Editor’s Notes:

– Email Summary: Vaccines: The Week in Review is available as a weekly email summary: please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.

– pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_25 August 2012

– Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.

– 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…

Meeting Report: WHO Technical Working Group on creation of an oral cholera vaccine stockpile
Geneva, 26–27 April 2012
Authors: WHO
Publication details: 15 pages; WHO reference number: WHO/HSE/PED/2012

Overview
The 64th World Health Assembly (2011) called for an integrated, comprehensive strategy of cholera prevention and control. The WHA Resolution 64.15 included consideration of the use of oral cholera vaccines (OCV) “where appropriate, in conjunction with other recommended prevention and control methods and not as a substitute for such methods”.

This consideration was taken forward at a September 2011 consultation, which noted that an OCV stockpile for outbreak control could be initiated in the near future.

This is the report of a Technical Working Group which was convened, in April 2012, to develop an OCV stockpile implementation framework. Participants advised on: the criteria for choice of stockpiled vaccine and its deployment; the appropriate size of an OCV stockpile; the managing partnership and evaluation processes required; the decision-making procedure and operational issues; and the financing mechanism.

http://www.who.int/iris/bitstream/10665/75240/1/WHO_HSE_PED_2012_2_eng.pdf

PAHO reported on a meeting of its Technical Advisory Group on Vaccine-Preventable Diseases (TAG) focused on cholera. The meeting was heldin Washington, D.C. on 16 August 2012. The group reported that elimination of cholera transmission on the Island of Hispaniola can be achieved by increasing and sustaining access to clean drinking water and adequate sanitation, and that “reaching the long-term goal will be greatly aided with complementary short-term actions such as the expanded use of oral cholera vaccine.” PAHO said the meeting of the Technical Advisory Group is “framed in the set of actions that governments of Haiti and Dominican Republic, PAHO/WHO, and other agencies and partners have been carrying out in the wake of the cholera outbreak in October 2010.” One example of this coordinated action is the launching last June of the Regional Coalition on Water and Sanitation for the Elimination of Cholera on the Island of Hispaniola, which helps governments to harmonize and streamline international assistance and investments in water and sanitation infrastructure on the island.  Dr. Jon Andrus, Deputy Director of PAHO, opened the meeting by tasking TAG with the provision of technical recommendations on cholera vaccination grounded in the best available science. “If the evidence indicates, especially with the recent experience of demonstration projects conducted in the field in Haiti, we should not fail to miss short-term opportunities to save more lives more quickly. However, such action must be balanced within the long-term vision of safe water and sanitation that will ultimately stop cholera transmission on the island.”

After the presentation of scientific evidence and the results of two demonstration projects, the Technical Advisory Group, chaired by Dr. Ciro de Quadros, recommended introduction of the oral cholera vaccine. This recommendation was supported by data presented by Partners in Health and GHESKIO, two nongovernmental health organizations with a long history of work in Haiti. Acting on PAHO’s suggestion, both had recently conducted projects which achieved high vaccination coverage of up to 90% for two doses of the oral cholera vaccine.

Given that current global supplies of the vaccine are limited, TAG experts also recommended prioritizing vaccination in densely populated urban areas with limited access to sanitation and drinking water, and in rural areas where access to health services is most challenging. As manufacturers ramp up production in the near future, the experts unanimously recommended moving toward universal vaccination. However, they noted that doing so will require urgent attention to mobilizing and sustaining the flow of financial resources, strengthening operational capacity, and insuring that vaccination efforts are well-integrated into the long-term vision of safe water and sanitation to stop cholera’s transmission. The Technical Advisory Group also highlighted the importance of finding solutions to the global scarcity of the cholera vaccine, as well as the need to strengthen epidemiological surveillance processes, which are critical in securing cholera prevention and control. TAG members additionally stressed the need to conduct research to close current knowledge gaps on the vaccine.

Members of PAHO’s Technical Advisory Group for Vaccine-Preventable Disease include Dr. Ciro de Quadros (Chairperson and Executive Vice- President of the Sabin Vaccine Institute), Dr. Peter Figueroa (Rapporteur and Acting Chief Medical Officer at the Ministry of Health of Jamaica), Dr. Roger Glass (Fogarty International Center, U.S. National Institutes of Health), Dr. Anne Schuchat (National Center for immunization and Respiratory Diseases, U.S. Centers for Disease Control and Prevention), Dr. Jeannette Vega (Center for Epidemiology and Health Policy, Chile), Dr. Akira Homma (Policy and Strategy Council, Bio-Manguinhos Institute, Fiocruz, Brazil), Dr. Arlene King (Ministry of Health and Long-term Care, Canada), Dr. Ramiro Guerrero-Carvajal (PROESA, Colombia), Dr. José Ignacio Santos (Department of Experimental Medicine, National Autonomous University of Mexico) and Cuahtémoc Ruiz (PAHO).

The U.S. Global Health Initiative (GHI) published interim reports on its “aspirational goals in eight broad health areas.” The reports focus on progress against GHI targets through links provided on the program graphic here:

http://www.ghi.gov/about/goals/index.htm

The Global Fund said it signed two grant agreements with Nigeria worth a total of US$225 million to support programs that will prevent and treat malaria. The grant agreements “expand a partnership with the Global Fund that has yielded remarkable progress in recent years, such as undertaking the largest distribution of bed nets done anywhere – more than 45 million to date.”  Included is an additional US$50 million for bed nets, “approved in an unusual move by the Global Fund Board that was linked to additional commitments by the Government of Nigeria.” During a transformation of the Global Fund’s grant management structure this year, Nigeria was identified as one of 20 ‘high impact’ countries now under a special designation.

http://www.theglobalfund.org/en/mediacenter/newsreleases/2012-08-24_Nigeria_and_the_Global_Fund_Sign_Grant_Agreements_worth_USD_225_Million_to_Fight_Malaria/

   NIAID said it awarded 14 grants totaling US$7.8 million in first-year funding for “basic research to identify new approaches for designing a safe and effective HIV vaccine.” The grants were awarded under the Innovation for HIV Vaccine Discovery (IHVD) initiative, which is expected to receive up to $34.8 million over the next four years. NIAID Director Anthony S. Fauci, M.D. commented, “Recent discoveries about the basic biology of HIV and how the virus adapts to its host have provided useful information and new opportunities to guide vaccine development. These grants are designed to build on that information and stimulate discovery of new ways to design a robust vaccine that prevents acquisition and establishment of latent infection.” The 14 IHVD grant recipient organizations include:

– Altravax Inc. (Sunnyvale, Calif.)

– Catholic University of America (Washington, D.C.)

– Dartmouth College (Hanover, N.H.)

– Duke University (Durham, N.C.)

– Harvard Medical School (Boston)

– Massachusetts General Hospital (Boston)

– NYU Langone Medical Center (New York City)

– University of California (Irvine)

– University of Maryland (Baltimore)

– University of Medicine and Dentistry of New Jersey (Newark)

– University of Minnesota (Minneapolis)

– University of North Carolina (Chapel Hill)

– University of Rochester (Rochester, N.Y.)

