Perspective
Poverty, Wealth, and Access to Pandemic Influenza Vaccines
Tadataka Yamada, M.D.

New England Journal of Medicine
Volume 361 — September 17, 2009 — Number 12
http://content.nejm.org/current.shtml

On June 11, 2009, Margaret Chan, director general of the World Health Organization (WHO), declared that the status of the influenza A (H1N1) pandemic had reached phase 6 — active transmission on a global scale. Until now, the case fatality rate of this influenza has been quite low, but history teaches us that the situation could take a turn for the worse during the next wave of the pandemic. If a 1918-like pandemic were to occur today, tens of millions of people could die, the vast majority of them in the world’s poorest countries.

Fortunately, the prospects for developing an effective vaccine to prevent infection with the current H1N1 virus are excellent, and the world’s pharmaceutical companies are working diligently at this task. In contemplating equal access to such a vaccine, it is important to consider three key issues: manufacturing capacity, cost, and delivery.

Only a few countries in the world have plants for manufacturing influenza vaccine, and three companies — GlaxoSmithKline, Sanofi-Aventis, and Novartis — account for most of the world’s manufacturing capacity. The number of doses of vaccine against H1N1 influenza that could be produced with the existing capacity is very large, but the sobering truth is that even if production were switched over completely from seasonal influenza vaccine to pandemic influenza vaccine, there would not be nearly enough for everyone in the world. The size of the gap in potential supply depends greatly on the dose that is required, and it may be possible to reduce the necessary dose by as much as 75% with the use of an adjuvant. The challenging problem is that much, if not most, of the manufacturing capacity is already spoken for through purchasing contracts held by many of the world’s wealthy countries.

The second issue is cost. Despite the enormous technological investment required to create a vaccine, the traditional cost of seasonal influenza vaccines even in wealthy countries is quite low. For the pandemic H1N1 influenza vaccine, the major manufacturers have indicated a willingness to offer tiered pricing, with affordable prices for poor countries. Going even further, Sanofi-Aventis has committed to donating 100 million doses of its vaccine to a stockpile for poor countries, and GlaxoSmithKline has committed to donating 50 million doses. Nevertheless, financial commitments from wealthy countries will be needed to help poorer countries purchase vaccines — cost should not be a barrier to access.

Finally, the scope of access to vaccines will in part be determined by the infrastructure required to deliver them to all citizens in mass campaigns. Ironically, poor countries may have an advantage on this front, since many have recent experience with mass campaigns involving vaccines against polio, measles, and hepatitis B; delivery may therefore be less of a challenge for them, provided that the vaccines reach them in a timely fashion. By contrast, in many wealthier countries, such campaigns have not been undertaken for some time. Getting the vaccine to large numbers of young adults, in particular, may be a formidable task for which preparations must surely be made as soon as possible.

Our limited capacity for producing potentially lifesaving vaccines presents a pressing moral challenge. I believe wholeheartedly that all lives have equal value (this is the basic principle motivating the Bill and Melinda Gates Foundation, where I work), and I believe that every stakeholder has a responsibility to ensure that the pandemic does not take a 1918-like toll on the world. We have therefore worked with partner stakeholders to develop a proposed set of principles to guide the global allocation of pandemic vaccine (see Principles to Guide Global Allocation of Pandemic Vaccine below).

Rich countries have a responsibility to stand in line and receive their vaccine allotments alongside poor countries, even if they have paid for their vaccine before others could do so. It would be inexcusable to force poor countries to wait until the rich have been served under their existing contracts with vaccine manufacturers. Moreover, rich countries must also consider how they can provide contributions to offset the cost of vaccines for countries that cannot afford to pay for them. Countries that are home to influenza-vaccine manufacturing plants have a special responsibility to avoid nationalizing those facilities in an effort to reserve their output for their own citizens before others. And all countries must prepare now for the rapid delivery of the vaccines as soon as they become available.

Manufacturers have a responsibility to apply their full capabilities to creating the greatest possible quantity of vaccine doses. Despite contractual obligations to supply many wealthy countries with their vaccines, manufacturers must resist the temptation to commit all their capacity to those who can pay the most. This is not a time to adhere to the “first come, first served” model of business, since we may be facing a health crisis of global proportions in which all people and countries are equally at risk. To ensure fairness, full adherence to a tiered pricing scheme in which the cost to the purchaser is proportionate to its ability to pay is essential. The generous donations made by Sanofi-Aventis and GlaxoSmithKline set an example that all manufacturers should emulate. In return for their responsible actions, it would be reasonable for manufacturers to be indemnified against liability from potential adverse reactions to their vaccines.

Regulatory agencies have an important responsibility in this impending crisis because they stand between the manufacturers of pandemic influenza vaccines and the people who will benefit from them. It is critically important that regulators apply their usual rigorous standards in approving the new vaccines — but also that they do so in a timely fashion. A special task facing them is the rapid review and consideration of the safety and efficacy of adjuvants, whose use could greatly reduce the required dose of vaccine and thereby expand the number of doses that could be manufactured.

The WHO has provided strong leadership as the world has contemplated the prospect of an influenza pandemic. We are counting on the organization to guide us, wisely and fairly, through the complex challenges that lie ahead.

The prospect of a worsening global influenza pandemic is real and will not go away anytime soon. I cannot imagine standing by and watching if, at the time of crisis, the rich live and the poor die. It will take collective commitment and action by all of us to prevent this from happening.

Principles to Guide Global Allocation of Pandemic Vaccine.

1. The global community should take steps to protect all populations, including those without resources to protect themselves.

2. Vaccination should be considered in the context of comprehensive pandemic preparedness and response efforts in all nations.

3. Developed countries and vaccine manufacturers should urgently agree upon a mechanism to ensure access to vaccine by developing countries.

4. Influenza vaccine manufacturers should identify strategies such as tiered pricing and donations to make pandemic vaccine more accessible to developing nations.

5. Pandemic vaccines allocated to developing nations should become available in the same time frame as vaccines for developed nations.

6. The global community should obtain data to help establish a consensus on the safety and efficacy of adjuvants, and efforts should be made to ensure the fullest use of this and other dose-sparing strategies.

7. All countries obtaining pandemic vaccine should ensure that mechanisms are in place to provide the vaccine to their populations, to ensure that this scarce resource is not wasted, and donors should be prepared to provide resources and technical assistance to help countries bolster these mechanisms.

8. The World Health Organization is uniquely positioned to lead the global response to a pandemic virus and should support governments and industry in their efforts to implement these principles.

* From the Pneumonia and Flu Web site of the Bill and Melinda Gates Foundation (www.gatesfoundation.org/topics/Pages/pneumonia-flu.aspx).

Dr. Yamada reports holding equity in GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported.

