Vaccine vials and wastage: introducing pneumococcal vaccines in developing countries

Human Vaccines
Volume 6, Issue 3  March 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/3/

Research Papers
Impact of wastage on single and multi-dose vaccine vials: Implications for introducing pneumococcal vaccines in developing countries
Divya Parmar, Elaine M Baruwa, Patrick Zuber and Souleymane Kone

Introduction: Pneumococcal conjugate vaccines are expensive relative to those in the EPI systems of low-income countries. The current single-dose presentation costs more to store in the cold chain relative to multi-dose presentations but also has lower wastage rates. It is, therefore, important to determine the optimal balance of vial size and storage costs after adjusting for wastage.

Objectives: To project the cost implications of wastage when vaccine wastage rates vary across vial sizes using country specific wastage data. Methods: For each potential vial size, we estimated cold chain costs and the cost of wasted vaccine doses using country level wastage data and projections of the price per dose of vaccine and cold chain storage.

Results: Only 19 (26%) of 72 GAVI eligible countries had analyzable wastage data at WHO/HQ. The median wastage rates for single, 2- and 10-dose vials were 5%, 7% and 10% respectively. However wastage varied between 1%-10%, 1%-27% and 4%-44% for single, 2- and 10-dose vials respectively. The increased variance for multi-dose vial wastage implied wastage costs potentially greater than the savings realized from lower storage volumes.

Conclusions: The optimal vial-size for PCV is dependent upon country specific wastage rates but few countries have these data. There may be a role for both single and multi-dose vials that is best determined by local management and storage capacities making local wastage data critical. Without effective wastage monitoring and control there is a risk that wastage costs will possibly exceed the savings from multi-dose vials’ lower storage costs.

Losing the Opportunity to Study Influenza Drugs

JAMA
Vol. 303 No. 9, pp. 813-902, March 3, 2010
http://jama.ama-assn.org/current.dtl

Losing the Opportunity to Study Influenza Drugs
Andrea Meyerhoff; Paul Lietman

[First 150 words per JAMA convention]
Shortly after 2009 influenza A(H1N1) emerged, we advocated for real-time clinical trials to make use of the rare opportunity—and an ethical imperative—to study influenza drugs while the pandemic is ongoing.1 Tran et al2 further emphasized this need for prospective clinical trials during the outbreak. Persistent gaps in knowledge about drugs to treat influenza and the recent decision by the US Food and Drug Administration (FDA) to issue an Emergency Use Authorization for peramivir,3 an unapproved drug, make this need even more acute.

The efficacy of oseltamivir and zanamivir, the main drugs available to treat influenza A(H1N1) in the United States, was based on findings that these drugs shorten the duration of flu symptoms by 1.3 and 1.5 days, respectively. However, a recent meta-analysis of 12 clinical trials of oseltamivir suggested that this drug did not reduce the rate of pneumonia in . . .

Household Transmission of 2009 Influenza A (H1N1)

Journal of Infectious Diseases
1 April 2010  Volume 201, Number 7
http://www.journals.uchicago.edu/toc/jid/current

Major Articles and Brief Reports
Viruses
Household Transmission of 2009 Influenza A (H1N1) Virus after a SchoolBased Outbreak in New York City, April–May 2009
Anne Marie France, Michael Jackson, Stephanie Schrag, Michael Lynch, Christopher Zimmerman, Matthew Biggerstaff, and James Hadler

Abstract
In April 2009, an outbreak due to infection with the 2009 pandemic influenza A (H1N1) virus (pH1N1) was investigated in a New York City high school. We surveyed household contacts of ill students to characterize the extent of transmission within households, identify contact groups at highest risk for illness, and assess the potential for preventing household transmission. Influenza‐like illness (ILI) was reported by 79 of 702 household contacts (11.3% attack rate). Multivariate analysis showed that older age was protective: for each increasing year of age, the risk of ILI was reduced 5%. Additional protective factors included antiviral prophylaxis and having had a household discussion about influenza. Providing care for the index case patient and watching television with the index case patient were risk factors among parents and siblings, respectively. Fifty percent of cases occurred within 3 days of onset of illness in the student. These factors have implications for mitigating the impact of pH1N1 transmission.

