.bmj.com/content/current

Viewpoint  – Published Online First 18 August 2014
Refugees, humanitarian aid and the right to decline vaccinations
A L Caplan, David R Curry
Author Affiliations
Population Health, Medical Ethics, New York University School of Medicine, New York, New York, USA
Abstract
Recent instances of governments and others refusing humanitarian assistance to refugees and IDPs (internally-displaced persons) unless they agreed to polio immunization for their children raise difficult ethical challenges. The authors argue that states have the right and a responsibility to require such vaccinations in instances where the serious vaccine-preventable disease(s) at issue threaten others, including local populations, humanitarian workers, and others in camps or support settings.

The Lancet
Aug 23, 2014 Volume 384 Number 9944 p637 – 713
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Ebola: a failure of international collective action
The Lancet
When a 2-year-old boy in the Guéckédou region of Guinea fell ill on Dec 6, 2013, no one knew that his illness signalled the start of the biggest, most complex outbreak of Ebola the world has ever seen. As of mid-August, 2240 cases and 1229 deaths have been reported from Guinea, Liberia, Nigeria, and Sierra Leone. But WHO believes that these numbers could be a vast underestimation, as the numbers of deaths and infections increase rapidly in Liberia and Sierra Leone. On Aug 8, after a 2 day meeting of the International Health Regulations Emergency Committee, WHO declared the outbreak a “public health emergency of international concern”. This is not because the outbreak has pandemic potential. It does not. If Ebola arrives in high-income and middle-income nations, it should be contained quickly. WHO declared the emergency to escalate the national, regional, and international response to the outbreak’s epicentre in west Africa, recognising that it constituted an “extraordinary event”.

The outbreak continues to be difficult to bring under control. Health workers are dealing with numerous issues they have not had to deal with to this extent when battling Ebola in the past in central and east Africa. These include incredibly weak health systems, with few staff, little equipment, and poor facilities, making disease surveillance, isolation, and supportive care virtually impossible without external assistance. High levels of fear and mistrust about the disease and about health professionals have also led to removal of patients from hospitals and hiding of sick people in communities. Additionally, cross-border movement between the three main affected countries has facilitated spread across a huge expanse. All these factors have made effective contact tracing, which is crucial for containment, extremely difficult, especially in remote, rural areas.

Although WHO is now leading the international response to the crisis, it was initially slow to act at the high level that was needed. Its concern did not match that of the other major player in this outbreak—Médecins Sans Frontières (MSF). On June 24, MSF said that the outbreak was “out of control”, that its teams had reached the limits of what they could do, and it called for a massive deployment of resources to the region. Only on July 31, did WHO launch its joint response plan calling for US$71 million from donors and for the deployment of several hundred more personnel to west Africa. But WHO is not solely to blame for not moving more swiftly. Member states and donors are responsible too. WHO has experienced severe budget cuts over recent years. Its budget for responding to crises and outbreaks fell by 50% from 2012—13 ($469 million) to 2014—15 ($228 million). The crisis shows the importance of sufficient levels of multilateral funding for WHO—the only international agency capable of coordinating the response to a health crisis with global dimensions.

There are other lessons from this outbreak, including the need for increased investment in health system strengthening. Fragile health systems are unable to respond when a sudden, rapidly evolving emergency arises. Communities’ experiences of poorly functioning health facilities might also explain some of their mistrust during this crisis. The World Bank has pledged $200 million to deal with the outbreak and bolster health systems in west Africa, but further investments will be needed from other sources to develop resilient health sectors in the region.

No vaccine or cure exists for Ebola. Interest in developing treatments has been spurred by this outbreak. An experimental vaccine is being fast-tracked into human trials by the US National Institutes of Health. Last week, a WHO-convened ethics committee decided that it was right to use untested drugs in this outbreak. However, as others have commented, a vaccine would probably exist today if Ebola affected a large number of people in high-income countries, making research and development financially attractive to drug companies—a situation that John Ashton, president of the UK Faculty of Public Health, has described as “the moral bankruptcy of capitalism acting in the absence of an ethical and social framework”.

The US Centers for Disease Control and Prevention estimates that the outbreak will last for at least another 3—6 months. On Aug 15, MSF, which has nearly 700 staff on the ground, called the international effort to contain the outbreak “dangerously inadequate”; immediate and massive mobilisation of human and technical resources to the region is still needed not only to deal with the outbreak but also to restore collapsing health systems. The international community must show the collective responsibility and global solidarity absent at the start of this outbreak to bring it to an end. Its failure to do so is allowing a disaster of unprecedented proportions to unfold in west Africa.

