This is the pdf version of Vaccines: The Week in Review  11 April 2011 comprising all the posts for this date:

Vaccines_The Week in Review_11 April 2011

WHO and partners were honored with the Ludwig Rajchman Prize of the Committee of the Scientific Council of the National Institute of Public Health of Poland for the research work validating the shake test for detecting freeze damage to adsorbed vaccines. WHO noted that “good temperature control during the storage and transport of vaccines is critical to ensure their potency and safety. Liquid formulations of aluminium-based vaccines against diphtheria, pertussis, tetanus, hepatitis B and Haemophilus influenzae type b, alone or in combination, should not be frozen. However, practices that expose vaccines to sub-zero temperatures are widespread in both developed and developing countries.

“The shake test is designed to determine whether adsorbed vaccines have been affected by freezing. Although widely practiced in the field by staff at all levels of the health system, prior to this research it had never been validated as a reference test by comparison to a “gold standard”, i.e. visual observation under a phase contrast microscope. The concordance in establishing the status of a vaccine as frozen or non-frozen was 100% between the microscopy test and the shake test performed by health-care workers. The results of the study fully support the hypothesis that the accuracy of the shake test does not vary by product, type of vaccine, vaccine manufacturer, aluminium content or expiry date.

The Ludwig Rajchman Prize “was established to commemorate Ludwig Rajchman, the first Director of the National Institute of Hygiene of Poland, in order to promote original achievements in public health research.”

http://www.who.int/immunization/newsroom/newsstory_award_shake_test/en/index.html

GAVI said the Democratic Republic of Congo (DRC) enhanced its immunization programme by including pneumococcal vaccines, initiating the expanded programme in two of the country’s 11 provinces. http://www.gavialliance.org/media_centre/press_releases/drc_pneumococcal.php

German Development Minister, Dirk Niebel, and Bill Gates, co-chair of the Bill & Melinda Gates Foundation, met in Berlin and signed an agreement “for close cooperation between the Federal Ministry for Economic Cooperation and Development, BMZ*, and the Gates Foundation” in the areas of “global health policy, agriculture and rural development, water and sanitation, urban development, as well as microfinance.” The Partnership “will commence with a joint increase to the GAVI Alliance with the commitment of the BMZ to increase its contribution through innovative bilateral contributions. The ministry will increase its funding by €14m in 2011 for childhood immunization. In turn, the Gates Foundation will match this amount through multilateral contributions to GAVI; the foundation will also match any further increase in funds for 2012 and 2013 should Germany announce these contributions ahead of the June GAVI Pledging Conference.”

http://www.gatesfoundation.org/press-releases/Pages/close-cooperation-bmz-110406.aspx

WHO noted World Malaria Day – 25 April 2011, stating that “approximately half of the world’s population is at risk of malaria, particularly those living in lower-income countries. It infects more than 500 million people per year and kills more than 1 million. The burden of malaria is heaviest in sub-Saharan Africa but the disease also afflicts Asia, Latin America, the Middle East and even parts of Europe.” http://www.who.int/mediacentre/events/annual/malaria/en/index.html

Related links

More about World Malaria Day

Roll Back Malaria Partnership

WHO Global Malaria Programme

Topical overview: malaria

Sabin Vaccine Institute and Eisai Co., Ltd. announced a memorandum of understanding (MOU) “to advance the development of vaccines to combat neglected tropical diseases (NTDs), a group of parasitic and bacterial infections that afflict more than 1.4 billion people who live on less than $1.25 a day.” Sabin and Eisai “will collaborate on research and development for NTD vaccines and help deepen the pharmaceutical industry’s role in global health initiatives for NTDs. In addition, Sabin Vaccine Development-a product development partnership of the Sabin Vaccine Institute-intends to test Eisai’s vaccine adjuvant technology in preclinical studies with antigens that are currently in development. Eisai’s adjuvant technology may serve as a valuable tool for enhancing immunogenicity of Sabin’s vaccine antigens for human hookworm infection and schistosomiasis.”

http://sabin.org/news-resources/releases/2011/04/05/sabin-vaccine-institute-and-eisai-co-ltd-announce-collaboration-a

The Weekly Epidemiological Record (WER) for 8 April 2011, vol. 86, 15 (pp 141–152) includes: Outbreak news – Outbreak of poliomyelitis, Republic of the Congo, September 2010–February 2011; Meningitis in Burkina Faso, Chad, Niger, Nigeria and Ghana: 2010 epidemic season

http://www.who.int/entity/wer/2011/wer8615.pdf

The MMWR for April 8, 2011 / Vol. 60 / No. 13 includes:
– Measles Imported by Returning U.S. Travelers Aged 6–23 Months, 2001–2011

– Assessment of ESSENCE Performance for Influenza-Like Illness Surveillance After an Influenza Outbreak — U.S. Air Force Academy, Colorado, 2009

– Assessing Completeness of Perinatal Hepatitis B Virus Infection Reporting Through Comparison of Immunization Program and Surveillance Data — United States

– Notes from the Field: Measles Outbreak — Hennepin County, Minnesota, February–March 2011

http://www.cdc.gov/mmwr/pdf/wk/mm6013.pdf

Twitter Watch
A selection of items of interest this week from a variety of twitter feeds. This capture is highly selective and by no means intended to be exhaustive.

