Vaccines: The Week in Review 27 July 2013

Vaccines: The Week in Review is a weekly digest — summarizing news, events, announcements, peer-reviewed articles and research in the global vaccine ethics and policy space. Content is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage. You are viewing the blog version of our weekly digest, typically comprised of between 30 and 40 posts below all dated “29 June 2013″
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David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy
a program of the
– Division of Medical Ethics, NYU Medical School
– The Wistar Institute Vaccine Center
– Children’s Hospital of Philadelphia Vaccine Education Center
Associate Faculty, Division of Medical Ethics, NYU Medical School

HPV Vaccination Coverage Among Adolescent Girls, 2007–2012; Postlicensure Vaccine Safety Monitoring, 2006–2013 — U.S.

CDC/MMWR Watch [to 27 July 2013]
CDC Telebriefing on human papillomavirus (HPV) vaccination coverage and vaccine safety monitoring
Thursday, July 25, 2013 at Noon ET

Press Briefing Transcript
Excerpt [Editor’s text bolding]
“…Just last month, I had a chance to share with you really good news that HPV vaccination works even better than we anticipated.  The types of HPV, that’s human papillomavirus, that commonly cause cervical cancer in the U.S., had dropped by about half in girls aged 14 to 19 in the seven years since we recommended routinely vaccinating against HPV.  I noted at that time that the results were striking, and would serve – should serve as a wake-up call to increase vaccination rates, because we really can protect the next generation of adolescents against cancers caused by HPV.  Unfortunately, today we have disappointing news.  An article in today’s MMWR shows that HPV vaccination coverage for girls getting the anti-cancer vaccine has not increased at all from one year to the next.  Zero.  We’re dropping the ball.  We’re missing opportunities to give HPV vaccines, and that needs to change to protect girls from cervical cancer.  I’ll provide some more detail and then discuss missed opportunities and information about vaccine safety.

But the article published today has data from what’s called the National Immunization Survey on teen vaccinations.  This is how we measure how we’re doing.  It collects vaccine information for 13 to 17-year-olds using a random digit sample of landlines and, starting in 2011, cellular telephone phones as well.  After a teen’s parental guardian gives permission, we contact the vaccination provider, doctor, nurse practitioner or other provider and mail a questionnaire to get the vaccination history.  The 2012 survey which we’re reporting about today included vaccination records of about 19,000 teens.  And today’s article focuses on HPV vaccination among girls from 2007 to 2012.  Next month we’ll share the data we collected last year on other vaccines recommended specifically for preteens and teens, and that will include vaccination coverage estimates for HPV vaccinations among boys, something that’s only more recently been recommended.

These national data show no progress, zero, with HPV vaccine coverage in 2012.  We’re used to seeing coverage increases of 10 percent per year when a new vaccine hits the market.  Last year we were disappointed at the increase in HPV vaccine was only 4 percentage points.  This year, it’s zero percentage points.  The HPV vaccine coverage hasn’t kept pace with other vaccines recommended for preteens and teens.  One dose does not provide all of the protection that the HPV vaccine series has to offer so we want all girls to get their second and third doses.  By 2011, 34.8 percent of teen girls finished their three-dose series.  2012 data is not different.  It’s 33.4 percent.  Actually, slightly fewer teen girls are given all doses from the previous years.  This is a huge disappointment, but I’m confident that we will turn it around.  And one of the reasons for that is in the next piece of data that we got from this survey.

We assumed that one of the reasons we had such low rates was that adolescents don’t see the doctor regularly so it’s hard to get a three-dose series in.  But actually, we found that – that the data showed that if HPV vaccine were given every single time a young person went to the doctor to get another vaccine, the completion of those series would be at 93 percent.  That’s important, because if we get three-dose series to 80 percent, an estimated 53,000 cases of cervical cancer could be prevented over the lifetimes of girls aged 12 and younger.  Now there are lots of ways we can work together to increase vaccination rates.  A key one is to take advantage of every opportunity to vaccinate against HPV.  The teens are in the doctor’s office, they’re getting another vaccination, but they’re not getting the HPV second and third doses.

We also asked parents why they haven’t gotten their daughters vaccinated.  And one of the top reasons is that their doctors didn’t recommend it.  This is critical.  Research consistently showed that a provider’s recommendation to vaccinate is the single most influential factor in determining whether a parent gets their kid vaccinated.  So we need to step up our efforts by talking to parents about the importance of this vaccine.  Doctors need to recommend this vaccine just as they recommend others, and ensure that they’re given every opportunity.  Parents have also told us in other research there are concerns about this – this may be in some way a license or permission to have sex.  But multiple studies have found that preteens and teens who receive this vaccine do not have sex any sooner than their peers who have not received the vaccine.  HPV vaccine does not open the door to sex.  HPV vaccine closes the door to cancer.  The vaccine has to be given before onset of sexual activity.  We can’t let this opportunity go to waste.  And I really would make the analogy to many of our other vaccines.  We make sure that people get vaccinations well before they get exposed.  We’re not saying they’re going to be exposed immediately after.  Just that we want to make sure they get vaccinated well before…”

Human Papillomavirus Vaccination Coverage Among Adolescent Girls, 2007–2012, and Postlicensure Vaccine Safety Monitoring, 2006–2013 — United States
MMWR Weekly
July 26, 2013 / 62(29);591-595
Since mid-2006, the Advisory Committee on Immunization Practices (ACIP) has recommended routine vaccination of adolescent girls at ages 11 or 12 years with 3 doses of human papillomavirus (HPV) vaccine (1). Two HPV vaccines are currently available in the United States. Both the quadrivalent (HPV4) and bivalent (HPV2) vaccines protect against HPV types 16 and 18, which cause 70% of cervical cancers and the majority of other HPV-associated cancers; HPV4 also protects against HPV types 6 and 11, which cause 90% of genital warts.* This report summarizes national HPV vaccination coverage levels among adolescent girls aged 13–17 years from the 2007–2012 National Immunization Survey-Teen (NIS-Teen) and national postlicensure vaccine safety monitoring. Although vaccination coverage with ≥1 dose of any HPV vaccine increased from 25.1% in 2007 to 53.0% in 2011, coverage in 2012 (53.8%) was similar to 2011. If HPV vaccine had been administered during health-care visits when another vaccine was administered, vaccination coverage for ≥1 dose could have reached 92.6%. Safety monitoring data continue to indicate that HPV4 is safe. Despite availability of safe and effective vaccines and ample opportunities for vaccine delivery in the health-care setting, HPV vaccination coverage among adolescent girls failed to increase from 2011 to 2012…

Saudi Arabia MOH Issues Health Regulations for Hajj-1434H

Kingdom of Saudi Arabia: MOH Issues Health Regulations for Those Flocking to Saudi Arabia to Perform Umrah and Hajj-1434H
12 July 2013

[Full text]
Proceeding from the keenness of the government of the Custodian of the Two Holy Mosques to maintain the public health and ensure a safe and healthy atmosphere for the performers of Pilgrimage “Hajj” and Umrah, Allah Willing; in order to enable them to perform the rituals easily, healthily and conveniently, and within the framework of the precautionary measures against Novel Coronavirus (MERS-COV), the Ministry of Health (MOH) has issued health regulations and requirements that must be met by those coming to the Kingdom for performing Umrah  and Hajj for the year 1434 H.

These regulations included the recommendation of postponing the performance of Umrah and Hajj this year in case of the elderly people and patients suffering from chronic diseases such as heart, kidney, and respiratory diseases, not to forget diabetes, as well as patients with congenital and acquired immune deficiency, in addition to patients suffering from tumors, and pregnant women and children.

Within the same vein, the regulations included some tips and health awareness guidelines for citizens, residents and visitors to perform Umrah or Hajj such as: washing hands well and continually with water and soap, or with other hand disinfectants, especially after coughing, sneezing, using a tissue when coughing or sneezing, then getting rid of it in a waste basket, avoiding touching eyes, nose or mouth directly with hands, limiting direct contact with infectious people and avoiding sharing their personal tools, wearing face-masks in overcrowded places, and maintaining hygiene in general. Furthermore, these regulations included obtaining a valid certificate of vaccination against meningitis at least 10 days before travelling to the Kingdom, and up to 3 years, as well as getting a certificate of vaccination against polio-affected countries, according to specific requirements.

It is worth mentioning that the health regulations have shed light on the importance of vaccination against seasonal influenza vaccine, especially for people with chronic diseases such as heart and kidney diseases, diabetes and respiratory and neurological diseases, as well as people with congenital and acquired immune deficiency diseases, metabolic diseases, pregnant women and children under 5 years, aside from people suffering from obesity and overweight.

To view the Health Regulations for Travellers to Saudi Arabia to Perform Umrah & Hajj-1434H.​

Novartis, Biological E Limited in agreement for two vaccines to protect against typhoid and paratyphoid fevers

Novartis announced a development and licensing agreement with Biological E Limited (BioE, India) ) for two vaccines to protect against typhoid and paratyphoid fevers. Under the license, Novartis Vaccines Institute for Global Health (NVGH) will transfer technology to BioE, which will have financial and operational responsibility for manufacturing, further clinical development, approval and distribution in the developing world. The typhoid vaccine (Vi-CRM197) involved has achieved Proof of Concept, had successful Phase 2 results, and will be transferred to BioE. A combined typhoid-paratyphoid vaccine will be transferred once Proof of Concept is completed through early, small-scale studies in humans to determine safety and immunogenicity. The Wellcome Trust continues to support the development of the dual-acting vaccine through a Strategic Award that was awarded in 2009. BioE said it is committed to achieving WHO pre-qualification and fulfill specific obligations to meet Novartis standards. The agreement is worldwide except for developed countries, where Novartis will retain rights.

WHO: World Hepatitis Day 2013

WHO: World Hepatitis Day 2013
News Release
24 July 2013

On World Hepatitis Day (28 July), WHO is urging governments to act against the five hepatitis viruses that can cause severe liver infections and lead to 1.4 million deaths every year. Some of these hepatitis viruses, most notably types B and C, can also lead to chronic and debilitating illnesses such as liver cancer and cirrhosis, and in addition to, loss of income and high medical expenses for hundreds of millions of people worldwide…

…“The fact that many hepatitis B and C infections are silent, causing no symptoms until there is severe damage to the liver, points to the urgent need for universal access to immunization, screening, diagnosis and antiviral therapy,” says Dr Keiji Fukuda, WHO Assistant Director-General for Health Security and the Environment.