– University of Texas at El Paso

http://www.nih.gov/news/health/aug2012/niaid-21.htm

Post: A Global Partnership for Vaccine Design
USID – IMPACT blog
Posted by Guest blogger Margaret McGlynn, IAVI President and CEO on Monday, August 13th 2012

When you’re dealing with a global public health crisis, having an international presence isn’t just advisable – it is imperative. This applies as much to the development of new tools to prevent disease as it does to treatment. An AIDS vaccine candidate, for example, must be tested in the people who will eventually use it and against the strains of HIV it is devised to protect them from.

That’s why the International AIDS Vaccine Initiative (IAVI), in partnership with USAID, has worked diligently over the past several years to establish itself as a truly global non-profit partner. Using donor funds, IAVI has created an enviable network of research centers in sub-Saharan Africa dedicated to assessing novel AIDS vaccine candidates in clinical trials and conducting supporting epidemiological studies on HIV. These partnerships have made meaningful contributions to the research capacity of many developing countries—a capability that is now helping local researchers tackle other diseases.

IAVI and its partners are now applying that same model to support the design of a new generation of AIDS vaccine candidates. Today, IAVI and the Translational Health Sciences and Technology Institute (THSTI), an autonomous institute of the Indian government’s Department of Biotechnology (DBT), launched an HIV Vaccine Design Programme near New Delhi. The Programme is dedicated to the large-scale generation and preclinical evaluation of immunogens, the active ingredients of vaccines. It will focus on devising immunogens capable of eliciting antibodies that can prevent infection by a broad range of the circulating genetic variants of HIV.

That challenge, known to researchers as the neutralizing antibody problem, has long stymied progress toward an AIDS vaccine. But recent discoveries of antibodies capable of blocking a number of HIV variants have provided researchers with clues to the design of potentially powerful new vaccine candidates. The HIV Vaccine Design Programme will use these insights to develop new methods to generate large numbers of potential HIV immunogens and rapidly assess their potential for use in candidate vaccines. Much of the work will take place in a laboratory housed within THSTI that is being built and staffed with support from IAVI, DBT and THSTI.

The Programme’s location is no accident. Over the past decade, IAVI has enjoyed a productive partnership for the clinical evaluation of candidate AIDS vaccines with key medical research institutions of the Indian government. Indian scientists have also actively participated in an international consortium of HIV laboratories supported by IAVI to advance HIV vaccine research. The government of India, meanwhile, is in the early phase of its “Decade of Innovation”, a policy that seeks to harness a growing roster of home-grown biotechs, the nation’s deep pool of scientific talent and global research partnerships to boost innovation in a variety of high-tech fields.

The HIV Vaccine Design Programme provides an opportunity to engage an emerging economy in the global quest to develop a vaccine against HIV. For India, it creates an opportunity to address a crisis of significant relevance to Indians.  As importantly, it seeds the kinds of collaborations that often foster scientific and technical innovation and generate ideas that might be applied to address other diseases that have long hampered development.

http://blog.usaid.gov/2012/08/a-global-partnership-for-vaccine-design/

PATH’s Malaria Vaccine Initiative (MVI) announced a new collaboration with the International AIDS Vaccine Initiative (IAVI) and Imperial College London “to measure the capacity of different vaccine candidates in human clinical testing to elicit an immune response aimed at protecting against deadly malaria parasites.” David C. Kaslow, M.D., director of MVI, said, “Until now, malaria vaccine scientists have struggled to directly compare the cellular immune response elicited in humans by one vaccine to that of another, and this has hampered the ability to prioritize a portfolio of vaccine candidates. We are fortunate to have in IAVI and Imperial College London partners with a track record of developing validated human immunological assays. Through this new collaboration, we look forward to being able to make better informed decisions about if and how various malaria vaccines elicit immune responses at the cellular level in humans.” MVI said the tests will help “prioritize investments and allow scientists to refine vaccine strategies by showing whether a particular formulation, delivery approach, or vaccine adjuvant elicits a superior cell-mediated immune response.” More at: http://www.malariavaccine.org/pr2012Aug20-referencelab.php

MVI said it recently named “some of the world’s most eminent malaria scientists and vaccinologists to its Vaccine Science Portfolio Advisory Council (VSPAC) — “a group of external experts tasked with providing strategic input and advice on the MVI’s scientific portfolio and overall research and development (R&D) program.” The new members of the VSPAC are: Dr. Norman Baylor, President and CEO of Biologics Consulting Group, Inc. and former Director of the Office of Vaccines Research and Review (OVRR) in the FDA’s Center for Biologics Evaluation and Research; Dr. Kamini Mendis, an independent consultant on malaria and tropical medicine, formerly the Coordinator of Malaria Treatment and Malaria Elimination at WHO; Dr. Rafick-Pierre Sékaly, Co-Director and Chief Scientific Officer of VGTI Florida; and Dr. Fidel Zavala, Professor at the Department of Molecular Microbiology and Immunology at the Bloomberg School of Public Health, Johns Hopkins University. Dr. David C. Kaslow, director of MVI and former chair of the VSPAC, said, “We’re fortunate to have some of the world’s most distinguished scientists advising us on MVI’s malaria vaccine research and development strategy. The expertise of the VSPAC members is a critical resource to realizing our near-term strategic goal of supporting development of a first-generation malaria vaccine that could protect millions against disease and death, as well as our long-term goals of developing more highly effective second-generation vaccines, including vaccines to support future elimination and eradication efforts.”

http://www.path.org/news/pr120814-mvi-vspac.php

The FDA (U.S.) said it approved the 2012-2013 influenza (flu) vaccine formulation for all six manufacturers licensed to produce and distribute the vaccines in the United States. Based on that information and the recommendations of the FDA’s Vaccines and Related Biological Products Advisory Committee, the strains selected for inclusion in the 2012-2013 flu vaccines are:

– A/California/7/2009 (H1N1)-like virus
– A/Victoria/361/2011 (H3N2)-like virus
– B/Wisconsin/1/2010-like virus.

The FDA noted that while the H1N1 virus is the same as what was included in the 2011-2012 influenza vaccines, this year’s influenza H3N2 and B viruses differ from those in the 2011-2012 influenza vaccines. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315365.htm

The MMWR Weekly for August 24, 2012 / Vol. 61 / No. 33 includes:
Vaccination Coverage Among Children in Kindergarten — United States, 2011–12 School Year

The Weekly Epidemiological Record (WER):

– 24 August 2012, vol. 87, 34 (pp. 317–328) includes: Global leprosy situation, 2012
http://www.who.int/entity/wer/2012/wer8734.pdf

– 17 August 2012, vol. 87, 33 (pp. 305–316) includes: Meeting of the International Task Force for Disease Eradication, April 2012; Progress towards eliminating onchocerciasis in the WHO Region of the Americas in 2011: interruption of transmission in Guatemala and Mexico; Monthly report on dracunculiasis cases, January–May 2012
http://www.who.int/entity/wer/2012/wer8733.pdf

WHO Fact Sheet: Pneumonia
Fact sheet N°331
August 2012

Key Facts
– Pneumonia is the leading cause of death in children worldwide.

– Pneumonia kills an estimated 1.4 million children under the age of five years every year – more than AIDS, malaria and tuberculosis combined.

– Pneumonia can be caused by viruses, bacteria or fungi.

– Pneumonia can be prevented by immunization, adequate nutrition and by addressing environmental factors.

– Pneumonia can be treated with antibiotics, but around 30% of children with pneumonia receive the antibiotics they need.