ClintonTweet Clinton Foundation
PHOTO: President Clinton announces National Cholera Education & Awareness Campaign in #Haiti: http://ow.ly/i/a9Iw

SingerPeter Peter Singer
Future MDGs? Rohinton Medhora has some interesting ideas: http://blog.idrc.ca/medhora/ @IDRC_CRDI

eurovaccine ECDC Eurovaccine
Public health & illegal migration are interconnected say EU Health Ministers; seeking EU-wide help http://bit.ly/earMDV

GAVIAlliance GAVI Alliance
Introduction of pneumococcal #vaccines in Yemen http://ht.ly/4urx5

GAVIAlliance GAVI Alliance
RT @unfoundation: UN-backed partners including @GAVIAlliance @UNICEF @whonews help DR Congo introduce #pneumonia vaccine http://ow.ly/4sP0P

VaccinesToday VaccinesToday
Interesting speech by @ECDC_EU chief Marc Sprenger addressing EU Health Ministers http://tinyurl.com/6ebd2b9

The Lancet
Apr 09, 2011  Volume 377  Number 9773  Pages 1211 – 1288
http://www.thelancet.com/journals/lancet/issue/current

Comment
A cytomegalovirus vaccine tames the troll of transplantation
Mark R Schleiss

Health-systems strengthening: current and future activities
Jesper Sundewall, R Chad Swanson, Arvind Betigeri, David Sanders, Téa E Collins, George Shakarishvili, Ruairi Brugha

There is strong consensus in the global health community, among donors, recipient countries, and policy makers, about the need for health-system strengthening in low-income and middle-income countries.1,2 Traditional donors and new disease-specific aid initiatives, such as the GAVI Alliance, the US President’s Emergency Plan for AIDS Relief (PEPFAR), and the Global Fund to Fight AIDS, Tuberculosis and Malaria, are directly or indirectly funding health-system strengthening. The need for greater capacity to produce a better evidence-base for health-system strengthening has resulted in the first global symposium on health-systems research, to be held in Montreux, Switzerland, in November, 2010.

The Lancet
Apr 09, 2011  Volume 377  Number 9773  Pages 1211 – 1288
http://www.thelancet.com/journals/lancet/issue/current

Articles
Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
Paul D Griffiths, Anna Stanton, Erin McCarrell, Colette Smith, Mohamed Osman, Mark Harber, Andrew Davenport, Gareth Jones, David C Wheeler, James O’Beirne, Douglas Thorburn, David Patch, Claire E Atkinson, Sylvie Pichon, Paul Sweny, Marisa Lanzman, Elizabeth Woodford, Emily Rothwell, Natasha Old, Ruth Kinyanjui, Tanzina Haque, Sowsan Atabani, Suzanne Luck, Steven Prideaux, Richard SB Milne, Vincent C Emery, Andrew K Burroughs

Summary
Background
Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.

Methods
We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov, NCT00299260.

Findings
67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593—23 840) versus 86 (63—118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503—217 272) versus 24 682 (17 909—34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients.

Interpretation
Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients.

Funding
National Institute of Allergy and Infectious Diseases, Grant R01AI051355 and Wellcome Trust, Grant 078332. Sponsor: University College London (UCL).

The Lancet
Apr 09, 2011  Volume 377  Number 9773  Pages 1211 – 1288
http://www.thelancet.com/journals/lancet/issue/current

Seminar
Viral pneumonia
Olli Ruuskanen, Elina Lahti, Lance C Jennings, David R Murdoch

Summary
About 200 million cases of viral community-acquired pneumonia occur every year—100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient’s age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.

Nature
Volume 472 Number 7341 pp5-130  7 April 2011
http://www.nature.com/nature/current_issue.html

Rare-disease project has global ambitions
Consortium aims for hundreds of new therapies by 2020.
Alison Abbott

Prader–Willi syndrome. Fabry renal disease. Spinocerebellar ataxia. Few people have heard of these and the other ‘rare diseases’, some of which affect only hundreds of patients worldwide. Drug companies searching for the next blockbuster pay them little attention. But the diseases are usually incurable — and there are thousands of them.

This week, the US National Institutes of Health (NIH) and the European Commission launch a joint assault on these conditions, whose small numbers of patients make it difficult to test new treatments and develop diagnostic methods. The International Rare Disease Research Consortium being formed under the auspices of the two bodies has the ambitious goal of developing a diagnostic tool for every known rare disease by 2020, along with new therapies to treat 200 of them. At the launch meeting in Bethesda, Maryland, on 6–8 April, prospective partners will map out research strategies to identify diagnostic biomarkers, design clinical trials and coordinate genome sequencing in these diseases. Nearly all the rare diseases, of which there are an estimated 6,000–8,000, are the result of small genetic changes.