September 17, 2009

President Announces Plan to Expand Fight Against Global H1N1 Pandemic

Today, President Obama announced the United States will continue to act aggressively to stop the global spread of the pandemic 2009-H1N1 influenza virus and is prepared to make 10 percent of its H1N1 vaccine supply available to other countries through the World Health Organization (WHO). In recognition that diseases know no borders and that the health of the American people is inseparable from the health of people around the world, the United States is taking this action in concert with Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, and the United Kingdom. The United States will make the H1N1 vaccine available to the WHO on a rolling basis as vaccine supplies become available, in order to assist countries that will not otherwise have direct access to the vaccine.

This week, the Food and Drug Administration officially licensed the 2009-H1N1 influenza vaccine. Last week, the Department of Health and Human Services and the National Institutes of Health announced that one dose of the vaccine – instead of two doses – will be effective in developing immunity in most adults, and HHS Secretary Sebelius announced the vaccine would be available in the coming weeks, earlier than originally anticipated. We remain confident that the United States will have sufficient doses of the vaccine to ensure that every American who wants a vaccine is able to receive one. We continue to recommend that early priority at home and abroad should be given to pregnant women, health care workers, individuals caring for infants less than 6 months of age, and other high-risk populations.

There is broad international recognition that the 2009-H1N1 pandemic presents a global health risk. Millions of people around the world have been affected, thousands have died and the virus continues to spread across international borders. The United States recognizes that just as this challenge transcends borders, so must our response.      We invite other nations to join in this urgent global health effort. Working together, we can ensure that this vaccine limits the spread of the disease, reduces the burden on health care systems, reduces the risk of an even more virulent strain emerging and, most importantly, saves lives—in the United States and around the world.

http://www.whitehouse.gov/the_press_office/President-Announces-Plan-to-Expand-Fight-Against-Global-H1N1-Pandemic/

18 September 2009

Statement by WHO Director-General Dr Margaret Chan on Pandemic vaccine donations for the developing world

WHO applauds and welcomes the announcement of donations of pandemic vaccine made today by the United States of America, in concert with Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, and the United Kingdom.

The announcement demonstrates the commitment of these countries to fairness in sharing of scarce resources as the 2009 H1N1 influenza pandemic continues to evolve.

Current supplies of pandemic vaccine are inadequate for a world population in which virtually everyone is susceptible to infection by a new and readily contagious virus.

Given that current demand outstrips supply, these donations, together with the doses pledged by manufacturers, will help increase supplies of pandemic vaccines to populations that would otherwise not have access.

WHO continues to support developing countries to ensure donated vaccines are distributed where they are most needed. http://www.who.int/mediacentre/news/statements/2009/pandemic_vaccine_donations_20090918/en/index.html

September 18, 2009

Gates Foundation Statement on Global Agreement to Supply H1N1 Vaccine to Developing Countries by Dr. Tachi Yamada, president of the Global Health Program of the Bill & Melinda Gates Foundation.

We heartily applaud the commitment by nine nations to donate a portion of their H1N1 vaccine supply on a rolling basis to the World Health Organization for distribution to countries that would otherwise not have direct access.
Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, the United Kingdom, and the United States have all shown tremendous leadership. Wealthier countries have an obligation to ensure more equitable access to vaccines in this global pandemic. This issue is surely one of the most pressing moral challenges of our time.
This announcement underscores the interdependency of all people when it comes to matters of health. As important as the announced generosity is, we must keep in mind that the needs are great, and more must be done to ensure that all nations have access to vaccines and other tools.
We understand that these are hard decisions to make right now. We hope and expect that more nations will join this effort.”

http://www.gatesfoundation.org/press-releases/Pages/gates-foundation-statement-on-global-agreement-h1n1-vaccine-090918.aspx

The WHO continues to issue weekly “updates” and briefing notes as below:
Pandemic (H1N1) 2009 – update 66: 18 September 2009

Weekly update
In the temperate regions* of the northern hemisphere, influenza activity remains widely variable. In North America, the United States is reporting increases in influenza-like-illness activity above the seasonal baseline, most notably in the southern, southeastern, and parts of the northeastern United States.

In Canada, influenza activity remains low. In Europe and Central Asia influenza activity remains low overall, except in France, which is reporting increases in influenza-like-illness activity (for week 37) above the seasonal epidemic threshold. Geographically localized influenza activity is being reported in several countries (Austria, Georgia, Ireland, Luxembourg, Norway, Portugal, the Czech Republic, Cyprus, and Israel). In Japan, influenza activity remains stably increased above the seasonal epidemic threshold with the most notable increases being reported on the southern island of Okinawa.

In the tropical regions of the Americas and Asia, influenza transmission remains active. Geographically regional to widespread influenza activity continues to be reported throughout much of South and Southeast Asia, with increasing trends in respiratory diseases being reported in India and Bangladesh. Geographically regional to widespread influenza activity continues to be reported for the tropical regions of Central and South America without a consistent pattern in the trend of respiratory diseases (continued increases are being reported in Bolivia and Venezuela).

In the temperate regions* of the southern hemisphere, influenza activity continues to decrease or has returned to the seasonal baseline in most countries. In Australia, later affected areas are also now reporting declining levels of influenza-like-illness. In South Africa, influenza activity appears to have recently passed over the second peak (the first peak was due to seasonal influenza A (H3N2) and second peak was due to pandemic (H1N1) 2009).

WHO Collaborating Centres and other laboratories continue to report sporadic isolates of oseltamivir resistant influenza virus. Twenty six such virus isolates have now been described from around the world, all of which carry the same H275Y mutation that confers resistance to the antiviral oseltamivir but not to the antiviral zanamivir. Of these, 12 have been associated with post-exposure prophylaxis, five with long term oseltamivir treatment in patients with immunosuppression. Worldwide, over 10,000 clinical samples and isolates of the pandemic (H1N1) 2009 virus have been tested and found to be sensitive to oseltamivir. WHO will continue to monitor the situation closely in collaboration with its partners.

Pandemic (H1N1) influenza virus continues to be the predominant circulating influenza virus, both in the northern and southern hemisphere. See below for detailed laboratory surveillance update.

*Countries in temperate regions are defined as those north of the Tropic of Cancer or south of the Tropic of Capricorn, while countries in tropical regions are defined as those between these two latitudes.