Full Fact Sheet: http://www.who.int/mediacentre/factsheets/fs331/en/index.html

UNICEF said it launched the Innovate for Children website to “draw attention to health and education challenges faced by children in developing countries – and the potential for innovative product design and inventive use of technology to find solutions.” The website “welcomes comments and ideas, and invites online submissions on projects designed to accelerate reduction of child mortality. UNICEF’s methodology in innovation work “emphasizes the importance of understanding the needs of users and the geographic, social and economic barriers that limit access to life-saving supplies and services.”

Website: http://www.unicefinnovation.org/
http://www.unicef.org/media/media_65582.html

Proceedings: Progress Toward Rubella Elimination and CRS Prevention in Europe

This meeting was held 8-10 February, 2012 in Rome, Italy. Over 150 people from 47 countries came together to review the latest developments in the fight against rubella and CRS in Europe. A special session on measles was also convened to review the numerous overlaps in these two areas. Proceedings are now available for download.

Progress Toward Rubella Elimination and CRS Prevention in Europe_finalweb.pdf(3.26mb pdf)

Workshop Summary: Accelerating the Development of New Drugs and Diagnostics: Maximizing the Impact of the Cures Acceleration Network
August 22, 2012

Summary
Advances in technologies and knowledge are creating new avenues for research and opportunities for the discovery and clinical development of innovative therapies and diagnostics. However, despite these opportunities, only a small fraction of investigational products are successfully developed into cures and therapies that can be accessed by patients. One response to the ever-widening gap between the number and promise of basic scientific discoveries and the translation of those discoveries into therapies is a renewed emphasis on collaborative approaches among federal agencies, academia, and industry, all directed at the advancement of the drug development enterprise.

The newly developed Cures Acceleration Network (CAN) — a part of the National Center for Advancing Translational Sciences (NCATS) within the National Institutes of Health (NIH) — has the potential to catalyze widespread changes in NCATS, NIH, and the drug development ecosystem in general.

On June 4–5, 2012, the IOM Forum on Drug Discovery, Development, and Translation held, at the request of NCATS, a workshop — bringing together members of federal government agencies, the private sector, academia, and advocacy groups — to explore options and opportunities in the implementation of CAN. This document summarizes the workshop.

http://iom.edu/Reports/2012/Accelerating-the-Development-of-New-Drugs-and-Diagnostics.aspx?utm_medium=etmail&utm_source=Institute%20of%20Medicine&utm_campaign=08.22.12+Report+-+Cures+Acceleration+Network&utm_content=New%20Reports&utm_term=Academic

Emerging Infectious Diseases
Volume 18, Number 9—September 2012
http://www.cdc.gov/ncidod/EID/index.htm

Perspective
Hepatitis E, a Vaccine-Preventable Cause of Maternal Deaths
A. B. Labrique et al.

Abstract
Hepatitis E virus (HEV) is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Although HEV vaccine trials, including trials conducted in populations in southern Asia, have shown candidate vaccines to be effective and well-tolerated, these vaccines have not yet been produced or made available to susceptible populations. Surveillance data collected during 2001–2007 from >110,000 pregnancies in a population of ≈650,000 women in rural Bangladesh suggest that acute hepatitis, most of it likely hepatitis E, is responsible for ≈9.8% of pregnancy-associated deaths. If these numbers are representative of southern Asia, as many as 10,500 maternal deaths each year in this region alone may be attributable to hepatitis E and could be prevented by using existing vaccines.

JAMA   
August 15, 2012, Vol 308, No. 7
http://jama.jamanetwork.com/issue.aspx?journalid=67&issueid=24772&direction=P

Viewpoint
The State of the World’s Refugees: Adapting Health Responses to Urban Environments
António Guterres, MEng; Paul Spiegel, MD, MPH

Extract [Free full text]
The forced displacement of populations, across borders and within their own countries, is one of the most visible and enduring manifestations of persecution and conflict. At the end of 2011, more than 42 million people had been forcibly displaced from their homes by conflict, including 15 million refugees and 26 million internally displaced people (IDPs).1 In 2011, more than 4.3 million people were newly uprooted, with some 800 000 fleeing to neighboring countries in humanitarian crises stretching from Côte d’Ivoire, Libya, Syria, the border between Sudan and South Sudan, to the Horn of Africa1 and more recently due to conflict in Mali.2

These new emergencies unfolded alongside unresolved crises that have resulted in millions of people living in situations of protracted displacement, often for decades. Millions of refugees and IDPs from countries such as Somalia, Afghanistan, Eritrea, Colombia, the Democratic Republic of Congo, and Iraq remain unable to return to their homes after extended periods in exile. The vast majority of refugees—approximately 80%—are hosted in the developing world, primarily in neighboring countries…

JAMA   
August 15, 2012, Vol 308, No. 7
http://jama.jamanetwork.com/issue.aspx?journalid=67&issueid=24772&direction=P

Viewpoint
A Framework for Catastrophic Disaster Response
Dan Hanfling, MD; Bruce M. Altevogt, PhD; Lawrence O. Gostin, JD

Extract
The Japanese tsunami, Haitian earthquake, and Gulf Coast hurricane offered stark reminders of how vulnerable organized societies are to catastrophic events. They also show how public health emergencies—whether naturally occurring (eg, a pandemic outbreak of novel influenza) or deliberate (eg, a terrorist attack using an improvised nuclear device)—will stress the health system beyond its current capacity. This will require a health and medical response that is fundamentally different from the status quo.

The Lancet Infectious Disease
Sep 2012  Volume 12  Number 9  p647 – 736
http://www.thelancet.com/journals/laninf/issue/current

Comment
Global mortality of 2009 pandemic influenza A H1N1
Cécile Viboud, Lone Simonsen

Preview
More than 3 years after the emergence of the 2009 pandemic influenza A H1N1 virus, the associated global mortality remains unclear. Of 18 500 laboratory-confirmed pandemic-associated deaths identified during April, 2009, to April, 2010, worldwide, less than 12% were reported from Africa and southeast Asia, although these regions are home to more than 38% of the world’s population. Laboratory-confirmed deaths are gross underestimates of influenza-related mortality because of the lack of routine laboratory tests and difficulties in identification of influenza-related deaths triggered by bacterial superinfections or exacerbation of chronic illnesses.

Research
Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study
Fatimah S Dawood, A Danielle Iuliano, Carrie Reed, Martin I Meltzer, David K Shay, Po-Yung Cheng, Don Bandaranayake, Robert F Breiman, W Abdullah Brooks, Philippe Buchy, Daniel R Feikin, Karen B Fowler, Aubree Gordon, Nguyen Tran Hien, Peter Horby, Q Sue Huang, Mark A Katz, Anand Krishnan, Renu Lal, Joel M Montgomery, Kåre Mølbak, Richard Pebody, Anne M Presanis, Hugo Razuri, Anneke Steens, Yeny O Tinoco, Jacco Wallinga, Hongjie Yu, Sirenda Vong, Joseph Bresee, Marc-Alain Widdowson

Summary
Background
18 500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country.

Methods
We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0—17 years, 18—64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths.

Findings
We estimate that globally there were 201 200 respiratory deaths (range 105 700—395 600) with an additional 83 300 cardiovascular deaths (46 000—179 900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa.

Interpretation
Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics.