Nature Medicine
April 2011, Volume 17 No 4
http://www.nature.com/nm/index.html

News
Straight talk with…Seth Berkley – p404
Roxanne Khamsi
doi:10.1038/nm0411-404

On 13 June, donors to the GAVI Alliance will gather in London to affirm their commitment to fund immunizations in the developing world. At the meeting, participants will address the estimated $3.7 billion financing gap needed over the next four years to scale up childhood vaccination efforts to meet the demand forecasts for those countries that receive assistance from the Geneva-based organization. But attendees of the pledging conference will also be discussing something not on the formal agenda: the announcement last month that Seth Berkley, who founded and heads the International AIDS Vaccine Initiative (IAVI), will take over the helm of the alliance in August.
Berkley will lead a unique chapter in GAVI’s development as the organization narrows in on the looming deadline set by Millennium Development Goal 4, which aims to reduce child mortality by two thirds by 2015. Yet, in a sense, these efforts will be a continuation of the work Berkley has fostered at IAVI since he formally launched the New York–based nonprofit in 1996. Berkley, an epidemiologist who previously held jobs with the Rockefeller Foundation, the Carter Center and the US Centers for Disease Control and Prevention, has witnessed ups and downs in the vaccination field, from the disappointing STEP trial in 2007 to the more recent good news from the 2009 Thai study, which reported as much as 31% protection against HIV. Roxanne Khamsi spoke with Berkley about what he has learned in his quest for a preventative shot against AIDS.

New England Journal of Medicine
April 7, 2011  Vol. 364 No. 14
http://content.nejm.org/current.shtml

An Inactivated Cell-Culture Vaccine against Yellow Fever
T.P. Monath and Others

PLoS Medicine
(Accessed 10 April 2011)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study
Stefan Flasche, Albert Jan Van Hoek, Elizabeth Sheasby, Pauline Waight, Nick Andrews, Carmen Sheppard, Robert George, Elizabeth Miller Research Article, published 05 Apr 2011
doi:10.1371/journal.pmed.1001017

This is the pdf version of Vaccines: The Week in Review  4 April 2011 comprising all the posts below for this date.

Vaccines_The Week in Review_4 April 2011

The Fourth IHR Review Committee meeting convened 28-30 March 2011 in Geneva. The meeting considered a preview document prepared by the Review Committee on the Functioning of the International Health Regulations (2005) in Relation to Pandemic (H1N1) 2009.  Meeting materials include:

– Agenda of the meeting  pdf, 19kb

– Preview Report of the Review Committee  pdf, 924kb

– Note from the Chairman of the Review Committee  pdf, 15kb

WHO Director-General Dr Margaret Chan responded to the preliminary assessment of WHO’s handling of the influenza pandemic in remarks delivered at the fourth meeting of the Review Committee of the International Health Regulations on 28 March 2011.

[Excerpt]

“…For me, personally, as head of this agency, the assessment of the pandemic response needed to address two absolutely critical questions and to give everyone a firm answer.

First, did WHO make the right call? Was this a real pandemic or not?

Second, were WHO decisions, advice, and actions shaped in any way by ties with the pharmaceutical industry?

In other words, did WHO declare a fake pandemic in order to line the pockets of industry?

The document exonerates WHO on both counts.

Had the Committee identified shortcomings in either of these two areas, such findings would have raised grave questions about the Organization’s neutrality, technical credibility, and integrity.

At no point does the report question the decision to declare a pandemic. As noted, evidence from early outbreaks led many experts at WHO and elsewhere to anticipate a potentially more severe pandemic than subsequently occurred.

As also noted, WHO did not rush to declare a pandemic, but did so only when fully satisfied that all criteria for doing so had been met.

As stated, “no critic of WHO has produced any direct evidence of commercial influence on decision-making.” The Committee found “no evidence of attempted or actual influence by commercial interests on advice given to or decisions made by WHO.”

The report suggests that WHO responded with insufficient vigour to criticism that questioned its integrity. It is in this spirit that I am responding, hopefully with sufficient vigour, on these two specific points.

Ladies and gentlemen,

As the document clearly states: “The world is ill-prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public health emergency…”

http://www.who.int/dg/speeches/2011/ihr_review_20110328/en/index.html

Sabin Vaccine Institute convened the Global Colloquium on Sustainable Immunization Financing, held 28-29 March 2011, in Addis Ababa, Ethiopia. Sabin said that this first-ever high-level meeting, focused on sustainable immunization financing, brought together over 75 delegates representing ministries of health and finance and parliaments in 18 African, Asian and Latin American countries. Dr. Ciro de Quadros, Sabin Executive Vice President, commented, “We know that effective vaccination programs contribute to healthier, more productive societies. Immunization is one of the best investments a country can make. Our goal for each country we work with is to identify long-term sources of financing and assure a fiscally sustainable national immunization program.”  Sabin noted that as national immunization programs expand and new vaccines become available, increasing costs place strains on low-income countries, and that possible sustainable funding mechanisms include increased funding from current government revenues, development of decentralized immunization budgets and the creation of national immunization trust funds. To date, six of the countries attending the colloquium – Sierra Leone, Senegal, the Democratic Republic of Congo, Mali, Cambodia and Nepal – have achieved government budgetary increases for routine immunizations following targeted SIF advocacy efforts and nine countries are preparing new immunization legislation that will safeguard immunization funding, Sabin said.

