WHO: H1N1 Weekly update: 20 November 2009

The WHO continues to issue weekly “updates” and briefing notes as below:
Pandemic (H1N1) 2009 – update 75
Weekly update
20 November 2009 –

As of 15 November 2009, worldwide more than 206 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6770 deaths.

As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

Situation update:

The situation remains similar since the last update. In temperate regions* of the northern hemisphere, the early arriving winter influenza season continues to intensify across parts of North America and much of Europe. However, there are early signs of a peak in disease activity in some areas of the northern hemisphere.

More detail at: http://www.who.int/csr/don/2009_11_20a/en/index.html

WHO briefing note 16: Safety of pandemic vaccines

Pandemic (H1N1) 2009 briefing note 16
Safety of pandemic vaccines
19 NOVEMBER 2009 | GENEVA –

To date, WHO has received vaccination information from 16 of around 40 countries conducting national H1N1 pandemic vaccine campaigns. Based on information in these 16 countries, WHO estimates that around 80 million doses of pandemic vaccine have been distributed and around 65 million people have been vaccinated. National immunization campaigns began in Australia and the People’s Republic of China in late September.

Vaccination campaigns currently under way to protect populations from pandemic influenza are among the largest in the history of several countries, and numbers are growing daily. Given this scale of vaccine administration, at least some rare adverse reactions, not detectable during even large clinical trials, could occur, underscoring the need for rigorous monitoring of safety. Results to date are encouraging.

Common side effects
As anticipated, side effects commonly reported include swelling, redness, or pain at the injection site, which usually resolves spontaneously a short time after vaccination.

Fever, headache, fatigue, and muscle aches, occurring shortly after vaccine administration, have also been reported, though with less frequency. These symptoms also resolve spontaneously, usually within 48 hours. In addition, a variety of allergic reactions has been observed. The frequency of these reactions is well within the expected range.

Guillain-Barre syndrome
To date, fewer than ten suspected cases of Guillain-Barre syndrome have been reported in people who have received vaccine. These numbers are in line with normal background rates of this illness, as reported in a recent study. Nonetheless, all such cases are being investigated to determine whether these are randomly occurring events or if they might be associated with vaccination.

WHO has received no reports of fatal outcomes among suspected or confirmed cases of Guillain-Barre syndrome detected since vaccination campaigns began. All cases have recovered. WHO recommends continued active monitoring for Guillain-Barre syndrome.

Investigations of deaths
A small number of deaths have occurred in people who have been vaccinated. All such deaths, reported to WHO, have been promptly investigated. Although some investigations are ongoing, results of completed investigations reported to WHO have ruled out a direct link to pandemic vaccine as the cause of death.

In China, for example, where more than 11 million doses of pandemic vaccine have been administered, health authorities have informed WHO of 15 cases of severe side effects and two deaths that occurred following vaccination. Thorough investigation of these deaths, including a review of autopsy results, determined that underlying medical conditions were the cause of death, and not the vaccine.

Safety profile of different vaccines
Campaigns are using nonadjuvanted inactivated vaccines, adjuvanted inactivated vaccines, and live attenuated vaccines. No differences in the safety profile of severe adverse events among different vaccines have been detected to date.

Although intense monitoring of vaccine safety continues, all data compiled to date indicate that pandemic vaccines match the excellent safety profile of seasonal influenza vaccines, which have been used for more than 60 years. http://www.who.int/csr/disease/swineflu/notes/briefing_20091119/en/index.html

WHO Briefing Note 17: H1N1 virus mutation detected in Norway

Pandemic (H1N1) 2009 briefing note 17
Public health significance of virus mutation detected in Norway

20 NOVEMBER 2009 | GENEVA –
The Norwegian Institute of Public Health has informed WHO of a mutation detected in three H1N1 viruses. The viruses were isolated from the first two fatal cases of pandemic influenza in the country and one patient with severe illness.