Funding
None.

The Lancet Infectious Disease
Sep 2012  Volume 12  Number 9  p647 – 736
http://www.thelancet.com/journals/laninf/issue/current

Comment
Effectiveness of H1N1 vaccination in Scotland, UK
John S Oxford
Preview
The inherent scientific strength of the UK National Health Service (NHS) is exemplified in The Lancet Infectious Diseases by the report by Colin Simpson and colleagues.1 Few countries have nationally linked primary care, hospital records, death certificates, and virological swab data. The numbers in the study are large, with nearly 24 million person-days of observation during the two waves of the H1N1 2009 influenza pandemic in the early summer and the autumn, with the numbers vaccinated and outcomes ranging from hospital admission to death.

Research
Effectiveness of H1N1 vaccine for the prevention of pandemic influenza in Scotland, UK: a retrospective observational cohort study
Colin R Simpson, Lewis D Ritchie, Chris Robertson, Aziz Sheikh, Jim McMenamin
Summary
Background
A targeted vaccination programme for pandemic H1N1 2009 influenza was introduced in Scotland, UK, in October, 2009. We sought to assess the effectiveness of this vaccine in a sample of the Scottish population during the 2009—10 pandemic.

Methods
We assessed the effectiveness of the Scottish pandemic H1N1 2009 influenza vaccination with a retrospective cohort design. We linked data of patient-level primary care, hospital records, death certification, and virological swabs to construct our cohort. We estimated vaccine effectiveness in a nationally representative sample of the Scottish population by establishing the risk of hospital admission and death (adjusted for potential confounders) resulting from influenza-related morbidity in vaccinated and unvaccinated patients and laboratory-confirmed cases of influenza H1N1 2009 in a subset of patients.

Findings
Pandemic H1N1 2009 influenza vaccination began in week 43 of 2009 (Oct 21, 2009) and was given to 38 296 (15·5%, 95% CI 15·4—15·6) of 247 178 people by the end of the study period (Jan 31, 2010). 208 882 (85%) people were unvaccinated. There were 5207 emergency hospital admissions and 579 deaths in the unvaccinated population and 924 hospital admissions and 71 deaths in the vaccinated population during 23 893 359 person-days of observation. The effectiveness of H1N1 vaccination for prevention of emergency hospital admissions from influenza-related disorders was 19·5% (95% CI 0·8—34·7). The vaccine’s effectiveness in preventing laboratory-confirmed influenza was 77·0% (95% CI 2·0—95·0).

Interpretation
Pandemic H1N1 2009 influenza vaccination was associated with protection against pandemic influenza and a reduction in hospital admissions from influenza-related disorders in Scotland during the 2009—10 pandemic.

Funding
National Institute for Health Research Health Technology Assessment Programme (UK).

Nature Reviews Immunology
September 2012 Vol 12 No 9
http://www.nature.com/nri/journal/v12/n8/index.html

The impact of differential antiviral immunity in children and adults
Andrew J. Prendergast, Paul Klenerman & Philip J. R. Goulder
p636 | doi:10.1038/nri3277

Abstract
The course of immune maturation has evolved to favour survival at each stage of development in early life. Fetal and neonatal immune adaptations facilitate intrauterine survival and provide early postnatal protection against extracellular pathogens, but they leave infants susceptible to intracellular pathogens such as viruses that are acquired perinatally. This Review focuses on three such pathogens — HIV, hepatitis B virus and cytomegalovirus — and relates the differential impact of these infections in infants and adults to the antiviral immunity that is generated at different ages. A better understanding of age-specific antiviral immunity may inform the development of integrated prevention, treatment and vaccine strategies to minimize the global disease burden resulting from these infections.

The Pediatric Infectious Disease Journal
September 2012 – Volume 31 – Issue 9  pp: A7-A8,889-1002,e141-e175
http://journals.lww.com/pidj/pages/currenttoc.aspx

Eradication of Invasive Pneumococcal Disease due to the Seven-valent Pneumococcal Conjugate Vaccine Serotypes in Calgary, Alberta
Leal, Jenine; Vanderkooi, Otto G.; Church, Deirdre L.; MacDonald, Judy; Tyrrell, Gregory J.; Kellner, James D.
Pediatric Infectious Disease Journal. 31(9):e169-e175, September 2012.
doi: 10.1097/INF.0b013e3182624a40

Abstract:
Background: The seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in Canada in 2001. Routine infant vaccination programs in Alberta began in 2002. Several years after PCV7 introduction, the routine use of PCV7 in infants and high-risk children has led to near elimination of invasive pneumococcal disease (IPD) caused by vaccine serotypes.

Methods: Prospective, population-based surveillance of all IPD cases was conducted from January 1998 to December 2010. Demographic, clinical and microbiologic data were collected.

Results: There were 1462 IPD cases over 13 years. Comparing PCV7 serotype IPD incidence in the prevaccine period (1998–2001) to the late postvaccine period (2007–2010), there were declines in children 0–5 months (100%), 6–23 months (98%), 2–4 years (97%), 5–15 years (100%) as well as in adults 16–64 years (73%), 65–84 years (90%) and ≥85 years of age (100%). From 2008 to 2010, there were no cases of PCV7 serotype IPD in children under 2 years of age. There have been increases in non-PCV7 serotype IPD; notably, serotypes 5 and 19A have increased significantly in adults and 19A in children.

Conclusions: PCV7 serotype IPD has been eliminated in vaccine-eligible young children and nearly eliminated in all other age groups. Serotype 19A increased significantly at all ages before the introduction of an expanded valency pneumococcal conjugate vaccine

PLoS One
[Accessed 25 August 2012]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

The Effectiveness of U.S. Public Health Surveillance Systems for Situational Awareness during the 2009 H1N1 Pandemic: A Retrospective Analysis
Michael A. Stoto
PLoS ONE: Research Article, published 22 Aug 2012 10.1371/journal.pone.0040984

Abstract 
Background
The 2009 H1N1 outbreak provides an opportunity to learn about the strengths and weaknesses of current U.S. public health surveillance systems and to identify implications for measuring public health emergency preparedness.

Methodology/Principal Findings
We adopted a “triangulation” approach in which multiple contemporary data sources, each with different expected biases, are compared to identify time patterns that are likely to reflect biases versus those that are more likely to be indicative of actual infection rates. This approach is grounded in the understanding that surveillance data are the result of a series of decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities. Although limited by the lack of a gold standard, this analysis suggests that children and young adults are over-represented in many pH1N1 surveillance systems, especially in the spring wave. In addition, the nearly two-month delay between the Northeast and the South in the Fall peak in some surveillance data seems to at least partially reflect regional differences in concerns about pH1N1rather than real differences in pH1N1 infection rates.

Conclusions/Significance
Although the extent of the biases suggested by this analysis cannot be known precisely, the analysis identifies underlying problems with surveillance systems – in particular their dependence on patient and provider behavior, which is influenced by a changing information environment – that could limit situational awareness in future public health emergencies. To improve situational awareness in future health emergencies, population-based surveillance systems such as telephone surveys of representative population samples and seroprevalence surveys in well-defined population cohorts are needed.