The 18 countries participating in the colloquium include SIF’s 15 pilot countries-Cambodia, Cameroon, the Democratic Republic of Congo, Ethiopia, Kenya, Liberia, Madagascar, Mali, Nepal, Nigeria, Rwanda, Senegal, Sierra Leone, Sri Lanka and Uganda-as well as Bolivia, Colombia and El Salvador. Funded by the Bill & Melinda Gates Foundation, the Sustainable Immunization Financing Program “has been working since 2007 to ensure accessibility and affordability of immunizations, an essential public health good, in each of its 15 pilot countries.”

http://sabin.org/news-resources/releases/2011/03/28/sabin-vaccine-institute-convenes-global-colloquium-sustainable-im

WHO announced Immunization Week 2011, noting that for the first time countries across the WHO regions of Africa, Americas, Eastern Mediterranean, Europe and the Western Pacific are taking part in simultaneous immunization weeks. WHO said that starting on 23 April, “countries unite under the umbrella of immunization week and implement activities to raise awareness, inform and engage key audiences on the value, importance and challenges regarding immunization. These activities include dissemination of information, education and communication materials; and training sessions, workshops, exhibitions, press conferences and round-table discussions with political decision-makers.” In addition, vaccination services such as tracking of unvaccinated people, implementing large-scale vaccination campaigns and using Child Health Days to deliver an integrated package of life-saving health interventions will take place. These health interventions include: providing vitamin A supplementation to boost children’s immune systems; provision of de-worming medicine; growth monitoring; and distribution of insecticide-treated nets to prevent malaria.

http://www.who.int/immunization/newsroom/events/immunization_week_2011/en/index.html

The GAVI Alliance announced that “to further increase transparency of the oversight of its cash-based support it will make public when it suspends a cash programme to investigate possible misuse of funds.” GAVI also announced that it has suspended funding to three cash-based programmes in Niger, Cote d’Ivoire, and Cameroon “after its oversight processes raised credible concerns about the use of funds in these programmes,” and that it had earlier informed its Board about an investigation of two cash programmes in Mali last year, which is expected to be completed in May 2011. Investigations have recently commenced in Niger and Cameroon, and will follow in Cote d’Ivoire once the political situation in the country improves. The amount under investigation in the suspended programmes totals approximately $18 million. The investigations “will determine how much, if any, of this has been misused.” The governments of Mali, Niger and Cameroon are fully cooperating with the investigations. GAVI noted that “although some cash programmes have been halted, GAVI is ensuring that children in these countries continue to receive life-saving vaccines.”

Helen Evans, GAVI interim CEO, said, “Our mission is to make sure life-saving vaccines reach even the poorest children and cash-support programmes help make that happen. But we do not tolerate any abuse of funds that puts children at risk.”    Between 2000 and 2010, GAVI said it delivered US$2.1 billion worth of vaccines and paid US$672 million in cash grants. During this period, cash programmes equaled about 24% of total disbursements but have dropped to approximately 15% over the past two years. In 2009 and 2010, 45 countries received cash grants. Of these, 39 are subject to GAVI’s financial management assessments. To date, 32 FMAs have been conducted, starting with those that are deemed to be of higher risk.

http://www.gavialliance.org/media_centre/statements/transparency.php

The U.S. Department of Health and Human Services launched Vaccines.gov – “an innovative new website to help parents and other consumers learn about the most effective way to protect themselves and their children from infectious diseases and learn about immunization.” The new site –– “brings together the best in federal resources on vaccine and immunizations to provide consumers with easy-to-understand health information specifically for their needs.”  Vaccines.gov was described as ”the first cross-government website devoted to providing consumer information about vaccines and immunization, combining content and expertise from agencies across the Department. It is the result of unprecedented collaboration among federal health and communications experts to offer online content about vaccine and immunization based on consumer needs.”  http://www.businesswire.com/news/home/20110330006388/en/HHS-Launches-Consumer-Focused-Immunization-Website

The Weekly Epidemiological Record (WER) for 1 April 2011, vol. 86, 14 (pp 129–140) includes: Measles outbreaks and progress towards meeting measles pre-elimination goals: WHO African Region, 2009–2010; Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2010

http://www.who.int/entity/wer/2011/wer8614.pdf

The MMWR for April 1, 2011 / Vol. 60 / No. 12 includes:

– Tetanus Surveillance — United States, 2001–2008

– Measles Outbreaks and Progress Toward Measles Preelimination — African Region, 2009–2010

– Announcements: Autism Awareness Month — April 2011

– Announcements: Epidemiology in Action: Intermediate Analytic Methods Course — May 31–June 1, 2011

– Announcements: STD Awareness Month — April 2011

Twitter Watch
A selection of items of interest this week from a variety of twitter feeds. This capture is highly selective and by no means intended to be exhaustive.

eurovaccine ECDC Eurovaccine
ECDC commits to help EU Member States in reaching under-vaccinated populations http://bit.ly/hQ6nKf #vaccine

usaid_info USAID
Statement by Amie Batson, Deputy Assistant Administrator for Global Health, before the House Appropriations S… http://1.usa.gov/hyMBQs

EndPolioNow EndPolioNow
Rotarians have raised about US$163.4 million for Rotary’s $200 Million Challenge to eradicate polio. http://cot.ag/a5lkhN #endpolionow

GAVIAlliance GAVI Alliance
News Update: GAVI Alliance steps up transparency – GAVI Alliance steps up transparency on oversight of its cash prog… http://ow.ly/1bYQh6

IHME_UW IHME at UW
Photos and video of presentations now available from the Global Health Metrics and Evaluation conference 2011! http://ghme.org/

HHSGov HHSGov
Check out the new http://www.vaccines.gov/ – a one-stop shop to learn abt recommended vaccines, get local immunization info, and more.

sabinvaccine Sabin Vaccine Inst.
Today we kicked off our two-day Sustainable Immunization FInancing Colloquium in Addis Ababa, Ethiopia, read more: http://ht.ly/4o6n4

British Medical Journal
2 April 2011 Volume 342, Issue 7800
http://www.bmj.com/content/current

Editorial
The production of generic drugs in India
James Love,

A new trade agreement with the EU would hinder access to drugs in developing countries

The European Union is negotiating a trade agreement with India, the consequences of which will be serious for billions of people living in developing countries. Government officials in India are focused on economic growth and are keen to complete a trade deal with the EU. In exchange for market access in other areas of the economy, the EU wants India, a country with very low per capita incomes, to embrace tough new rules on ownership and enforcement of intellectual property for medical inventions.