Norwegian scientists have analysed samples from more than 70 patients with clinical illness and no further instances of this mutation have been detected. This finding suggests that the mutation is not widespread in the country. The virus with this mutation remains sensitive to the antiviral drugs, oseltamivir and zanamivir, and studies show that currently available pandemic vaccines confer protection.

Worldwide, laboratory monitoring of influenza viruses has detected a similar mutation in viruses from several other countries, with the earliest detection occurring in April. In addition to Norway, the mutation has been observed in Brazil, China, Japan, Mexico, Ukraine, and the US.

Although information on all these cases is incomplete, several viruses showing the same mutation were detected in fatal cases, and the mutation has also been detected in some mild cases. Worldwide, viruses from numerous fatal cases have not shown the mutation. The public health significance of this finding is thus unclear.

The mutations appear to occur sporadically and spontaneously. To date, no links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread.

The significance of the mutation is being assessed by scientists in the WHO network of influenza laboratories. Changes in viruses at the genetic level need to be constantly monitored. However, the significance of these changes is difficult to assess. Many mutations do not alter any important features of the virus or the illness it causes. For this reason, WHO also uses clinical and epidemiological data when making risk assessments.

Although further investigation is under way, no evidence currently suggests that these mutations are leading to an unusual increase in the number of H1N1 infections or a greater number of severe or fatal cases.

Laboratories in the WHO Global Influenza Surveillance Network closely monitor influenza viruses worldwide and will remain vigilant for any further changes in the virus that may have public health significance.

http://www.who.int/csr/disease/swineflu/notes/briefing_20091120/en/index.html

GAVI announces its impact on the vaccine market is bringing down prices

GAVI announced that its impact on the vaccine market is bringing down prices. The announcement was made “just before the GAVI Partners’ Forum, which unites some 400 participants from all over the world including ministers of health, donors, civil society and industry representatives, researchers and development experts.”  GAVI CEO Julian Lob-Levyt said, “This is the ‘GAVI effect’ at work: encouraging and pooling growing demand from countries, attracting new manufacturers and increasing competition to drive down prices. The price drop has come later than we had hoped and it needs to fall further. But this is a clear indication that our market-shaping efforts work.”

The majority of vaccines financed through GAVI is purchased by Alliance member UNICEF. GAVI said that a recent tender for pentavalent vaccine “has shown a significant price drop with the weighted average price for 2010 falling below US$3.00, a decrease of almost 50 cents per dose on the 2009 price. This will create approximately US$55 million in savings in 2010 and enable GAVI to finance the immunisation of 6.3 million more children.  UNICEF Deputy Executive Director Saad Houry commented, “This price drop is no accident, but rather the result of a strategy to leverage the purchasing power of hundreds of millions of people. Clearly, industry understands and responds to a market, regardless of whether that market is in poor or rich countries. The Alliance’s model is beginning to work, and we are optimistic that the trend will continue, as competition and demand increase over time.”

GAVI said its business model is “based on the expectation that rising demand for immunisation in developing countries induces more companies to produce vaccines, thus creating competition and driving prices down. Through the new data, success becomes evident. Whereas in 2001, there was only one company producing the pentavalent vaccine, now there are four. Two are Indian companies, whose products came on the market in 2008. Today, 50% of the vaccines funded by GAVI are from developing country manufacturers.”

At the Hanoi meeting, GAVI Board Chair Mary Robinson noted that progress in immunisation coverage and price decline must be tempered by the fact that more than 20 million children in the world today continue to go without basic life-saving vaccines.