PLoS Medicine
(Accessed 25 August 2012)
http://www.plosmedicine.org/article/browse.action?field=date
Why We Need Urban Health Equity Indicators: Integrating Science, Policy, and Community
Jason Corburn, Alison K. Cohen
Policy Forum, published 14 Aug 2012
doi:10.1371/journal.pmed.1001285

Summary Points
– As the urban population of the planet increases and puts new stressors on infrastructure and institutions and exacerbates economic and social inequalities, public health and other disciplines must find new ways to address urban health equity.

– Urban indicator processes focused on health equity can promote new modes of healthy urban governance, where the formal functions of government combine with science and social movements to define a healthy community and direct policy action.

– An inter-related set of urban health equity indicators that capture the social determinants of health, including community assets, and track policy decisions, can help inform efforts to promote greater urban health equity.

– Adaptive management, a strategy used globally by scientists, policy makers, and civil society groups to manage complex ecological resources, is a potential model for developing and implementing urban health equity indicators.

– Urban health equity indicators are lacking and needed within cities of both the global north and south, but universal sets of indicators may be less useful than context-specific measures accountable to local needs.

Science        
17 August 2012 vol 337, issue 6096, pages 769-876
http://www.sciencemag.org/content/337/6096.toc
News & Analysis
Public Health
Policy Shifts on Emergency Use of Cholera Vaccines
Martin Enserink

Summary
Many experts have argued that in outbreak situations—especially in the poor, messy places where cholera often strikes—existing vaccines are too expensive, not effective enough, and too impractical to roll out; they might even make matters worse, some fear, because they distract health workers from treating patients or improving water and sanitation, the cornerstones of cholera control. But now, the tide appears to have turned. This week, a technical working group at the World Health Organization is set to publish a report advocating for the creation of a global stockpile of cholera vaccines that would be rushed to countries when an outbreak begins.

Science Translational Medicine
22 August 2012 vol 4, issue 148
http://stm.sciencemag.org/content/current

Review
IMMUNOENGINEERING
Engineering Approaches to Immunotherapy
Melody A. Swartz, Sachiko Hirosue, and Jeffrey A. Hubbell
22 August 2012: 148rv9

Abstract
As the science of immunology grows increasingly mechanistic, motivation for developing quantitative, design-based engineering approaches has also evolved, both for therapeutic interventions and for elucidating immunological pathways in human disease. This has seeded the nascent field of “immunoengineering,” which seeks to apply engineering analyses and design approaches to problems in translational immunology. For example, cell engineers are creating ways to tailor and use immune cells as living therapeutics; protein engineers are devising new methods of rapid antibody discovery; biomaterials scientists are guiding vaccine delivery and immune-cell activation with novel constructs; and systems immunologists are deciphering the evolution and maintenance of T and B cell receptor repertoires, which could help guide vaccine design. The field is multidisciplinary and collaborative, with engineers and immunologists working together to better understand and treat disease. We discuss the scientific progress in this young, yet rapidly evolving research area, which has yielded numerous start-up companies that are betting on impact in clinical and commercial translation in the near future.

Science Translational Medicine
22 August 2012 vol 4, issue 148
http://stm.sciencemag.org/content/current

Health Care
Measuring the Benefits of HPV Vaccination
Ruanne V. Barnabas
22 August 2012: 148ec149
[No abstract] Costs of HPV disease in the United States could be offset by vaccination.
15 August 2012 vol 4, issue 147
http://stm.sciencemag.org/content/4/147.toc

Vaccine: Development and Therapy
(Accessed 25 August 2012)
http://www.dovepress.com/vaccine-development-and-therapy-journal

Reasons for not having received influenza vaccination and its predictors in Canadians
Original Research
Authors: Chen Y, Wu J, Yi QL, Laroche J, Wong T
Published Date August 2012 Volume 2012:2 Pages 23 – 33
DOI: http://dx.doi.org/10.2147/VDT.S32618
Yue Chen,1 Jun Wu,2 Qi-long Yi,1 Julie Laroche,3 Thomas Wong2
1Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, 2Professional Guidelines and Public Health Practice Division, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, 3Immunization Assessment and Information, Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada, Ottawa, Ontario, Canada

Background: Influenza vaccination is the most effective way to prevent influenza. However, only about one-third of Canadians receive an annual seasonal influenza vaccination.
Methods: The reasons for not having received influenza vaccination were examined among 131,061 Canadians ≥ 12 years of age who participated in a national survey in 2007–2008. Among them, 127,297 subjects responded to the questions concerning their flu shot history and were grouped into three categories: never (n = 51,767), 1+ year ago (n = 29,310), last year (n = 46,220). Subjects who reported not having had a flu shot during the past year were asked the reasons for not having it. The log binomial regression model was used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for the associations of various reasons for not having received influenza vaccination and their predictors.
Results: When weighted to the Canadian population, 44.0% had never previously received influenza vaccine and 24.5% had received the vaccine > 12 months ago. The most common reasons for not having received influenza vaccination in the past 12 months were “Respondent did not think it necessary” (71.3%) and “Have not gotten around to it” (17.6%). Log binomial regression analysis shows that females were less likely to report these two reasons compared to males with PRs of 0.98 (0.97, 0.99) and 0.84 (0.81, 0.87), respectively. Younger participants were more likely to report, “Have not gotten around to it.” For those who had an influenza vaccination previously, the primary reason for not having an influenza vaccination in the last year was “Have not gotten around to it.”
Conclusions: More than two-thirds of Canadians 12+ years of age did not receive an influenza vaccination in the past year, and “Respondent did not think it necessary” and “Have not gotten around to it” were the main reasons.

Thesis: Evaluation of the impact of access to free influenza vaccine on immunization rates for children with cystic fibrosis
By Jones, Katie, M.P.H., THE UNIVERSITY OF TEXAS SCHOOL OF PUBLIC HEALTH, 2012, 47 pages; 1511823

Abstract:
Children with cystic fibrosis are at increased risk of seasonal influenza associated complications, which makes them a judicious target of interventions designed to increase influenza vaccination rates. The Baylor College of Medicine/Texas Children’s Hospital Pediatric Cystic Fibrosis (BCM/TCH CF) Care Center implemented an enhanced multi-component initiative designed to increase influenza vaccination rates in its patient population during the 2011-2012 influenza season. We evaluated the impact of specific components of this intervention on vaccination rates among the clinic’s patient population via a historical medical chart review and examined the relationship between vaccination status and the number of pulmonary exacerbations requiring hospital admission during the influenza season. The multi-component intervention was comprised of providing influenza free of charge in the CF Care Center, reminders via phone call and letters, and drive through influenza vaccine clinics on nights and weekends. The intervention to increase influenza vaccination rates led to overall improved vaccination rates among the patients at the BCM/TCH CF Care Center, increasing from 90% adherence observed during the 2010-2011 season to 94% adherence during the 2011-2012 season. The availability of free influenza vaccine in the CF Care Center, combined with reminders about being vaccinated early in the season proved to be the most effective practices for improving the vaccination rate in the CF Care Center.
http://gradworks.umi.com/15/11/1511823.html

CURRENT OPINION – Advances in hepatitis immunization (A, B, E): public health policy and novel vaccine delivery
G Hendrickx, A Vorsters, P Van Damme – Curr Opin Infect Dis, 2012

Summary
Follow-up of vaccinated individuals confirms the long-term protection offered by
the hepatitis A as well as hepatitis B vaccines. Data confirm the safety and immunogenicity profile of both vaccines, also when used in patient groups. The first data on the hepatitis E…

CURRENT OPINION – Meningococcal disease in travelers: update on vaccine options
JP Cramer, A Wilder-Smith – Curr Opin Infect Dis, 2012

Summary
The vaccine of choice for travelers at risk of invasive meningococcal disease is a
tetravalent conjugate meningococcal vaccine. Data on the need for re-vaccination
schedules are still lacking, and so are data on immunogenicity in very young children and …

Analysis of indexes used to evaluate immunization coverage rate of first dose of measles containing vaccine.
Beijing Da Xue Xue Bao. 2012 Aug 18;44(4):617-21.
http://www.ncbi.nlm.nih.gov/pubmed/22898859
[Article in Chinese]

Rui LP, Zhang L, Tang N, Wang T.