The negotiation is between two very different entities. The EU is now the world’s largest economy; its gross domestic product (GDP) was estimated at more than $16.4 trillion (£10.2 trillion; €11.8 trillion) in 2009—about 28% of the entire world’s GDP ⇑ .

India has a large population—estimated at nearly 1.16 billion in 2009, or 17% of the world’s population. This is also about the same as the population of Europe plus all other countries in the Organisation for Economic Co-operation and Development combined.

India’s GDP was estimated at $1.3 trillion in 2009, about 8% of the size of the EU economy. On a per capita basis, Indian incomes were 3.5% of those in Europe. At the bottom of the income distribution, the differences are even more stark. An estimated 317 million Indians live with incomes below the official poverty line—$12 a month for urban areas and $8 a month for rural areas.

In 1970, India eliminated patents on drug products. 1 This move enabled …

Clinical Infectious Diseases
Volume 52 Issue 8 April 15, 2011
http://www.journals.uchicago.edu/toc/cid/current

Ruben O. Donis and Nancy J. Cox
Editorial Commentary: Prospecting the Influenza Hemagglutinin to Develop Universal Vaccines
Clin Infect Dis. (2011) 52(8): 1010-1012 doi:10.1093/cid/cir129

(See the article by Sui et al, on pages 1003–1009 .)

Influenza pandemics are among the most serious infectious threats to public health. The 1918–1919 influenza pandemic caused up to 500,000 deaths during a single influenza season in the United States, representing the most fatalities within such a short period in US public health history. The 2009 H1N1 influenza pandemic caused much less mortality but nevertheless exposed important limitations of global pandemic preparedness. [ 1, 2, 3]. First, the 2009 H1N1 virus was not detected by animal health surveillance systems for >10 years, exposing the inadequacy of current surveillance for viruses in animals that have pandemic potential for humans [ 4]. Second, the emergence of a pandemic virus with the same HA and NA subtypes as viruses that had been circulating in humans for decades (seasonal H1N1 virus) underscored the need to better understand immunity to emerging influenza viruses in the human population [ 4]. Finally, the 2009 H1N1 pandemic exposed our current inability to develop, manufacture, deliver, and administer billions of doses of vaccine directed against a newly emerging virus in the 4 months or less that would have been required to mitigate the impact of the spread of the 2009 H1N1 virus. [ 5]. Thus, several strategic changes in pandemic vaccine preparedness plans have been recommended [ 6]. The proposed changes are costly and often not affordable for low- and middle-income countries. Thus, sustainable long-term solutions will require the development of novel immunization strategies. The concept of a universal influenza vaccine that would elicit protection against a broad …

Emerging Infectious Diseases
Volume 17, Number 4–April 2011
http://www.cdc.gov/ncidod/EID/index.htm

Policy Reviews
Should Remaining Stockpiles of Smallpox Virus (Variola) Be Destroyed?
R.S. Weinstein

Abstract
In 2011, the World Health Organization will recommend the fate of existing smallpox stockpiles, but circumstances have changed since the complete destruction of these cultures was first proposed. Recent studies suggest that variola and its experimental surrogate, vaccinia, have a remarkable ability to modify the human immune response through complex mechanisms that scientists are only just beginning to unravel. Further study that might require intact virus is essential. Moreover, modern science now has the capability to recreate smallpox or a smallpox-like organism in the laboratory in addition to the risk of nature re-creating it as it did once before. These factors strongly suggest that relegating smallpox to the autoclave of extinction would be ill advised.

Human Vaccines
Volume 7, Issue 4    April 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/2/

SHORT REPORT
Development of a survey to identify vaccine-hesitant parents: The parent attitudes about childhood vaccines survey
Douglas J. Opel, Rita Mangione-Smith, James A. Taylor, Carolyn Korfiatis, Cheryl Wiese, Sheryl Catz and Diane P. Martin

Objective: To develop a survey to accurately assess parental vaccine hesitancy.

Methods: An iterative process was used to develop the survey. First, we reviewed previous studies and surveys on parental health beliefs regarding vaccination to develop content domains and draft initial survey items. Focus groups of parents and pediatricians generated additional themes and survey items. Six immunization experts reviewed the items in the resulting draft survey and ranked them on a 1-5 scale for significance in identifying vaccine-hesitant parents (5 indicative of a highly significant item). The lowest third of ranked items were dropped. The revised survey was pretested with 25 parents to assess face validity, usability, and item understandability.