“Our Alliance is not providing charity but rather securing a basic human right, which is the right to equal access to basic standards of health. It is time to recognise that the availability of life-saving vaccines for children worldwide, regardless of where they live, is not a luxury but a fundamental right.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20091117006382&newsLang=en

GAVI Alliance Board appoints Dr Jaime Sepulved as new Vice-Chair

The GAVI Alliance Board appointed Dr Jaime Sepulveda, Director of the Integrated Health Solutions Development programme at the Bill & Melinda Gates Foundation, as its new Vice-Chair. GAVI said that Dr. Sepulveda will replace Dennis Aitken of the World Health Organization who has retired, and that Daisy Mafubelu, Assistant Director-General for Family and Community Health, will become WHO’s representative on the board. The Bill & Melinda Gates Foundation will be represented by its alternate member. The announcement said that Dr Sepulveda served for more than 20 years in a variety of senior health posts in the Mexican government. From 2003 to 2006, he was director of the National Institutes of Health of Mexico. He also served as Director-General of Mexico’s National Institute of Public Health and dean of the National School of Public Health. In addition to his research credentials, Sepulveda is an experienced implementer of effective health programmes. As Mexico’s Director-General of epidemiology and later Vice-Minister of Health, Sepulveda designed Mexico’s Universal Vaccination Programme, which eliminated polio, measles, and diphtheria by more than doubling childhood immunisation coverage in two years. He also designed a national health surveillance system and founded Mexico’s National AIDS Council. Dr Sepulveda holds a medical degree from National Autonomous University of Mexico and three advanced degrees from the Harvard School of Public Health. He was a recent member of the Board of Overseers of Harvard University and is a member of the Institute of Medicine of the U.S. National Academy of Sciences.

http://www.gavialliance.org/media_centre/statements/2009_11_17_new_vice_chair.php

MMWR: Mumps Outbreak – New York, New Jersey, Quebec, 2009

The MMWR Weekly (November 20, 2009 / 58(45);1270-1274) includes:

Mumps Outbreak — New York, New Jersey, Quebec, 2009
Mumps is a vaccine-preventable viral infection characterized by fever and inflammation of the salivary glands and whose complications include orchitis, deafness, and meningo-encephalitis (1). In August 2009, CDC was notified of the onset of an outbreak of mumps in a summer camp in Sullivan County, New York. The outbreak has spread and gradually increased in size and is now the largest U.S. mumps outbreak since 2006, when the United States experienced a resurgence of mumps with 6,584 reported cases (2). On August 18, public health departments in Sullivan County, New York state, and CDC began an investigation into the mumps outbreak, later joined by departments in New York City and other locales. As of October 30, a total of 179 confirmed or probable cases had been identified from multiple locations in New York and New Jersey (Figure), and an additional 15 cases had been reported from Canada. The outbreak primarily has affected members of a tradition-observant religious community; median age of the patients is 14 years, and 83% are male. Three persons have been hospitalized. Although little transmission has occurred outside the Jewish community, mumps can spread rapidly in congregate settings such as colleges and schools; therefore, public health officials and clinicians should heighten surveillance for mumps and ensure that children and adults are appropriately vaccinated.

Mumps cases in the United States have been classified according to the 2008 case definition of the Council of State and Territorial Epidemiologists,* and cases in Canada have been classified in accordance with Case Definitions for Diseases Under National Surveillance.† Patients in the United States are considered to have age-appropriate vaccinations for mumps if they are aged 1–6 years and have received 1 dose of a mumps-containing vaccine, aged 7–18 years and have received 2 doses of vaccine, or aged 19–52 years and have received 1 dose of vaccine (3,4). Patients aged 7–18 years who have received 1 dose are considered to have received a partially age-appropriate vaccination.

More at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5845a5.htm

Hajj and 2009 pandemic influenza A H1N1

The Lancet
Nov 21, 2009  Volume 374  Number 9703  Pages 1723 – 1792
http://www.thelancet.com/journals/lancet/issue/current

Hajj and 2009 pandemic influenza A H1N1
The Lancet

More than 2·5 million Muslims from over 160 countries will be going on Hajj—a pilgrimage to Mecca, Saudi Arabia—this year during Nov 25—30. Such a mass gathering, with up to seven people per m2, increases the risk of spreading infectious diseases, particularly the 2009 pandemic influenza A H1N1.

