WHO: Influenza A(H1N1) – update 51; Confirmed Human Cases of Avian Influenza A/(H5N1)

The WHO continues to issue regular updates on both A/(H1N1) and A/(H5N1) posted on the WHO main page, as well as other advisories linked from that page. Here are the current updates:

– Influenza A(H1N1) – update 51
19 June 2009 — As of 07:00 GMT, 12 June 2009, WHO notes 44,287 officially reported cases of influenza A(H1N1) infection, including 180 deaths.

WHO has included an interactive “timeline of all cases” (requires Flash player) at:

– Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO
2 June 2009  [No update since 2 June 2009]
The published tabular chart reports 433 confirmed cases and 262 deaths.

Novel Influenza A (H1N1) Virus Infections Among HCWs: U.S., April–May 2009

The MMWR Weekly: June 19, 2009 / 58(23);641-645 includes:

Novel Influenza A (H1N1) Virus Infections Among Health-Care Personnel — United States, April–May 2009

“Soon after identification of novel influenza A (H1N1) virus infections in the United States in mid-April 2009, CDC provided interim recommendations to reduce the risk for transmission in health-care settings. These included recommendations on use of personal protective equipment (PPE), management of health-care personnel (HCP) after unprotected exposures, and instruction of ill HCP not to report to work (1). To better understand the risk for acquiring infection with the virus among HCP and the impact of infection-control recommendations, CDC solicited reports of infected HCP from state health departments. As of May 13, CDC had received 48 reports of confirmed or probable infections with novel influenza A (H1N1) virus* (2); of these, 26 reports included detailed case reports with information regarding risk factors that might have led to infection. Of the 26 cases, 13 (50%) HCP were deemed to have acquired infection in a health-care setting, including one instance of probable HCP to HCP transmission and 12 instances of probable or possible patient to HCP transmission. Eleven HCP had probable or possible acquisition in the community, and two had no reported exposures in either health-care or community settings. Among 11 HCP with probable or possible patient to HCP acquisition and available information on PPE use, only three reported always using either a surgical mask or an N95 respirator. These findings suggest that transmission of novel influenza A (H1N1) virus to HCP is occurring in both health-care and community settings and that additional messages aimed at reinforcing current infection-control recommendations are needed.”


Influenza Vaccines for Elderly Individuals

Journal of Infectious Diseases
15 July 2009   Volume 200, Number 2

Editorial Commentaries
Influenza Vaccines for Elderly Individuals—An Evolving Story
Gregory A. Poland and Mark J. Mulligan
[No abstract published]

Randomized, Double-Blind Controlled Phase 3 Trial Comparing the Immunogenicity of High-Dose and Standard-Dose Influenza Vaccine in Adults 65 Years of Age and Older
Ann R. Falsey,1,2; John J. Treanor,2; Nadia Tornieporth,3; Jose Capellan,5 and Geoffrey J. Gorse4
1Department of Medicine, Rochester General Hospital and 2University of Rochester School of Medicine, Rochester, New York; 3sanofi pasteur, Swiftwater, Pennsylvania; 4Saint Louis Department of Veterans Affairs Medical Center and Saint Louis University, Saint Louis, Missouri; 5sanofi pasteur, Toronto, Canada

Background.Influenza‐associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high‐dose (HD) trivalent, inactivated influenza vaccine was developed.

Methods.A multicenter, randomized, double‐blind controlled study was conducted to compare HD vaccine (which contains 60 μg of hemagglutinin per strain) with the licensed standard‐dose (SD) vaccine (which contains 15 μg of hemagglutinin per strain) in adults 65 years of age.

Results.HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects. There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine, compared with those who received SD vaccine. Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1, 609 for H3N2, and 69 for B strain; for those who received SD vaccine, mean postvaccination titers were as 67 for H1N1, 333 for H3N2, and 52 for B strain. The HD vaccine met superiority criteria for both A strains, and the responses for B strain met noninferiority criteria. Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine, for all strains. Local reactions were more frequent in individuals who received HD vaccine, but the reactions were mild to moderate.

Conclusions.There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine, compared with that induced by SD vaccine, without an attendant increase in the rate or severity of clinically relevant adverse reactions. These results suggest that the high‐dose vaccine may provide improved protective benefits for older adults.

Trial registration.ClinicalTrials.gov identifier: NCT00391053.

Who runs global health?

The Lancet
Jun 20, 2009  Volume 373  Number 9681  Pages 2083 – 2170

Who runs global health?
The Lancet

The past two decades have seen dramatic shifts in power among those who share responsibility for leading global health. In 1990, development assistance for health—a crude, but still valid measure of influence—was dominated by the UN system (WHO, UNICEF, and UNFPA) and bilateral development agencies in donor countries. Today, while donor nations have maintained their relative importance, the UN system has been severely diluted. This marginalisation, combined with serious anxieties about the unanticipated adverse effects of new entrants into global health, should signal concern about the current and future stewardship of health policies and services for the least advantaged peoples of the world.

Access to health care for undocumented migrants in Italy

The Lancet
Jun 20, 2009  Volume 373  Number 9681  Pages 2083 – 2170

Access to health care for undocumented migrants in Italy
R Ravinetto, C Lodesani, U D’Alessandro, L De Filippi, A Pontiroli

In Italy, since 1998, undocumented migrants have had the right to receive health care under national law, without being reported to immigration authorities. This aspect of the legislation is in line with Article 32 of the Italian Constitution, which states that health is a fundamental right of the individual (not only of the citizen) and statutes free health care for the poor.

Financing of global health: tracking development assistance for health from 1990 to 2007

The Lancet
Jun 20, 2009  Volume 373  Number 9681  Pages 2083 – 2170

Financing of global health: tracking development assistance for health from 1990 to 2007

Nirmala Ravishankar, Paul Gubbins, Rebecca J Cooley, Katherine Leach-Kemon, Catherine M Michaud, Dean T Jamison, Christopher JL Murray

This study documents the substantial rise of resources for global health in recent years. Although the rise in DAH has resulted in increased funds for HIV/AIDS, other areas of global health have also expanded. The influx of funds has been accompanied by major changes in the institutional landscape of global health, with global health initiatives such as the Global Fund and GAVI having a central role in mobilising and channelling global health funds.

Compulsory childhood vaccination

The Lancet Infectious Disease
Jul 2009  Volume 9  Number 7   Pages 393 – 454

Leading Edge
Compulsory childhood vaccination
The Lancet Infectious Diseases

The UK faces an outbreak of measles virus infection on a scale not seen since vaccination became available. Figures released in February for England and Wales show a 36% rise in confirmed cases of measles, from 990 in 2007 to 1348 in 2008, the highest number since monitoring was introduced in 1995. A further 382 cases were reported in the first 3 months of this year. According to the Health Protection Agency, most cases are among children who have not been fully vaccinated with the combined measles, mumps, and rubella (MMR) vaccine.

Protecting children with HIV against pneumococcal disease

The Lancet Infectious Disease
Jul 2009  Volume 9  Number 7   Pages 393 – 454

Protecting children with HIV against pneumococcal disease
Andrea Meehan, Grant Mackenzie, Delane Shingadia, Robert Booy

Rwanda has become the first developing nation to introduce pneumococcal conjugate vaccine. The aim is to vaccinate nearly all Rwandan infants by the end of 2009. However, equally at risk older children with HIV are unfortunately not yet on the agenda.1 WHO estimates that disease due to Streptococcus pneumoniae claims the lives of up to 1 million children every year.2 These deaths are disproportionately represented in the developing world, particularly in children infected with HIV3 of whom there are about 2 million in sub-Saharan Africa alone.

Emergence and pandemic potential of swine-origin H1N1 influenza virus

Volume 459 Number 7249 pp889-1026

Emergence and pandemic potential of swine-origin H1N1 influenza virus

Gabriele Neumann1, Takeshi Noda2 & Yoshihiro Kawaoka1,2,3,4

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.

Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
International Research Center for Infectious Diseases,
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan

Correspondence to: Yoshihiro Kawaoka1,2,3,4 Correspondence should be addressed to Y.K. (Email: kawaokay@svm.vetmed.wisc.edu).