Results: The initial survey contained 17 items in 4 content domains: (1) immunization behavior; (2) beliefs about vaccine safety and efficacy; (3) attitudes about vaccine mandates and exemptions; and (4) trust. Focus group data yielded an additional 10 survey items. Expert review of the survey resulted in the deletion of 9 of 27 items and revisions to 11 of the remaining 18 survey items. Parent pretesting resulted in the deletion of 1 item, the addition of 1 item, the revision of 4 items, and formatting changes to enhance usability. The final survey contains 18 items in the original 4 content domains.

Conclusions: The Parent Attitudes about Childhood Vaccines survey was constructed using qualitative methodology to identify vaccine-hesitant parents and has content and face validity. Further psychometric testing is needed.

Human Vaccines
Volume 7, Issue 4    April 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/2/

Cost of pneumococcal infections and cost-effectiveness analysis of pneumococcal vaccination at risk adults and elderly in Turkey
Open Access Article
Levent Akin, Mehmet Kaya, Serdar Altinel and Laure Durand

Pneumococcal infections have a substantial burden in Turkey, particularly in the elderly (>60 years) and at-risk adults (18–59 years). VCR are low at approximately 2%. The first aim of this study was the evaluation of the burden of pneumococcal infections (pneumonia and bacteremia) from a public payer perspective in elderly and at-risk adults. The second aim was the evaluation of cost effectiveness of implementing a large PPV program in these populations. A decision tree model was employed using demographic and epidemiological input obtained from Turkish official sources and international literature. Vaccination was assumed to protect for 5 years with 60% and 50% effectiveness against BPP in elderly and at-risk adults respectively. Vaccination effectiveness of 21% against NBPP was assumed for both populations. Costs input were obtained from a previous study conducted between 2002 and 2008 in a public university hospital in Ankara, Turkey. Univariate sensitivity analyses and Monte-Carlo simulations were performed. The vaccination program was cost effective and cost saving compared to no vaccination, pneumococcal vaccination with 60% coverage led to a mean of 4,695 LYG in the elderly and 2,134 LYG in at-risk adults with 40% coverage. Mean incremental savings reached 45.4 million YTL in the elderly and 21.8 million YTL in at-risk adults. This analysis suggests that pneumococcal vaccination of elderly and at-risk adults is associated with a positive return on investment from a public payer perspective and supports the continued recommendation of pneumococcal vaccines, as well as their full funding in Turkey.

Human Vaccines
Volume 7, Issue 4    April 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/2/

Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children
Hitt J. Sharma, Sangita Yadav, Sanjay K. Lalwani, Subhash V. Kapre, Suresh S. Jadhav, Anita Chakravarty, Sameer S. Parekh, Sonali Palkar, Subodh H. Bhardwaj, Gajanan S. Namjoshi and Vikas Verma

Objective: An open label, controlled clinical study was conducted in Indian infants aged 6-14 weeks to compare the immunogenicity and safety of a reconstituted pentavalent vaccine (DTwP-HBV+Hib) of Serum Institute of India Ltd (SIIL) with TritanrixHB+Hiberix vaccine of Glaxo Smithkline (GSK).

Methods: Eligible infants were randomized to receive three doses of the study / comparator vaccine. The vaccines were reconstituted prior to administration, by mixing DTwP-HBV (liquid) with the Hib (lyophilized) vaccine. IgG antibody titres were assessed by ELISA at baseline and after one month following the 3-dose primary immunization schedule. Safety was evaluated after each dose. Further, safety and immunogenicity was also evaluated following a booster dose in the same cohort of children (aged between 15-24 months).

Setting: Tertiary-care hospitals in India

Important outcome measures: Immunogenicity and safety following a 3-dose primary vaccination series and a booster vaccination.

Results: Post-primary immunization, 100% seroprotection was noted for Diphtheria, Tetanus, Hepatitis B and PRP-Hib components in both the vaccine groups. For pertussis, response was 96.1% in SIIL and 95.4% in GSK group. The overall safety profile as well as persistence of antibodies against all vaccine components up to the time of booster immunization was comparable between the SIIL and GSK groups. A marked rise of all antibody concentrations indicated effective priming. The booster dose was safe, well tolerated with a significant increase in antibody concentrations of all the vaccine antigens in both the groups.

Conclusion: DTwP-HBV+Hib vaccine of SIIL was found to be safe and immunogenic. This Indian vaccine compared well with the licensed vaccine and is a cost-effective alternative for incorporating into the immunization schedule of various countries so as to control worldwide Hepatitis B and Hib infections.

Human Vaccines
Volume 7, Issue 4    April 2011
http://www.landesbioscience.com/journals/vaccines/toc/volume/7/issue/2/

Commentaries
Provenge: Revolutionary technology or ethical bust?
Justin B. Dickerson

Sipuleucel-T (known by the trade name, “Provenge”) is the first prostate cancer vaccine approved by the Food and Drug Administration (FDA), and represents a new type of cancer therapy termed, Autologous Cellular Immunotherapy (ACT). This therapy has been described as a revolution in technology by clinicians and researchers alike. However, policy-makers and health economists question the efficacy of such treatment given its costs, while mainstream media often bemoan Provenge as yet another example of a healthcare system gone awry. This paper examines the debate for and against Provenge, and discusses why Medicare adoption of payment protocols for the vaccine may violate the egalitarian and feminist principles of distributive justice theory. The paper also acknowledges the larger context of the Provenge debate within the bioethical community; that is, how much should society be willing to invest to prevent death? The paper concludes by arguing for a more thorough ethical review of such new technologies by policy-makers prior to the adoption of funding protocols.