7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults

New England Journal of Medicine
Volume 362 — March 4, 2010 — Number 9
http://content.nejm.org/current.shtml

Original Articles
A Trial of a 7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults
N. French and Others

ABSTRACT
Background
Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed.

Methods
In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A.

Results
From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003).

Conclusions
The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731

Patient-Held Vaccination Records and Coverage Rates

Pediatrics
March 2010 / VOLUME 125 / ISSUE 3
http://pediatrics.aappublications.org/current.shtml

Articles
Are Patient-Held Vaccination Records Associated With Improved Vaccination Coverage Rates?
James T. McElligott and Paul M. Darden

OBJECTIVE The goal was to determine whether patient-held vaccination records improve vaccination rates.

METHODS The public-use files of the 2004–2006 National Immunization Survey, a national, validated survey of households with children 19 to 35 months of age, were used. The main outcome was up-to-date (UTD) vaccination status (4 diphtheria-tetanus-acellular pertussis/diphtheria-tetanus vaccine, 3 poliovirus vaccine, 1 measles vaccine, 3 Haemophilus influenza type B vaccine, and 3 hepatitis B vaccine doses), and the main predictor was the use of a vaccination record. Control variables were race/ethnicity, maternal education, poverty status, language, number of children in the home, state of residence, and number of health care providers.

RESULTS Overall, 80.8% of children were UTD, and 40.8% of children had vaccination records. Children with vaccination records were more likely to be UTD (83.9% vs 78.6%; P < .0001). The largest effects associated with vaccination records were seen for children with multiple providers, comparing with and without a vaccination record (82.8% vs 71.9%; P < .0001), those with low maternal education, (81.6% vs 72.9%; P < .0001), and those with 4 children in the household, (76% vs 69.6%; P < .004). Logistic regression predicting UTD status and controlling for race/ethnicity, maternal education, poverty level, language, number of children in the home, and number of vaccine providers revealed the vaccination record to be associated with a 62% increase in the odds of UTD status (odds ratio: 1.62 [95% confidence interval: 1.49–1.77]).

CONCLUSIONS Use of patient-held vaccination records is an easily implemented strategy that is associated with increased immunization rates. A greater effect was seen in groups at risk for underimmunization. Methods to incorporate and to ensure effective use of these records should be implemented.

Drivers of Inequality in MDG Progress

PLoS Medicine
(Accessed 7 March 2010)
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

Drivers of Inequality in Millennium Development Goal Progress: A Statistical Analysis David Stuckler, Sanjay Basu, Martin McKee

Abstract
Background
Many low- and middle-income countries are not on track to reach the public health targets set out in the Millennium Development Goals (MDGs). We evaluated whether differential progress towards health MDGs was associated with economic development, public health funding (both overall and as percentage of available domestic funds), or health system infrastructure. We also examined the impact of joint epidemics of HIV/AIDS and noncommunicable diseases (NCDs), which may limit the ability of households to address child mortality and increase risks of infectious diseases.

Methods and Findings
We calculated each country’s distance from its MDG goals for HIV/AIDS, tuberculosis, and infant and child mortality targets for the year 2005 using the United Nations MDG database for 227 countries from 1990 to the present. We studied the association of economic development (gross domestic product [GDP] per capita in purchasing-power-parity), the relative priority placed on health (health spending as a percentage of GDP), real health spending (health system expenditures in purchasing-power-parity), HIV/AIDS burden (prevalence rates among ages 15–49 y), and NCD burden (age-standardised chronic disease mortality rates), with measures of distance from attainment of health MDGs. To avoid spurious correlations that may exist simply because countries with high disease burdens would be expected to have low MDG progress, and to adjust for potential confounding arising from differences in countries’ initial disease burdens, we analysed the variations in rates of change in MDG progress versus expected rates for each country. While economic development, health priority, health spending, and health infrastructure did not explain more than one-fifth of the differences in progress to health MDGs among countries, burdens of HIV and NCDs explained more than half of between-country inequalities in child mortality progress (R2-infant mortality = 0.57, R2-under 5 mortality = 0.54). HIV/AIDS and NCD burdens were also the strongest correlates of unequal progress towards tuberculosis goals (R2 = 0.57), with NCDs having an effect independent of HIV/AIDS, consistent with micro-level studies of the influence of tobacco and diabetes on tuberculosis risks. Even after correcting for health system variables, initial child mortality, and tuberculosis diseases, we found that lower burdens of HIV/AIDS and NCDs were associated with much greater progress towards attainment of child mortality and tuberculosis MDGs than were gains in GDP. An estimated 1% lower HIV prevalence or 10% lower mortality rate from NCDs would have a similar impact on progress towards the tuberculosis MDG as an 80% or greater rise in GDP, corresponding to at least a decade of economic growth in low-income countries.