Signature Features of Influenza Pandemics — Implications for Policy

New England Journal of Medicine
Volume 360 — June 18, 2009 — Number 25

The Signature Features of Influenza Pandemics — Implications for Policy
M. A. Miller, C. Viboud, M. Balinska, and L. Simonsen

[Initial text per NEJM convention]
Vast amounts of time and resources are being invested in planning for the next influenza pandemic, and one may indeed have already begun. Data from past pandemics can provide useful insights for current and future planning. Having conducted archeo-epidemiologic research, we can clarify certain “signature features” of three previous influenza pandemics — A/H1N1 from 1918 through 1919, A/H2N2 from 1957 through 1963, and A/H3N2 from 1968 through 1970 — that should inform both national plans for pandemic preparedness and required international collaborations.

Past pandemics were characterized by a shift in the virus subtype, shifts of the highest death rates to…

Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans

New England Journal of Medicine
Volume 360 — June 18, 2009 — Number 25

Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team

Background On April 15 and April 17, 2009, novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in specimens obtained from two epidemiologically unlinked patients in the United States. The same strain of the virus was identified in Mexico, Canada, and elsewhere. We describe 642 confirmed cases of human S-OIV infection identified from the rapidly evolving U.S. outbreak.

Methods Enhanced surveillance was implemented in the United States for human infection with influenza A viruses that could not be subtyped. Specimens were sent to the Centers for Disease Control and Prevention for real-time reverse-transcriptase–polymerase-chain-reaction confirmatory testing for S-OIV.

Results From April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. Of patients with available data, 18% had recently traveled to Mexico, and 16% were identified from school outbreaks of S-OIV infection. The most common presenting symptoms were fever (94% of patients), cough (92%), and sore throat (66%); 25% of patients had diarrhea, and 25% had vomiting. Of the 399 patients for whom hospitalization status was known, 36 (9%) required hospitalization. Of 22 hospitalized patients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously.

Conclusions A novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred.

Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings

19 June 2009   Vol 324, Issue 5934, Pages 1477-1602

Pandemic Potential of a Strain of Influenza A (H1N1): Early Findings

Christophe Fraser,1,* Christl A. Donnelly,1,* Simon Cauchemez,1 William P. Hanage,1 Maria D. Van Kerkhove,1 T. Déirdre Hollingsworth,1 Jamie Griffin,1 Rebecca F. Baggaley,1 Helen E. Jenkins,1 Emily J. Lyons,1 Thibaut Jombart,1 Wes R. Hinsley,1 Nicholas C. Grassly,1 Francois Balloux,1 Azra C. Ghani,1 Neil M. Ferguson,1, Andrew Rambaut,2 Oliver G. Pybus,3 Hugo Lopez-Gatell,4 Celia M. Alpuche-Aranda,5 Ietza Bojorquez Chapela,4 Ethel Palacios Zavala,4 Dulce Ma. Espejo Guevara,6 Francesco Checchi,7 Erika Garcia,7 Stephane Hugonnet,7 Cathy Roth,7 The WHO Rapid Pandemic Assessment Collaboration

A novel influenza A (H1N1) virus has spread rapidly across the globe. Judging its pandemic potential is difficult with limited data, but nevertheless essential to inform appropriate health responses. By analyzing the outbreak in Mexico, early data on international spread, and viral genetic diversity, we make an early assessment of transmissibility and severity. Our estimates suggest that 23,000 (range 6000 to 32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range: 0.3 to 1.8%) based on confirmed and suspected deaths reported to that time. In a community outbreak in the small community of La Gloria, Veracruz, no deaths were attributed to infection, giving an upper 95% bound on CFR of 0.6%. Thus, although substantial uncertainty remains, clinical severity appears less than that seen in the 1918 influenza pandemic but comparable with that seen in the 1957 pandemic. Clinical attack rates in children in La Gloria were twice that in adults (<15 years of age: 61%; 15 years: 29%). Three different epidemiological analyses gave basic reproduction number (R0) estimates in the range of 1.4 to 1.6, whereas a genetic analysis gave a central estimate of 1.2. This range of values is consistent with 14 to 73 generations of human-to-human transmission having occurred in Mexico to late April. Transmissibility is therefore substantially higher than that of seasonal flu, and comparable with lower estimates of R0 obtained from previous influenza pandemics.

1 MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
2 Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3JT, UK.
3 Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
4 Directorate General of Epidemiology, FCO. De P. Miranda, 177 5th Floor, Mexico City, 01480, Mexico.
5 National Institute of Epidemiological Diagnosis and Reference, Prolongación Carpio No. 470 (3° piso), Col Santo Tomás, México City, C.P. 11340, Mexico.
6 Secretaría de Salud – Servicios de Salud de Veracruz Soconusco No. 36, Colonia Aguacatal, C.P. 910 Xalapa, Veracruz, México State.
7 World Health Organization.

* These authors contributed equally to this work.
All authors are members of this collaboration.
To whom correspondence should be addressed. E-mail: neil.ferguson@imperial.ac.uk

Pneumococcal vaccination in developing countries

Volume 27, Issue 32, Pages 4247-4380 (9 July 2009)

Pneumococcal vaccination in developing countries: Where does science end and commerce begin?
Pages 4247-4251
Joseph L. Mathew
Recently Pneumococcal vaccines have generated considerable interest in developing countries as an intervention for protecting children from pneumonia and thereby reducing childhood mortality. Many convincing scientific arguments have been put forward, although they are often based either on extension of information from developed countries, or estimation plus extrapolation of limited local data. In addition, there is also significant commercial pressure to prescribe/recommend Pneumococcal vaccine(s). Against such a background, it is important for developing countries to critically appraise the issues involved in order to make a rational choice. This brief paper explores these issues, showing that the current Pneumococcal vaccines have limited effectiveness in developing countries and the hype surrounding them is more commercial than scientific.

Evaluating the impact of HPV vaccines

Volume 27, Issue 32, Pages 4247-4380 (9 July 2009)

Regular papers
Evaluating the impact of human papillomavirus vaccines
Pages 4355-4362
Yuli Chang, Noel T. Brewer, Allen C. Rinas, Karla Schmitt, Jennifer S. Smith
While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines’ effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.

– Influenza A(H1N1) – update 48; Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1)

The WHO continues to issue regular updates on both A/(H1N1) and A/(H5N1) posted on the WHO main page, as well as other advisories linked from that page. Here are the current updates:

– Influenza A(H1N1) – update 48
12 June 2009 — As of 07:00 GMT, 12 June 2009, 74 countries have officially reported 29,669 cases of influenza A(H1N1) infection, including 145 deaths.

– Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO
2 June 2009  [No update since 2 June 2009]
The published tabular chart reports 433 confirmed cases and 262 deaths.

The WHO released an FAQ around the announcement of pandemic level 6 for A/(H1N1). The question and answer provided about severity is provided below:
What about severity?

At this time, WHO considers the overall severity of the influenza pandemic to be moderate. This assessment is based on scientific evidence available to WHO, as well as input from its Member States on the pandemic’s impact on their health systems, and their social and economic functioning.

The moderate assessment reflects that:
– Most people recover from infection without the need for hospitalization or medical care.
– Overall, national levels of severe illness from influenza A(H1N1) appear similar to levels seen during local seasonal influenza periods, although high levels of disease have occurred in some local areas and institutions.
– Overall, hospitals and health care systems in most countries have been able to cope with the numbers of people seeking care, although some facilities and systems have been stressed in some localities.

WHO is concerned about current patterns of serious cases and deaths that are occurring primarily among young persons, including the previously healthy and those with pre-existing medical conditions or pregnancy.

Large outbreaks of disease have not yet been reported in many countries, and the full clinical spectrum of disease is not yet known.


WHO Director-General Dr Margaret Chan: “the world (is) now at the start of 2009 influenza pandemic”

WHO Director-General Dr Margaret Chan said the “the world (is) now at the start of 2009 influenza pandemic” in raising A/(H1N1) pandemic level to “6”.