In The Lancet today, Ziad Memish and colleagues report several recommendations, based on the current status of this pandemic, for provision of the best health services to pilgrims and to keep disease transmission to a minimum among pilgrims and their contacts at home. These recommendations—which are to be put into practice before and during this year’s Hajj—were made after a consultation in Jeddah during June 26—30, 2009, between global agencies at the invitation of the Saudi Arabian Ministry of Health. They are grouped according to screening and isolation; surveillance, epidemiology, and informatics; laboratory testing; infection control; and treatment of the 2009 pandemic influenza A H1N1 infection.

The most important recommendation is that people at risk of infection—such as those older than 64 years, children younger than 5 years, pregnant women, and immunosuppressed individuals—should not go on Hajj this year. However, because Hajj is one of the five pillars of Islam and should be done at least once in a Muslim’s lifetime, individuals will probably not want to postpone after they have spent much time saving money and planning for this purpose. Some of the other recommendations, such as isolation of pilgrims with influenza-like illness, might not only deter individuals from reporting their illness but will undoubtedly also cause them distress and difficulty reuniting with their companions. Improvement of hand hygiene for infection control might be more acceptable than some of the other recommendations because pilgrims should wash before they pray.

These recommendations are a starting point, but they will need to be assessed. Some recommendations might need to be adjusted or discarded as the pandemic develops. However, pandemic influenza A H1N1 alone is understandably unlikely to dissuade many Muslims from going on Hajj.

Establishment of public health security in Saudi Arabia for the 2009 Hajj in response to pandemic influenza A H1N1

ZA Memish, SJN McNabb, F Mahoney, F Alrabiah, N Marano, QA Ahmed, J Mahjour, RA Hajjeh, P Formenty, FH Harmanci, H El Bushra, TM Uyeki, M Nunn, N Isla, M Barbeschi, the Jeddah Hajj Consultancy Group

Public Health
Establishment of public health security in Saudi Arabia for the 2009 Hajj in response to pandemic influenza A H1N1
ZA Memish, SJN McNabb, F Mahoney, F Alrabiah, N Marano, QA Ahmed, J Mahjour, RA Hajjeh, P Formenty, FH Harmanci, H El Bushra, TM Uyeki, M Nunn, N Isla, M Barbeschi, the Jeddah Hajj Consultancy Group

Summary
Mass gatherings of people challenge public health capacities at host locations and the visitors’ places of origin. Hajj—the yearly pilgrimage by Muslims to Saudi Arabia—is one of the largest, most culturally and geographically diverse mass gatherings in the world. With the 2009 pandemic influenza A H1N1 and upcoming Hajj, the Saudi Arabian Ministry of Health (MoH) convened a preparedness consultation in June, 2009. Consultants from global public health agencies met in their official capacities with their Saudi Arabian counterparts. The MoH aimed to pool and share public health knowledge about mass gatherings, and review the country’s preparedness plans, focusing on the prevention and control of pandemic influenza. This process resulted in several practical recommendations, many to be put into practice before the start of Hajj and the rest during Hajj. These preparedness plans should ensure the optimum provision of health services for pilgrims to Saudi Arabia, and minimum disease transmission on their return home. Review of the implementation of these recommendations and their effect will not only inform future mass gatherings in Saudi Arabia, but will also strengthen preparedness efforts in other settings.

20 years on: the clinical importance of children’s rights

The Lancet
Nov 21, 2009  Volume 374  Number 9703  Pages 1723 – 1792
http://www.thelancet.com/journals/lancet/issue/current

Editorials
20 years on: the clinical importance of children’s rights
The Lancet

Preview
During the past week, the Australian Government apologised for the mistreatment of UK children who were resettled in Australia between 1930 and 1970 as part of the child migrants programme; a similar apology from the UK Government is expected. This forced resettlement of 500 000 children is a reminder of their vulnerability. The 20th anniversary on Nov 20 of the UN Convention on the Rights of the Child (CRC) gives an opportunity to reflect on children’s rights today—and the responsibility of health professionals to respect and defend those rights in all settings, including the clinic.