The Lancet Infectious Disease
Apr 2011  Volume 11  Number 4  Pages 253 – 332
http://www.thelancet.com/journals/laninf/issue/current

Towards a conceptual framework to support one-health research for policy on emerging zoonoses
Richard Coker, Jonathan Rushton, Sandra Mounier-Jack, Esron Karimuribo, Pascal Lutumba, Dominic Kambarage, Dirk U Pfeiffer, Katharina Stärk, Mark Rweyemamu

Summary
In the past two decades there has been a growing realisation that the livestock sector was in a process of change, resulting from an expansion of intensive animal production systems and trade to meet a globalised world’s increasing demand for livestock products. One unintended consequence has been the emergence and spread of transboundary animal diseases and, more specifically, the resurgence and emergence of zoonotic diseases. Concurrent with changes in the livestock sector, contact with wildlife has increased. This development has increased the risk of transmission of infections from wildlife to human beings and livestock. Two overarching questions arise with respect to the real and perceived threat from emerging infectious diseases: why are these problems arising with increasing frequency, and how should we manage and control them? A clear conceptual research framework can provide a guide to ensure a research strategy that coherently links to the overarching goals of policy makers. We propose such a new framework in support of a research and policy-generation strategy to help to address the challenges posed by emerging zoonoses.

New England Journal of Medicine
March 31, 2011  Vol. 364 No. 13
http://content.nejm.org/current.shtml

Perspective
Teaching Clinicians about Drugs — 50 Years Later, Whose Job Is It?
J. Avorn

[Free Full Text]

PLoS Medicine
(Accessed 3 April 2011)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Towards Open and Equitable Access to Research and Knowledge for Development
Leslie Chan, Barbara Kirsop, Subbiah Arunachalam Essay, published 29 Mar 2011
doi:10.1371/journal.pmed.1001016

Summary Points
Unequal access to and distribution of public knowledge is governed by Northern standards and is increasingly inappropriate in the age of the networked “Invisible College”.

Academic journals remain the primary distribution mechanism for research findings, but commercial journals are largely unaffordable for developing countries; local journals—more relevant to resolving problems in the South—are near-invisible and under-valued.

Donor solutions are unsustainable, are governed by markets rather than user needs, and instil dependency.

Open access is sustainable and research driven and builds independence and the capacity to establish a strong research base; it is already converting local journals to international journals.

However, as open access becomes the norm, standards for the assessment of journal quality and relevance remain based on Northern values that ignore development needs and marginalise local scholarship.

Science Translational Medicine
30 March 2011 vol 3, issue 76
http://stm.sciencemag.org/content/current

Commentary – Therapeutics Discovery
The Precompetitive Space: Time to Move the Yardsticks
Thea Norman, Aled Edwards, Chas Bountra, and Stephen Friend
30 March 2011: 76cm10

Abstract
Industry, government, patient advocacy groups, public funders, and academic thought leaders met in Toronto, Canada, to set into motion an initiative that addresses some of the scientific and organizational challenges of modern therapeutics discovery. What emerged from the meeting was a public-private partnership that seeks to establish proof of clinical mechanism (POCM) for selected “pioneer” disease targets using lead compounds—all accomplished in the precompetitive space. The group will reconvene in April 2011 to create a business plan that specifies the generation of two positive POCM results per year.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 16  pp. 2823-3092 (5 April 2011)

Editorial
Why not destroy the remaining smallpox virus stocks?
Pages 2823-2824
J. Michael Lane, Gregory A. Poland

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 16  pp. 2823-3092 (5 April 2011)

Short Communications
Effectiveness of age-based strategies to increase influenza vaccination coverage among high risk subjects in Madrid (Spain)
Pages 2840-2845
Rodrigo Jiménez-García, Cristina Rodríguez-Rieiro, Valentín Hernández-Barrera, Ana Lopez de Andres, Agustin Rivero Cuadrado, Angel Rodriguez Laso, Pilar Carrasco-Garrido

Abstract
We aim to assess the effectiveness of age-based strategies to increase influenza vaccination coverage among high risk subjects. To do so, we describe and compare the influenza vaccination coverage in the 2006/2007 campaign between the Autonomous Community of Madrid (ACM), where in year 2005 the recommendation was extended by 5 years to cover all those aged 60 and over, and other regions of Spain where the universally recommended age was 65 years and above.

We used individualized secondary data provided by two surveys carried out in 2007 in ACM and in the rest of Spain. The total number of subjects included in the study was 21,948. For the 60–64 years age group influenza vaccination coverage was significantly higher 40.1% (CI 95% 36.4–43.8) in ACM residents than among residents in the Rest of Spain 29.1% (CI 95% 24.5–33.7). The difference in vaccine uptake was even greater, 59% (CI 95% 51.8–66.2) vs. 43.5%(CI 95% 34.3–52.7), when we compared subjects who suffered a chronic condition, which represents an indication for the anti-influenza vaccination. The results of the multivariate analysis show that the probability of a subject aged 60–64 living in ACM of being vaccinated was almost two times higher (OR 1.95 CI 95% 1.46–2.61) than a person of the same age who lived in a region of Spain where the universal recommendation for influenza vaccine started at 65 years.