Weekly update (Virological surveillance data)

http://www.who.int/csr/don/2009_09_18/en/index.html

The U.S. Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus. The vaccines are made by CSL Limited, MedImmune LLC, Novartis Vaccines and Diagnostics Limited, and sanofi pasteur. All four firms manufacture the H1N1 vaccines using the same processes. Jesse Goodman, M.D., FDA acting chief scientist, commented, “The H1N1 vaccines approved today undergo the same rigorous FDA manufacturing oversight, product quality testing and lot release procedures that apply to seasonal influenza vaccines.” The FDA said that, as with the seasonal influenza vaccines, the 2009 H1N1 vaccines are being produced in formulations that contain thimerosal, a mercury-containing preservative, and in formulations that do not contain thimerosal.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm

The Wellcome Trust and Merck announced the creation of the MSD Wellcome Trust Hilleman Laboratories (www.hillemanlaboratories.in), described as “the first of its kind research and development joint venture with a not-for-profit mission to focus on developing affordable vaccines to prevent diseases that commonly affect low-income countries.” The joint venture “marks the first time a research charity and a pharmaceutical company have partnered to form a separate entity with equally shared funding and decision-making rights. Pairing two of the world’s preeminent healthcare institutions provides an opportunity to integrate the best of both to drive the investment and expertise needed to develop and deliver vaccines to low-income countries.”

The organizations described the vision as “a sustainable, not-for-profit operating model to turn innovative science into practical solutions for those in greatest need.”

The new Hilleman Laboratories “will also work on optimizing existing vaccines, an important and powerful way of increasing the impact of vaccination in resource-limited settings. By working in partnership, the Wellcome Trust and Merck seek to achieve what neither can do alone.”

Merck and the Wellcome Trust will invest equally in the R&D joint venture, which will be primed with a combined cash contribution of 90 million GBP (approximately US$130 million) over the next seven years, and will support a staff of approximately 60 researchers and developers. The venture will be based in India to facilitate engagement and partnership with a broad range of experts in vaccine research, policy and manufacturing to develop and mature its R&D pipeline. The Hilleman Laboratories will work to advance projects to ‘proof of concept’ by providing key expertise in product development and optimization that is typically available only within large vaccine companies. The Hilleman Laboratories will also work with vaccine manufacturers to ensure production can be scaled and that the vaccines are affordable. Through this model, the Hilleman Laboratories “will help deliver vaccines to registration that are specifically designed to meet the needs and practical realities in developing countries.”

Altaf A. Lal, Ph.D., was named CEO of the Hilleman Laboratories. Dr. Lal spent 20 years working for the National Center for Infectious Diseases at the U.S. Centers for Disease Control and Prevention (CDC) and was the Chief of the Molecular Vaccine Section in the Division of Parasitic Diseases. Dr. Lal is currently Health Attaché and Department of Health and Human Services Regional Representative for South Asia at the Embassy of the United States of America, New Delhi, India. His extensive experience in global public health gives him the expertise needed to lead this new public-private research partnership.

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20090917005186&newsLang=en

GAVI CEO Dr Lob-Levyt, speaking at a reception to celebrate the Alliance’s status as an independent international institution in Switzerland, noted that, “The demand by low-income countries for new, life-saving vaccines has never been higher. We must answer their call.” GAVI said that nearly 2.3 million children continue to die each year from vaccine-preventable diseases, even while the overall mortality rate of children continues to drop, based on UNICEF’s announcement last week that the number of children dying before their fifth birthday each year has fallen below nine million for the first time on record. GAVI said that 25% of the remaining deaths could still be prevented through proper vaccination. Dr. Lob-Levyt said that, by far, the biggest vaccine-preventable killers of children are pneumonia and diarrhoeal diseases, and that the new Accelerated Vaccine Introduction initiative has targeted delivery of pneumococcal vaccine in 42 countries and rotavirus vaccine in 44 countries by 2015.

http://www.gavialliance.org/media_centre/press_releases/2009_09_17_challenges_ahead.php

The Weekly Epidemiological Record (WER) for 18 September 2009, vol. 84, 38 (pp 385–396) includes: Onchocerciasis (river blindness); Vaccine-derived polioviruses detected worldwide, January 2008–June 2009

http://www.who.int/wer/2009/wer8438.pdf

The MMWR for September 18, 2009 / Vol. 58 / No. 36 includes:

  Updated Recommendations from the Advisory Committee on Immunization Practices (ACIP) for Use of Hepatitis A Vaccine in Close Contacts of Newly Arriving International Adoptees

  Licensure of a Haemophilus influenzae Type b (Hib) Vaccine (Hiberix) and Updated Recommendations for Use of Hib Vaccine

JAMA
Vol. 302 No. 11, pp. 1141-1248, September 16, 2009
http://jama.ama-assn.org/current.dtl

Commentaries
What Mexico Taught the World About Pandemic Influenza Preparedness and Community Mitigation Strategies
Alexandra Minna Stern; Howard Markel

JAMA
Vol. 302 No. 11, pp. 1141-1248, September 16, 2009
http://jama.ama-assn.org/current.dtl

Book and Media Reviews
Principles and Practice of Pediatric Infectious Diseases
Mark D. Widome
JAMA. 2009;302(11):1233-1234.

Science
18 September 2009  Vol 325, Issue 5947, Pages 1461-1584
http://www.sciencemag.org/current.dtl

News of the Week
Swine Flu Outbreak: China First to Vaccinate Against Novel H1N1 Virus
Richard Stone

No country has taken stricter measures than China to protect residents from pandemic swine flu. Although its draconian quarantine system sparked scientific debate and more than a few diplomatic spats before it was scaled back a couple of months ago, China’s latest exploit is winning praise: Earlier this week, China was first off the blocks to launch a mass vaccination campaign against the novel H1N1 virus. As the swine flu pandemic picks up steam, China is racing to immunize a sizable percentage of its 1.3 billion people before the pandemic’s expected peak here this autumn or early winter. Epidemiologists here forecast that, without mass vaccination, tens of millions will become infected in China and hundreds of thousands will seek treatment.

The WHO continues to issue weekly “updates” and briefing notes as below:

Pandemic (H1N1) 2009 – update 65: 11 September 2009

“In the temperate region of the southern hemisphere (represented by countries such as Chile, Argentina, Australia, New Zealand, and South Africa), influenza activity continues to decrease or return to baseline.
Active transmission persists in tropical regions of the Americas and Asia. Many countries in Central America and the Caribbean continue to report declining activity for the second week in a row. However, countries in the tropical region of South America (represented by countries such as Bolivia, Ecuador, and Venezuela) are reporting increasing levels of respiratory disease. In the tropical regions of Asia, respiratory disease activity remains geographically regional or widespread but the trend is generally increasing as noted in India, Bangladesh, and Cambodia.
In the temperate regions of the Northern Hemisphere activity is variable. In the United States, regional increases in influenza activity are being reported, most notably in the south eastern states. Most of Europe is reporting low or moderate respiratory diseases activity, but parts of Eastern Europe are beginning to report increases in activity.
WHO Collaborating Centres and other laboratories continue to report sporadic isolates of oseltamivir-resistant influenza virus. 21 such virus isolates have now been described from around the world, all of which carry the same H275Y mutation that confers resistance to the antiviral oseltamivir but not to the antiviral zanamivir. Of these, 12 have been associated with post-exposure prophylaxis, four with long term oseltamivir treatment in patients with immunosuppression. Worldwide, over 10,000 isolates of the pandemic (H1N1) 2009 virus have been tested and found to be sensitive to oseltamivir. WHO will continue to monitor the situation closely in collaboration with its partners, but is not changing its guidelines for use of antiviral drugs at this time.
Pandemic (H1N1) influenza virus continues to be the predominant circulating virus of influenza, both in the northern and southern hemisphere. All pandemic H1N1 2009 influenza viruses analysed to date have been antigenically and genetically similar to A/California/7/2009-like pandemic H1N1 2009 virus. See below for detailed laboratory surveillance update.
Of note, the U.S. Centers for Disease Control and Prevention this week reported on an analysis of 36 fatal pandemic influenza cases in children under the age of 18 years. Sixty-seven percent of the children had one or more high-risk medical conditions, most commonly neurodevelopmental disorders. In addition, ten of 23 children for whom data were available were found to have strong evidence of secondary bacterial co-infections.

Weekly update (Virological surveillance data)

http://www.who.int/csr/don/2009_09_11/en/index.html

Pandemic (H1N1) 2009 briefing note 10: 11 September 2009

Measures in school settings

“WHO is today issuing advice on measures that can be undertaken in schools to reduce the impact of the H1N1 influenza pandemic. Recommendations draw on recent experiences in several countries as well as studies of the health, economic, and social consequences of school closures. These studies were undertaken by members of a WHO informal network for mathematical modelling of the pandemic.

Experience to date has demonstrated the role of schools in amplifying transmission of the pandemic virus, both within schools and into the wider community. While outbreaks in schools are clearly an important dimension of the current pandemic, no single measure can stop or limit transmission in schools, which provide multiple opportunities for spread of the virus.

WHO recommends the use of a range of measures that can be adapted to the local epidemiological situation, available resources, and the social role played by many schools. National and local authorities are in the best position to make decisions about these measures and how they should be adapted and implemented.

WHO continues to recommend that students, teachers, and other staff who feel unwell should stay home. Plans should be in place, and space made available, to isolate students and staff who become ill while at school.

Schools should promote hand hygiene and respiratory etiquette and be stocked with appropriate supplies. Proper cleaning and ventilation and measures to reduce crowding are also advised.

School closures and class suspensions

Decisions about if and when schools should be closed during the pandemic are complex and highly context-specific. WHO cannot provide specific recommendations for or against school closure that are applicable to all settings. However, some general guidance comes from recent experience in several countries in both the northern and southern hemispheres, mathematical modelling, and experience during seasonal epidemics of influenza.

School closure can operate as a proactive measure, aimed at reducing transmission in the school and spread into the wider community. School closure can also be a reactive measure, when schools close or classes are suspended because high levels of absenteeism among students and staff make it impractical to continue classes.

The main health benefit of proactive school closure comes from slowing down the spread of an outbreak within a given area and thus flattening the peak of infections. This benefit becomes especially important when the number of people requiring medical care at the peak of the pandemic threatens to saturate or overwhelm health care capacity. By slowing the speed of spread, school closure can also buy some time as countries intensify preparedness measures or build up supplies of vaccines, antiviral drugs, and other interventions.

The timing of school closure is critically important. Modelling studies suggest that school closure has its greatest benefits when schools are closed very early in an outbreak, ideally before 1% of the population falls ill. Under ideal conditions, school closure can reduce the demand for health care by an estimated 30–50% at the peak of the pandemic. However, if schools close too late in the course of a community-wide outbreak, the resulting reduction in transmission is likely to be very limited.

Policies for school closure need to include measures that limit contact among students when not in school. If students congregate in a setting other than a school, they will continue to spread the virus, and the benefits of school closure will be greatly reduced, if not negated.

Economic and social costs

When making decisions, health officials and school authorities need to be aware of economic and social costs that can be disproportionately high when viewed against these potential benefits.

The main economic cost arises from absenteeism of working parents or guardians who have to stay home to take care of their children. Studies estimate that school closures can lead to the absence of 16% of the workforce, in addition to normal levels of absenteeism and absenteeism due to illness. Such estimates will, however, vary considerably across countries depending on several factors, including the structure of the workforce.

Paradoxically, while school closure can reduce the peak demand on health care systems, it can also disrupt the provision of essential health care, as many doctors and nurses are parents of school-age children.

Decisions also need to consider social welfare issues. Children’s health and well-being can be compromised if highly beneficial school-based social programmes, such as the provision of meals, are interrupted or if young children are left at home without supervision.

http://www.who.int/csr/disease/swineflu/notes/h1n1_school_measures_20090911/en/index.html

Statement by Dr. Anthony Fauci, Director, National Institute of Allergy and Infections Diseases, NIH, Regarding Early Results from Clinical Trials of 2009 H1N1 Influenza Vaccines in Healthy Adults

WASHINGTON–(BUSINESS WIRE)–We are encouraged by reports that are now emerging from various clinical trials of 2009 H1N1 influenza vaccines, conducted by various vaccine manufacturers. We expect additional companies to announce their preliminary trial results shortly. The early data from these trials indicate that 2009 H1N1 influenza vaccines are well tolerated and induce a strong immune response in most healthy adults when administered in a single unadjuvanted 15-microgram dose. We congratulate the companies on these trials, which are an important part of the ongoing worldwide effort to develop vaccines to protect the public from 2009 H1N1 influenza.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, also is conducting clinical trials of 2009 H1N1 influenza vaccines, produced by Sanofi Pasteur and CSL Limited. The NIAID trials are testing two different dosages (15 micrograms versus 30 micrograms) and evaluating the immune response to one and two doses of these vaccines. More than 2,800 people are participating in ongoing NIAID trials of these vaccines.

We are pleased to note that preliminary analyses of early data from the NIAID trials align with the recently announced findings and those to be announced imminently by other companies in that both vaccines studied induced what is likely to be a protective immune response in most adults following a single dose in the same amount (15 micrograms) used in seasonal flu vaccines. Specifically, in blood samples obtained 8 to 10 days after vaccination:

Among healthy adults who received a single 15-microgram dose of the Sanofi Pasteur vaccine, a robust immune response was measured in 96 percent of adults aged 18 to 64 and in 56 percent of adults aged 65 and older.

Similarly, among healthy adults who received a single 15-microgram dose of the CSL Limited vaccine, a robust immune response was measured in 80 percent of adults aged 18 to 64 and in 60 percent of adults aged 65 and older.