Source
Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.

Abstract
OBJECTIVE:
To obtain an objective index of evaluating the immunization coverage rate of first dose of measles containing vaccine (MCV1)by comparison of the indexes in Guizhou Province.

METHODS:
Multistage random sampling method was applied to draw subjects from healthy children who had no measles history and aged from 8 months to 6 years of age. The investigated immunization coverage rate (IIR) and the estimated immunization coverage rate (EIR) were evaluated according to the positive rate of measles antibody as a gold standard, and the data of incidence cases as a reference.

RESULTS:
The IIR was 86.0% for the group aged from 8 months to 1 year, 90.1% for the group aged from 2 to 3 years and 90.2% for the group aged from 4 to 6 years. The adjusted estimated immunization coverage rate (AIIR) was 89.8%, 94.8% and 95.3%, respectively. Given the vaccine efficacy (VE) was 82.9%, the EIR1 was 59.8%, 71.6% and 77.9%, respectively and the AEIR1 was 68.2%, 79.7% and 86.8%, respectively; given the VE was 95%, the EIR1 was 84.3%, 90.1% and 92.7%, respectively, and the AEIR1 was 88.6%, 93.4% and 96.0%, respectively. The EIR2 was 97.9%, 94.5% and 91.4%, respectively. The relative difference was from 0 to 2.4% when compared with the estimated positive rate of AIIR and AEIR1 given the VE was 95% with the actual positive rate of measles antibody, the difference had no statistical significance(P>0.05). The relative error was low for the estimate positive rates of AIIR and EIR2 and AEIR1 (given the VE was 95%) for the children that had not suffered from measles, the relative error varied from 7.0% to 15.8%.

CONCLUSION:
The investigated immunization coverage rate after adjustment and the AEIR1 (VE 95%) were in line with the actual positive rate of measles antibody, which suggests that we should set an integral evaluation system for the immunization coverage rate based on AIIR and AEIR1.

PMID: 22898859
[PubMed – in process]
Free full text

New York Times
http://www.nytimes.com/
Accessed 25 August 2012
August 24, 2012, 7:03 am
Opinion
Tropical Diseases: The New Plague of Poverty
By PETER J. HOTEZ
Published: August 18, 2012

Extract
Houston
In the United States, 2.8 million children are living in households with incomes of less than $2 per person per day, a benchmark more often applied to developing countries. An additional 20 million Americans live in extreme poverty. In the Gulf Coast states of Louisiana, Mississippi and Alabama, poverty rates are near 20 percent. In some of the poorer counties of Texas, where I live, rates often approach 30 percent. In these places, the Gini coefficient, a measure of inequality, ranks as high as in some sub-Saharan African countries.

Poverty takes many tolls, but in the United States, one of the most tragic has been its tight link with a group of infections known as the neglected tropical diseases, which we ordinarily think of as confined to developing countries…

http://www.nytimes.com/2012/08/19/opinion/sunday/tropical-diseases-the-new-plague-of-poverty.html?_r=2

Editor’s Notes:

– Email Summary: Vaccines: The Week in Review is available as a weekly email summary: please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.

– pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_11 August 2012

– Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.

– 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…

CDC Update on H3N2v Cases Telebriefing Transcript – August 9, 2012

MMWR Early Release
August 10, 2012 / Vol. 61 / Early Release
Evaluation of Rapid Influenza Diagnostic Tests for Influenza A (H3N2)v Virus and Updated Case Count — United States, 2012

The Bill & Melinda Gates Foundation named Dr. Orin Levine as Director of Vaccine Delivery within the Global Development Program. Dr. Levine is currently Professor of International Health and Executive Director of the International Vaccine Access Center (IVAC) at the Johns Hopkins University’s Bloomberg School of Public Health. He will start work at the foundation on October 1. Chris Elias, president of the foundation’s Global Development Program, said, “Dr. Levine is a recognized expert in the fields of international public health, immunization, child survival and pneumonia, and we are very fortunate to have him join the foundation. His leadership at IVAC has accelerated global access to vaccines, helping save millions of lives each year.” http://www.gatesfoundation.org/press-releases/Pages/orin-levine-joins-gatesfoundation.aspx

    IVAC named Deputy Director Kate O’Brien as Acting Executive Director while a process takes place to name a permanent Executive Director. The action follows the announcement that Dr. Orin Levine will be taking up a new position at the Bill & Melinda Gates Foundation as Director of Vaccine Delivery starting October 1st .
http://www.jhsph.edu/research/centers-and-institutes/ivac/about-us/news.html

The Global Fund to Fight AIDS, Tuberculosis and Malaria named Daniel Camus as Chief Financial Officer. Mr. Camus is described as having “more than 25 years of experience as a senior executive, implementing long-term expansion in complex financial operations, including a recent position as Group Executive Director of Electricité de France (EDF), where he also oversaw international operations at the largest electric utility company in the world.” He holds a PhD in Finance and Economics from the Sorbonne in Paris. Gabriel Jaramillo, General Manager of the Global Fund, commented, “Daniel is a keystone of our transformation. He brings rock-solid financial expertise, private-sector perspective and unparalleled strategic thinking to the Global Fund. We are thrilled to have him join us.” http://www.theglobalfund.org/en/mediacenter/newsreleases/2012-08-06_Global_Fund_Appoints_Daniel_Camus_as_Chief_Financial_Officer/

 Solicitation: Nominations for GAVI Alliance Board Member Representing Technical and Heath Research Institutes
Applications deadline:  September 15, 2012
Background: GAVI’s board includes members representing specific constituencies in addition to several unaffiliated members. One seat on the board is designated for Technical and health research institutes. Nominations for a candidate to serve in this role are sought to replace outgoing board member, Dr. Anne Schuchat (Centers for Disease Control and Prevention) after her three-year term ends in December 2012.
Application instructions:  Nomination packages should include a cover letter documenting the nominee’s qualifications related to vaccines and immunization, global technical advisory experience, and institutional support to carry out duties associated with service on the Board and related committees.  The package should also include the candidate’s Curriculum Vitae as well as a letter confirming support from the nominee’s institution director.
Additional information related to the GAVI Alliance is available at www.gavialliance.org.
Applications should be submitted by email with the subject line ‘GAVI Nomination’ to
duk3@cdc.gov.
http://www.gavialliance.org/about/governance/

Global Immunization News  31 July 2012

– Country-specific Estimates of Immunization Coverage for 1980-2011

– Information on Vaccines for an Intergovernmental Negotiating Committee to Prepare a Global Legally Binding Instrument on the Use of Mercury