In conclusion, the available evidence indicates the effectiveness of age-based strategies to increase influenza vaccination coverage among high risk subjects aged 60–64 years in our population.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 16  pp. 2823-3092 (5 April 2011)

Implementation of mandatory immunisation of healthcare workers: Observations from New South Wales, Australia

Original Research Article
Pages 2895-2901
Charles Helms, Julie Leask, Spring Cooper Robbins, Maria Yui Kwan Chow, Peter McIntyre

Abstract
Objective
To identify factors influencing implementation of a state-wide mandatory immunisation policy for healthcare workers (HCWs) in New South Wales (NSW), Australia, in 2007. Vaccines included were measles, mumps, rubella, varicella, hepatitis B, diphtheria, tetanus and pertussis, but not influenza.

Methods
We evaluated the first 2 years of this policy directive in 2009. A qualitative study was conducted among 4 stakeholder groups (the central health department, hospitals, health professional associations, and universities). 58 participants were identified using maximum variation sampling and data were analysed using a hierarchical thematic framework. Quantitative data on policy compliance were reviewed at the regional level.

Results
Success in policy implementation was associated with effective communication, including support of clinical leaders, provision of free vaccine, access to occupational health services which included immunisation, and appropriate data collection and reporting systems. Achieving high vaccine uptake was more challenging with existing employees and with smaller institutions.

Conclusion
These findings may apply to other jurisdictions in Australia or internationally considering mandatory approaches to HCW vaccination.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 16  pp. 2823-3092 (5 April 2011)

Workplace efforts to promote influenza vaccination among healthcare personnel and their association with uptake during the 2009 pandemic influenza A (H1N1)

Original Research Article
Pages 2978-2985
Katherine Harris, Jürgen Maurer, Carla Black, Gary Euler, Srikanth Kadiyala

Abstract
Background
Survey data suggest that, in a typical year, less than half U.S. healthcare personnel (HCP) are vaccinated for influenza. We measured workplace efforts to promote influenza vaccination among HCP in the U.S. and their association with seasonal and pandemic vaccination during the 2009–10 influenza season.

Methods
Self-reported survey data collected in June 2010 from eligible HCP (n = 1714) participating in a nationally representative, online research panel. HCP eligible for participation in the survey were those reporting as patient care providers and/or working in a healthcare setting. The survey measured workplace exposure to vaccination recommendations, vaccination requirements, on-site vaccination, reminders, and/or rewards, and being vaccinated for seasonal or H1N1 influenza.

Results
At least two-thirds of HCP were offered worksite influenza vaccination; about one half received reminders; and 10% were required to be vaccinated. Compared to HCP in other work settings, hospital employees were most (p < 0.001) likely to be the subject to efforts to promote vaccination. Vaccination requirements were associated with increases in seasonal and pandemic vaccination rates of between 31 and 49% points (p < 0.005). On-site vaccination was associated with increases in seasonal and pandemic vaccination of between 13 and 29% points (p < 0.05). Reminders and incentives were not associated with vaccination.

Conclusions
Our findings provide empirical support for vaccination requirements as a strategy for increasing influenza vaccination among HCP. Our findings also suggest that making influenza vaccination available to HCP at work could increase uptake and highlight the need to reach beyond hospitals in promoting vaccination among HCP.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 29, Issue 16  pp. 2823-3092 (5 April 2011)

Intussusception following rotavirus vaccine administration: Post-marketing surveillance in the National Immunization Program in Australia

Original Research Article
Pages 3061-3066
J.P. Buttery, M.H. Danchin, K.J. Lee, J.B. Carlin, P.B. McIntyre, E.J. Elliott, R. Booy, J.E. Bines and for the PAEDS/APSU Study Group

Abstract
Introduction
In Australia, post-marketing surveillance for intussusception following vaccination commenced with funding of RotaTeq® and Rotarix® vaccines under the National Immunization Program (NIP) in July 2007.

Methods
Two active surveillance mechanisms (hospital-based case ascertainment and monthly reports from paediatricians) identified intussusception cases between 1st July 2007 and 31st December 2008 in four states. Linkage to vaccination records identified cases occurring within 1–7 and 1–21 days of rotavirus vaccination. Expected cases within the post-vaccination windows were calculated by applying rates of intussusception from national hospitalisation data over 6 years (mid-2000 to mid-2006), by age and state, to numbers vaccinated (by dose) according to the Australian Childhood Immunization Register.

Results
Combining exposure windows associated with all doses of rotavirus vaccine from 1 to 9 months of age, there was no evidence of an increased risk of intussusception following vaccination for either vaccine. However, in infants 1 to <3 months of age, there was suggestive evidence of excess intussusception cases 1–7 and 1–21 days following dose 1 (1–7 days: RotaTeq® relative risk (RR) = 5.3, 95% confidence interval [CI] 1.1,15.4; Rotarix® RR 3.5, 95% CI 0.7,10.1; 1–21 days: RotaTeq® RR 3.5, 95% CI 1.3, 7.6; Rotarix®RR 1.5, 95% CI 0.4, 3.9). There was no evidence that clinical outcome of intussusception occurring within 21 days of rotavirus vaccination differed from that in cases occurring later post-vaccination.

Conclusion
Although we found no overall increase in intussusception following receipt of rotavirus vaccine, there was some evidence of an elevated risk following the first dose of both vaccines. Larger population-based studies using linked databases are required to provide more definitive evidence.