“Many of the measures needed to prevent the spread of viral hepatitis disease can be put in place right now, and doing so will offset the heavy economic costs of treating and hospitalizing patients in future.”

This year, in the run up to World Hepatitis Day, the Organization is releasing its first-ever country hepatitis survey, covering 126 countries. The WHO “Global policy report on the prevention and control of viral hepatitis in WHO Member States” identifies successes as well as gaps at country level in the implementation of four priority areas. The priority areas are raising awareness, evidence-based data for action, prevention of transmission, and screening, care and treatment.

The findings show that 37% of the countries have national strategies for viral hepatitis, and more work is needed in treating hepatitis. It also highlights that while most of the countries (82%) have established hepatitis surveillance programmes, only half of them include the monitoring of chronic hepatitis B and C, which are responsible for most severe illnesses and deaths…

World Hepatitis Day Statement by HHS Secretary Kathleen Sebelius and HHS Assistant Secretary for Health Dr. Howard Koh

IVI launches new matrix-based organization

IVI said it launched a new matrix-based organization “as part of its efforts to increase efficiency and accountability in management and implementation of its research projects.” The key elements of the new organization, which has been put in place in line with IVI’s new Strategic Plan, are the introduction of formal portfolio and project management, and a greater focus on vaccine pipeline and delivery. IVI now comprises of the following units:
:: Portfolio Management
:: Development and Delivery
:: Laboratory Sciences
:: Finance & Administration
:: Communications & Advocacy
:: Human Resources

The Portfolio Management Unit has three main programs as of now: Cholera, Typhoid and Dengue, and also includes the functions of Portfolio Manager, Grant Manager, and Business Development Manager. The Development and Delivery Unit has four departments: Clinical Development and Regulatory, Epidemiology, Biostatistics and Data Management, and Access. As well, an internal Portfolio Management Committee has been created to overlook IVI’s research and development projects.

IVI noted that these changes have been made “to ensure that IVI will be well-positioned to achieve maximal impact and deliver on its mission – the discovery, development, and delivery of safe, effective and affordable vaccines for developing nations.”

UN to establish WHO-led Interagency Task Force on the Prevention and Control of Noncommunicable Diseases

United Nations to establish WHO-led Interagency Task Force on the Prevention and Control of Noncommunicable Diseases
Note for media

22 July 2013 | Geneva – The Economic and Social Council (ECOSOC) adopted a resolution requesting the UN Secretary-General to establish a United Nations Interagency Task Force on the Prevention and Control of Noncommunicable Diseases. The Task Force will be convened and led by the WHO and will be created by expanding the mandate of the existing United Nations Ad Hoc Interagency Task Force on Tobacco Control and the work to support the implementation of the WHO Framework Convention on Tobacco Control (WHO FCTC). The resolution was adopted in ECOSOC’s 2013 Substantive Session being held in Geneva, Switzerland.

The Task Force will coordinate the activities of all UN organizations to implement the WHO Global Action Plan for the Prevention and Control of NCDs 2013-2020, adopted by the World Health Assembly in May 2013. This is important because new WHO estimates show that 3 of the 4 leading causes of death worldwide are linked to noncommunicable diseases, specifically cardiovascular diseases and chronic obstructive pulmonary disease.

The Action Plan aims to achieve 9 voluntary global targets, including a 25% reduction in premature mortality from cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases by 2025. The plan provides a road map and a menu of policy options for Member States, WHO, other UN organizations, NGOs and private sector entities to implement collectively.

Heads of State and Government in 2011 recognized the role and responsibility of governments in reducing noncommunicable diseases through the United Nations Political Declaration on the Prevention and Control of NCDs. With this resolution, ECOSOC is following up on those commitments.

WHO will convene a formal meeting with Member States on 13 November 2013 to complete the work on a draft terms of reference for the UN Task Force on NCDs.

EFPIA/PhRMA: Joint Principles for Responsible Clinical Trial Data Sharing

EFPIA/PhRMA: Joint Principles for Responsible Clinical Trial Data Sharing to Benefit Patients
Media Release: July 24, 2013

The European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) today strengthened their long-standing commitment to enhancing public health by endorsing joint “Principles for Responsible Clinical Trial Data Sharing: Our Commitment to Patients and Researchers.”

“Companies routinely publish their clinical research, collaborate with academic researchers, and share clinical trial information on public websites,” said Christopher Viehbacher, President of EFPIA and CEO of Sanofi. “By endorsing the Principles, biopharmaceutical companies commit to enhance these efforts by making additional information available to the public, patients who participate in clinical trials, and to qualified researchers.

Under the new commitments, biopharmaceutical companies will dramatically increase the amount of information available to researchers, patients, and members of the public.

Patient-level clinical trial data, study-level clinical trial data, full clinical study reports, and protocols from clinical trials in patients for medicines approved in the United States and European Union will be shared with qualified scientific and medical researchers upon request and subject to terms necessary to protect patient privacy and confidential commercial information. Researchers who obtain such clinical trial data will be encouraged to publish their findings.

Companies will work with regulators to provide a factual summary of clinical trial results to patients who participate in clinical trials.

The synopses of clinical study reports for clinical trials in patients submitted to the Food and Drug Administration [FDA], European Medicines Agency [EMA], or national authorities of EU member states will be made publicly available upon the approval of a new medicine or new indication.

Biopharmaceutical companies have also reaffirmed their commitment to publish clinical trial results regardless of the outcome. At a minimum, results from all phase 3 clinical trials and clinical trial results of significant medical importance should be submitted for publication….

Implementation of the commitments begins on January 1, 2014. The Principles are available at and

GPEI Update: Polio this week – As of 24 July 2013

Update: Polio this week – As of 24 July 2013
Global Polio Eradication Initiative
[Editor’s extract and bolded text]
:: In Nigeria, the first circulating vaccine-derived poliovirus type 2 (cVDPV2) case of 2013 was reported, from Borno state. It is linked to cVDPV2 currently circulating in Chad. Previously, no cVDPV2 cases had been reported from Nigeria since November. See ‘Nigeria’ section for more.

:: One new cVDPV2 case was reported in the past week – the first in the country in 2013. Previously, no cVDPV2 cases had been reported since November 2012. This most recent cVDPV2 case had onset of paralysis on 6 June (from Borno).

:: This latest case is linked to cVDPV2 currently circulating in Chad, which have also been detected in Cameroon. In addition to the case in Borno, cVDPV2 linked to this transmission chain had previously been isolated from an environmental sample in Kano in March, indicating circulation in Nigeria.

Horn of Africa
:: Eight new WPV1 cases were reported in the past week (seven from Somalia and one from Kenya), bringing the total number of WPV1 cases in the region to 81 (72 from Somalia and nine from Kenya). The most recent case in the region had onset of paralysis on 3 July (from Kenya).

:: One of the newly-reported cases from Somaliland, in the north, the first in that area associated with this outbreak and close to the border with Ethiopia. Additionally, some of the newly-reported cases are from inaccessible areas of south-central Somalia.

:: In Somalia, NIDs are currently ongoing (21-25 July), targeting children under the age of five years. Specific radio messages had been developed with the involvement of the Ministry of Religious Affairs, as this latest campaign is being implemented during Ramadan.

:: The next SIAs in Kenya are planned for 27-30 July, targeting host communities around the Dadaab camps.

:: Campaigns across the Horn of Africa, including in Ethiopia and Yemen, will continue throughout August.

WHO: Global policy report on the prevention and control of viral hepatitis

Global policy report on the prevention and control of viral hepatitis
World Health Organization
Number of pages: 220
Publication date: July 2013
Languages: English
ISBN: 978 92 4 156463 2

The periodic evaluation of implementation of the WHO strategy requires an initial baseline survey of all Member States. In mid-2012, WHO, in collaboration with the World Hepatitis Alliance, conducted such a survey, asking Member States to provide information relating to the four axes of the WHO strategy. In particular, Member States were asked whether key prevention and control activities are being conducted. This report presents the results.

The first chapter provides an introduction to viral hepatitis and to the global response to this group of diseases. The second chapter provides a global overview of the survey findings. Chapters three through eight present findings from the six WHO regions, including summaries of data from all responding countries. Additional survey data, study methodology information and the survey instrument can be found in Annexes A–E.

pH1N1 – a comparative analysis of public health responses in Ontario to the influenza outbreak, public health and primary care: lessons learned and policy suggestions

BMC Public Health
(Accessed 27 July 2013)

Research article  
pH1N1 – a comparative analysis of public health responses in Ontario to the influenza outbreak, public health and primary care: lessons learned and policy suggestions
Paul Masotti, Michael E Green, Richard Birtwhistle, Ian Gemmill, Kieran Moore, Kathleen O¿Connor, Adrienne Hansen-Taugher, Ralph Shaw BMC Public Health 2013, 13:687 (27 July 20 Abstract (provisional)

Ontario’s 36 Public Health Units (PHUs) were responsible for implementing the H1N1 Pandemic Influenza Plans (PIPs) to address the first pandemic influenza virus in over 40 years. It was the first under conditions which permitted mass immunization. This is therefore the first opportunity to learn and document what worked well, and did not work well, in Ontario’s response to pH1N1, and to make recommendations based on experience.

Our objectives were to: describe the PIP models, obtain perceptions on outcomes, lessons learned and to solicit policy suggestions for improvement. We conducted a 3-phase comparative analysis study comprised of semi-structured key informant interviews with local Medical Officers of Health (n = 29 of 36), and Primary Care Physicians (n = 20) and in Phase 3 with provincial Chief-Medical Officers of Health (n = 6) and a provincial Medical Organization. Phase 2 data came from a Pan-Ontario symposium (n = 44) comprised leaders representing: Public Health, Primary Care, Provincial and Federal Government.

PIPs varied resulting in diverse experiences and lessons learned. This was in part due to different PHU characteristics that included: degree of planning, PHU and Primary Care capacity, population, geographic and relationships with Primary Care. Main lessons learned were: 1) Planning should be more comprehensive and operationalized at all levels. 2) Improve national and provincial communication strategies and eliminate contradictory messages from different sources. 3) An integrated community-wide response may be the best approach to decrease the impact of a pandemic. 4) The best Mass Immunization models can be quickly implemented and have high immunization rates. They should be flexible and allow for incremental responses that are based upon: i) pandemic severity, ii) local health system, population and geographic characteristics, iii) immunization objectives, and iv) vaccine supply.