Additional data from the NIAID trials are forthcoming. However, on the basis of these strong early data, our results are consonant with other reports that a single 15-microgram dose of unadjuvanted 2009 H1N1 influenza vaccine is well tolerated and induces a robust immune response in healthy adults between the ages of 18 and 64. For adults aged 65 and over, the immune response to 2009 H1N1 influenza vaccine is somewhat less robust, as is the case with seasonal influenza vaccines.

We note that the slight discrepancies seen in our trials between the Sanofi Pasteur and CSL Limited vaccines may be due to technical differences in the preliminary measurement of the amounts of antigen in the doses used in the clinical trial lots and the relatively limited numbers of samples studied to date, as well as the fact that our data are drawn from a very early time point after immunization.

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20090911005820&newsLang=en

The National Institute of Allergy and Infectious Diseases (NIAID) launched the first trial testing a candidate 2009 H1N1 influenza vaccine in pregnant women. NIAID Director Anthony S. Fauci, M.D. said, “Women are at higher risk of developing severe illness if they become infected with influenza virus while pregnant, which is why they are strongly encouraged to receive the seasonal influenza vaccine every year. Data indicate that pregnant women are at higher risk for complications from the 2009 H1N1 influenza virus as well, so this trial will provide critical information for public health planning.”

The trial is being conducted through the NIAID-funded national network of Vaccine and Treatment Evaluation Units (VTEUs). Up to 120 women 18 to 39 years of age who are in their second or third trimester (14 to 34 weeks) of pregnancy will be enrolled into this initial trial. Volunteers will receive 15 micrograms or 30 micrograms of a candidate 2009 H1N1 influenza vaccine manufactured by Sanofi Pasteur. All women will receive an initial injection and a second injection 21 days later. Safety data will be collected and assessed continuously throughout the trial by the study investigators and by an independent safety monitoring committee. The design of this trial in pregnant women is patterned after clinical trials that opened in August through NIAID’s VTEU network. Those trials are testing the same vaccine in various groups of healthy individuals, including adults, the elderly and children. http://www.nih.gov/news/health/sep2009/niaid-09.htm

Harvard School of Public Health (HSPH), in a national survey of businesses, reported that “four-fifths of businesses foresee severe problems maintaining operations in a significant H1N1 fu outbreak.” HSPH researchers said they found that only one-third of respondents believe they could sustain their business without severe operational problems if half their workforce were absent for two weeks due to H1N1. Just one-fifth believe they could avoid such problems for one month with half their employees out. The survey also reported that “74% of businesses offer paid sick leave for employees, only 35% of businesses offer paid leave that would allow employees to take care of sick family members, and even fewer would allow paid time off to care for children if schools/daycares were closed (21%).” The survey is part of an ongoing series about the country’s response to the H1N1 flu outbreak undertaken by the Harvard Opinion Research Program at HSPH. The polling was done July 16-August 12, 2009..

http://www.hsph.harvard.edu/news/press-releases/2009-releases/businesses-problems-maintaining-operations-significant-h1n1-flu-outbreak.html

Merck announced today that the U.S. Food and Drug Administration’s (FDA) Vaccines and Related Biological Products Advisory Committee “agreed that efficacy, immunogenicity and safety data from clinical trials in males support the use of GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] in boys and men 9 through 26 years of age for the prevention of genital warts caused by human papillomavirus (HPV) types 6 and 11.” Peter S. Kim, Ph.D., executive vice president, and president of Merck Research Laboratories, said, “Merck has been committed to pursuing the use of GARDASIL in both males and females since the vaccine was discovered over a decade ago. We are pleased that the Advisory Committee agrees that the data support the use of GARDASIL in boys and men.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20090909006540&newsLang=en

Inviragen said it received a US$600,000 grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, “to partially support its continued efforts to develop a safe and effective dengue vaccine.” The two-year grant will fund a collaborative effort led by Inviragen and involving scientists at the University of Wisconsin and Division of Vector-Borne Infectious Diseases at the Centers for Disease Control and Prevention (CDC). The supported work will include additional optimization of Inviragen’s vaccine to generate more potent immune responses. Dr. Jorge Osorio, Inviragen’s Chief Scientific Officer and Assistant Professor at the University of Wisconsin, said, “During the preclinical characterization of our first dengue vaccine, we learned that the immune response could be further enhanced by making genetic improvements in one of the four vaccine components. This grant will fund the engineering and preclinical testing of a second generation dengue vaccine. If successful, we will incorporate the new constructs into future clinical trials.”

“Dengue viruses threaten over 3.5 billion people worldwide and cause an estimated 50 – 100 million cases of dengue fever every year. Due to global urbanization and increased travel, dengue continues to spread worldwide. Dengue fever is caused by infection with one of four different RNA viruses: DEN-1, DEN-2, DEN-3 or DEN-4. To be safe and effective, a dengue vaccine must be capable of neutralizing all four of the dengue viruses. Inviragen’s dengue vaccine technology, developed by researchers at the CDC, is based on a safe virus backbone that generates long-lasting anti-dengue immune responses. Using this technology, Inviragen has developed a four-way vaccine to protect against all four of the different viruses that cause dengue fever. Human clinical testing of the Inviragen vaccine is expected to begin in the coming months. If Inviragen’s dengue vaccine is proven to be safe and effective in human clinical trials, it may be used to protect children and adults who live in dengue-endemic countries and to protect travelers to those regions from this debilitating and dangerous disease.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20090910005432&newsLang=en

The Weekly Epidemiological Record (WER) for 11 September 2009, vol. 84, 37 (pp 373–384) includes: Completion of national laboratory inventories for wild poliovirus containment – WHO Western Pacific Region, December 2008; Onchocerciasis: elimination is feasible.

http://www.who.int/wer/2009/wer8437/en/index.html

The Lancet
Sep 12, 2009  Volume 374  Number 9693  Pages 851 – 948
http://www.thelancet.com/journals/lancet/issue/current

Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates
Original Text
Dr Katherine L O’Brien MD a, Lara J Wolfson PhD b, James P Watt MD c, Emily Henkle MPH a, Maria Deloria-Knoll PhD a, Natalie McCall MD a, Ellen Lee MD a, Prof Kim Mulholland MD d, Orin S Levine PhD a, Thomas Cherian MD b, for the Hib and Pneumococcal Global Burden of Disease Study Team‡
a GAVI’s PneumoADIP, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
b World Health Organization, Geneva, Switzerland
c Hib Initiative, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
d London School of Hygiene and Tropical Medicine, London, UK

Summary
Background
Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years.

Methods
We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b.