Conclusions
Unequal progress in health MDGs in low-income countries appears significantly related to burdens of HIV and NCDs in a population, after correcting for potentially confounding socioeconomic, disease burden, political, and health system variables. The common separation between NCDs, child mortality, and infectious syndromes among development programs may obscure interrelationships of illness affecting those living in poor households—whether economic (e.g., as money spent on tobacco is lost from child health expenditures) or biological (e.g., as diabetes or HIV enhance the risk of tuberculosis).

Universal HIV Testing and Treatment

Science
5 March 2010  Vol 327, Issue 5970, Pages 1163-1284
http://www.sciencemag.org/current.dtl

News Focus
17TH CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS, 16-19 FEBRUARY, SAN FRANCISCO, CA: Treatment as Prevention
Jon Cohen

An ambitious idea to slow the HIV/AIDS epidemic is gaining traction: Test everyone for the virus and immediately start all HIV-infected people on treatment. But the test-and-treat scheme has epidemic modelers battling it out, with some insisting it’s feasible, both financially and practically, and others denouncing it as a pipe dream and warning that it could increase drug resistance. At the 17th Conference on Retroviruses and Opportunistic Infections, two groups presented some of the firmest data yet to support the concept.

Vaccine adjuvants: A priority for research

Vaccine
Volume 28, Issue 12, Pages 2361-2472 (11 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

Conference Report
Vaccine adjuvants: A priority for vaccine research
Pages 2363-2366
Ali M. Harandi, Donata Medaglini, Robin J. Shattock and Working Group convened by EUROPRISE

Abstract
The workshop on vaccine adjuvants was held in July of 2009 at the European Commission in Brussels, with the goal of identifying key scientific priorities as they pertain to the development of effective vaccines against life-threatening diseases especially those associated with poverty, including HIV/AIDS, malaria and tuberculosis as well as neglected infectious diseases. On the basis of new advances in adjuvant research and related technology as well as potential challenges and roadblocks, six priorities were identified to accelerate development of improved or novel vaccine adjuvants for human use.

Cost-effectiveness of routine infant vaccination/ Prevnar

Vaccine
Volume 28, Issue 12, Pages 2361-2472 (11 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

Short Communication
Huge impact of assumptions on indirect effects on the cost-effectiveness of routine infant vaccination with 7-valent conjugate vaccine (Prevnar)
Pages 2367-2369
Mark H. Rozenbaum, Albert Jan van Hoek, Eelko Hak, Maarten J. Postma

Abstract
Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar®) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data. Net-indirect effects result from herd protection minus serotype replacement effects. In this study we analyze the impact of net-indirect effects in non-vaccine protected groups of 5 years of age and older with updated assumptions regarding epidemiologic data and health care unit costs. Without net-indirect benefits for non-vaccine protected groups included the cost-effectiveness ratio is estimated at €72,360 per QALY. In order to obtain cost-effectiveness ratios below the threshold of €50,000 per QALY – which is in the middle of the range that is often referred to in the Netherlands – the net-indirect protective effect should at least be 16% of which has been observed in the USA after the introduction of PCV-7.