“We were very lucky that pH1N1 was not more severe.” Consensus existed for more detailed planning and the inclusion of multiple health system and community stakeholders. PIPs should be flexible, allow for incremental responses and have important decisions (E.g., under which conditions Public Health, Primary Care, Pharmacists or others act as vaccine delivery agents.) made prior to a crisis.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

A cross sectional survey of attitudes, awareness and uptake of the parental pertussis booster vaccine as part of a cocooning strategy, Victoria, Australia

BMC Public Health
(Accessed 27 July 2013)

Research article  
A cross sectional survey of attitudes, awareness and uptake of the parental pertussis booster vaccine as part of a cocooning strategy, Victoria, Australia
Ellen J Donnan, James E Fielding, Stacey L Rowe, Lucinda J Franklin, Hassan Vally BMC Public Health 2013, 13:676 (23 July 2013)

Abstract (provisional)
The Victorian Government Department of Health funded a diphtheria, tetanus and acellular pertussis vaccine for parents of infants from June 2009 to June 2012 as part of a cocooning strategy for the control of pertussis. The aim of this study was to assess parents’ attitudes and awareness of the vaccination program, and to estimate vaccine uptake.

A cross-sectional survey of 253 families with a child born in the first quarter of 2010 residing within five metropolitan and four rural local government areas in Victoria was conducted. Univariate analyses were performed to describe the relationship between demographic variables, knowledge and awareness of the disease, the vaccine program and vaccine uptake. Multivariate analyses examining predictors for awareness of the vaccine program and for the uptake of vaccination were also conducted.

One hundred and five families were surveyed (response rate 43%). Of these, 93% indicated that they had heard of ‘pertussis’ or ‘whooping cough’ and 75% of mothers and 69% of fathers were aware the pertussis vaccine was available and funded for new parents. Overall, 70% of mothers and 53% of fathers were vaccinated following their child’s birth, with metropolitan fathers less likely to be vaccinated as rural fathers (RR = 0.6, p = 0.002). Being a younger mother (p = 0.02) or father (p = 0.047), and being an Australian-born father (RR = 1.9, p = 0.03) were found to predict uptake of the vaccine in parents.

Parents indicated a reasonable level of knowledge of pertussis and a willingness to be vaccinated to protect their child. However, vaccine uptake estimates indicated further opportunity for program improvement. Future cocooning strategies would benefit from specifically targeting fathers and metropolitan maternity hospitals to increase vaccine uptake. Wider promotion of the availability of vaccine providers may increase uptake to maximise the success of cocooning programs. Further investigation of the effectiveness of the cocooning strategy in decreasing infant morbidity and mortality is required.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Determinants of government HIV/AIDS financing: A 10-year trend analysis from 125 low- and middle-income countries

BMC Public Health
(Accessed 27 July 2013)

Research article  
Determinants of government HIV/AIDS financing: A 10-year trend analysis from 125 low- and middle-income countries
Carlos Ávila, Dejan Loncar, Peter Amico, Paul De Lay BMC Public Health 2013, 13:673 (19 July 2013)

Abstract (provisional)
Trends and predictors of domestic spending from public sources provide national authorities and international donors with a better understanding of the HIV financing architecture, the fulfillment of governments’ commitments and potential for long-term sustainability.

We analyzed government financing of HIV using evidence from country reports on domestic spending. Panel data from 2000 to 2010 included information from 647 country-years amongst 125 countries. A random-effects model was used to analyze ten year trends and identify independent predictors of public HIV spending.

Low- and middle-income countries spent US$ 2.1 billion from government sources in 2000, growing to US$ 6.6 billion in 2010, a three-fold increase. Per capita spending in 2010 ranged from 5 cents in low-level HIV epidemics in the Middle East to US$ 32 in upper-middle income countries with generalized HIV epidemics in Southern Africa. The analysis found that GDP per capita and HIV prevalence are positively associated with increasing levels of HIV-spending from public sources; a 10 percent increase in HIV prevalence is associated with a 2.5 percent increase in domestic funding for HIV. Additionally, a 10 percent increase in GDP per capita is associated with an 11.49 percent increase in public spending for HIV and these associations were highly significant at the .001 percent level.

Domestic resources in low- and middle-income countries showed a threefold increase between 2000 and 2010 and currently support 50 percent of the global response with 41 percent coming from sub-Saharan Africa. Domestic spending in LMICs was associated with increased economic growth and an increased burden of HIV. Sustained increases in funding for HIV from public sources were observed in all regions and emphasize the increasing importance of government financing.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Editorial: The next step in controlling HBV in China

British Medical Journal
27 July 2013 (Vol 347, Issue 7918)

The next step in controlling HBV in China
BMJ 2013; 347 doi: (Published 16 July 2013)
Yuanyong Xu, associate professor1, Huihui Liu, research assistant2, Yong Wang, associate professor1, Rongzhang Hao, research assistant1, Zhenjun Li, associate professor3, Hongbin Song, professor1

Focus on preventing perinatal transmission of the virus
Infection with hepatitis B virus (HBV) is one of the most important infectious diseases in China.1 Although highly effective vaccines against HBV have been available since 1982, about 93 million people in China carry the virus, and treatment costs about ¥100bn (£10.6bn; €12.3bn; $16bn) a year.2 As well as being at increased risk of developing cirrhosis and hepatocellular carcinoma,3 carriers often encounter discrimination at school, at work, in relationships, and with families.4

The Chinese government introduced infant vaccination with HPV vaccine in 1992, followed by a national expanded programme for immunisation in 1999, with special efforts to provide a timely dose at birth. Since 2002, the government has paid for the vaccine. Furthermore, from 2009 to 2011, the government provided the vaccine free of charge to all children under 15 who had not been vaccinated.

These measures have helped control the transmission of HBV in China, and the proportion of carriers in the population has dropped from 9.8% to 7.2% between 1992 and 2006. Over the …

Effectiveness of pertussis vaccines for adolescents and adults: case-control study

British Medical Journal
27 July 2013 (Vol 347, Issue 7918)

Effectiveness of pertussis vaccines for adolescents and adults: case-control study
BMJ 2013; 347 doi: (Published 17 July 2013)
BMJ 2013;347:f4249
Roger Baxter, codirector, Joan Bartlett, analyst/programmer, Ali Rowhani-Rahbar, vaccine safety fellow, Bruce Fireman, statistician, Nicola P Klein, codirector

Objective: To assess the effectiveness of reduced acellular pertussis (Tdap) vaccines in adolescents and adults.

Setting:  Kaiser Permanente Northern California.

Design:  Case-control study.

Participants:  All polymerase chain reaction (PCR) confirmed cases of pertussis in members aged 11 years and older from January 2006 to December 2011. We compared the Tdap vaccination status of PCR positive cases with two control groups: people testing negative for pertussis by PCR and closely matched people from the general Kaiser Permanente Northern California population.

Main outcome measure: PCR confirmed pertussis. The association of Tdap vaccination with the odds of pertussis infection was estimated by conditional logistic regression, with adjustment for calendar time, pertussis vaccine type received in early childhood, age, sex, race or ethnic group, and medical clinic. We calculated Tdap vaccine effectiveness as 1 minus the adjusted odds ratio.

Results:  The study population included 668 PCR positive cases, 10 098 PCR negative controls, and 21 599 Kaiser Permanente Northern California matched controls. Tdap vaccination rates were 24.0% in PCR positive cases and 31.9% in PCR negative controls (P<0.001). The adjusted estimate of effectiveness of Tdap vaccination against pertussis was 53.0% (95% confidence interval 41.9% to 62.0%) in the comparison with PCR controls, and 64.0% (55.5% to 70.9%) in the comparison with Kaiser Permanente Northern California controls.

Conclusion:  Tdap vaccination was moderately effective at preventing PCR confirmed pertussis among adolescents and adults.

A Novel Method to Value Real Options in Health Care: The Case of a Multicohort Human Papillomavirus Vaccination Strategy

Clinical Therapeutics
Vol 35 | No. 7 | July 2013 | Pages 901-1050

A Novel Method to Value Real Options in Health Care: The Case of a Multicohort Human Papillomavirus Vaccination Strategy
Giampiero Favato, DBA, Gianluca Baio, PhD, Alessandro Capone, MD, Andrea Marcellusi, MSc,
Francesco Saverio Mennini, MSc

A large number of economic evaluations have already confirmed the cost-effectiveness of different human papillomavirus (HPV) vaccination strategies. Standard analyses might not capture the full economic value of novel vaccination programs because the cost-effectiveness paradigm fails to take into account the value of active management. Management decisions can be seen as real options, a term used to refer to the application of option pricing theory to the valuation of investments in nonfinancial assets in which much of the value is attributable to flexibility and learning over time.

The aim of this article was to discuss the potential advantages shown by using the payoff method in the valuation of the cost-effectiveness of competing HPV immunization programs.

This was the first study, to the best of our knowledge, to use the payoff method to determine the real option values of 4 different HPV vaccination strategies targeting female subjects aged 12, 15, 18, and 25 years. The payoff method derives the real option value from the triangular payoff distribution of the project’s net present value, which is treated as a triangular fuzzy number. To inform the real option model, cost-effectiveness data were derived from an empirically calibrated Bayesian model designed to assess the cost-effectiveness of a multicohort HPV vaccination strategy in the context of the current cervical cancer screening program in Italy. A net health benefit approach was used to calculate the expected fuzzy net present value for each of the 4 vaccination strategies evaluated.

Costs per quality-adjusted life-year gained seemed to be related to the number of cohorts targeted: a single cohort of girls aged 12 years (€10,955 [95% CI, –1,021 to 28,212]) revealed the lowest cost among the 4 alternative strategies evaluated. The real option valuation challenged the cost-effectiveness dominance of a single cohort of 12-year-old girls. The simultaneous vaccination of 2 cohorts of girls aged 12 and 15 years yielded a real option value (€17,723) equivalent to that attributed to a single cohort of 12-year-old girls (€17,460).

The payoff method showed distinctive advantages in the valuation of the cost-effectiveness of competing health care interventions, essentially determined by the replacement of the nonfuzzy numbers that are commonly used in cost-effectiveness analysis models, with fuzzy numbers as an input to inform the real option pricing method. The real option approach to value uncertainty makes policy making in health care an evolutionary process and creates a new “space” for decision-making choices.