Full text of statement to the press by WHO:
11 June 2009

Dr Margaret Chan
Director-General of the World Health Organization

“Ladies and gentlemen,

In late April, WHO announced the emergence of a novel influenza A virus.

This particular H1N1 strain has not circulated previously in humans. The virus is entirely new.

The virus is contagious, spreading easily from one person to another, and from one country to another. As of today, nearly 30,000 confirmed cases have been reported in 74 countries.

This is only part of the picture. With few exceptions, countries with large numbers of cases are those with good surveillance and testing procedures in place.

Spread in several countries can no longer be traced to clearly-defined chains of human-to-human transmission. Further spread is considered inevitable.

I have conferred with leading influenza experts, virologists, and public health officials. In line with procedures set out in the International Health Regulations, I have sought guidance and advice from an Emergency Committee established for this purpose.

On the basis of available evidence, and these expert assessments of the evidence, the scientific criteria for an influenza pandemic have been met.

I have therefore decided to raise the level of influenza pandemic alert from phase 5 to phase 6.

The world is now at the start of the 2009 influenza pandemic.

We are in the earliest days of the pandemic. The virus is spreading under a close and careful watch.

No previous pandemic has been detected so early or watched so closely, in real-time, right at the very beginning. The world can now reap the benefits of investments, over the last five years, in pandemic preparedness.

We have a head start. This places us in a strong position. But it also creates a demand for advice and reassurance in the midst of limited data and considerable scientific uncertainty.

Thanks to close monitoring, thorough investigations, and frank reporting from countries, we have some early snapshots depicting spread of the virus and the range of illness it can cause.

We know, too, that this early, patchy picture can change very quickly. The virus writes the rules and this one, like all influenza viruses, can change the rules, without rhyme or reason, at any time.

Globally, we have good reason to believe that this pandemic, at least in its early days, will be of moderate severity. As we know from experience, severity can vary, depending on many factors, from one country to another.

On present evidence, the overwhelming majority of patients experience mild symptoms and make a rapid and full recovery, often in the absence of any form of medical treatment.

Worldwide, the number of deaths is small. Each and every one of these deaths is tragic, and we have to brace ourselves to see more. However, we do not expect to see a sudden and dramatic jump in the number of severe or fatal infections.

We know that the novel H1N1 virus preferentially infects younger people. In nearly all areas with large and sustained outbreaks, the majority of cases have occurred in people under the age of 25 years.

In some of these countries, around 2% of cases have developed severe illness, often with very rapid progression to life-threatening pneumonia.

Most cases of severe and fatal infections have been in adults between the ages of 30 and 50 years.

This pattern is significantly different from that seen during epidemics of seasonal influenza, when most deaths occur in frail elderly people.

Many, though not all, severe cases have occurred in people with underlying chronic conditions. Based on limited, preliminary data, conditions most frequently seen include respiratory diseases, notably asthma, cardiovascular disease, diabetes, autoimmune disorders, and obesity.

At the same time, it is important to note that around one third to half of the severe and fatal infections are occurring in previously healthy young and middle-aged people.

Without question, pregnant women are at increased risk of complications. This heightened risk takes on added importance for a virus, like this one, that preferentially infects younger age groups.

Finally, and perhaps of greatest concern, we do not know how this virus will behave under conditions typically found in the developing world. To date, the vast majority of cases have been detected and investigated in comparatively well-off countries.

Let me underscore two of many reasons for this concern. First, more than 99% of maternal deaths, which are a marker of poor quality care during pregnancy and childbirth, occurs in the developing world.

Second, around 85% of the burden of chronic diseases is concentrated in low- and middle-income countries.

Although the pandemic appears to have moderate severity in comparatively well-off countries, it is prudent to anticipate a bleaker picture as the virus spreads to areas with limited resources, poor health care, and a high prevalence of underlying medical problems.

Ladies and gentlemen,

A characteristic feature of pandemics is their rapid spread to all parts of the world. In the previous century, this spread has typically taken around 6 to 9 months, even during times when most international travel was by ship or rail.

Countries should prepare to see cases, or the further spread of cases, in the near future. Countries where outbreaks appear to have peaked should prepare for a second wave of infection.

Guidance on specific protective and precautionary measures has been sent to ministries of health in all countries. Countries with no or only a few cases should remain vigilant.

Countries with widespread transmission should focus on the appropriate management of patients. The testing and investigation of patients should be limited, as such measures are resource intensive and can very quickly strain capacities.

WHO has been in close dialogue with influenza vaccine manufacturers. I understand that production of vaccines for seasonal influenza will be completed soon, and that full capacity will be available to ensure the largest possible supply of pandemic vaccine in the months to come.

Pending the availability of vaccines, several non-pharmaceutical interventions can confer some protection.

WHO continues to recommend no restrictions on travel and no border closures.

Influenza pandemics, whether moderate or severe, are remarkable events because of the almost universal susceptibility of the world’s population to infection.

We are all in this together, and we will all get through this, together.

Thank you.


Weekly Epidemiological Record (WER), 12 June 2009

The Weekly Epidemiological Record (WER), 12 June 2009, vol. 84, 24 (pp 227–248) includes: Human infection with new influenza A (H1N1) virus: clinical observations from a school-associated outbreak in Kobe, Japan, May 2009; Strategic Advisory Group of Experts: recommendations on the use of licensed human H5N1 influenza vaccines in the interpandemic period


HHS and DHS Comment on WHO Action on Level 6 Pandemic

HHS Secretary Kathleen Sebelius and DHS Secretary Janet Napolitano commented on WHO’s decision to declare novel A/(H1N1) outbreak a pandemic. Secretary Kathleen Sebelius said, “today’s decision by the WHO was expected and doesn’t change what we have been doing here in the United States to prepare for and respond to this public health challenge. Once we saw how fast this virus was spreading, we activated our pandemic plans and started doing all the things we needed to do to keep the public as safe and secure as possible. What this declaration does do is remind the world that flu viruses like H1N1 need to be taken seriously. Although we have not seen large numbers of severe cases in this country so far, things could possibly be very different in the fall, especially if things change in the Southern Hemisphere, and we need to start preparing now in order to be ready for a possible H1N1 immunization campaign starting in late September.”

Secretary Janet Napolitano said, “We responded to the H1N1 outbreak from the outset with the presumption that a pandemic was likely, so this decision comes as no surprise. We acted aggressively to stay ahead of the virus as it spread across the country. Now our challenge is to prepare for a possible return in the fall,” said Secretary Napolitano. “The Obama Administration has been working together across the government and will continue to do so over the weeks and months ahead to keep the American people safe. We are reaching out to our partners in state and local government, in school districts and the private sector to urge them to modify and update their pandemic plans. We are working with our scientists to test and prepare a possible vaccine. And we are working with governments around the world to share what we know and learn from what is happening in their countries.”


(BUSINESS WIRE, 11 June 2009)

Baxter International now in full-scale production of a commercial A/H1N1 vaccine

Baxter International announced that it “has completed testing and evaluation of the A/H1N1 influenza virus and is now in full-scale production of a commercial A/H1N1 vaccine using its Vero cell culture technology.” Baxter said it received an A/H1N1 strain from the U.S. CDC in early May and “is diligently working to deliver a pandemic vaccine for use as early as July.” Baxter noted that “a number of national public health authorities have existing pandemic agreements with Baxter that allow them to place orders for a vaccine now that a pandemic has been declared by WHO.” These public health authorities will be evaluating their needs to determine their orders for vaccine supply. Baxter said that despite its “existing obligations to supply vaccine under a pandemic phase 6 alert, Baxter is also committed to working with WHO to allocate a portion of the company’s commercial production to address global public health issues deemed most urgent.”