Findings
In 2000, about 14·5 million episodes of serious pneumococcal disease (uncertainty range 11·1—18·0 million) were estimated to occur. Pneumococcal disease caused about 826 000 deaths (582 000—926 000) in children aged 1—59 months, of which 91 000 (63 000—102 000) were in HIV-positive and 735 000 (519 000—825 000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449 000 [316 000—501 000]) occurred in ten African and Asian countries.

Interpretation
S pneumoniae causes around 11% (8—12%) of all deaths in children aged 1—59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden.

Funding
GAVI Alliance and the Vaccine Fund.

Vaccine
Volume 27, Issue 42, Pages 5709-5920 (25 September 2009)
http://www.sciencedirect.com/science/journal/0264410X

Conference reports
Control of pertussis—Lessons learnt from a 10-year surveillance programme in Sweden
Pages 5709-5718
Rose-Marie Carlsson, Birger Trollfors

Abstract
Sweden was the only country in the world without any general pertussis vaccination when acellular pertussis (aP) vaccines were introduced. Since 1996 aP vaccines are given at the ages of 3, 5 and 12 months, with a 99% coverage, and until 2007 without a later booster. The long-term effects of aP vaccines, monitored within an enhanced surveillance project, were discussed at an international workshop in Stockholm in November 2008. The unique Swedish experience demonstrates that aP vaccines are capable of achieving the primary goal of a national vaccination programme, i.e., to significantly reduce the burden of pertussis in pre-school children. Throughout the 10-year surveillance period the highest age-specific incidence was reported in unvaccinated infants or those who had received only one dose, with most hospitalisations in this age group and eight deaths among unvaccinated infants. Complementary strategies are needed to achieve further reduction in morbidity from circulation of Bordetella pertussis.

Vaccine
Volume 27, Issue 42, Pages 5709-5920 (25 September 2009)
http://www.sciencedirect.com/science/journal/0264410X

Short Communications
Does receipt of seasonal influenza vaccine predict intention to receive novel H1N1 vaccine: Evidence from a nationally representative survey of U.S. adults
Pages 5732-5734
Jürgen Maurer, Katherine M. Harris, Andrew Parker, Nicole Lurie

Abstract
We analyze data on the intention of U.S. adults to receive novel H1N1 vaccine if available this fall, and studies the relationship between the intention to be vaccinated against novel H1N1 and the uptake of seasonal influenza vaccine last year. We surveyed a nationally representative sample of U.S. adults (n = 2067) via the Internet between May 26th and June 8th, 2009. Our results imply a vaccination rate for novel H1N1 of 49.6%, which corresponds to roughly 115 million adult vaccinations. Moreover, novel H1N1 vaccination intentions are strongly associated with seasonal influenza vaccinations, suggesting common attitudinal barriers to both vaccines.

Vaccine
Volume 27, Issue 42, Pages 5709-5920 (25 September 2009)
http://www.sciencedirect.com/science/journal/0264410X

Review
Prevention of otitis media: Now a reality?
Pages 5748-5754
Lode Schuerman, Dorota Borys, Bernard Hoet, Arne Forsgren, Roman Prymula

Abstract
Acute otitis media (AOM), one of the most common childhood diseases, is associated with a substantial medical, social and economic burden. Non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae are the two main causes of bacterial OM. The 7-valent pneumococcal CRM197-conjugate vaccine (7vCRM, Prevnar™/Prevenar™, Wyeth) demonstrated efficacy against AOM caused by vaccine pneumococcal serotypes. Protection against overall AOM was also observed with an 11-valent pneumococcal protein D-conjugate vaccine (11Pn-PD) in the Pneumococcal Otitis Efficacy Trial (POET). Following POET, an optimized 10-valent pneumococcal non-typeable H. influenzae protein D-conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Biologicals) was developed. This vaccine includes serotypes 1, 5, and 7F, in addition to those already included in 7vCRM, and was recently licensed in Europe for active immunization against invasive disease and AOM caused by S. pneumoniae in infants and children from 6 weeks up to 2 years of age. The use of protein D as carrier protein permits avoidance of possible interferences known to occur with some conjugate vaccines, and has the added potential benefit of providing protection against NTHi. This review seeks to highlight the recent advances in the field of OM vaccination, with a focus on data regarding the recently licensed PHiD-CV.

The WHO continues to issue weekly “updates” and briefing notes as below:

Pandemic (H1N1) 2009 – update 64  Weekly update  4 September 2009

“Tropical regions of South and Southeast Asia continue to experience geographically regional or widespread influenza activity (represented by countries such as India, Bangladesh, Myanmar, Thailand, Cambodia, Sri Lanka, and Indonesia). Many countries in the region are reporting increasing or sustained high levels of respiratory disease, and a few (Thailand and Brunei Darussalam) have begun to report a declining trend in the level of respiratory diseases.
In tropical regions of Central America and the Caribbean (represented by countries such as Costa Rica, El Salvador, Guatemala, Honduras, Panama, and Cuba), influenza activity continues to be geographically regional or widespread, however, most are now reporting a declining trend in the level of respiratory diseases.
Countries in the equatorial and tropical regions of South America (represented by Ecuador, Venzezuela, Peru, and parts of Brazil) continue to experience geographically regional or widespread influenza activity, with many reporting an increasing trend in the level of respiratory diseases.
Although many countries in temperate regions of the southern hemisphere (Chile, Argentina, Australia, and New Zealand) have passed the peak of their winter influenza epidemic, sustained influenza activity continues to be reported in South Africa and in the Southern and Western parts of Australia.
In temperate regions of the northern hemisphere, there are wide geographical variations in the level of influenza activity being reported. In Japan, influenza activity continues to increase past the seasonal epidemic threshold, indicating an early beginning to the to annual influenza season. In Canada and the United States, influenza activity remain low overall, however regional increases are being detected in the Southeastern United States. In Europe and Central and Western Asia, although little influenza activity is being reported, a few countries are reporting geographically widespread influenza activity (Austria and Israel) or an increasing trend in respiratory diseases (Netherlands and Romania).
Pandemic (H1N1) influenza virus continues to be the predominant circulating virus of influenza, both in the northern and southern hemisphere. All pandemic H1N1 2009 influenza viruses analysed to date have been antigenically and genetically similar to A/California/7/2009-like pandemic H1N1 2009 virus. See below for detailed laboratory surveillance update. http://www.who.int/csr/don/2009_09_04/en/index.html

On 1 September 2009, President Barack Obama made a statement on “2009-H1N1 NATIONAL PREPAREDNESS AND RESPONSE” noting:

“…As I said when we saw the first cases of this virus back in the spring, I don’t want anybody to be alarmed, but I do want everybody to be prepared. We know that we usually get a second, larger wave of these flu viruses in the fall, and so response plans have been put in place across all levels of government. Our plans and decisions are based on the best scientific information available, and as the situation changes, we will continue to update the public.