Perspective: The New Global Health

Emerging Infectious Diseases
Volume 19, Number 8—August 2013

The New Global Health
Kevin M. De Cock , Patricia M. Simone, Veronica Davison, and Laurence Slutsker

Global health reflects the realities of globalization, including worldwide dissemination of infectious and noninfectious public health risks. Global health architecture is complex and better coordination is needed between multiple organizations. Three overlapping themes determine global health action and prioritization: development, security, and public health. These themes play out against a background of demographic change, socioeconomic development, and urbanization. Infectious diseases remain critical factors, but are no longer the major cause of global illness and death. Traditional indicators of public health, such as maternal and infant mortality rates no longer describe the health status of whole societies; this change highlights the need for investment in vital registration and disease-specific reporting. Noncommunicable diseases, injuries, and mental health will require greater attention from the world in the future. The new global health requires broader engagement by health organizations and all countries for the objectives of health equity, access, and coverage as priorities beyond the Millennium Development Goals are set.

Perspective: Norovirus Disease in the United State

Emerging Infectious Diseases
Volume 19, Number 8—August 2013

Norovirus Disease in the United State
Aron J. Hall , Ben A. Lopman, Daniel C. Payne, Manish M. Patel, Paul A. Gastañaduy, Jan Vinjé, and Umesh D. Parashar

Although recognized as the leading cause of epidemic acute gastroenteritis across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570–800 deaths, 56,000–71,000 hospitalizations, 400,000 emergency department visits, 1.7–1.9 million outpatient visits, and 19–21 million total illnesses per year. Persons >65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by ≤50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease.

Swine influenza and vaccines: an alternative approach for decision making about pandemic prevention

The European Journal of Public Health
Volume 23 Issue 4 August 2013

Swine influenza and vaccines: an alternative approach for decision making about pandemic prevention
Marcello Basili1, Silvia Ferrini2 and Emanuele Montomoli3

Background: During the global pandemic of A/H1N1/California/07/2009 (A/H1N1/Cal) influenza, many governments signed contracts with vaccine producers for a universal influenza immunization program and bought hundreds of millions of vaccines doses. We argue that, as Health Ministers assumed the occurrence of the worst possible scenario (generalized pandemic influenza) and followed the strong version of the Precautionary Principle, they undervalued the possibility of mild or weak pandemic wave.

Methodology: An alternative decision rule, based on the non-extensive entropy principle, is introduced, and a different Precautionary Principle characterization is applied. This approach values extreme negative results (catastrophic events) in a different way and predicts more plausible and mild events. It introduces less pessimistic forecasts in the case of uncertain influenza pandemic outbreaks. A simplified application is presented using seasonal data of morbidity and severity among Italian children influenza-like illness for the period 2003–10.

Principal Findings: Established literature results predict an average attack rate of not less than 15% for the next pandemic influenza [Meltzer M, Cox N, Fukuda K. The economic impact of pandemic influenza in the United States: implications for setting priorities for interventions. Emerg Infect Dis 1999;5:659–71; Meltzer M, Cox N, Fukuda K. Modeling the Economic Impact of Pandemic Influenza in the United States: Implications for Setting Priorities for Intervention. Background paper. Atlanta, GA: CDC, 1999. Available at: (7 January 2011, date last accessed))]. The strong version of the Precautionary Principle would suggest using this prediction for vaccination campaigns. On the contrary, the non-extensive maximum entropy principle predicts a lower attack rate, which induces a 20% saving in public funding for vaccines doses.

Conclusions: The need for an effective influenza pandemic prevention program, coupled with an efficient use of public funding, calls for a rethinking of the Precautionary Principle. The non-extensive maximum entropy principle, which incorporates vague and incomplete information available to decision makers, produces a more coherent

Modelling the risk–benefit impact of H1N1 influenza vaccines

The European Journal of Public Health
Volume 23 Issue 4 August 2013

Modelling the risk–benefit impact of H1N1 influenza vaccines
Lawrence D. Phillips1,2, Barbara Fasolo1,2, Nikolaos Zafiropoulous1, Hans-Georg Eichler1, Falk Ehmann1, Veronika Jekerle1, Piotr Kramarz3, Angus Nicoll3 and Thomas Lönngren4

Background: Shortly after the H1N1 influenza virus reached pandemic status in June 2009, the benefit–risk project team at the European Medicines Agency recognized this presented a research opportunity for testing the usefulness of a decision analysis model in deliberations about approving vaccines soon based on limited data or waiting for more data. Undertaken purely as a research exercise, the model was not connected to the ongoing assessment by the European Medicines Agency, which approved the H1N1 vaccines on 25 September 2009. Methods: A decision tree model constructed initially on 1 September 2009, and slightly revised subsequently as new data were obtained, represented an end-of-September or end-of-October approval of vaccines. The model showed combinations of uncertain events, the severity of the disease and the vaccines’ efficacy and safety, leading to estimates of numbers of deaths and serious disabilities. The group based their probability assessments on available information and background knowledge about vaccines and similar pandemics in the past. Results: Weighting the numbers by their joint probabilities for all paths through the decision tree gave a weighted average for a September decision of 216 500 deaths and serious disabilities, and for a decision delayed to October of 291 547, showing that an early decision was preferable. Conclusions: The process of constructing the model facilitated communications among the group’s members and led to new insights for several participants, while its robustness built confidence in the decision. These findings suggest that models might be helpful to regulators, as they form their preferences during the process of deliberation and debate, and more generally, for public health issues when decision makers face considerable uncertainty.

Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster

Journal of Infectious Diseases
Volume 208 Issue 4 August 15, 2013

Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster
Vicki A. Morrison1, Michael N. Oxman2, Myron J. Levin3, Kenneth E. Schmader4, John C. Guatelli2, Robert F. Betts5, Larry D. Gelb6, Constance T. Pachucki7, Susan K. Keay8, Barbara Menzies9, Marie R. Griffin10, Carol A. Kauffman11, Adriana R. Marques12, John F. Toney13, Michael S. Simberkoff14, Richard Serrao15, Robert D. Arbeit15, John W. Gnann16, Richard N. Greenberg17, Mark Holodniy18, Wendy A. Keitel19, Shingshing S. Yeh20, Larry E. Davis21, George E. Crawford22, Kathy M. Neuzil9, Gary R. Johnson23, Jane H. Zhang23, Rith Harbecke2, Ivan S. F. Chan24, Paul M. Keller24, Heather M. Williams2, Kathy D. Boardman25, Jeffrey L. Silber24, Paula W. Annunziato24, for the Shingles Prevention Study Group

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ).

Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS.

Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable.

Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥60 years of age with no contraindications, regardless of a prior history of HZ.

Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and -Uninfected Zimbabwean Infants

Journal of Infectious Diseases
Volume 208 Issue 4 August 15, 2013

Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and -Uninfected Zimbabwean Infants
Stephanie B. Troy1, Georgina Musingwini2, Meira S. Halpern4, ChunHong Huang4, Lynda Stranix-Chibanda2,3, Diana Kouiavskaia5, Avinash K. Shetty2,6, Konstantin Chumakov5,
Kusum Nathoo3 and Yvonne A. Maldonado2,4

Background. With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV.

Methods. We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes.

Results. We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0–2 OPV doses but significantly higher in the HIV-infected versus uninfected children after ≥3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates.

Conclusions. HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.

Progress towards Demonstrating the Impact of Haemophilus influenzae Type b Conjugate Vaccines Globally

Journal of Pediatrics

Special Supplement:  Haemophilus influenzae type b (Hib)
July 2013 – 14 articles

Progress towards Demonstrating the Impact of Haemophilus influenzae Type b Conjugate Vaccines Globally
Rana Hajjeh, MD, Kim Mulholland, MBBS, FRACP, MD, Anne Schuchat, MD, Mathuram Santosham, MD, MPH

Prior to the introduction of vaccines, Haemophilus influenzae type b (Hib) was the most common cause of bacterial meningitis and an important cause of severe pneumonia in children <5 years of age. Hib conjugate vaccines were introduced in developed countries during the early 1990s, resulting in a virtual elimination of Hib disease.1 However, the introduction of Hib vaccine in developing countries was delayed significantly due to multiple barriers, with major obstacles being the lack of local data on disease burden and the lack of awareness of the potential impact of the vaccine. In 2002, a group of scientific experts and public health officials gathered in Arizona, US, to discuss the epidemiology and control of Hib disease and recommended a multifaceted approach to overcome barriers for Hib vaccine introduction.2 In 2005, the GAVI Alliance funded the Hib Initiative, a consortium of public and private institutions (Johns Hopkins School of Public Health, the World Health Organization [WHO], the London School for Hygiene and Tropical Medicine, and the US Centers for Diseases Control and Prevention) to assist countries eligible for GAVI funding in making evidence-based decisions regarding the introduction of Hib vaccines into national immunizations programs. The Hib Initiative adopted a strategy based on improved communications, coordination with key partners at country, regional, and global levels, and supporting selected research studies to address gaps in Hib knowledge, particularly studies that could provide evidence and capacity to sustain vaccine programs beyond the period of GAVI support. Fortunately, significant progress in introduction of Hib vaccines has occurred over the last few years with all GAVI countries, having either introduced the vaccine already or are expected to introduce in 2013.3

A database on global health research in Africa

The Lancet Global Health
Aug 2013  Volume 1  Number 2  e55 – 115

The good, the bad, and the neglected
Zoë Mullan
There is a lot to celebrate and applaud in this month’s issue of The Lancet Global Health, but also some sobering findings and a clear demonstration of the need for more research. To start with the positive, Osman Sankoh and fellow INDEPTH Network colleagues announce a new freely accessible repository of Health and Demographic Surveillance System data generated by its member centres across Africa, Asia, and the Pacific. This triumph of dedication, which currently holds data on around 800 000 individuals and more than 3·7 million person-years of observation, represents the first harmonised database of longitudinal population-based data from low-income and middle-income countries.

A database on global health research in Africa
Francis Collins, Alain Beaudet, Ruxandra Draghia-Akli, Peter Gruss, John Savill, André Syrota, Alice Dautry, Mats Ulfendahl, Mark Walport, James Onken, Roger I Glass
Over the past decade, global concern about the disproportionate burden of disease and mortality in low-income countries, especially in sub-Saharan Africa, has led to a substantial influx of funding for research by many donor and research agencies.1 This investment has energised in-country research; advanced the discovery and the use of new treatments for HIV/AIDS, tuberculosis, and malaria; and stimulated new research strategies for the prevention and control of these and other diseases. Questions have been raised about whether these international efforts could be better coordinated to increase efficiency and improve outcomes, while ensuring that research institutions and universities are supported with these funds.