(BUSINESS WIRE, 12 June 2009)

First Advance Market Commitment (AMC) pilot project formally launched: pneumococcal diseases in developing countries

The Finance Ministers of Italy, Canada and Russia, together with the United Kingdom, Norway and the Bill & Melinda Gates Foundation, the World Bank Group, the GAVI Alliance, UNICEF and WHO, “formally activated the implementation phase of the Advance Market Commitment (AMC) pilot project to accelerate introduction of vaccines against pneumococcal diseases in developing countries.” The action represents a formal step in their $1.5-billion commitment, made in Rome on February 9, 2007, “when they decided to adopt the innovative AMC approach to save lives in the world’s poorest nations.”

The AMC against pneumococcal disease “will prompt the establishment of new production plants dedicated to pneumococcal vaccines (and) over the long term, this will create a self-sustainable market at affordable prices for recipient countries.” The currently existing pneumococcal vaccine is sold at over US$70 in industrialized countries. But thanks to the AMC, the long term price for developing countries will be US$3.50. In June 2008 the GAVI Alliance Board confirmed its intent to provide US$1.3 billion to support the purchase of pneumococcal vaccines by poor countries interested in buying them. GAVI hopes to assist up to 60 of the world’s poorest countries to introduce these vaccines by 2015. With today’s ceremony, “donors are making the AMC fully operational, helping create a new market with all parties having signed the package of legal agreements that outline their respective roles.”

AMC donor contributions (US$)

Italy – $635 million
UK – $485 million
Canada – $200 million
Russia – $80 million
Norway – $50 million
The Bill & Melinda Gates Foundation – $50 million

TOTAL – $ 1.5 Billion


Lancet Editorial: Right-to-health responsibilities of pharmaceutical companies

The Lancet
Jun 13, 2009  Volume 373  Number 9680  Pages 1997 – 2082

Right-to-health responsibilities of pharmaceutical companies
Original Text
The Lancet

Almost 2 billion people worldwide lack access to essential medicines. The human rights responsibility to improve access lies mainly with the state. However, non-state actors, such as the pharmaceutical industry, share that responsibility too. On June 3, a UN independent human rights report on the practices and policies of GlaxoSmithKline (GSK) in relation to their right-to-health responsibilities and access to medicines was presented to the UN Human Rights Council. It is the first time that such a mission on a pharmaceutical company has ever been done. GSK should be commended for subjecting themselves to the process.

In 2008, Paul Hunt, UN Special Rapporteur on the right to highest attainable standard of health (2002—08), prepared human rights guidelines for the pharmaceutical industry that addressed transparency, management, monitoring and accountability, pricing, and ethical marketing. Recommendations from Hunt’s recent GSK report in these areas will apply to other companies and include: greater transparency to ensure access to reliable information about medicines; greater accountability in relation to right-to-health standards, such as wider access to medicines especially for marginalised populations; and finally, as patent holders of life-saving medicines, to make the medicine as accessible as possible, as soon as possible, to all those in need within a viable business model. More specifically, companies should favour using commercial voluntary licences.

GSK was uncomfortable with the recommendations. It insisted that the right to health is not well-defined for non-state actors, and hence they cannot be held accountable to this international human right. On the contrary, both UN reports set out with reasonable precision how the right to health, in the international code of human rights, applies to the pharmaceutical industry, and both move from broad statements of principle to much more specific, operational requirements.

Pharmaceutical companies help deliver the right to health. They save lives. But with this role comes responsibilities—and companies must be better held to public account in relation to those responsibilities. The 2008 guidelines and the GSK report move us closer to that goal.

For GSK response see:

Vaccine Injury Claims/Litigation/Education

New England Journal of Medicine
Volume 360 — June 11, 2009 — Number 24

When Vaccine Injury Claims Go to Court
A. M. Stewart
[First 100 words per NEJM protocol]
In February 2009, the National Vaccine Injury Compensation Program (VICP) released decisions for the first three test cases heard under the program’s Omnibus Autism Proceeding. In each of the cases — Cedillo v. Secretary of Health and Human Services, Hazlehurst v. Secretary of Health and Human Services, and Snyder v. Secretary of Health and Human Services — the petitioners alleged that a child’s autism spectrum disorder was caused by the combination of the measles–mumps–rubella (MMR) vaccine and thimerosal-containing vaccines. The decisions will have a substantial effect on vaccine policy and practice in the United States and will influence the analysis . . .

Litigation, Regulation, and Education — Protecting the Public’s Health through Childhood Immunization
R. D. Silverman

Stopping Clinical Trials Early: Opportunity Costs

PLoS Medicine
(Accessed 8 June 2009)

Published 09 Jun 2009
In Global Health Research, Is It Legitimate To Stop Clinical Trials Early on Account of Their Opportunity Costs?
James V. Lavery, Peter A. Singer, Renee Ridzon, Jerome A. Singh, Arthur S. Slutsky, Joseph J. Anisko, David Buchanan

Background to the debate: After the failure of three large clinical trials of vaginal microbicides, a Nature editorial stated that the microbicide field “requires a mechanism to help it make rational choices about the best candidates to move through trials” [1]. In this month’s debate, James Lavery and colleagues propose a new mechanism, based on stopping trials early for “opportunity costs.” They argue that microbicide trial sites could have been saturated with trials of scientifically less advanced products, while newer, and potentially more promising, products were being developed. They propose a mechanism to reallocate resources invested in existing trials of older products that might be better invested in more scientifically advanced products that are awaiting clinical testing. But David Buchanan argues that the early stopping of trials for such opportunity costs would face insurmountable practical barriers, and would risk causing harm to the participants in the trial that was stopped.

Influenza vaccination of health care workers in hospitals—A review of studies on attitudes and predictors

Volume 27, Issue 30, Pages 3927-4078 (19 June 2009)

Influenza vaccination of health care workers in hospitals—A review of studies on attitudes and predictors
Pages 3935-3944
Helge G. Hollmeyer, Frederick Hayden, Gregory Poland, Udo Buchholz

Immunization guidelines from many countries recommend influenza vaccination of health care workers (HCW). However, influenza vaccination rates among HCW are universally low. To aid in designing effective immunization programs we reviewed the literature for studies reporting on (1) self-reported reasons of HCW regarding vaccination against influenza and (2) predictive factors for influenza vaccination in HCW.

We searched PUBMED for relevant publications from 1980 to 2008 with predetermined search strategies and applied pre-defined criteria for inclusion or exclusion. To be included in the review as a predictor study, a multivariate analysis must have been conducted.

We included 25 studies relevant to self-reported reasons for rejecting or accepting vaccination. These studies identified two major reasons for lack of vaccine uptake by HCW: firstly, a wide range of misconceptions or lack of knowledge about influenza infection; and secondly, a lack of convenient access to vaccine. In contrast, among studies reporting on reasons for vaccination acceptance, all but two found that HCW stated self-protection was the most important reason. In the area of “predictive factors for influenza vaccination”, we included 13 studies. At least five of them identified the following three factors: previous receipt of influenza vaccine, belief in the vaccine’s effectiveness, and older age.

Our findings indicate that if HCW get immunized against influenza, they do so primarily for their own benefit and not for the benefit to their patients. Misconceptions about influenza and influenza vaccine could be improved by education, and organizational barriers could be bridged with sustainable, structural changes to allow flexible and workplace vaccine delivery.

Acceptance of the HPV vaccine among women, parents, community leaders, and healthcare providers in Ohio Appalachia

Volume 27, Issue 30, Pages 3927-4078 (19 June 2009)

Acceptance of the HPV vaccine among women, parents, community leaders, and healthcare providers in Ohio Appalachia
Pages 3945-3952
Mira L. Katz, Paul L. Reiter, Sarah Heaner, Mack T. Ruffin, Douglas M. Post, Electra D. Paskett

To assess HPV vaccine acceptability, focus groups of women (18–26 years), parents, community leaders, and healthcare providers were conducted throughout Ohio Appalachia. Themes that emerged among the 23 focus groups (n = 114) about the HPV vaccine were: barriers (general health and vaccine specific), lack of knowledge (cervical cancer and HPV), cultural attitudes, and suggestions for educational materials and programs. Important Appalachian attitudes included strong family ties, privacy, conservative views, and lack of trust of outsiders to the region. There are differences in HPV vaccine acceptability among different types of community members highlighting the need for a range of HPV vaccine educational materials/programs to be developed that are inclusive of the Appalachian culture.