Influenza vaccination of children

The Lancet Infectious Disease
Dec 2009  Volume 9  Number 12   Pages 719 – 796
http://www.thelancet.com/journals/laninf/issue/current

Reflection and Reaction
Influenza vaccination of children
Terho Heikkinen, Ville Peltola

Preview
In this issue of The Lancet Infectious Diseases, Rogier Bodewes and colleagues state that influenza vaccination is beneficial for infants and young children, but at the same time they urge re-evaluation of vaccine recommendations because the inactivated vaccine available at present does not induce heterosubtypic immunity and might make infants more susceptible to pandemic influenza. Although there are numerous immunological mechanisms related to infection with influenza to be discovered, we feel that the conclusions should be put into perspective.

Vaccine safety: informing the misinformed

The Lancet Infectious Disease
Dec 2009  Volume 9  Number 12   Pages 719 – 796
http://www.thelancet.com/journals/laninf/issue/current

Leading Edge
Vaccine safety: informing the misinformed
The Lancet Infectious Diseases

Preview
At the time of going to press, the first major vaccination campaigns to prevent pandemic H1N1 are getting underway. The vaccine might not have been ready in quite the volume hoped; nonetheless, for the production of vaccine in any substantial quantity in such a short time while still providing seasonal vaccine, those involved—the scientist, the pharmaceutical companies, and the chickens that laid the millions of eggs used—should be applauded.

 

Mandatory Vaccination of Health Care Workers

New England Journal of Medicine
Volume 361 — November 19, 2009 — Number 21
http://content.nejm.org/current.shtml

Perspective
Mandatory Vaccination of Health Care Workers
A. M. Stewart

Mandatory vaccination of health care workers raises important questions about the limits of a state’s power to compel individuals to engage in particular activities in order to protect the public. In justifying New York State’s regulations requiring health care workers who have direct contact with patients or who may expose patients to disease to be vaccinated against seasonal and H1N1 influenza, New York State Health Commissioner Richard Daines recently argued, “[O]ur overriding concern . . . as health care workers, should be the interests of our patients, not our own sensibilities about mandates. . . . [T]he welfare of patients is . . . best served by . . . very high rates of staff immunity that can only be achieved with mandatory influenza vaccination — not the 40-50% rates of staff immunization historically achieved with even the most vigorous of voluntary programs. Under voluntary standards, institutional outbreaks occur. . . . Medical literature convincingly demonstrates that high levels of staff immunity confer protection on those patients who cannot be or have not been effectively vaccinated . . . while also allowing the institution to remain more fully staffed.”1

Workers at diagnostic and treatment centers, home health care agencies, and hospices are included in New York’s requirement, although workers who can show that they have a recognized medical contraindication to vaccination are exempt. Each facility will have the discretion to determine the steps that unvaccinated health care workers must take to reduce the risk of transmitting disease to patients (see table).
Many health care workers believe that the mandate violates fundamental individual rights and public health policy, and some have filed court actions. In response, one judge ordered a delay in implementing the regulation, and New York’s governor, David Paterson, suspended the requirement so that the limited supply of H1N1 vaccine currently available can be distributed to the populations most at risk for serious illness and death.

The workers argue, first, that compulsory vaccination violates the Fourteenth Amendment in depriving them of liberty without due process. But in 1905, in deciding the smallpox-vaccination case Jacobson v. Commonwealth of Massachusetts, the U.S. Supreme Court recognized that the “police powers” granted to states under the Tenth Amendment authorize them to require immunization. Police powers are government’s inherent authority to impose restrictions on private rights for the sake of public welfare. Thus, health administrators may develop measures that compel individuals to accept vaccinations in order to protect the public’s health.