Real-time economic evaluation: A/H1N1v vaccine in England

Vaccine
Volume 28, Issue 12, Pages 2361-2472 (11 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Vaccination against pandemic influenza A/H1N1v in England: A real-time economic evaluation
Pages 2370-2384
Marc Baguelin, Albert Jan Van Hoek, Mark Jit, Stefan Flasche, Peter J. White, W. John Edmunds

Abstract
Decisions on how to mitigate an evolving pandemic are technically challenging. We present a real-time assessment of the effectiveness and cost-effectiveness of alternative influenza A/H1N1v vaccination strategies. A transmission dynamic model was fitted to the estimated number of cases in real-time, and used to generate plausible autumn scenarios under different vaccination options. The proportion of these cases by age and risk group leading to primary care consultations, National Pandemic Flu Service consultations, emergency attendances, hospitalisations, intensive care and death was then estimated using existing data from the pandemic. The real-time model suggests that the epidemic will peak in early November, with the peak height being similar in magnitude to the summer wave. Vaccination of the high-risk groups is estimated to prevent about 45 deaths (80% credibility interval 26–67), and save around 2900 QALYs (80% credibility interval 1600–4500). Such a programme is very likely to be cost-effective if the cost of vaccine purchase itself is treated as a sunk cost. Extending vaccination to low-risk individuals is expected to result in more modest gains in deaths and QALYs averted. Extending vaccination to school-age children would be the most cost-effective extension. The early availability of vaccines is crucial in determining the impact of such extensions. There have been a considerable number of cases of H1N1v in England, and so the benefits of vaccination to mitigate the ongoing autumn wave are limited. However, certain groups appear to be at significantly higher risk of complications and deaths, and so it appears both effective and cost-effective to vaccinate them. The United Kingdom was the first country to have a major epidemic in Europe. In countries where the epidemic is not so far advanced vaccination of children may be cost-effective. Similar, detailed, real-time modelling and economic studies could help to clarify the situation.

WHO: A(H1N1) “Pandemic Phase” Unchanged

The WHO Director-General issued a statement on 24 February 2010 following the seventh meeting of the Emergency Committee on 23 February 2010 in which the Committee’s views on the determination of the pandemic status were assessed:

“A detailed update was provided to the Committee on the global pandemic situation. After asking additional questions and reviewing the evidence and holding extensive discussion, the Committee was of the view that there was mixed evidence showing declining or low pandemic activity in many countries, but new community level transmission activity in West Africa. Moreover, they expressed concern that the winter months of the Southern Hemisphere had not yet started and there was uncertainty whether additional generalized waves of activity might occur and the need to not undermine preparations.

“The Committee advised that it was premature to conclude that all parts of the world have experienced peak transmission of the H1N1 pandemic influenza and that additional time and information was needed to provide expert advice on the status of the pandemic. The Committee accordingly suggested that the Committee be re-convened in a few weeks to review intervening developments and related epidemiological information.

“Having considered these views, the current epidemiological evidence and other relevant information, the Director-General determined that there had been no change in the pandemic phase, and decided to continue to monitor the situation and developments closely and to convene the Committee again within the next several weeks.

“The WHO Director-General asked the Committee for their views on continuance of the three current temporary IHR recommendations issued for the public health emergency of international concern. The consensus view of the Committee was in favor of continuation but to update the second recommendation by replacing “Intensify” with “Maintain” in recognition of the increased pandemic surveillance already implemented by countries and the need to maintain this activity. Having considered the views of the Emergency Committee, and the ongoing pandemic situation, the Director-General determined to continue the three temporary recommendations, as modified, namely:

– countries should not close borders or restrict international traffic and trade;

– maintain surveillance of unusual flu-like illness & severe pneumonia;

– if ill, it is prudent to delay travel. http://www.who.int/csr/disease/swineflu/7th_meeting_ihr/en/index.html

WHO: Pandemic (H1N1) 2009 – update 89: 26 February 2010

The WHO continues to issue weekly “updates” and briefing notes on the H1N1 pandemic at: http://www.who.int/csr/disease/swineflu/en/index.html
Pandemic (H1N1) 2009 – update 89
Weekly update
26 February 2010

As of 21 February 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16226 deaths…

Situation update:
In the temperate zone of the northern hemisphere, pandemic influenza virus continues to be detected across many countries, however, overall influenza activity continues to wane in most places. The most active areas of transmission are currently in parts of south and southeast Asia and in limited areas of east and southeastern Europe.

In Southeast Asia, pandemic influenza virus continued to circulate in areas, however, the overall intensity of respiratory diseases activity remained low and unchanged, except in a few countries.