We’re also making steady progress on developing a safe and effective H1N1 flu vaccine, and we expect a flu shot program will begin soon. This program will be completely voluntary, but it will be strongly recommended.

For all that we do in the federal government, however, every American has a role to play in responding to this virus. We need state and local governments on the front lines to make antiviral medications and vaccines available, and be ready to take whatever steps are necessary to support the health care system. We need hospitals and health care providers to continue preparing for an increased patient load, and to take steps to protect health care workers. We need families and businesses to ensure that they have plans in place if a family member, a child, or a co-worker contracts the flu and needs to stay home.

And most importantly we need everyone to get informed about individual risk factors, and we need everyone to take the common-sense steps that we know can make a difference. Stay home if you’re sick. Wash your hands frequently. Cover your sneezes with your sleeve, not your hands. And take all the necessary precautions to stay healthy. I know it sounds simple, but it’s important and it works…”

http://www.whitehouse.gov/the_press_office/Remarks-by-the-President-on-2009-H1N1-National-Preparedness-and-Response/

The CDC Media Briefing: Update on 2009 H1N1 Flu (unedited transcript) for September 3, 2009, included the following comments on H1N1 vaccination:

“…The next issue that I’d like to discuss has to do with vaccination.  There’s a lot going on with vaccination.  We continue to anticipate that vaccine will be available by the middle of October.  The vaccine itself will be free.  The administration may be charged by individual providers, although in the public health system, all vaccination will be free, we anticipate.  It will not be easy to get vaccine uptick.  We have the possibility or even likelihood that it will be a two-dose series for children, at least, and perhaps for others.

“We are going to be trying to reach out to children in large number and parents to get kids’ vaccines, because we know that so many kids can get the flu, and the vaccine is likely to be quite effective.  My kids will get the flu vaccine when it becomes available, and I would recommend that all school children get vaccinated.

“We also are recommending that all people with underlying conditions get vaccinated, people who have asthma, diabetes, lung disease, heart disease, neuromuscular conditions, neurological conditions that increase their risk factors and women who are pregnant.

“Vaccination programs will be run by the states and localities throughout the United States.  We are working closely with all jurisdictions to help them identify the challenges that they’ll face in vaccinating the people in their area and in addressing those challenges.  We are in the process of releasing about $1.5 billion in vaccine planning, preparedness and administration funding.  That will allow each jurisdiction to identify what are the strengths there.  And some jurisdictions will work largely with the public sector.  Other jurisdictions will work largely with the private sector.  Each place will know what the strengths are in their area best and will be able to reach out to the speciality clinics.

“For example, children with special needs or people with asthma or diabetes, to have the detailed planning available.  We also are looking very closely at the possibility of reports of adverse events.  We know that every year, there are cases of paralysis, Guillain-Barre syndrome, there are women who have miscarriages, there are people who have sudden death.  In all of those situations, we need to know very clearly how many we would expect if the vaccine doesn’t cause any problems whatsoever.  In an average flu season, just as an example, around 500,000 pregnant women get vaccinated.  That’s important, because pregnant women are more likely to get severely ill from flu.  So, it’s a way of protecting them and ensuring that they have a healthy pregnancy.  Among those 500,000 women, if they hadn’t gotten vaccinated, we would have expected more than 1,000 miscarriages within a week after vaccine.  If they hadn’t been vaccinated.  If they’re vaccinated, we expect about 1,000, 1,500 among women who are vaccinated.  That’s the kind of number we need to track and understand to see whether when we do see adverse event reports, because we know there will be adverse event reports, they’re occurring at a higher rate than expected or not.

“In the coming weeks and months, with school resuming, we do expect to see more cases.  We’re seeing it now.  We expect that will continue.  How long?  No one can predict with certainty.  Influenza is unpredictable.  That means we need to monitor closely and be willing and ready to adapt to different approaches…”

http://www.cdc.gov/media/transcripts/2009/t090903.htm

The MMWR for September 4, 2009 / Vol. 58 / No. 34, includes:

Surveillance for Pediatric Deaths Associated with 2009 Pandemic Influenza A (H1N1) Virus Infection
United States, April-August 2009

The Advisory Committee on Immunization Practices has prioritized influenza prevention and treatment for children aged <5 years and for those with certain chronic medical and immunosuppressive conditions. CDC monitors child influenza deaths through influenza-associated pediatric mortality case reporting. Through August 8, 2009, CDC received reports of 477 deaths associated with 2009 pandemic influenza A (H1N1) in the United States, including 36 deaths among children aged <18 years. This report describes those pediatric cases.

The U.S. Department of Defense said all military personnel will be vaccinated against the H1N1 flu virus, and that the vaccine will be available to all military family members who want it. DOD said the vaccine, which has been licensed by the Food and Drug Administration, “will be mandatory for uniformed personnel,” targeting those who are at highest risk for transmission. DOD said health-care workers, deploying troops, those serving on ships and submarines, and new accessions are at the top of the list. The department initially will receive 1 million doses of the H1N1 vaccine, and another 1.7 million doses later in October.
http://www.defenselink.mil/news/newsarticle.aspx?id=55698

The Weekly Epidemiological Record (WER) for 4 September 2009, vol. 84, 36 (pp 361–372) includes: Global influenza surveillance network: laboratory surveillance and response to pandemic H1N1 2009; Global detection of wild and vaccine-derived polioviruses, January 2008–June 2009; Monthly report on dracunculiasis cases, January–July 2009. http://www.who.int/wer/2009/wer8436.pdf

The Bulletin of the World Health Organization (BLT) Volume 87, Number 9, September 2009, 645-732, carries an interview with Dr Marie-Paule Kieny, director of the Initiative for Vaccine Research: “WHO supports fair access to influenza A (H1N1) vaccine.” In the article, Dr. Kieny speaks to developing nation access to H1N1 vaccines:

“…Q: WHO has recommended the use of adjuvant in pandemic vaccines, but some countries don’t plan to follow this guidance.

A: Many countries, including the USA, have not licensed vaccines with adjuvants of any kind yet. Other vaccines with the same type of adjuvant as planned for pandemic influenza A (H1N1) vaccines have, however, been licensed in European countries. Countries that intend to use vaccine with adjuvant will find that there is a large body of safety data for adults and some for children. In any case, all countries will need to carry out good post-marketing surveillance to make sure that they pick up any early sign of a safety problem with a particular vaccine.

Q: These must be the fastest vaccines ever produced. Given their fast-tracking, what is the guarantee of safety and efficacy?