– Hepatitis A Vaccination should be part of a Comprehensive Plan for Prevention and Control of Viral Hepatitis

– Notes From the Field: Salmonella Typhi Infec-tions Associated with Contaminated Water in Zimbabwe

– Vaccine pharmacovigilance system in Ghana

– AMP’s Africhol Monitors Impact of Mass Cholera Vaccination Campaign in Guinea

should be part of a Comprehensive Plan for Prevention and Control of Viral Hepatitis AMERICAS

– The Dominican Republic Introduces Rotavirus Vaccine into National Immunization Schedule

– International Workshop on Cold Chain Operations in Nicaragua

– Guatemala Celebrates the World Hepatitis Day

SOUTH EAST ASIA

– DPR Korea Launches Pentavalent Vaccine

WESTERN PACIFIC

– Effective Vaccine Management (EVM) Assessment in Fiji

– China’s continued progress towards maternal and neonatal tetanus (MNT) elimination

– Regional Meetings & Key Events

http://www.who.int/entity/immunization/GIN_July_2012.pdf

Book: Ethical and Scientific Issues in Studying the Safety of Approved Drugs
Authoring Institutions:
Board on Population Health and Public Health Practice (BPH)
Institute of Medicine (IOM)
ISBN-10: 0-309-21813-6
ISBN-13: 978-0-309-21813-9
Free pdf: https://download.nap.edu/login.php?record_id=13219&page=%2Fcatalog.php%3Frecord_id%3D13219%26utm_medium%3Detmail%26utm_source%3DThe%2520National%2520Academies%2520Press%26utm_campaign%3DNAP%2Bmail%2Bnew%2B8.7.12%26utm_content%3D%26utm_term%3D

Description:
An estimated 48 percent of the population takes at least one prescription drug in a given month. Drugs provide great benefits to society by saving or improving lives. Many drugs are also associated with side effects or adverse events, some serious and some discovered only after the drug is on the market. The discovery of new adverse events in the postmarketing setting is part of the normal natural history of approved drugs, and timely identification and warning about drug risks are central to the mission of the Food and Drug Administration (FDA). Not all risks associated with a drug are known at the time of approval, because safety data are collected from studies that involve a relatively small number of human subjects during a relatively short period.

Written in response to a request by the FDA, Ethical and Scientific Issues in Studying the Safety of Approved Drugs discusses ethical and informed consent issues in conducting studies in the postmarketing setting. It evaluates the strengths and weaknesses of various approaches to generate evidence about safety questions, and makes recommendations for appropriate followup studies and randomized clinical trials. The book provides guidance to the FDA on how it should factor in different kinds of evidence in its regulatory decisions….

Book: The Impact of Health Insurance on Low- and Middle-Income Countries
EDITORS
Charles C. Griffin, Maria-Luisa Escobar, R. Paul Shaw
Publisher: Brookings Institution Press
ISBN-13: 978-0-8157-0546-8
Pdf: http://www.brookings.edu/~/media/press/books/2011/1/theimpactofhealthinsuranceonlowandmiddleincomecountries/theimpactofhealthinsurance_fulltext.pdf

Over the past twenty years, many low- and middle-income countries have experimented with health insurance options. While their plans have varied widely in scale and ambition, their goals are the same: to make health services more affordable through the use of public subsidies while also moving care providers partially or fully into competitive markets.
Colombia embarked in 1993 on a fifteen-year effort to cover its entire population with insurance, in combination with greater freedom to choose among providers. A decade later Mexico followed suit with a program tailored to its federal system. Several African nations have introduced new programs in the past decade, and many are testing options for reform. For the past twenty years, Eastern Europe has been shifting from government-run care to insurance-based competitive systems, and both China and India have experimental programs to expand coverage. These nations are betting that insurance-based health care financing can increase the accessibility of services, increase providers’ productivity, and change the population’s health care use patterns, mirroring the development of health systems in most OECD countries.
Until now, however, we have known little about the actual effects of these dramatic policy changes. Understanding the impact of health insurance–based care is key to the public policy debate of whether to extend insurance to low-income populations—and if so, how to do it—or to serve them through other means.
Using recent household data, this book presents evidence of the impact of insurance programs in China, Colombia, Costa Rica, Ghana, Indonesia, Namibia, and Peru. The contributors also discuss potential design improvements that could increase impact. They provide innovative insights on improving the evaluation of health insurance reforms and on building a robust knowledge base to guide policy as other countries tackle the health insurance challenge.

Journal of Infectious Diseases
Volume 206 Issue 5 September 1, 2012
http://www.journals.uchicago.edu/toc/jid/current
Deborah Watson-Jones, Kathy Baisley, Riziki Ponsiano, Francesca Lemme, Pieter Remes, David Ross, Saidi Kapiga, Philippe Mayaud, Silvia de Sanjosé, Daniel Wight, John Changalucha, and Richard Hayes

Human Papillomavirus Vaccination in Tanzanian Schoolgirls: Cluster-Randomized Trial Comparing 2 Vaccine-Delivery Strategies
J Infect Dis. (2012) 206(5): 678-686 doi:10.1093/infdis/jis407
Abstract
Background. We compared vaccine coverage achieved by 2 different delivery strategies for the quadrivalent human papillomavirus (HPV) vaccine in Tanzanian schoolgirls.

Methods. In a cluster-randomized trial of HPV vaccination conducted in Tanzania, 134 primary schools were randomly assigned to class-based (girls enrolled in primary school grade [class] 6) or age-based (girls born in 1998; 67 schools per arm) vaccine delivery. The primary outcome was coverage by dose.

Results. There were 3352 and 2180 eligible girls in schools randomized to class-based and age-based delivery, respectively. HPV vaccine coverage was 84.7% for dose 1, 81.4% for dose 2, and 76.1% for dose 3. For each dose, coverage was higher in class-based schools than in age-based schools (dose 1: 86.4% vs 82.0% [P = .30]; dose 2: 83.8% vs 77.8% [P = .05]; and dose 3: 78.7% vs 72.1% [P = .04]). Vaccine-related adverse events were rare. Reasons for not vaccinating included absenteeism (6.3%) and parent refusal (6.7%). School absenteeism rates prior to vaccination ranged from 8.1% to 23.5%.

Conclusions. HPV vaccine can be delivered with high coverage in schools in sub-Saharan Africa. Compared with age-based vaccination, class-based vaccination located more eligible pupils and achieved higher coverage. HPV vaccination did not increase absenteeism rates in selected schools. Innovative strategies will be needed to reach out-of-school girls.

Clinical Trials Registration. NCT01173900.

Nature Medicine
August 2012, Volume 18 No 8 pp1155-1302
http://www.nature.com/nm/journal/v18/n7/index.html

Opinion
The time for pharmaceutical compulsory licensing has expired
Randall Kuhn & Reed F Beall
doi:10.1038/nm0812-1168
Published online
06 August 2012

The compulsory license mechanism is broken and will not bring drug access to the world’s poorest nations. It’s time to consider another option—a tax levied on patents—to fund drugs for developing countries, rather than the erratic compulsory licensing mechanism.