Evaluation of pandemic influenza prototype vaccines in clinical trials: WHO 5th Meeting

Volume 27, Issue 31, Pages 4079-4246 (24 June 2009)

Report of the 5th meeting on the evaluation of pandemic influenza prototype vaccines in clinical trials: World Health Organization, Geneva, Switzerland, 12–13 February 2009
Pages 4079-4089
Frederick G. Hayden, Wendy A. Howard, Laszlo Palkonyay, Marie Paule Kieny
Influenza vaccines are potentially the most efficacious means of mitigating the impact of influenza pandemic and might contribute to the rapid containment of an emerging pandemic virus.

On the 12–13 February 2009, the Initiative For Vaccine Research (IVR) of the World Health Organisation convened the 5th meeting on the ‘Evaluation of pandemic influenza prototype vaccines in clinical trials’ in Geneva. This was a follow-up meeting to the 4th meeting held on 14–15 February 2008 [Girard M, Palkonyay L, Kieny MP. Report of the 4th meeting on the evaluation of pandemic influenza prototype vaccines in clinical trials. Vaccine 2008;26:4975–7], and presentations were made by representatives from industry, academia, and governmental organisations. This year’s meeting aimed to update the progress made during the past year on H5N1 and other prototype pandemic vaccines that have undergone clinical trials. A number of vaccine types were covered, including classical egg-derived inactivated vaccines, cell-derived inactivated vaccines, live-attenuated vaccines (LAIV) and vaccines developed using new technologies. The effects of different adjuvants and prime-boosting schedules were important topics, and further data were presented to show that children mount vigorous antibody responses to several H5N1 vaccines. Other subjects presented and discussed were standardisation, and regulatory issues concerning pandemic vaccines.

Scheduling of measles vaccination in low-income countries: Projections of a dynamic model

Volume 27, Issue 31, Pages 4079-4246 (24 June 2009)

Scheduling of measles vaccination in low-income countries: Projections of a dynamic model
Pages 4090-4098
C.T. Bauch, E. Szusz, L.P. Garrison

Large-scale vaccination campaigns (SIAs) and improved routine immunization (RI) have greatly reduced measles incidence in low-income countries. However, the interval between SIAs required to maintain these gains over the long term is not clear. We developed a dynamic model of measles transmission to assess measles vaccination strategies in Cambodia, Ghana, India, Morocco, Nigeria, and Uganda. We projected measles cases from 2008 to 2050 under (a) holding SIAs every 2, 4, 6, or 8 years, (b) improvements in first dose routine measles vaccine (MCV1) coverage of 0%, 1%, 3% annually, and (c) introducing MCV2 once MCV1 coverage reaches 70%, 80%, 90%. If MCV1 continues improving, then India and Nigeria could hold SIAs every 4 years without significant probability of large outbreaks, and the other countries every 6–8 years. If RI remains stagnant, India and Nigeria should hold SIAs every 2 years, and the other countries every 4–6 years.

HCW knowledge, attitudes and vaccination coverage: occupational vaccinations/Paris

Volume 27, Issue 31, Pages 4079-4246 (24 June 2009)

Knowledge, attitudes and vaccination coverage of healthcare workers regarding occupational vaccinations
Pages 4240-4243
P. Loulergue, F. Moulin, G. Vidal-Trecan, Z. Absi, C. Demontpion, C. Menager, M. Gorodetsky, D. Gendrel, L. Guillevin, O. Launay


Immunization of healthcare workers (HCWs) is a major issue for infection control in healthcare facilities. The aim of this study was to evaluate knowledge regarding occupational vaccinations, HBV, varicella and influenza vaccination rates and attitudes towards influenza vaccine among HCWs.

Design and setting
A cross-sectional survey was conducted in two wards (Medicine and Paediatrics) of a 1182-bed teaching hospital in Paris, France.

A standardized, anonymous, self-administered questionnaire was used.

Of 580 HCWs, 395 (68%) completed the questionnaire. Knowledge about the occupational vaccinations of HCWs was low. HBV (69%), tuberculosis (54%) and influenza (52%) were the most cited vaccinations. Paediatric staff was more aware of influenza and pertussis immunizations (p < .05). HBV vaccination rate was 93%, among whom 65% were aware of their immune status. Influenza vaccination rate for 2006–2007 was 30% overall, ranging from 50% among physicians to 20% among paramedical staff (p < .05). Physicians based their refusal on doubts about vaccine efficacy, although paramedics feared side effects. Influenza vaccination was associated with knowledge of vaccine recommendations [OR = 1.75, 95% CI: 1.13–2.57] and contact with patients [OR = 3.05, 95% CI: 1.50–5.91].

Knowledge of recommended occupational vaccinations is insufficient in HCWs, except for HBV and influenza. Although the HBV vaccine coverage of HCWs is satisfactory, a large proportion of them is unaware of immune status. Influenza vaccine coverage remains low, especially among paramedical staff because of fear of side effects. As vaccine coverage is associated with knowledge, educational campaigns should be strengthened to increase the adhesion of HCWs to vaccinations.

WHO: (novel) A/(H1N1) and A/(H5N1) updates

The WHO continues to issue regular updates on both A/(H1N1) and A/(H5N1) posted on the WHO main page, as well as other advisories linked from that page. Here are the current updates:
– Influenza A(H1N1) – update 45
8 June 2009 — As of 06:00 GMT, 8 June 2009, 73 countries have officially reported 25,288 cases of influenza A(H1N1) infection, including 139 deaths.

– Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO
2 June 2009
The published tabular chart reports 433 confirmed cases and 262 deaths.

WHO Convenes International Health Regulations (IHR) Emergency Committee: A/(H1N1) Management

WHO Director-General Margaret Chan convened a third meeting of the International Health Regulations (IHR) Emergency Committee on 5 June 2009. The purpose of the meeting was “to update the committee on the global situation and seek advice on proposals to introduce severity assessments in any future announcements of pandemic phase changes by WHO.” There was “broad consensus on the importance of including information on severity in future announcements. The committee gave further advice regarding a number of parameters, the monitoring of which will provide information for the assessment of the severity of the epidemic.” Based on the advice of the committee, the Director-General “determined that it was appropriate to continue the existing temporary recommendations, namely:

– That all countries intensify surveillance for unusual outbreaks of influenza-like illness and severe pneumonia.

– Not to close borders and not to restrict international travel. It is considered prudent for people who are ill to delay international travel and for people developing symptoms following travel to seek medical attention.

– That the production of seasonal influenza vaccine should continue at this time, subject to re-evaluation as the situation evolves.


WHO recommends “rotavirus vaccination be included in all national immunization programmes”

The World Health Organization recommended that “rotavirus vaccination be included in all national immunization programmes in order to provide protection against a virus that is responsible for more than 500,000 diarrheal deaths and two million hospitalizations annually among children.” The new recommendation was made by the WHO’s Strategic Advisory Group of Experts (SAGE), and “extends an earlier recommendation made in 2005 on vaccination in the Americas and Europe, where clinical trials had demonstrated safety and efficacy in low and intermediate mortality populations.” WHO said new data from clinical trials which evaluated vaccine efficacy in countries with high child mortality led to the recommendation for global use of the vaccine. WHO said that the clinical trial, funded in part by GAVI and conducted by PATH, WHO, GlaxoSmithKline (GSK), and “research institutions in high-mortality, low-socioeconomic settings of South Africa and Malawi, found that rotavirus vaccine significantly reduced severe diarrhea episodes due to rotavirus.” The clinical trial investigators from Malawi and South Africa will present and publish their data on the GSK Rotarix vaccine later this summer. Clinical trial sites in Bangladesh and Vietnam—along with sites in Ghana, Mali, and Kenya—evaluated the performance of Merck’s rotavirus vaccine, RotaTeq, and data are expected in Fall 2009.