More at: http://www.who.int/csr/don/2010_02_26/en/index.html

FDA approves Prevnar 13

The U.S. Food and Drug Administration approved Prevnar 13, a pneumococcal 13-valent conjugate vaccine for infants and young children ages 6 weeks through 5 years. Prevnar 13 will be the successor to Prevnar, the pneumococcal 7-valent conjugate vaccine licensed by the FDA in 2000 to prevent invasive pneumococcal disease (IPD) and otitis media. The new vaccine extends the protection to six additional types of the disease causing bacteria.  Prevnar 13 is approved for the prevention of invasive disease caused by 13 different serotypes of the bacterium Streptococcus pneumoniae. It also is approved for the prevention of otitis media caused by the seven serotypes shared with Prevnar. The bacterium can cause infections of the blood, middle ear, and the covering of the brain and spinal cord, as well as pneumonia.

Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research, said, “Although the rates of invasive pneumococcal disease have declined dramatically, there are still children in the United States who are suffering with this serious illness. The availability of Prevnar 13 will help prevent pneumococcal disease caused by the six additional serotypes.”

The FDA said that safety was evaluated in 5,084 infants and young children who received Prevnar 13, compared with 2,760 who received Prevnar, the control vaccine. Common adverse reactions reported after administration of Prevnar 13 were pain, redness and swelling at the injection site, irritability, decreased appetite and fever. These reactions were similar to what has been observed with Prevnar, which has a good safety record in the United States. Post marketing studies will include continued monitoring for reduction in IPD and otitis media, as well as continued evaluation of safety.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm201758.htm

ACIP votes expanded influenza vax for all aged 6 months and older

CDC’s Advisory Committee on Immunization Practices (ACIP) voted on 24 February to expand the recommendation for annual influenza vaccination to include all people aged 6 months and older. The expanded recommendation is to take effect in the 2010 – 2011 influenza season. The new recommendation “seeks to remove barriers to influenza immunization and signals the importance of preventing influenza across the entire population.” Prior to the action, ACIP recommendations for seasonal influenza vaccination – which focused on vaccination of higher risk persons, children 6 months through 18 years of age and close contacts of higher risk persons – already applied to about 85 percent of the U.S. population.
CDC said that discussion at the ACIP meeting “focused on the value of protecting all people 19 to 49 years of age, who have been hard hit by the 2009 H1N1 pandemic virus, which is likely to continue circulating into next season and beyond. Another reason cited in favor of a universal recommendation for vaccination is that many people in currently recommended “higher risk” groups are unaware of their risk factor or that they are recommended for vaccination. The ACIP discussion also recognized the practicality and value of issuing a simple and clear message regarding the importance of influenza vaccination in the hopes that this would remove impediments to vaccination and expand coverage. Finally, new data collected over the course of the 2009 H1N1 pandemic indicates that some people who do not currently have a specific recommendation for vaccination may also be at higher risk of serious flu-related complications, including those people who are obese, post-partum women and people in certain racial/ethnic groups”

http://www.cdc.gov/media/pressrel/2010/r100224.htm

Comment: Time for fair trade in research data

The Lancet
Feb 27, 2010  Volume 375  Number 9716  Pages 697 – 776
http://www.thelancet.com/journals/lancet/issue/current

Comment
Time for fair trade in research data
Elizabeth Pisani, James Whitworth, Basia Zaba, Carla Abou-Zahr
Preview
Geneticists, astrophysicists, and molecular biologists routinely share research data with colleagues and rivals alike. The reason is that scientists and their funders know we will understand complex issues sooner if people build on one another’s work.1,2 Yet scientists in the complex area of public health have been left behind in the data-sharing revolution.

Editorial: Gates Foundation’s decade of vaccines

The Lancet Infectious Disease
Mar 2010  Volume 10 Number 3  Pages 139 – 212
http://www.thelancet.com/journals/laninf/issue/current

Editorial
Gates Foundation’s decade of vaccines
Original Text
The Lancet Infectious Diseases

The GAVI Alliance celebrated the tenth anniversary of its foundation on Jan 29 this year. During its 10 years GAVI has overseen the delivery of vaccines to around 250 million children in the world’s poorest countries, a programme that has probably averted around 5 million deaths.

To mark GAVI’s birthday, the Bill and Melinda Gates Foundation announced that it will commit US$10 billion over the next 10 years to a so-called decade of vaccines—ie, research and development and delivery of vaccines to the world’s poorest. As an agency whose role is vaccine delivery, rather than research and development, it is not clear how much of the Gates billions will be coming to GAVI. However, GAVI is already the foundation’s largest grantee, having received $1·5 billion in its 10 year history.