Pharmacoeconomics
September 1, 2012 – Volume 30 – Issue 9  pp: 749-858
http://adisonline.com/pharmacoeconomics/pages/currenttoc.aspx

Systematic Review
Assessing the Quality of Pharmacoeconomic Studies in India: A Systematic Review
Desai, Pooja R.; Chandwani, Hitesh S.; Rascati, Karen L.
Pharmacoeconomics. 30(9):749-762, September 1, 2012.
doi: 10.2165/11590140-000000000-00000

Abstract:
Objective: The aim of the study was to evaluate the quality of pharmacoeconomic studies based in India.

Methods: A literature search was conducted using PubMed, MEDLINE, EconLit, PsycInfo and Google Scholar to identify published work on pharmacoeconomics studies based in India. Articles were included if they were original studies that evaluated pharmaceuticals, were based in India and were conducted between 1990 and 2010. Two reviewers independently reviewed the articles using a subjective 10-point quality scale in addition to the 100-point Quality of Health Economic Studies (QHES) questionnaire.

Results: Twenty-nine articles published between 1998 and May 2010 were included in the review. The included articles were published in 23 different journals. Each article was written by an average of five authors. The mean subjective quality score of the 29 articles was 7.8 (standard deviation [SD] = 1.3) and the mean QHES scores for the complete pharmacoeconomic studies (n = 24) was 86 (SD = 6). The majority of authors resided in India (62%) at the time of publication and had a medical background (90%). The quality score was significantly (p ≤ 0.05) related to the country of residence of the primary author (non-India = higher) and the study design (randomized controlled trials = higher).

Conclusion: Although the overall quality scores were comparable to (e.g. Nigeria) or higher than (e.g. Zimbabwe) similar studies in other developing countries, key features such as an explicit study perspective and the use of sensitivity analyses were missing in about 40% of the articles. The need for economic evaluation of pharmaceuticals is imperative, especially in developing countries such as India as this helps decision makers allocate scarce resources in a justifiable manner.

PLoS One
[Accessed 11 August 2012]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Optimizing Reactive Responses to Outbreaks of Immunizing Infections: Balancing Case Management and Vaccination
Petra Klepac, Ottar N. Bjørnstad, C. Jessica E. Metcalf, Bryan T. Grenfell
PLoS ONE: Research Article, published 10 Aug 2012 10.1371/journal.pone.0041428

Abstract 
For vaccine-preventable infections, immunization generally needs to be supplemented by palliative care of individuals missed by the vaccination. Costs and availability of vaccine doses and palliative care vary by disease and by region. In many situations, resources for delivery of palliative care are independent of resources required for vaccination; however we also need to consider the conservative scenario where there is some trade-off between efforts, which is of potential relevance for resource-poor settings. We formulate an SEIR model that includes those two control strategies – vaccination and palliative care. We consider their relative merit and optimal allocation in the context of a highly efficacious vaccine, and under the assumption that palliative care may reduce transmission. We investigate the utility of a range of mixed or pure strategies that can be implemented after an epidemic has started, and look for rule-of-thumb principles of how best to reduce the burden of disease during an acute outbreak over a spectrum of vaccine-preventable infections. Intuitively, we expect the best strategy to initially focus on vaccination, and enhanced palliative care after the infection has peaked, but a number of plausible realistic constraints for control result in important qualifications on the intervention strategy. The time in the epidemic when one should switch strategy depends sensitively on the relative cost of vaccine to palliative care, the available budget, and R0. Crucially, outbreak response vaccination may be more effective in managing low- diseases, while high R0 scenarios enhance the importance of routine vaccination and case management.

PLoS One
[Accessed 11 August 2012]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Human Papillomavirus Infection: Knowledge, Attitudes, and Behaviors among Lesbian, Gay Men, and Bisexual in Italy
Concetta P. Pelullo, Gabriella Di Giuseppe, Italo F. Angelillo
PLoS ONE: Research Article, published 08 Aug 2012 10.1371/journal.pone.0042856

Abstract 
Background
This cross-sectional study assess knowledge, attitudes, and behavior towards the human papillomavirus (HPV) and the vaccination among a random sample of 1000 lesbian, gay men, and bisexual women and men.

Methods
A face-to-face interview sought information about: socio-demographic characteristics, knowledge about HPV infection, perception of risk towards HPV infection and/or cervical, anal, and oropharyngeal cancers, perception of the benefits of a vaccination to prevent cervical, anal, and oropharyngeal cancers, sexual behaviors, health-promoting behaviors, and willingness to receive the HPV vaccine.

Results
Only 60.6% had heard about the HPV infection and this knowledge was significantly higher in female, in those being a member of a homosexual association, in those having had the first sexual experience at a younger age, in those having received information about the HPV infection from physicians, and in those having no need of information about HPV infection. A higher perceived risk of contracting HPV infection has been observed in those younger, lesbian and gay men, who have heard of HPV infection and knew the risk factors and its related diseases, who have received information about HPV infection from physicians, and who need information about HPV infection. Only 1.7% have undergone HPV immunization and 73.3% professed intent to obtain it in the future. The significant predictors of the willingness to receive this vaccine were belief that the vaccination is useful, perception to be at higher risk of contracting HPV infection, and perception to be at higher risk of developing cervical, anal, and oropharyngeal cancers.

Conclusions
Information and interventions are strongly needed in order to overcome the lack of knowledge about HPV infection and its vaccination. Inclusion of boys in the national vaccination program and initiate a catch-up program for men who have sex with men up to 26 years may reduce their burden of HPV-related disease.

PLoS One
[Accessed 11 August 2012]
http://www.plosone.org/article/browse.action;jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Understanding Reduced Rotavirus Vaccine Efficacy in Low Socio-Economic Settings
Benjamin A. Lopman, Virginia E. Pitzer, Rajiv Sarkar, Beryl Gladstone, Manish Patel, John Glasser, Manoj Gambhir, Christina Atchison, Bryan T. Grenfell, W. John Edmunds, Gagandeep Kang, Umesh D. Parashar
PLoS ONE: Research Article, published 06 Aug 2012 10.1371/journal.pone.0041720

Abstract 
Introduction
Rotavirus vaccine efficacy ranges from >90% in high socio-economic settings (SES) to 50% in low SES. With the imminent introduction of rotavirus vaccine in low SES countries, understanding reasons for reduced efficacy in these settings could identify strategies to improve vaccine performance.

Methods
We developed a mathematical model to predict rotavirus vaccine efficacy in high, middle and low SES based on data specific for each setting on incidence, protection conferred by natural infection and immune response to vaccination. We then examined factors affecting efficacy.

Results
Vaccination was predicted to prevent 93%, 86% and 51% of severe rotavirus gastroenteritis in high, middle and low SES, respectively. Also predicted was that vaccines are most effective against severe disease and efficacy declines with age in low but not high SES. Reduced immunogenicity of vaccination and reduced protection conferred by natural infection are the main factors that compromise efficacy in low SES.

Discussion
The continued risk of severe disease in non-primary natural infections in low SES is a key factor underpinning reduced efficacy of rotavirus vaccines. Predicted efficacy was remarkably consistent with observed clinical trial results from different SES, validating the model. The phenomenon of reduced vaccine efficacy can be predicted by intrinsic immunological and epidemiological factors of low SES populations. Modifying aspects of the vaccine (e.g. improving immunogenicity in low SES) and vaccination program (e.g. additional doses) may bring improvements.