Financing tuberculosis control: promising trends and remaining challenges

The Lancet Global Health
Aug 2013  Volume 1  Number 2  e55 – 115

Financing tuberculosis control: promising trends and remaining challenges
Anna Vassall, Michelle Remme
The financing of essential health services for the world’s poor is changing. Development assistance to health (DAH) seems to be flat-lining, and use of domestic resources and value for money are increasingly emphasised.1,2 Many development agencies are re-examining thematic and geographic priorities and implementing new cofinancing agreements. The Global Fund to Fight AIDS, Tuberculosis and Malaria, for example, now requires 5–60% counterpart financing, depending on a country’s income.3 Ensuring that scarce development funds flow at a sufficient scale to effective interventions that serve people who need them most remains a challenge.

Domestic and donor financing for tuberculosis care and control in low-income and middle-income countries: an analysis of trends, 2002—11, and requirements to meet 2015 targets
Dr Katherine Floyd PhD a , Christopher Fitzpatrick MSc a, Andrea Pantoja MSc a, Mario Raviglione MD a

Progress in tuberculosis control worldwide, including achievement of 2015 global targets, requires adequate financing sustained for many years. WHO began yearly monitoring of tuberculosis funding in 2002. We used data reported to WHO to analyse tuberculosis funding from governments and international donors (in real terms, constant 2011 US$) and associated progress in tuberculosis control in low-income and middle-income countries between 2002 and 2011. We then assessed funding needed to 2015 and how this funding could be mobilised.

We included low-income and middle-income countries that reported data about financing for tuberculosis to WHO and had at least three observations between 2002 and 2011. When data were missing for specific country—year combinations, we imputed the missing data. We aggregated country-specific results for eight country groups defined according to income level, political and economic profile, geography, and tuberculosis burden. We compared absolute changes in total funding with those in the total number of patients successfully treated and did cross-country comparisons of cost per successfully treated patient relative to gross domestic product. We estimated funding needs for tuberculosis care and control for all low-income and middle-income countries to 2015, and compared these needs with domestic funding that could be mobilised.

Total funding grew from $1.7 billion in 2002 to $4·4 billion in 2011. It was mostly spent on diagnosis and treatment of drug-susceptible tuberculosis. 43 million patients were successfully treated, usually for $100—500 per person in countries with high burdens of tuberculosis. Domestic funding rose from $1.5 billion to $3.9 billion per year, mostly in Brazil, Russia, India, China, and South Africa (BRICS), which collectively account for 45% of global cases, where national contributions accounted for more than 95% of yearly funding. Donor funding increased from $0.2 billion in 2002 to $0.5 billion in 2011, and accounted for a mean of 39% of funding in the 17 countries with the highest burdens (excluding BRICS) and a mean of 67% in low-income countries by 2011. BRICS and upper middle-income countries could mobilise almost all of their funding needs to 2015 from domestic sources. A full response to the tuberculosis epidemic to 2015, including investments to tackle multidrug-resistant tuberculosis, will require international donor funding of $1.6—2.3 billion each year.

Funding for tuberculosis control increased substantially between 2002 and 2011, resulting in impressive and cost-effective gains. The increasing self-sufficiency of many countries, including BRICS, which account for almost half the world’s tuberculosis cases, is a success story for control of tuberculosis. Nonetheless, international donor funding remains crucial in many countries and more is needed to achieve 2015 targets.


Universal access to care for multidrug-resistant tuberculosis: an analysis of surveillance data

The Lancet Infectious Diseases
Aug 2013  Volume 13  Number 8  p639 – 724

Universal access to care for multidrug-resistant tuberculosis: an analysis of surveillance data
Dennis Falzon, Ernesto Jaramillo, Fraser Wares, Matteo Zignol, Katherine Floyd, Mario C Raviglione

Preview |
Six countries (Belarus, Brazil, Kazakhstan, Peru, South Africa, and Ukraine) can achieve universal access to MDR-tuberculosis care by 2015 should they sustain their current pace of progress. In other countries a radical scale-up will be needed for them to have an effect on their MDR-tuberculosis burden. Unless barriers to diagnosis and successful treatment are urgently overcome, and new technologies in diagnostics and treatment effectively implemented, the global targets for 2015 are unlikely be achieved.

Biological features of novel avian influenza A (H7N9) virus

Volume 499 Number 7459 pp379-514  25 July 2013

Biological features of novel avian influenza A (H7N9) virus
Jianfang Zhou, Dayan Wang, Rongbao Gao, Baihui Zhao, Jingdong Song+ et al.
An initial characterization of the receptor-binding properties of the novel avian influenza A (H7N9) shows that the virus has acquired the ability to bind human receptors while retaining the ability to bind avian receptors; the virus infects epithelial cells in the human lower respiratory tract and type II pneumocytes in the alveoli, and hypercytokinaemia was seen in infected patients.

Mapping the Journey to an HIV Vaccine

New England Journal of Medicine
July 25, 2013  Vol. 369 No. 4

Mapping the Journey to an HIV Vaccine
Margaret Ackerman, Ph.D., and Galit Alter, Ph.D.
N Engl J Med 2013; 369:389-391
DOI: 10.1056/NEJMcibr130443

“Universal” vaccines that elicit cross-reactive and broadly neutralizing antibodies (bNAbs) are the ultimate goal of efforts to provide protective immunity against both the influenza virus and the human immunodeficiency virus (HIV). Infection with either virus leads to the induction of abundant strain-specific antibodies that are easily evaded by subsequent viral variants. However, the circulating diversity of HIV is greater than that of influenza by orders of magnitude, posing a tremendous challenge to the achievement of vaccine-mediated protection.

New hope for a universal sterilizing HIV vaccine arose several years ago with the evidence that bNAbs emerge in 10 to 30% of infected persons.1 Because these bNAb responses typically appear after 2 to 3 years of infection, they fail to control established infection: the kinetics of the evolving B-cell response lag behind the rapidly diversifying virus, and they cannot “catch up” to control established infection. However, these bNAbs have provided protection from infection at remarkably low doses in animals, suggesting that vaccine-induced bNAbs could provide sterilizing immunity if they were present before infection. Translating our current knowledge of bNAbs into a vaccine remains a daunting challenge, since the mechanism by which such antibodies are induced remains enigmatic.

As compared with other antibodies, bNAbs have unusual characteristics, including odd physical structures (e.g., elongated antigen-binding loops) and remarkably high levels of mutation that affect antibody–antigen binding and structural domains.2 These changes accumulate over years of infection as exposure to diverse viral variants drives antibody evolution, resulting in the generation of a set of antibodies that bears little similarity to their original antigen-naive B-cell ancestors (i.e., germline sequences).

Liao et al.3 have recently described the path along which bNAbs develop. They tracked the evolution of a single bNAb and the counter-evolution of an HIV virus (Figure 1Figure 1The Coevolution of Virus and Antibody.), starting in the first weeks of infection. Their findings offer a roadmap for the induction of bNAbs through vaccination (Figure 2Figure 2Leading Antibodies Down the Path to Neutralization.).

Two key events distinguished the interaction of B-cell and virus during the developing natural history of this bNAb. First, whereas in most scenarios the naive B-cell population cannot bind to HIV, the naive B-cell repertoire in this infected person bound to the earliest incoming virus (the transmitted virus), which suggests that early rapid diversification of the B-cell response was initiated very soon after infection. Second, the rapid evolution of mutations affecting antibodies, which is required for potent antibody neutralization, occurs simultaneously with the rapid diversification of the virus in the first few months of infection. This occurrence suggests that the timing of the exposure to diverse viral variants may be crucial to the induction of protective antibody immunity.

Although the early evolution of the antibody response predominantly occurred within the antigen-recognition site, Liao et al. found that later evolutionary changes in the antibody occurred in structural regions, which are thought to have a limited role in antigen recognition.    However, in a recent publication by Klein et al.,4 the authors report that mutations affecting these structural regions can potentiate antibody function. The authors found that among a set of diverse bNAbs, mutations affecting the structural regions are not just incidental to extensive mutation but are actually critical to neutralization, providing breadth and potency through multiple mechanisms — by expanding the antigen-recognition footprint, by subtly altering binding-loop positioning, and perhaps by changing the conformational dynamics of antibody–antigen binding.

Together, these studies highlight key features of the immune system’s natural induction of bNAbs. First, effective initiation of the antibody response depends on the early interactions between the virus and the naive B-cell repertoire. Second, an explosion of viral diversity can drive the molecular evolution of a bNAb. Finally, neutralization potency arises in an unanticipated way — by means of mutations affecting structural regions of the antibody.

Although we encode a finite number of B-cell–receptor sequences within our naive antibody repertoire, these sequences can become hugely diversified after initial selection and driven in specific directions by subsequent antigen exposure, in a process called affinity maturation, permitting nearly infinite exploration of antibody-recognition space. This idea raises the following questions: How can this finite set of naive sequences be effectively recruited initially, and how can the evolution of the antibody response be constrained to recognize HIV in a way that leads to neutralization? These studies suggest that the rational design of an effective HIV vaccine will require directed-antigen evolution to generate HIV-envelope immunogens that will robustly bind and trigger the germline-naive B-cell repertoire5 (Figure 2).

Despite the 200 years that have elapsed since Edward Jenner’s smallpox vaccine, the development of vaccines has remained, for the most part, an empirical process. The studies by Liao et al. and Klein et al. outline the evolution of bNAb activity and may therefore enable the design of a universally protective vaccine against HIV and possibly other viruses.

Influenza among the elderly in the Americas: a consensus statement

Revista Panamericana de Salud Pública/Pan American Journal of Public Health (RPSP/PAJPH)
June 2013  Vol. 33, No. 6

 Influenza among the elderly in the Americas: a consensus statement [La gripe en los ancianos de la Región de las Américas: una declaración de consenso]
Ricardo W. Rüttimann, Pablo E. Bonvehí, Diana Vilar-Compte, Raúl E. Isturiz, Jaime A. Labarca, and Edison I. Vida

Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease

PLoS One
[Accessed 27 July 2013]

Research Article
Physicians Infrequently Adhere to Hepatitis Vaccination Guidelines for Chronic Liver Disease
Kavitha Thudi, Dhiraj Yadav, Kaitlyn Sweeney, Jaideep Behari mail

Background and Goals
Hepatitis A (HAV) and hepatitis B (HBV) vaccination in patients with chronic liver disease is an accepted standard of care. We determined HAV and HBV vaccination rates in a tertiary care referral hepatology clinic and the impact of electronic health record (EHR)-based reminders on adherence to vaccination guidelines.

We reviewed the records of 705 patients with chronic liver disease referred to our liver clinic in 2008 with at least two follow-up visits during the subsequent year. Demographics, referral source, etiology, and hepatitis serology were recorded. We determined whether eligible patients were offered vaccination and whether patients received vaccination. Barriers to vaccination were determined by a follow-up telephone interview.