Other major GAVI donors are national governments, of which 16 have contributed to the alliance plus the European Commission. Countries that have donated the most to GAVI’s core funding include Canada, the Netherlands, Norway, the UK, and the USA. Although the direct donation made by Gates far outstrip those made by any national government, France and the UK have committed billions of dollars to a funding mechanism called the International Finance Facility for Immunisation and other governments have promised substantial amounts to this scheme.

GAVI currently disburses around $1 billion per year among the 65 countries in which it supports vaccination programmes. The alliance focuses its activities on delivery of a childhood pentavalent vaccine that protects against diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b. However, to roll out this vaccine to all 65 countries by 2015, plus achieve its goal of adding pneumococcal and rotavirus vaccines to the immunisation schedule, will require an additional $3 billion.

A lot more than just wishful thinking has gone into Gates’ decision to donate $10 billion. A model developed at the Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA), indicated that 90% vaccine coverage—including the rotavirus and pneumococcal vaccines—would prevent the deaths of 7·6 million children younger than 5 years between now and 2020. Adding the malaria vaccine, which is undergoing clinical trials, from 2014 could save an additional 1·1 million lives. The Gates Foundation will certainly not be funding this expansion in vaccine coverage on its own, but its financial commitment should act as an incentive for donor governments to provide the additional funds to achieve 90% coverage with childhood vaccines in developing countries within the next 10 years.

In addition to the diseases already mentioned, vaccination against measles will likely be targeted for some of the Gates’ billions. Progress in preventing deaths from measles has been remarkable, with around 82% of those eligible worldwide now receiving vaccine and the number of measles-related deaths falling from around 750 000 in 2000 to 164 000 in 2008. GAVI does not currently fund measles vaccination programmes; rather, another international collaboration, the Measles Initiative, provides technical and financial support for national vaccination programmes in developing countries. Other areas that might benefit include the provision of autodisposable syringes that cannot be reused, funding for new vaccines against group A meningococcal meningitis and against tuberculosis, and perhaps even a final push to eliminate polio.

Although the life-saving benefits of vaccination are beyond question, no immunisation programme is without an element of controversy. As pointed out in Newsdesk, GAVI is optimistic about rolling out pneumococcal vaccine on a large scale to developing countries, because it believes the cost of the vaccine can be reduced by 90%; however, little research has been done on the public health effect of widespread pneumococcal vaccine use in the targeted countries—might there, for example, be replacement of the vaccine pneumococcal serotypes with other serotypes, thus making the vaccine only temporarily effective? Given the present influenza pandemic, some of the Gates money could be spent on researching the effect of influenza in developing countries and, if necessary, developing vaccines against influenza that are cheap enough for widespread use in these countries.

These caveats are, of course, minor compared with the beneficial effect on global health that the commitment made by the Gates Foundation is likely to have. The foundation does need to set out a clear plan for how it intends to disburse its money over the decade of vaccines. Nevertheless, many more national governments than are currently backing global vaccine coverage should be inspired to follow the lead taken by the foundation.

Polio eradication within 5 years now a real possibility

The Lancet Infectious Disease
Mar 2010  Volume 10 Number 3  Pages 139 – 212
http://www.thelancet.com/journals/laninf/issue/current

Newsdesk
Polio eradication within 5 years now a real possibility
Kathryn Senior

Last year was a significant one for polio eradication. Real progress was made simultaneously in northern Nigeria, on the Afghanistan–Pakistan border, and in the remaining pockets in Bihar and Uttar Pradesh in India, cutting the number of cases worldwide to 1597 (correct as of Feb 2, 2010). The new bivalent oral polio vaccine (bOPV), which targets type 1 and type 3 polioviruses, was licensed in late 2009 and has been in use since December. Starting in February, March, and April, 2010, multiple mass immunisations are planned in all four remaining countries where polio is endemic, at the start of a 3-year intensive effort to finally halt polio transmission worldwide.