Comment
Influenza vaccination in the off-label grey zone
Bruce G Weniger
Preview |
In The Lancet, Linda McAllister and colleagues1 report the findings from their influenza vaccination trial conducted in the USA during the 2012–13 season, showing non-inferiority of Stratis, a disposable-syringe jet injector (DSJI) versus needle and syringe for geometric mean titres and seroconversion. As expected for this delivery method, local reactions were more common in patients who received DSJI vaccination, but were generally mild and well tolerated: grade 3 reactions were 6•0% (37 of 616) versus 3•5% (21 of 607) with needle and syringe.
Needle-free jet injection for administration of influenza vaccine: a randomised non-inferiority trial
Linda McAllister, Jonathan Anderson, Kristen Werth, Iksung Cho, Karen Copeland, Nancy Le Cam Bouveret, David Plant, Paul M Mendelman, David K Cobb
Preview |
The immune response to influenza vaccine given with the jet injector device was non-inferior to the immune response to influenza vaccine given with needle and syringe. The device had a clinically acceptable safety profile, but was associated with a higher frequency of local injection site reactions than was the use of needle and syringe. The Stratis needle-free jet injector device could be used as an alternative method of administration of Afluria trivalent influenza vaccine.

PLoS One
[Accessed 23 August 2014]
http://www.plosone.org/

Research Article
Have Preferences of Girls Changed Almost 3 Years after the Much Debated Start of the HPV Vaccination Program in the Netherlands? A Discrete Choice Experiment
Robine Hofman mail, Esther W. de Bekker-Grob, Jan Hendrik Richardus, Harry J. de Koning, Marjolein van Ballegooijen, Ida J. Korfage
Published: August 19, 2014
DOI: 10.1371/journal.pone.0104772
Abstract
Objectives
To assess how girls’ preferences have changed almost 3 years after the much debated start of the human papillomavirus (HPV) vaccination program.
Methods
A discrete choice experiment (DCE) was conducted among girls aged 11–15 years who were invited, or were not yet invited, to get vaccinated. A panel latent class model was used to determine girls’ preferences for vaccination based on five characteristics: degree of protection against cervical cancer; duration of protection; risk of mild side-effects; age of vaccination; and the number of required doses of the vaccine.
Results
The response rate was 85% (500/592). Most girls preferred vaccination at age 14 years (instead of at age 9 years) and a 2-dose scheme (instead of the current 3-dose scheme). Girls were willing to trade-off 7% (CI: 3.2% to 10.8%) of the degree of protection to have 10% less risk of mild side-effects, and 4% (CI: 1.2% to 5.9%) to receive 2 doses instead of 3 doses. Latent class analyses showed that there was preference heterogeneity among girls, i.e., higher educated girls and HPV vaccinated girls had a higher probability to opt for HPV vaccination at a higher age than lower educated girls or non-vaccinated girls.
Conclusions
Three years after the start of HPV vaccination program the risk of mild side-effects and age at vaccination seem to have become less important. For the Dutch national immunization program, we recommend not to lower the current target age of 12 years. A 2-dose scheme may result in a higher uptake and we recommend that if this scheme is introduced, it needs to receive adequate publicity.

PLoS One
[Accessed 23 August 2014]
http://www.plosone.org/

Research Article
Vaccination Management and Vaccination Errors: A Representative Online-Survey among Primary Care Physicians
Birgitta M. Weltermann mail, Marta Markic, Anika Thielmann, Stefan Gesenhues, Martin Hermann
Published: August 13, 2014
DOI: 10.1371/journal.pone.0105119
Abstract
Background
Effective immunizations require a thorough, multi-step process, yet few studies comprehensively addressed issues around vaccination management.
Objectives
To assess variations in vaccination management and vaccination errors in primary care.
Methods
A cross sectional, web-based questionnaire survey was performed among 1157 primary physicians from North Rhine-Westphalia, Germany: a representative 10% random sample of general practitioners (n = 946) and all teaching physicians from the University Duisburg-Essen (n = 211). Four quality aspects with three items each were included: patient-related quality (patient information, patient consent, strategies to increase immunization rates), vaccine-related quality (practice vaccine spectrum, vaccine pre-selection, vaccination documentation), personnel-related quality (recommendation of vaccinations, vaccine application, personnel qualification) and storage-related quality (storage device, temperature log, vaccine storage control). For each of the four quality aspects, “good quality” was reached if all three criteria per quality aspect were fulfilled. Good vaccination management was defined as fulfilling all twelve items. Additionally, physicians’ experiences with errors and nearby-errors in vaccination management were obtained.
Results
More than 20% of the physicians participated in the survey. Good vaccination management was reached by 19% of the practices. Patient-related quality was good in 69% of the practices, vaccine-related quality in 73%, personnel-related quality in 59% and storage-related quality in 41% of the practices. No predictors for error reporting and good vaccination management were identified.
Conclusions
We identified good results for vaccine- and patient-related quality but need to improve issues that revolve around vaccine storage.