HAV and HBV serologic testing prior to referral and at the liver clinic were performed in 14.5% and 17.7%; and 76.7% and 74% patients, respectively. Hepatologists recommended vaccination for HAV in 63% and for HBV in 59.7% of eligible patients. Patient demographics or disease etiology did not influence recommendation rates. Significant variability was observed in vaccination recommendation amongst individual providers (30–98.6%), which did not correlate with the number of patients seen by each physician. Vaccination recommendation rates were not different for Medicare patients with hepatitis C infection for whom a vaccination reminder was automatically generated by the EHR. Most patients who failed to get vaccination after recommendation offered no specific reason for noncompliance; insurance was a barrier in a minority.

Hepatitis vaccination rates were suboptimal even in an academic, sub-speciality setting, with wide-variability in provider adherence to vaccination guidelines.

Targeting Imperfect Vaccines against Drug-Resistance Determinants: A Strategy for Countering the Rise of Drug Resistan

PLoS One
[Accessed 27 July 2013]

Research Article
Targeting Imperfect Vaccines against Drug-Resistance Determinants: A Strategy for Countering the Rise of Drug Resistance
Regina Joice, Marc Lipsitch

The growing prevalence of antimicrobial resistance in major pathogens is outpacing discovery of new antimicrobial classes. Vaccines mitigate the effect of antimicrobial resistance by reducing the need for treatment, but vaccines for many drug-resistant pathogens remain undiscovered or have limited efficacy, in part because some vaccines selectively favor pathogen strains that escape vaccine-induced immunity. A strain with even a modest advantage in vaccinated hosts can have high fitness in a population with high vaccine coverage, which can offset a strong selection pressure such as antimicrobial use that occurs in a small fraction of hosts. We propose a strategy to target vaccines against drug-resistant pathogens, by using resistance-conferring proteins as antigens in multicomponent vaccines. Resistance determinants may be weakly immunogenic, offering only modest specific protection against resistant strains. Therefore, we assess here how varying the specific efficacy of the vaccine against resistant strains would affect the proportion of drug-resistant vs. –sensitive strains population-wide for three pathogens – Streptococcus pneumoniae, Staphylococcus aureus, and influenza virus – in which drug resistance is a problem. Notably, if such vaccines confer even slightly higher protection (additional efficacy between 1% and 8%) against resistant variants than sensitive ones, they may be an effective tool in controlling the rise of resistant strains, given current levels of use for many antimicrobial agents. We show that the population-wide impact of such vaccines depends on the additional effect on resistant strains and on the overall effect (against all strains). Resistance-conferring accessory gene products or resistant alleles of essential genes could be valuable as components of vaccines even if their specific protective effect is weak.

Recent Shifts in Global Governance: Implications for the Response to Non-communicable Diseases

PLoS Medicine
(Accessed 27 July 2013)

Policy Forum
Recent Shifts in Global Governance: Implications for the Response to Non-communicable Diseases
Devi Sridharl, Claire E. Brolan, Shireen Durrani, Jennifer Edge, Lawrence O. Gostin, Peter Hill, Martin McKee

Summary Points
:: Despite evidence of links between non-communicable diseases (NCDs) and development, these diseases and their risk factors were not included in the Millennium Development Goals (MDGs).
:: Three major trends in global governance—the rise of emerging economies, the increase in multi-bi financing, and institutional proliferation—have implications for whether NCDs will be included in the post-2015 Sustainable Development Goals (SDGs) agenda.
:: While emerging economies are influential in global governance, it is not clear that the interests of poorer countries—or even health—will be advanced.
:: If NCDs are included in the new health goals, it likely will be via the broad umbrella of healthy life expectancy (HLE), or the sector-specific target of universal health coverage (UHC) or access.
:: UHC or HLE as currently conceived are unlikely to adequately incorporate NCDs that require alternative health system mechanisms and clear governmental intervention

Essay: Access to Drugs for Treatment of Noncommunicable Diseases

PLoS Medicine
(Accessed 27 July 2013)

Access to Drugs for Treatment of Noncommunicable Diseases
Thomas J. Bollyky

Summary Points
:: A decade ago, the HIV/AIDS treatment-access crisis helped elevate infectious diseases as a foreign policy issue and mobilized billions in global health aid.
:: A new controversy over patented medicines and their affordability in developing countries is emerging, this time over noncommunicable diseases (NCDs).
:: Conflicts over patented NCD medications are likely to increase, with potential adverse consequences for patients, drug firms, and developed and developing country governments alike.
:: The intergovernmental institutions designated to address trade and global health concerns are unlikely to resolve these conflicts and alternatives to intellectual property have not attracted significant donor and multilateral support.
:: Addressing the NCD treatment-access crisis will require another transformation in global health, this time focusing on low-cost interventions and patient-centered, rather than country-focused, strategies.

Preventing Newborn Infection with Maternal Immunization

Science Translational Medicine
24 July 2013 vol 5, issue 195

Preventing Newborn Infection with Maternal Immunization
Steven Black, Immaculada Margarit, and Rino Rappuoli
24 July 2013: 195ps11
Group B streptococcal disease is a common cause of bacterial sepsis in newborns and is often fatal. To protect these babies, a vaccination program must target pregnant women for immunization so that the resulting antibodies can be passively delivered from the mother to the fetus. Scientists met in Siena, Italy, to discuss potential approaches to maternal immunization for the prevention of perinatal group B streptococcal disease.

The marginal willingness-to-pay for attributes of a hypothetical HIV vaccine

Volume 31, Issue 36, Pages 3637-3762 (12 August 2013)

The marginal willingness-to-pay for attributes of a hypothetical HIV vaccine
Original Research Article
Pages 3712-3717
Michael P. Cameron, Peter A. Newman, Surachet Roungprakhon, Riccardo Scarpa

This paper estimates the marginal willingness-to-pay for attributes of a hypothetical HIV vaccine using discrete choice modeling. We use primary data from 326 respondents from Bangkok and Chiang Mai, Thailand, in 2008–2009, selected using purposive, venue-based sampling across two strata. Participants completed a structured questionnaire and full rank discrete choice modeling task administered using computer-assisted personal interviewing. The choice experiment was used to rank eight hypothetical HIV vaccine scenarios, with each scenario comprising seven attributes (including cost) each of which had two levels. The data were analyzed in two alternative specifications: (1) best-worst; and (2) full-rank, using logit likelihood functions estimated with custom routines in Gauss matrix programming language. In the full-rank specification, all vaccine attributes are significant predictors of probability of vaccine choice. The biomedical attributes of the hypothetical HIV vaccine (efficacy, absence of VISP, absence of side effects, and duration of effect) are the most important attributes for HIV vaccine choice. On average respondents are more than twice as likely to accept a vaccine with 99% efficacy, than a vaccine with 50% efficacy. This translates to a willingness to pay US$383 more for a high efficacy vaccine compared with the low efficacy vaccine. Knowledge of the relative importance of determinants of HIV vaccine acceptability is important to ensure the success of future vaccination programs. Future acceptability studies of hypothetical HIV vaccines should use more finely grained biomedical attributes, and could also improve the external validity of results by including more levels of the cost attribute.

Systematic review of economic evaluation analyses of available vaccines in Spain from 1990 to 2012

Volume 31, Issue 35, Pages 3461-3636 (2 August 2013)
Systematic review of economic evaluation analyses of available vaccines in Spain from 1990 to 2012

Review Article
Pages 3473-3484
Isabel Cortés, Santiago Pérez-Camarero, Juan del Llano, Luz María Peña, Álvaro Hidalgo-Vega
The objective of this survey was to describe the evolution of economic evaluation studies on vaccines available in Spain.

We conducted a systematic review of the economic evaluations published by Spanish researchers in major bibliographic databases available online from 1990 to 2012. For all references identified, we limited them to full economic evaluation carried out in Spanish vaccine programs. The following variables were analyzed: type of study, year of publication, vaccine evaluated, the herd immunity and the main methodological aspects proposed by international guidelines. The type of vaccines studied were Hepatitis A and B, Rotavirus, Influenza, Varicella, Tetanus, Measles, Human papillomavirus, Streptococcus pneumoniae infection and Neisseria meningitides serogroup C infection.

A total of 34 references was included in the study. The number of economic evaluations has been increasing over the years by 86%. For many of the vaccines there were no economic evaluations, while others such as the vaccine against S. pneumoniae infection took up most of the studies. The non-vaccinated comparison was the most used strategy. The cost-effectiveness model was selected in 60% of cases. The most common health outcome was “cost per case prevented” and in 82% of the studies did not consider herd immunity. The results showed a cost-effectiveness ratio which was below breakeven.

It is clear that the existence of a huge gap in this kind of work compared to other countries. Although the quality of the work discussed here was significant, we found many areas which could be improved. The reviewed literature exposed the great benefit of vaccination for society by analysing the health outcomes achieved for decades since its implementation. However, the evidence on the efficiency and effectiveness vaccination is not very high, and there are few studies about economic evaluation.

A brief history of the global effort to develop a preventive HIV vaccine

Volume 31, Issue 35, Pages 3461-3636 (2 August 2013)

A brief history of the global effort to develop a preventive HIV vaccine
Review Article
Pages 3502-3518
José Esparza

Soon after HIV was discovered as the cause of AIDS in 1983–1984, there was an expectation that a preventive vaccine would be rapidly developed. In trying to achieve that goal, three successive scientific paradigms have been explored: induction of neutralizing antibodies, induction of cell mediated immunity, and exploration of combination approaches and novel concepts. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. In 2009, the field was reinvigorated with the modest results obtained from the RV144 trial conducted in Thailand. Here, we review those vaccine development efforts, with an emphasis on events that occurred during the earlier years. The goal is to provide younger generations of scientists with information and inspiration to continue the search for an HIV vaccine.

Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines

Volume 31, Issue 35, Pages 3461-3636 (2 August 2013)

Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines
Original Research Article – Brighton Collaboration papers
Pages 3623-3627
Hector S. Izurieta, Patrick Zuber, Jan Bonhoeffer, Robert T. Chen, Osman Sankohg, Kayla F. Laserson, Miriam Sturkenboom, Christian Loucq, Daniel Weibel, Caitlin Dodd, Steve Black

With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC’s are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety.