Reducing empiricism in malaria vaccine design

The Lancet Infectious Disease
Mar 2010  Volume 10 Number 3  Pages 139 – 212
http://www.thelancet.com/journals/laninf/issue/current

Personal View
Reducing empiricism in malaria vaccine design
Vasee S Moorthy, Marie Paule Kieny

Preview
Gains in the control of malaria and the promising progress of a malaria vaccine that is partly efficacious do not reduce the need for a high-efficacy vaccine in the longer term. Evidence supports the feasibility of developing a highly efficacious malaria vaccine. However, design of candidate malaria vaccines remains empirical and is necessarily based on many unproven assumptions because much of the knowledge needed to design vaccines and to predict efficacy is not available. Data to inform key questions of vaccine science might allow the design of vaccines to progress to a less empirical stage, for example through availability of assay results associated with vaccine efficacy.

Tuberculosis and air travel: a systematic review and analysis of policy

The Lancet Infectious Disease
Mar 2010  Volume 10 Number 3  Pages 139 – 212
http://www.thelancet.com/journals/laninf/issue/current

Review
Tuberculosis and air travel: a systematic review and analysis of policy
Abrahim Abubakar

Preview
WHO international guidelines for the control of tuberculosis in relation to air travel require—after a risk assessment—tracing of passengers who sat for longer than 8 h in rows adjacent to people with pulmonary tuberculosis who are smear positive or smear negative. A further recommendation is that all commercial air travel should be prohibited until the person has two consecutive negative sputum smears for drug-susceptible tuberculosis or two consecutive cultures for multidrug-resistant tuberculosis.

VAMPSS (the Vaccines and Medications in Pregnancy Surveillance System)

Science
26 February 2010  Vol 327, Issue 5969, Pages 1043-1162
http://www.sciencemag.org/current.dtl

News of the Week
Drug Safety: New Network to Track Drugs and Vaccines in Pregnancy
Jennifer Couzin-Frankel

Both doctors and patients are jittery about whether to continue or drop potentially risky treatments during pregnancy. A new effort to bring risks into focus is being launched this week with $12.5 million from two U.S. agencies. It will start by examining asthma medications called short-acting beta agonists, as well as flu vaccines and antivirals for influenza. Called VAMPSS (the Vaccines and Medications in Pregnancy Surveillance System), the program will be funded for 5 years by the Agency for Healthcare Research and Quality and for 2 years by the Biomedical Advanced Research and Development Authority and coordinated by the American Academy of Allergy, Asthma, and Immunology. An advisory committee that includes members from pediatric and obstetric groups, and the Centers for Disease Control and Prevention, will guide VAMPSS’s research.

IP: Fixing the Legal Framework for Pharmaceutical Research

Science
26 February 2010  Vol 327, Issue 5969, Pages 1043-1162
http://www.sciencemag.org/current.dtl

Policy Forum
Intellectual Property: Fixing the Legal Framework for Pharmaceutical Research
Sherry M. Knowles

The cost of drug research and development (R&D) has increased from $230 million per drug in the early 1980s to $1.2 billion today, with R&D currently requiring about 10 to 15 years per drug (1–4). This investment of time and money cannot be sustained without a legal system that provides sufficient time to recoup the investment and to secure a reasonable return, as well as the ability to make important business decisions that remain correct over a long period of time. Pharmaceutical companies have historically relied on two kinds of market protection: (i) the exclusive ownership of their own clinical research and (ii) patents. However, the U.S. Hatch-Waxman Act (5), which is designed to strike a balance between innovative pharmaceutical research and access to generic drugs, is flawed. Further, U.S. courts sometimes retroactively change standards for patent protection long after large R&D efforts have been initiated, which increases the risk to defend and rely on patent protection.

Chief Patent Counsel, GlaxoSmithKline, King of Prussia, PA 19406, USA.