A: The testing of influenza vaccines is different from that of other vaccines, because the rabies and measles vaccines for example do not change. Since influenza viruses evolve constantly, it is impossible to carry out a complete clinical analysis of seasonal influenza vaccines yearly because the composition changes each year to adapt to the virus and so you are always a year behind. A complete clinical evaluation is not needed also because manufacturers produce seasonal influenza vaccines using the same procedure and equipment, but for a different virus each year. In the USA, vaccines for seasonal influenza are licensed without clinical trials on the basis of a “strain change”.

The US regulatory authorities consider the change from seasonal to pandemic H1N1 influenza vaccine production (using the same procedure) as a change in the strain and therefore will not request clinical trials before registration. Having said that, all manufacturers will perform clinical trials to find out whether one or two doses are necessary, to test it in special populations and to administer it jointly with other vaccines.

In Europe, a strain change is accompanied by a small clinical trial requested by the European Medicines Agency. In the last couple of years, manufacturers in the European Union registered “mock-up” or prototype H5N1 bird flu vaccines as nobody knows which H5N1 strain might become a pandemic strain. Manufacturers made clinical batches of an H5N1 vaccine with virus stocks from China, Indonesia and Viet Nam. They carried out clinical trials and submitted the results to the regulatory authorities who said the vaccines were fine. They are not allowed to sell H5N1 vaccines, since there is no H5N1 pandemic, but they can use the same procedure to make H1N1 pandemic vaccine. That way they can get a licence in a few days. This is another way vaccines can be licensed without clinical trials, while still ensuring safety on the basis of what is known about influenza vaccines. Based on the extensive knowledge available on seasonal vaccines and the results obtained through evaluation of H5N1 avian influenza vaccines, there is no doubt that it will be possible to make effective H1N1 pandemic vaccines.

Q: What’s been done to ensure that developing countries get enough vaccine?

A: It depends on what we mean by “enough”. Some countries want to vaccinate every member of the population, but there is no way we can do this for the whole world. WHO has a cross-organizational operation that is in place to secure vaccines for developing countries. This is spearheaded by the Director-General’s Office and the legal and vaccine departments. We are engaged in three types of activities. The first is to negotiate donations with manufacturers. Two have been announced: 100 million doses by sanofi-aventis and 50 million doses from GlaxoSmithKline. Second, we are working with other manufacturers to reserve a portion of their vaccine production for WHO at a reduced price. Third, we are working with governments to raise funds to purchase vaccines. We are also working with 11 vaccine manufacturers based in developing countries, providing them with seed financing and technical expertise to help them produce influenza vaccine domestically. We have also helped them access technology and given them sub-licences to use technology for producing live attenuated vaccine. These 11 companies will be manufacturing some of the 30 different expected vaccines.

Q: What happens if developing countries have only partial coverage?

A: Coverage will be partial and not only in developing countries. But we should not be “hypnotized” by vaccines. There are other measures, such as social distancing, school closure, avoidance of large gatherings, antibiotics and personal hygiene. This is not like rabies, which is 100% fatal: we are talking about a disease from which most people recover very well. We will try to help countries to gain access to as much vaccine as possible, at least to preserve their health systems functioning, but there is just not enough vaccine for every country in the world to vaccinate every member of the population twice. http://www.who.int/bulletin/volumes/87/9/09-030909/en/index.html

The NIH reported that preliminary findings in ferrets suggest that the novel 2009 H1N1 influenza virus may outcompete human seasonal influenza viruses. NIH said that tests in animals showed that levels of the 2009 H1N1 virus rose more quickly than levels of the seasonal virus strains, and the new virus caused more severe disease. In line with previous findings by other research groups, the University of Maryland researchers also observed that the novel H1N1 virus was transmitted more easily from infected to uninfected ferrets than either of the two seasonal influenza viruses.

The researchers found no evidence that the 2009 H1N1 virus combined with either of two seasonal flu viruses to form new, so-called reassortant viruses. These findings suggest that while 2009 H1N1 virus probably will predominate in the coming flu season, there may not be biological pressure for the new virus to re-combine with other circulating viruses, the researchers said. The work was done by Daniel Perez, Ph.D., and colleagues from the University of Maryland. The researchers were supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

http://www.nih.gov/news/health/aug2009/niaid-31.htm

The Bill & Melinda Gates Foundation announced that it is now accepting proposals for Round 4 of Grand Challenges Explorations, “an initiative to encourage bold and unconventional research on new global health solutions.” Proposals are being accepted through November 2, 2009. The program “offers scientists, inventors, and entrepreneurs the chance to earn $100,000 grants to further their work,” with projects showing success having an opportunity to receive additional funding up to US$1 million. The topic areas for which proposals are being accepted for this round are:

– Create New Ways to Protect Against Infectious Disease;

– Create New Technologies for Contraception;

– Create New Ways to Induce and Measure Mucosal Immunity;

– Create Low-Cost Diagnostics for Priority Global Health Conditions.

Gates said that one of the primary objectives of Grand Challenges Explorations is “to involve scientists around the world who do not typically work in the health field and may have never applied for a grant before. This includes those with innovative ideas in Africa, Asia, and other parts of the developing world; people working in the private sector; and young investigators.” Full descriptions of the topic areas and the online application tool are available at the Grand Challenges in Global Health web site.

http://www.gatesfoundation.org/press-releases/Pages/proposals-wanted-for-round-four-grand-challenges-explorations-090902.aspx

PATH said it is helping sponsor the 2009 Vaccines for Enteric Diseases conference in Malaga, Spain, from 9 – 11 September 2009.  PATH said the conference “brings together experts in the fields of vaccines and enteric diseases to address a variety of issues around research, development, and evaluation of vaccines for enteric infections. Each year, an estimated 1.8 million children die from severe, dehydrating diarrhea due to enteric infections.”  Dr. Duncan Steele, senior technical advisor for PATH’s Vaccine Development Global Program, will chair the conference. Dr. A. Louis Bourgeois, scientific director of PATH’s Enteric Vaccine Initiative, will moderate a session on enteric bacterial and parasitic vaccines. PATH’s work will also be presented in a session on a market assessment study for enterotoxigenic Escherichia coli (ETEC) vaccines, conducted in partnership with BioVentures for Global Health, and a session on the results from a clinical trial to refine the challenge model for evaluating ETEC vaccines, conducted with Johns Hopkins University. http://www.path.org/news/an090904-ved-conference.php

Journal of Infectious Diseases
1 October 2009   Volume 200, Number 7
http://www.journals.uchicago.edu/toc/jid/current

Perspective
What Is a Pandemic?
David M. Morens, Gregory K. Folkers, and Anthony S. Fauci

PLoS Medicine
(Accessed 7 September 2009)
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

Published 01 Sep 2009 Changing Patterns of Dengue Epidemiology and Implications for Clinical Management and Vaccines Cameron P. Simmons, Jeremy Farrar