A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus

Volume 31, Issue 35, Pages 3461-3636 (2 August 2013)

A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus
Original Research Article – Brighton Collaboration papers
Pages 3628-3635
Cindy Tamminga, Michael Kavanaugh, Charlotte Fedders, Santina Maiolatesi, Neethu Abraham, Jan Bonhoeffer, Ulrich Heininger, Carlos S. Vasquez, Vasee S. Moorthy, Judith E. Epstein, Thomas L. Richie

Malaria, tuberculosis (TB) and human immunodeficiency virus (HIV) are diseases with devastating effects on global public health, especially in the developing world. Clinical trials of candidate vaccines for these diseases are being conducted at an accelerating rate, and require accurate and consistent methods for safety data collection and reporting. We performed a systematic review of publications describing the safety results from clinical trials of malaria, TB and HIV vaccines, to ascertain the nature and consistency of safety data collection and reporting.

The target for the review was pre-licensure trials for malaria, TB and HIV vaccines published in English from 2000 to 2009. Search strategies were customized for each of the databases utilized (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Database of Reviews and Effects). Data extracted included age of trial participants, vaccine platform, route and method of vaccine administration, duration of participant follow-up, reporting of laboratory abnormalities, and the type, case definitions, severity, reporting methods and internal reporting consistency of adverse events.

Of 2278 publications screened, 124 were eligible for inclusion (malaria: 66, TB: 9, HIV: 49). Safety data reporting was found to be highly variable among publications and often incomplete: overall, 269 overlapping terms were used to describe specific adverse events. 17% of publications did not mention fever. Descriptions of severity or degree of relatedness to immunization of adverse events were frequently omitted. 26% (32/124) of publications failed to report data on serious adverse events.

The review demonstrated lack of standardized safety data reporting in trials for vaccines against malaria, TB and HIV. Standardization of safety data collection and reporting should be encouraged to improve data quality and comparability.

The search strategy missed studies published in languages other than English and excluded studies reporting on vaccine trials for diseases besides malaria, TB and HIV.

A Multidisciplinary Research Agenda for Understanding Vaccine-Related Decisions

Vaccines — Open Access Journal
Vaccines (ISSN 2076-393X), an international open access journal, is published by MDPI online quarterly. The first issue will be released in 2013.\
A Multidisciplinary Research Agenda for Understanding Vaccine-Related Decisions
Heidi Larson, Julie Leask, Sian Aggett, Nick Sevdalis and Angus Thomson
Vaccines 2013, 1(3), 293-304; doi:10.3390/vaccines1030293 – published online 18 July 2013
Abstract: There is increasingly broad global recognition of the need to better understand determinants of vaccine acceptance. Fifteen social science, communication, health, and medical professionals (the “Motors of Trust in Vaccination” (MOTIV) think tank) explored factors relating to vaccination decision-making as a step to building a multidisciplinary research agenda. One hundred and forty seven factors impacting decisions made by consumers, professionals, and policy makers on vaccine acceptance, delay, or refusal were identified and grouped into three major categories: cognition and decision-making; groups and social norms; and communication and engagement. These factors should help frame a multidisciplinary research agenda to build an evidence base on the determinants of vaccine acceptance to inform the development of interventions and vaccination policies.

Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care

Vaccines — Open Access Journal
Vaccines (ISSN 2076-393X), an international open access journal, is published by MDPI online quarterly. The first issue will be released in 2013.

Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care
Jennifer Young Pierce 1,*, Jeffrey E. Korte 2, Laura A. Carr 3, Catherine B. Gasper 1 and Susan C. Modesitt 4
Vaccines 2013, 1, 250-261; doi:10.3390/vaccines1030250
Abstract: Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11–12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11–12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child’s vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation (RR 0.72, Vaccines 2013, 1 251 95% CI 0.61–0.85 and RR 0.85, 95% CI 0.72–1.01, respectively). In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort.

From Google Scholar & other sources: Selected Journal Articles, Newsletters, Dissertations, Theses, Commentary [to 27 July 2013]

From Google Scholar & other sources: Selected Journal Articles, Newsletters, Dissertations, Theses, Commentary
Sociocultural Determinants of Anticipated Vaccine Acceptance for Acute Watery Diarrhea in Early Childhood in Katanga Province, Democratic Republic of Congo
Sonja Merten*, Christian Schaetti, Cele Manianga, Bruno Lapika, Raymond Hutubessy, Claire-Lise Chaignat and Mitchell Weiss
+ Author Affiliations
Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; Anthropologie, Université de Kinshasa, Kinshasa, Democratic Republic of Congo; Initiative for Vaccine Research and Global Task Force on Cholera Control, World Health Organization, Geneva, Switzerland
American Journal of Tropical Medicine and Hygiene
2013 12-0643
Published online July 22, 2013
doi: 10.4269/ajtmh.12-0643
Rotavirus and oral cholera vaccines have the potential to reduce diarrhea-related child mortality in low-income settings and are recommended by the World Health Organization. Uptake of vaccination depends on community support, and is based on local priorities. This study investigates local perceptions of acute watery diarrhea in childhood and anticipated vaccine acceptance in two sites in the Democratic Republic of Congo. In 2010, 360 randomly selected non-affected adults were interviewed by using a semi-structured questionnaire. Witchcraft and breastfeeding were perceived as potential cause of acute watery diarrhea by 51% and 48% of respondents. Despite misperceptions, anticipated vaccine acceptance at no cost was 99%. The strongest predictor of anticipated vaccine acceptance if costs were assumed was the educational level of the respondents. Results suggest that the introduction of vaccines is a local priority and local (mis)perceptions of illness do not compromise vaccine acceptability if the vaccine is affordable

Influenza vaccination for healthcare workers who care for people aged 60 or older living in long‐term care institutions
Roger E Thomas1,*, Tom Jefferson2, Toby J Lasserson3
The Cocchran Librrary
Editorial Group: Cochrane Acute Respiratory Infections Group
Published Online: 22 JUL 2013
Healthcare workers’ influenza rates are unknown but may be similar to those of the general public. Healthcare workers may transmit influenza to patients.
To identify all randomised controlled trials (RCTs) and non-RCTs assessing the effects of vaccinating healthcare workers on the incidence of laboratory-proven influenza, pneumonia, death from pneumonia and admission to hospital for respiratory illness in those aged 60 years or older resident in long-term care institutions (LTCIs).
Search methods
We searched CENTRAL 2013, Issue 2, MEDLINE (1966 to March week 3, 2013), EMBASE (1974 to March 2013), Biological Abstracts (1969 to March 2013), Science Citation Index-Expanded (1974 to March 2013) and Web of Science (2006 to March 2013).
Selection criteria
Randomised controlled trials (RCTs) and non-RCTs of influenza vaccination of healthcare workers caring for individuals aged 60 years or older in LTCIs and the incidence of laboratory-proven influenza and its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 years or older in LTCIs.
Data collection and analysis
Two authors independently extracted data and assessed risk of bias.
Main results
We identified four cluster-RCTs (C-RCTs) (n = 7558) and one cohort study (n = 12,742) of influenza vaccination for HCWs caring for individuals ≥ 60 years in LTCFs. Three RCTs (5896 participants) provided outcome data that met our criteria. These three studies were comparable in study populations, intervention and outcome measures. The studies did not report adverse events. The principal sources of bias in the studies related to attrition and blinding. The pooled risk difference (RD) from the three cluster-RCTs for laboratory-proven influenza was 0 (95% confidence interval (CI) -0.03 to 0.03) and for hospitalisation was RD 0 (95% CI -0.02 to 0.02). The estimated risk of death due to lower respiratory tract infection was also imprecise (RD -0.02, 95% CI -0.06 to 0.02) in individuals aged 60 years or older in LTCIs. Adjusted analyses which took into account the cluster design did not differ substantively from the pooled analysis with unadjusted data.
Authors’ conclusions
The results for specific outcomes: laboratory-proven influenza or its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract illness) did not identify a benefit of healthcare worker vaccination on these key outcomes. This review did not find information on co-interventions with healthcare worker vaccination: hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, antivirals and asking healthcare workers with influenza or influenza-like-illness (ILI) not to work.     This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in LTCIs. High-quality RCTs are required to avoid the risks of bias in methodology and conduct identified by this review and to test further these interventions in combination.
Plain language summary
Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions
Older individuals in long-term care institutions (LTCIs) at risk of influenza may be infected by their healthcare workers. There are no accurate data on rates of laboratory-proven influenza in healthcare workers. Vaccinating healthcare workers against influenza may reduce infections acquired from this source. Because the signs and symptoms of influenza are similar to those of many other respiratory illnesses, it is important in studies testing the effects of influenza vaccination to prove by laboratory tests which are highly accurate whether residents in LTCIs actually have influenza or another respiratory illness.
Three randomised controlled trials (RCTs) (5896 participants) provided outcome data meeting our criteria. For risk of bias: randomisation was at low risk in two trials and unclear in one; allocation concealment and blinding in all three trials was unclear; incomplete outcome data in one trial was at low risk and in two at high risk; selective reporting all three trials was at low risk; performance bias (incomplete influenza vaccination of healthcare workers in the intervention arms) in all three trials was at high risk. No studies reported on adverse events. Vaccinating healthcare workers who care for those aged 60 or over in LTCIs showed no effect on laboratory-proven influenza or complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract illness) in those aged 60 or over resident in LTCIs.
This review did not find information on other interventions used in conjunction with vaccinating healthcare workers (hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding new admissions, prompt use of antivirals and asking healthcare workers with an influenza-like illness not to work.
There is no evidence that only vaccinating healthcare workers prevents laboratory-proven influenza or its complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 or over in LTCIs and thus no evidence to mandate compulsory vaccination of healthcare workers. Other interventions, such as hand-washing, masks, early detection of influenza with nasal swabs, antivirals, quarantine, restricting visitors and asking healthcare workers with an influenza-like illness not to attend work, might protect individuals over 60 in LTCIs. High-quality randomised controlled trials testing combinations of these interventions are needed.