Long-term Vaccine Storage: Disaccharide Stabilizers

Science Translational Medicine
17 February 2010 vol 2, issue 19
http://stm.sciencemag.org/content/2/19/19cm7.abstract

Research Articles
Vaccines
Long-Term Thermostabilization of Live Poxviral and Adenoviral Vaccine Vectors at Supraphysiological Temperatures in Carbohydrate Glass

Robert Alcock, Matthew G. Cottingham, Christine S. Rollier, Julie Furze, Samodh D. De Costa, Marian Hanlon, Alexandra J. Spencer, Jared D. Honeycutt, David H. Wyllie, Sarah C. Gilbert, Migena Bregu, and Adrian V. S. Hill
17 February 2010:19ra12

Abstract [Bolding by Week in Review]
Live recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products. Here, we have exploited the ability of these sugars to vitrify on desiccation to develop a thermostabilization technique for live viral vaccine vectors. By slowly drying vaccines suspended in solutions of these disaccharide stabilizers onto a filter-like support membrane at ambient temperature, an ultrathin glass is deposited on the fibers of the inert matrix. Immobilization of two recombinant vaccine vectors—E1/E3-deleted human adenovirus type 5 and modified vaccinia virus Ankara—in this glass on the membranes enabled complete recovery of viral titer and immunogenicity after storage at up to 45°C for 6 months and even longer with minimal losses. Furthermore, the membrane carrying the stabilized vaccine can be incorporated into a holder attached to a syringe for almost simultaneous reconstitution and injection at point of use. The technology may potentially be developed for the deployment of viral vector–based biopharmaceuticals in resource-poor settings.

Second Geneva Consensus: Recommendations for novel live TB vaccines

Vaccine
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)
http://www.sciencedirect.com/science/journal/0264410X

Conference Report
The second Geneva Consensus: Recommendations for novel live TB vaccines
Pages 2259-2270
K.B. Walker, M.J. Brennan, M.M. Ho, J. Eskola, G. Thiry, J. Sadoff, R. Dobbelaer, L. Grode, M.A. Liu, U. Fruth, P.H. Lambert

Abstract
Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine.

The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including:

i. Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype.
ii. To identify the general criteria for further clinical development from Phase I through to Phase III.
iii. Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held.
iv. Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine.
v. Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme.

Cost-effectiveness of PCV7 in Argentina

Vaccine
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)
http://www.sciencedirect.com/science/journal/0264410X

Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina
Pages 2302-2310
Norberto D. Giglio, Alejandro D. Cane, Paula Micone, Angela Gentile

Abstract
Due to the region’s own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial.
Objective
To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina.

Design
A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination.

Main outcome measures
Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination.

Results
From the society’s perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00.

The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae.

The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity.

Conclusions
Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina.

Meningococcal conjugate vaccination: adolescents 13–17: U.S. 2007

Vaccine
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)
http://www.sciencedirect.com/science/journal/0264410X

Meningococcal conjugate vaccination among adolescents aged 13–17 years, United States, 2007
Pages 2350-2355
Peng-jun Lu, Nidhi Jain, Amanda C. Cohn

Abstract
Background
An estimated 1000–2000 cases of invasive meningococcal diseases occur annually in the United States. In 2005, a new quadrivalent meningococcal conjugate vaccine (MCV4) was approved and, because of supply constraints, was recommended for routine vaccination of some groups of adolescents. In August 2007, vaccination recommendations were expanded for all adolescents 11–18 years.

Methods
We analyzed data from the 2007 National Immunization Survey-Teen (NIS-Teen), a nationally representative random digit dialed telephone survey. Estimates of MCV4 coverage were assessed from provider-reported vaccination histories. A multivariable logistic regression analysis and predictive marginal model were performed to identify factors independently associated with MCV4 vaccination.

Results
Provider-reported vaccination histories were available for 2947 adolescents aged 13–17 years with a response rate of 55.9%. Overall, MCV4 coverage was 32.4% (95% confidence interval (CI) = 30.2–34.7%) in 2007. Vaccination coverage was similar among adolescents aged 13–14 years compared to those aged 15–17 years (32.1% vs. 32.6%, respectively). Coverage was 30.6% for non-Hispanic whites, 35.9% for non-Hispanic blacks, and 36.1% for Hispanics; however, these variations were not statistically significant. Characteristics independently associated with a higher likelihood of MCV4 vaccination included having ≥2 physician contacts in the past year, having a well child visit at age 11–12 years, and ever having a doctor recommendation for meningitis vaccination of the adolescent.

Conclusions
In 2007, MCV4 coverage among 13–17 years old increased 20.7 percentage points from 2006. Achieving high vaccination coverage among adolescents will be challenging. Targeting adolescents with no health insurance and no recent healthcare provider visits may be important to increase coverage.