Dr. Tachi Yamada, President of the Global Health Program at the Bill & Melinda Gates Foundation, said, “This WHO recommendation clears the way for vaccines that will protect children in the developing world from one of the most deadly diseases they face. We need to act now to deliver vaccines to children in Africa and Asia, where most rotavirus deaths occur.” WHO noted that “while efficacy data from Asian countries are forthcoming, SAGE recommended rotavirus vaccines for all populations, including Asia, since available evidence indicates that efficacy data can be extrapolated to populations with similar mortality patterns, regardless of geographic location.”



IVI Holds First HPV Vaccine Symposium

IVI held the “First Symposium on Human Papillomavirus Vaccination in the Asia-Pacific and Middle East Regions” 1-2 June 2009. IVI noted that “leading experts, policymakers, decision-makers, and opinion leaders from more than 35 countries in the Asia-Pacific and Middle East regions (gathered) in Seoul, Korea during June 1-2, 2009 to address issues, obstacles and propose solutions to fight against human papillomavirus, the second leading cause of cancer in women around the world.”

Presentation videos available at http://www.ivi.org/popup/HPV2009.html

Rotavirus Vaccine and Severe Rotavirus Diarrhea Among Children in Nicaragua

Vol. 301 No. 21, pp. 2185-2290, June 3, 2009

Association Between Pentavalent Rotavirus Vaccine and Severe Rotavirus Diarrhea Among Children in Nicaragua
Manish Patel, MD, MSc; Cristina Pedreira, MD, MSc; Lucia Helena De Oliveira, RN, MSc; Jacqueline Tate, PhD; Maribel Orozco, MD; Juan Mercado; Alcides Gonzalez, MD, PhD; Omar Malespin, MD; Juan José Amador, MD; Jazmina Umaña, MD; Angel Balmaseda, MD; Maria Celina Perez; Jon Gentsch, PhD; Tara Kerin, MSc; Jennifer Hull, BA; Slavica Mijatovic, MSc; Jon Andrus, MD; Umesh Parashar, MBBS, MPH

JAMA. 2009;301(21):2243-2251.

Context Pentavalent rotavirus vaccine (RV5), a live, oral attenuated vaccine, prevented 98% of severe rotavirus diarrhea in a trial conducted mainly in Finland and the United States. Nicaragua introduced RV5 in 2006, providing the first opportunity to assess the association between vaccination and rotavirus disease in a developing country.

Objective To assess the association between RV5 vaccination and subsequent rotavirus diarrhea requiring overnight admission or intravenous hydration.

Design, Setting, and Participants  Case-control evaluation in 4 hospitals in Nicaragua from June 2007 to June 2008. Cases were children age-eligible to receive RV5 who were admitted or required intravenous hydration for laboratory-confirmed rotavirus diarrhea. For each case (n = 285), 1 to 3 neighborhood (n = 840) and hospital (n = 690) controls were selected.

Main Outcome Measures Primary outcome was the association of RV5 and rotavirus diarrhea requiring overnight admission or intravenous hydration in the emergency department. Secondary analysis further classified disease as severe and very severe. We computed the matched odds ratio of vaccination in cases vs controls. Vaccine effectiveness was estimated using the formula 1 – matched odds ratio x 100%.

Results Of the 285 rotavirus cases, 265 (93%) required hospitalization; 251 (88%) received intravenous hydration. A single rotavirus strain (G2P[4]) was identified in 88% of the cases. Among cases and controls, respectively, 18% and 12% were unvaccinated, 12% and 15% received 1 dose of RV5, 15% and 17% received 2 doses, and 55% and 57% received 3 doses. Vaccination with 3 doses was associated with a lower risk of rotavirus diarrhea requiring overnight admission or intravenous hydration (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.36-0.82). Of the 285 rotavirus cases, 191 (67%) were severe and 54 (19%) were very severe. A progressively lower risk of severe (OR, 0.42; 95% CI, 0.26-0.70) and very severe rotavirus diarrhea (OR, 0.23; 95% CI, 0.08-0.61) was observed after RV5 vaccination. Thus, effectiveness of 3 doses of RV5 against rotavirus disease requiring admission or treatment with intravenous hydration was 46% (95% CI, 18%-64%); against severe rotavirus diarrhea, 58% (95% CI, 30%-74%); and against very severe rotavirus diarrhea, 77% (95% CI, 39%-92%).

Conclusion Vaccination with RV5 was associated with a lower risk of severe rotavirus diarrhea in children younger than 2 years in Nicaragua but to a lesser extent than that seen in clinical trials in industrialized countries.

Author Affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia (Drs Patel, Tate, Gentsch, and Parashar and Mss Kerin, Hull, and Mijatovic); Pan American Health Organization, Managua, Nicaragua (Dr Pedreira); Pan American Health Organization, Washington, DC (Ms De Oliveira and Dr Andrus); Ministerio de Salud, Managua, Nicaragua (Drs Orozco, Gonzalez, Malespin, Umaña, and Balmaseda and Mr Mercado and Ms Perez); and Program for Appropriate Technology in Health, Managua, Nicaragua (Dr Amador).

Comment: Preliminary HPV vaccine results for women older than 25 years

The Lancet
Jun 06, 2009   Volume 373  Number 9679  Pages 1919 – 1996

Preliminary HPV vaccine results for women older than 25 years
Diane M Harper
After prophylactic human papillomavirus (HPV) vaccination, cost-effectiveness models predict that a reduction in cervical cancer will occur decades from now, but only when 90% of all girls aged 11–12 years have been vaccinated for many years, assuming vaccines confer lifelong protection. Should prophylactic vaccination protect women for less than 15 years, the incidence of cervical cancer will shift to women older than 25 years, with no overall decrease in cervical cancers from early vaccination.

HPV vaccine in women aged 24–45 years: a randomised, double-blind trial

The Lancet
Jun 06, 2009   Volume 373  Number 9679  Pages 1919 – 1996

Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial
Nubia Muñoz, Ricardo Manalastas, Punee Pitisuttithum, Damrong Tresukosol, Joseph Monsonego, Kevin Ault, Christine Clavel, Joaquin Luna, Evan Myers, Sara Hood, Oliver Bautista, Janine Bryan, Frank J Taddeo, Mark T Esser, Scott Vuocolo, Richard M Haupt, Eliav Barr, Alfred Saah
The quadrivalent HPV vaccine is efficacious in women aged 24–45 years not infected with the relevant HPV types at enrolment.

Ratification of human-rights treaties and population health

The Lancet
Jun 06, 2009   Volume 373  Number 9679  Pages 1919 – 1996

Does ratification of human-rights treaties have effects on population health?
Alexis Palmer, Jocelyn Tomkinson, Charlene Phung, Nathan Ford, Michel Joffres, Kimberly A Fernandes, Leilei Zeng, Viviane Lima, Julio SG Montaner, Gordon H Guyatt, Edward J Mills
Human-rights treaties indicate a country’s commitment to human rights. Here, we assess whether ratification of human-rights treaties is associated with improved health and social indicators. Data for health (including HIV prevalence, and maternal, infant, and child [<5 years] mortalities) and social indicators (child labour, human development index, sex gap, and corruption index), gathered from 170 countries, showed no consistent associations between ratification of human-rights treaties and health or social outcomes.

Overseas Screening for Tuberculosis in U.S.-Bound Immigrants and Refugees

New England Journal of Medicine
Volume 360 — June 4, 2009 — Number 23

Original Articles
Overseas Screening for Tuberculosis in U.S.-Bound Immigrants and Refugees
Y. Liu and Others
Background In 2007, a total of 57.8% of the 13,293 new cases of tuberculosis in the United States were diagnosed in foreign-born persons, and the tuberculosis rate among foreign-born persons was 9.8 times as high as that among U.S.-born persons (20.6 vs. 2.1 cases per 100,000 population). Annual arrivals of approximately 400,000 immigrants and 50,000 to 70,000 refugees from overseas are likely to contribute substantially to the tuberculosis burden among foreign-born persons in the United States.