Providers lack of knowledge about herpes zoster in HIV-infected patients is among barriers to herpes zoster vaccination
M Aziz, MD, H Kessler, MD, G Huhn, MD MPH&TM
Rush University Medical Center/John H Stroger Hospital of Cook County, Chicago, IL, USA
Correspondence to:
M Aziz MD, Section of Infectious Diseases, Department of Medicine, Rush University Medical Center, 600 S. Paulina Street, Suites 140143, Chicago, IL, USA Email:
Identification of perceptions about herpes zoster (HZ) disease, vaccine effectiveness and safety, and vaccine recommendations may impact immunization practices of physicians for HIV-infected patients. A survey was used to quantify knowledge of HZ as well as determine physician immunization perceptions and practices. There were 272/1700 respondents (16). Correct answers for the incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ in HIV-infected patients were recorded by 14 and 10 of providers, respectively. Providers reported poor knowledge of the incidence of disease recurrence in HIV-infected patients (41 correct), potency of HZ vaccine (47.5 correct) and mechanism of protection against reactivation of VZV (66 correct). Most (88) agreed that HZ was a serious disease, and 73 believed that the burden of disease made vaccination important. A majority (75) did not vaccinate HIV patients with HZ vaccine regardless of antiretroviral therapy status. Barriers to administration included safety concerns, concern that vaccine would not prevent HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious Diseases Society of America (IDSA) guidelines. Only 38 of providers agreed that CDC guidelines were clear and 50 believed that clinical trials were needed prior to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among HIV providers. Providers perceived vaccination as important, but data on vaccine safety and clear guidance from the CDC on this issue are lacking.

[HTML] High HIV-1 prevalence, risk behaviours, and willingness to participate in HIV vaccine trials in fishing communities on Lake Victoria, Uganda
N Kiwanuka, A Ssetaala, J Mpendo, M Wambuzi… – Journal of the International …, 2013
Abstract Introduction: HIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years).

Selected Newsletters
RotaFlash (PATH) – July 22, 2013

Polio vaccines – Injecting competition [Serum Institute]

Accessed 27 July 2013

Polio vaccines
Injecting competition
Jul 19th 2013, 11:27 by E.C. | PUNE

WILL the world eradicate polio? If it does, some of the credit may go to a 73-year-old billionaire horse-breeder from the Indian city of Pune: he wants to provide injectable polio vaccine at a loss—at least for some time.

The world has made much progress in the fight against polio, a dreaded disease which leaves infected children paralysed. India is a good example. In 1985 the country counted more than 150,000 cases. Next January, after three years without a new case, the Global Polio Eradication Initiative will formally declare India polio-free.

The effort to get there has been monumental. During India’s National Immunisation Day, for instance, more than 2.5m volunteers inoculate over 170m children under the age of five. Since each child receives two drops of the vaccine, an astonishing 340m drops of oral polio vaccine (OPV), a vaccine developed in the 1950s by Albert Sabin, a Polish-American scientist, is needed.

Given such massive quantities, pharmaceutical companies such as GlaxoSmithKline and Sanofi Pasteur, have been able to keep the prices of the polio vaccine low. A two-drop dose of OPV costs between $0.10 and $0.13.

But the injectable polio vaccine (IPV) is a better way to inoculate children against the disease: it is safer because it does not carry the live virus. Unhappily, it is also more expensive. Still, nearly 140 countries, including India, will be relying on the IPV in the coming years, says Apoorva Mallya of Bill & Melinda Gates Foundation. The shift to IPV is a key part of the endgame in the fight against polio.

This is where Cyrus Poonawalla, the billionaire horse-breeder, comes in. He is the founder and chief executive of the Serum Institute. Although it is lesser known than its European and American competitors—GlaxoSmithKline, Sanofi-Aventis, Merck and Novartis—the firm is the world’s number one producer of measles and DTP (diphtheria, tetanus and pertussis) vaccines. Globally, two of three children receive a Serum vaccine, according to some estimates…

Vaccines: The Week in Review 20 July 2013

Vaccines: The Week in Review is a weekly digest — summarizing news, events, announcements, peer-reviewed articles and research in the global vaccine ethics and policy space. Content is aggregated from key governmental, NGO, international organization and industry sources, key peer-reviewed journals, and other media channels. This summary proceeds from the broad base of themes and issues monitored by the Center for Vaccine Ethics & Policy in its work: it is not intended to be exhaustive in its coverage. You are viewing the blog version of our weekly digest, typically comprised of between 30 and 40 posts below all dated “29 June 2013″
Email Summary: Vaccines: The Week in Review is published as a single email summary, scheduled for release each Saturday eveningbefore midnight (EDT in the U.S.). If you would like to receive the email version, please send your request to
pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_20 July 2013
Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.
Links: We endeavor to test each link as we incorporate it into any post, but recognize that some links may become “stale” as publications and websites reorganize content over time. We apologize in advance for any links that may not be operative. We believe the contextual information in a given post should allow retrieval, but please contact us as above for assistance if necessary.
Support: If you would like to join the growing list of individuals who support this service and its contribution to their roles in public health, clinical practice, government, IGOs/NGOs, research, industry and academia, please visit this page at The Wistar Institute, our co-founder and fiduciary. Thank you…
David R. Curry, MS
Executive Director
Center for Vaccine Ethics and Policy
a program of the
– Division of Medical Ethics, NYU Medical School
– The Wistar Institute Vaccine Center
– Children’s Hospital of Philadelphia Vaccine Education Center
Associate Faculty, Division of Medical Ethics, NYU Medical School

– email:

Sabin PDP launches soil-transmitted helminth (STH) vaccine discovery program

The Sabin Vaccine Institute Product Development Partnership (Sabin PDP) announced the launch of a soil-transmitted helminth (STH) vaccine discovery program.  The new Sabin PDP is supported by the Gary Karlin Michelson, M.D. Charitable Foundation, and will be based at the Baylor College of Medicine and Texas Children’s Hospital. The program “will endeavor to advance lead candidate antigens for ascariasis (roundworm) and trichuriasis (whipworm) infections and incorporate them into existing hookworm and schistosomiasis vaccines currently being developed by the Sabin PDP to create a vaccine against all four major human helminth infections.” Sabin noted that ascariasis, an infection of the small intestine, afflicts an estimated 800-900 million people and is a significant cause of acute intestinal obstruction in young children with high worm loads, leading to thousands of deaths annually. Trichuriasis, an infection of the large intestine, affects approximately 500 million people and is arguably the primary cause of inflammatory bowel disease in developing countries.

DFID: Multilateral Aid Review (MAR) update confirms GAVI as a highly effective organisation

DFID:  Multilateral Aid Review (MAR) update confirms GAVI as a highly effective organisation
Geneva, 18 July 2013 – The UK Department for International Development (DFID) today confirmed that the GAVI Alliance remains a highly effective organisation that is making progress on areas for improvement highlighted by the UK. DFID’s follows the 2011 MAR which found GAVI to be “very good value for money for UK aid”. The MAR update enables the UK Government to assess international organisations on progress made against the reforms proposed in the 2011 MAR. Progress made in all areas for reform “demonstrates GAVI’s on-going commitment to improvement,” DFID said. The MAR update also found that GAVI provides “highly cost-effective health interventions” and has “effective financial oversight” of its programmes.

WHO Statement: Second Meeting of the IHR Emergency Committee concerning MERS-CoV – PHEIC Conditions Not Met

WHO Statement: Second Meeting of the IHR Emergency Committee concerning MERS-CoV
17 July 2013
[Full text, editor’s bolding of selected text]

The second meeting of the Emergency Committee convened by the Director-General under the International Health Regulations (2005) [IHR (2005)] was held by teleconference on Wednesday, 17 July 2013, from 12:00 to 16:04 Geneva time (CET).

In addition to Members of the Emergency Committee, an expert advisor to the Committee1 participated in the meeting. During the informational session of the meeting, several affected States Parties were also on the teleconference. The States Parties on the teleconference were: France, Germany, Italy, Jordan, Kingdom of Saudi Arabia, Qatar, Tunisia, and the United Kingdom.

The Committee reviewed and deliberated on information on a range of aspects of MERS-CoV, which was prepared or coordinated by the Secretariat and States in response to questions presented by Members during the first meeting.

   It is the unanimous decision of the Committee that, with the information now available, and using a risk-assessment approach, the conditions for a Public Health Emergency of International Concern (PHEIC) have not at present been met.

While not considering the events currently to constitute a PHEIC, Members of the Committee did offer technical advice for consideration by WHO and Member States on a broad range of issues, including the following:
–       Improvements in surveillance, lab capacity, contact tracing and serological investigation
–       Infection prevention and control and clinical management
–       Travel-related guidance
–       Risk communications
–       Research studies (epidemiological, clinical and animal)
–       Improved data collection and the need to ensure full and timely reporting of all confirmed and probable cases of MERS-CoV to WHO in accordance with the IHR (2005).

The WHO Secretariat will provide regular updates to the Members and will reconvene the Committee, in September, on a date to be determined. However, serious new developments may require an urgent re-convening of the Committee before then.

Based on these views and the currently available information, the Director-General accepted the Committee’s assessment that the current MERS-CoV situation is serious and of great concern, but does not constitute a PHEIC at this time.

The Director-General expressed her gratitude to the Committee on its wide range of advice on health actions for countries to implement, and advice on follow-up work by WHO.

Emergency Committee Members

WHO: GAR – Disease Outbreak News MRS-CoV; Poliovirus [to 20 July 2013]

WHO: Global Alert and Response (GAR) – Disease Outbreak News

Middle East respiratory syndrome coronavirus (MERS-CoV) – update 18 July 2013
WHO has been informed of six additional laboratory-confirmed cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Of these, two cases have been reported from Saudi Arabia and four from the United Arab Emirates (UAE).

Both the cases in Saudi Arabia have mild symptoms and are not hospitalized. They are from Asir region. The first case is a 26-year-old man who is a close contact with a previously laboratory-confirmed case and the second case is a 42-year-old woman who is a health care worker.

In the UAE, the four cases are health care workers from two hospitals in Abu Dhabi who took care of an earlier laboratory-confirmed patient. Of these, two cases, a 28-year-old man and 30-year-old woman, did not develop symptoms of illness. The other two cases, both women of 30 and 40 years old, had mild upper respiratory symptoms and are in stable condition.

Globally, from September 2012 to date, WHO has been informed of a total of 88 laboratory-confirmed cases of infection with MERS-CoV, including 45 deaths…

Poliovirus detected from environmental samples in Israel – update 15 July 2013
Wild poliovirus type 1 (WPV1) has been isolated in 30 sewage samples from 10 sampling sites in Israel. The samples were collected from 3 February 2013 to 30 June 2013. Most positive WPV1 samples were detected from southern Israel. All viruses have been detected in sewage only; no cases of paralytic polio have been reported.

Detection of viruses across the country indicates increased geographic extent of circulation for a prolonged period of time. WHO assesses the risk of further international spread of WPV from Israel as moderate to high.

Health authorities in Israel are continuing to conduct a full epidemiological and public health investigation to actively search for potential cases of paralytic polio and any un-immunized persons. Routine immunization coverage is estimated at 94 percent or above over last eight years. The frequency of environmental surveillance sampling has been increased….