Methods The Centers for Disease Control and Prevention (CDC) collects information on overseas screening for tuberculosis among U.S.-bound immigrants and refugees, along with follow-up evaluation after their arrival in the United States. We analyzed screening and follow-up data from the CDC to study the epidemiology of tuberculosis in these populations.

Results From 1999 through 2005, a total of 26,075 smear-negative cases of tuberculosis (i.e., cases in which a chest radiograph was suggestive of active tuberculosis but sputum smears were negative for acid-fast bacilli on 3 consecutive days) and 22,716 cases of inactive tuberculosis (i.e., cases in which a chest radiograph was suggestive of tuberculosis that was no longer clinically active) were diagnosed by overseas medical screening of 2,714,223 U.S.-bound immigrants, representing prevalences of 961 cases per 100,000 persons (95% confidence interval [CI], 949 to 973) and 837 cases per 100,000 persons (95% CI, 826 to 848), respectively. Among 378,506 U.S.-bound refugees, smear-negative tuberculosis was diagnosed in 3923 and inactive tuberculosis in 10,743, representing prevalences of 1036 cases per 100,000 persons (95% CI, 1004 to 1068) and 2838 cases per 100,000 persons (95% CI, 2785 to 2891), respectively. Active pulmonary tuberculosis was diagnosed in the United States in 7.0% of immigrants and refugees with an overseas diagnosis of smear-negative tuberculosis and in 1.6% of those with an overseas diagnosis of inactive tuberculosis.

Conclusions Overseas screening for tuberculosis with follow-up evaluation after arrival in the United States is a high-yield intervention for identifying tuberculosis in U.S.-bound immigrants and refugees and could reduce the number of tuberculosis cases among foreign-born persons in the United States.

WHO Influenza A(H1N1) – update 41/29 May 2009

The WHO continues to issue regular updates posted on the WHO main page, as well as other advisories linked from that page. Here is the current update:
Influenza A(H1N1) – update 41
29 May 2009 — As of 06:00 GMT, 29 May 2009, 53 countries have officially reported 15,510 cases of influenza A(H1N1) infection, including 99 deaths. http://www.who.int/csr/don/2009_05_29/en/index.html

The Weekly Epidemiological Record (WER) 29 May 2009, vol. 84, 22 (pp 197–212) includes: Considerations for assessing the severity of an influenza pandemic; Estimating the global burden of foodborne diseases: a collaborative effort; Monthly report on dracunculiasis cases, January–April 2009

Merck’s GARDASIL wins WHO pre-qualification

Merck said GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant], has been awarded World Health Organization (WHO) pre-qualification, making the vaccine the first cervical cancer vaccine to receive this pre-qualification. WHO pre-qualification means that GARDASIL is now eligible for procurement by the United Nations Children’s Fund (UNICEF) and other United Nations (UN) agencies including the Pan American Health Organization (PAHO), for use in national immunization programs.

Merck said WHO pre-qualification is “a significant part of (its) approach to accelerating access to GARDASIL in the developing world through four key pillars: innovation, partnerships, pricing and implementation. This development follows the recent WHO position paper on the use of HPV vaccines.” Merck noted that it will offer GARDASIL to the public sectors of GAVI-eligible countries “at a price at which we do not profit.” Additionally, Merck said it is “exploring several ways to further reduce product cost for the developing world, including manufacturing efficiencies and reduction of royalties paid out to licensors on GARDASIL doses sold in the developing world.”

Additionally, Merck noted that it is partnering with PATH “to conduct demonstration projects of GARDASIL in the developing world by providing vaccine and technical support at no cost.”

(BUSINESS WIRE, 26 May 2009)

Sanofi Pasteur received first U.S. orders for A(H1N1) vaccine

Sanofi Pasteur announced it “received the first of what is expected to be a series of orders from the U.S. Department of Health and Human Services (HHS) to commence production of a vaccine to help protect against the new influenza A(H1N1) virus.” Sanofi said the order from HHS was issued “pursuant to an existing pandemic stockpile contract between Sanofi Pasteur and the U.S. government that allows HHS to purchase vaccines for viruses with pandemic potential.” The order is in the amount of $190 million. In addition to this initial HHS order, the company is in discussions with other governments to address their needs for A(H1N1) vaccine.

Wayne Pisano, President and CEO of Sanofi Pasteur, said, “This initial order for A(H1N1) vaccine received today under our existing contract is part of a major effort by Sanofi Pasteur to support global public health efforts to prepare the world for the possibility of an influenza pandemic.  Production of a new vaccine is not a simple task and there are a number of necessary and complex steps that must be taken before a vaccine can be made available to the public, but we have experience on our side. Previously, we developed and licensed the first pre-pandemic vaccine for H5N1 and we look forward to further demonstrating our experience and expertise in vaccine development as we prepare for this new threat from A(H1N1).”

Sanofi Pasteur said it is awaiting receipt of the seed virus to be used for vaccine production from the U.S. Centers for Disease Control and Prevention (CDC). Once the seed is received, Sanofi Pasteur will begin development efforts to prepare a working seed for vaccine production. Sanofi Pasteur noted that it is prepared to commence commercial scale production in June following certification of the working seed by the U.S. Food and Drug Administration (FDA). The company estimates that it will have the first bulk concentrate vaccine in a few months.

(PRNewswire, 25 May 2009)

GAVI Alliance appoints Helen Evans as its first Deputy CEO

The GAVI Alliance said it appointed Australian development expert Helen Evans as its first Deputy Chief Executive Officer. Ms. Evans will join GAVI in June after serving for the past four years as Deputy Executive Director at the Global Fund to fight AIDS, Tuberculosis and Malaria. GAVI said that in this new role, Ms. Evans “will oversee the performance and management of the Alliance secretariat as it strives to expand immunisation to developing countries with the new introduction of support for pneumococcal and rotavirus vaccines.”


West African meningitis outbreak strains vaccine supplies

The Lancet
May 30, 2009   Volume 373  Number 9678  Pages 1819 – 1918

World Report
West African meningitis outbreak strains vaccine supplies
Wairagala Wakabi
This year’s meningitis outbreak in west Africa, which UNICEF has called the worst in more than 5 years, has severely depleted limited global vaccine supplies. Wairagala Wakabi reports. With the meningitis outbreak this year having killed more than 2500 people in Africa’s so-called meningitis belt, shortage of vaccines has been blamed for the high case fatality rate (CFR) seen in some countries.

Mothers’ Intention for HPV Vaccination: National Study of Nurses

June 2009 / VOLUME 123 / ISSUE 6

Mothers’ Intention for Their Daughters and Themselves to Receive the Human Papillomavirus Vaccine: A National Study of Nurses
Jessica A. Kahn, MD, MPHa, Lili Ding, MSb, Bin Huang, PhDb, Gregory D. Zimet, PhDc, Susan L. Rosenthal, PhDd and A. Lindsay Frazier, MD, ScMe,f
a Division of Adolescent Medicine, Department of Pediatrics
b Center for Epidemiology and Biostatistics, Cincinnati Children’s Hospital, Cincinnati, Ohio
c Division of Adolescent Medicine, Indiana University, Indianapolis, Indiana
d Division of Adolescent and Behavioral Health, University of Texas Medical Branch at Galveston, Galveston, Texas
e Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
f Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

OBJECTIVES. The aims of this study were to examine mothers’ intention to vaccinate their daughters and themselves against human papillomavirus and to determine which demographic, behavioral, and attitudinal factors were associated with intention to vaccinate daughters.

METHODS. We surveyed 10 521 US mothers, all nurses, between June 2006 and February 2007. Multivariable logistic regression models were used to determine which of the following factors were associated with a mother’s intention to vaccinate a 9- to 12-year-old daughter: demographic factors, gynecologic history, belief that one’s daughter should have regular Papanicolaou testing, beliefs about Papanicolaou testing outcomes (3-item scale), and beliefs about human papillomavirus vaccines (7-item scale measuring beliefs about human papillomavirus vaccine efficacy, impact of vaccination on sexual and Papanicolaou screening behaviors, severity of and susceptibility to human papillomavirus, and anticipated clinician recommendations).

RESULTS. Of the 8832 mothers who completed a survey (84% response rate), 7207 had a daughter. Among mothers with a daughter, 48% intended to vaccinate a daughter if she were 9 to 12 years of age, 68% if she were 13 to 15 years of age, and 86% if she were 16 to 18 years of age. Forty-eight percent intended to receive the vaccine themselves if recommended. In multivariable regression models, variables significantly associated with intention to vaccinate a 9- to 12-year-old daughter included belief that one’s daughter should have regular Papanicolaou testing and beliefs about human papillomavirus vaccines.

CONCLUSIONS. In this first national study of mothers’ attitudes about human papillomavirus vaccines, mothers’ intention to vaccinate a daughter <13 years of age was lower than intention to vaccinate an older daughter, contrasting with national recommendations to target 11- to 12-year-old girls for vaccination. Educational interventions designed to affect mothers’ willingness to vaccinate daughters should focus on human papillomavirus vaccine efficacy, behavioral impact of vaccination, perceived risk of human papillomavirus, and clinician support for vaccination.

Parental Refusal of Pertussis Vaccination

June 2009 / VOLUME 123 / ISSUE 6


Parental Refusal of Pertussis Vaccination Is Associated With an Increased Risk of Pertussis Infection in Children

Jason M. Glanz, PhDa,b, David L. McClure, PhDa, David J. Magid, MD, MPHa,b, Matthew F. Daley, MDa,c,d, Eric K. France, MD, MSPHe, Daniel A. Salmon, PhD, MPHf and Simon J. Hambidge, MD, PhDa,b,d,g
a Institute for Health Research
e Department of Prevention, Kaiser Permanente Colorado, Denver, Colorado; Departments of
b Preventive Medicine and Biometrics
d Pediatrics, University of Colorado, Denver, Colorado
c Department of Pediatrics, Children’s Hospital, Denver, Colorado
f Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
g Community Health Services, Denver Health, Denver, Colorado

OBJECTIVE. The objective of this study was to determine if children who contracted pertussis infection were more likely to have parents who refused pertussis vaccinations than a similar group of children who did not develop pertussis infection.

METHODS. We conducted a case-control study of children enrolled in the Kaiser Permanente of Colorado health plan between 1996 and 2007. Each pertussis case was matched to 4 randomly selected controls. Pertussis case status and vaccination status were ascertained by medical chart review.

RESULTS. We identified 156 laboratory-confirmed pertussis cases and 595 matched controls. There were 18 (12%) pertussis vaccine refusers among the cases and 3 (0.5%) pertussis vaccine refusers among the controls. Children of parents who refused pertussis immunizations were at an increased risk for pertussis compared with children of parents who accepted vaccinations. In a secondary case-control analysis of children continuously enrolled in Kaiser Permanente of Colorado from 2 to 20 months of age, vaccine refusal was associated with a similarly increased risk of pertussis. In the entire Kaiser Permanente of Colorado pediatric population, 11% of all pertussis cases were attributed to parental vaccine refusal.

CONCLUSIONS. Children of parents who refuse pertussis immunizations are at high risk for pertussis infection relative to vaccinated children. Herd immunity does not seem to completely protect unvaccinated children from pertussis. These findings stress the need to further understand why parents refuse immunizations and to develop strategies for conveying the risks and benefits of immunizations to parents more effectively.

Efficacy of Pneumococcal Vaccination in Children Younger Than 24 Months

June 2009 / VOLUME 123 / ISSUE 6


Efficacy of Pneumococcal Vaccination in Children Younger Than 24 Months: A Meta-Analysis

Maria Pavia, MD, MPHa, Aida Bianco, MDa, Carmelo G. A. Nobile, MDa, Paolo Marinelli, MDb and Italo F. Angelillo, DDS, MPHb
a Department of Hygiene, Medical School, University of Catanzaro “Magna Græcia,” Catanzaro, Italy
b Department of Public, Clinical, and Preventive Medicine, Second University of Naples, Naples, Italy

CONTEXT. Pneumococcal conjugate bacterial vaccines that are able to prevent invasive disease and mucosal infections have been developed.

OBJECTIVE. A meta-analysis of published data from trials on pneumococcal conjugate vaccine was performed to determine the efficacy in reducing the incidence of invasive disease caused by Streptococcus pneumoniae, pneumonia, and acute otitis media in healthy infants younger than 24 months.

METHODS. A systematic search of the literature was conducted. Controlled clinical trials had to compare the protective efficacy of the pneumococcal conjugate vaccine in reducing the incidence of invasive disease caused by S pneumoniae, pneumonia, and acute otitis media in healthy infants with placebo or control vaccines. Information was extracted by using a standardized protocol.

RESULTS. The efficacy of pneumococcal conjugate vaccine in the reduction of invasive pneumococcal disease was 89% involving vaccine serotypes in both the intention-to-treat and per-protocol analyses and ranged from 63% to 74% for all serotypes. The efficacy to prevent acute otitis media sustained by vaccine serotypes was 55% in the intention-to-treat and 57% in the per-protocol analyses, whereas it was 29% to prevent otitis involving all serotypes in the per-protocol analysis. Finally, in the intention-to-treat and per-protocol analyses, the efficacy to prevent clinical pneumonia was 6% and 7%, respectively, whereas for the prevention of radiograph-confirmed pneumonia it was 29% and 32%, respectively.

CONCLUSIONS. The pneumococcal conjugate vaccine produces a significant effect regarding prevention of invasive pneumococcal disease. Results on prevention of otitis or pneumonia have been less striking, but considering the high burden of these diseases in infants, even a low efficacy has potential for tremendous impact on the health of infants in developing and industrialized countries.

Pediatric vaccination errors: Application of the “5 Rights” framework

Volume 27, Issue 29, Pages 3801-3926 (12 June 2009)

Pediatric vaccination errors: Application of the “5 Rights” framework to a national error reporting database
Pages 3890-3896
David G. Bundy, Andrew D. Shore, Laura L. Morlock, Marlene R. Miller
Little is known about vaccination errors. We analyzed 607 outpatient pediatric vaccination error reports from MEDMARX, a nationwide, voluntary medication error reporting system, occurring from 2003 to 2006. We used the “5 Rights” framework (right vaccine, time, dose, route, and patient) to determine whether vaccination error types were predictable. We found that “wrong vaccine” errors were more common among look-alike/sound-alike groups than among vaccines with no look-alike/sound-alike group. Scheduled vaccines were more often involved in “wrong time” errors than seasonal and intermittent vaccines. “Wrong dose” errors were more common for vaccines whose dose is weight-based and age-based than for vaccines whose dose is uniform. “Wrong route” and “wrong patient” errors were rare. In this largest-ever analysis of pediatric vaccination errors, error types were associated with predictable vaccine-related human factors challenges. Efforts to reduce pediatric vaccination errors should focus on these human factors.

Economic analysis of rotavirus vaccination in Italy

Volume 27, Issue 29, Pages 3801-3926 (12 June 2009)

An economic analysis of rotavirus vaccination in Italy
Pages 3904-3911
Maria Daniela Giammanco, Maria Anna Coniglio, Sarina Pignato, Giuseppe Giammanco
We have evaluated health and economic benefits of a universal infant vaccination with two rotavirus vaccines registered in Italy, on the bases of the burden of rotavirus gastroenteritis (RVGE) in a birth cohort of 520,000 Italian infants followed until 5 years of age. Estimates from published and unpublished sources of disease burden, costs, vaccine coverage, efficacy trials of both vaccines, and price were used to estimate cost-effectiveness from the perspectives of the Italian National Health Service (NHS) and society. According to our estimates, a universal rotavirus vaccination program would avoid 10,679 hospitalizations, 39,202 emergency visits, and 44,223 at home visits. At €65.6 per vaccination courses, the program would cost €30,700,800 and realize a net loss of €9,057,928 from the Italian NHS perspective. On the contrary, the program would provide a net savings of €24,324,198 from the societal perspective. From the Italian NHS perspective, the break-even price per vaccination course should be reduced at least to €46.25 to achieve a zero cost-effectiveness ratio.