Such measures include immunization requirements for school entry, which have been enacted by all states and the District of Columbia. These mandates have been shown to be the most effective method of increasing rates of coverage among school-age children and have withstood multiple legal challenges. In 1922, in Zucht v. King (a case regarding an immunization requirement for school entry in San Antonio, Texas), the Supreme Court endorsed these ordinances, finding that they “confer not arbitrary power, but only that broad discretion required for the protection of the public health.”     Opponents of such requirements argue that they are improper on the grounds that they amount to illegal search and seizure under the Fourth Amendment or that they violate either the equal protection clause of the Fourteenth Amendment (“no state shall . . . deny to any person within its jurisdiction the equal protection of the laws”) or the establishment clause of the First Amendment (“Congress shall make no law respecting an establishment of religion”). Yet on the basis of the principles outlined in Jacobson, the judiciary has consistently affirmed that an individual’s right to refuse immunization is outweighed by the community-wide protection conferred by immunization.

Some health care workers in New York have argued that Jacobson does not apply in the case of influenza because there is no health emergency and because the H1N1 influenza virus is not as serious as smallpox. In 2002, in Boone v. Boozman, an Arkansas court heard from opponents of a school-entry requirement for hepatitis B vaccination, who argued that both Jacobson and Zucht were irrelevant because they were decided during declared smallpox emergencies, whereas hepatitis B presented no “clear and present danger.” The court held that “the Supreme Court did not limit its holding in Jacobson to diseases presenting a clear and present danger.” Furthermore, “even if such a distinction could be made, the Court cannot say that hepatitis B presents no such clear and present danger. Hepatitis B may not be airborne like smallpox; however, this is not the only factor by which a disease could be judged dangerous.” The court concluded that “immunization of school children against hepatitis B has a real and substantial relation to the protection of the public health and the public safety.”

Health care workers in New York also argue that because the regulation offers no possibility for religious exemptions, it violates the “free exercise” clause of the First Amendment, which guarantees that government may not interfere with a person’s religious beliefs. But individuals may not engage in activities that threaten important societal interests and expect to be shielded by the First Amendment. When reviewing state initiatives that hinder religious expression, courts weigh the importance of a claim of religious exercise against the state interest. Courts have upheld school-entry vaccination requirements against objections that they infringed on individuals’ religious principles. States have the discretion to determine whether to permit religious exemptions, and Arizona, Mississippi, and West Virginia do not permit such exemptions. Thus, in the absence of a Supreme Court ruling, it is unlikely that the exclusion of a religious exemption from the New York regulation will be considered to be unconstitutional.

The health care workers also argue that the regulation violates the right to “freedom of contract” between employer and employee, as guaranteed by the Fifth and Fourteenth Amendments. However, states are obligated to protect the public welfare, even when doing so affects economic liberty. Furthermore, the Supreme Court has held that states may promulgate regulations restricting liberty of contract in order to protect community health or vulnerable populations.2,3,4 Although New York’s regulation affects employer–employee relationships, it is permissible because promoting patients’ health and safety is a legitimate state interest. Health care workers must receive other vaccinations as a condition of employment, yet they have not challenged those requirements.

The health care workers further claim that the regulation violates the Fourteenth Amendment right of competent adults to bodily autonomy and the right to refuse medical treatment. Yet the right to refuse treatment is not absolute. In determining whether the regulation violates the personal autonomy of health care workers, courts will, once again, balance individual rights against state interests. The state’s power weakens and the individual’s rights strengthen as the degree of bodily invasion increases and the effectiveness of the intervention decreases.5 Courts will consider the extent to which health care workers cause illness and death among patients by exposing them to influenza. Vaccinating health care workers is the most effective means of reducing outbreaks; health care workers are required to submit to the limited intrusion of vaccination in order to protect both themselves and the patients in their care. I believe that the state’s right to compel health care workers to receive vaccinations will supersede their individual rights because of the state’s substantial relation to protection of the public health and safety.

Certainly, courts must take into account Constitutional guarantees of personal autonomy, freedom of contract, and freedom of religion when reviewing the current lawsuits. These rights, however, have been constrained when they conflict with government measures that are intended to protect the community’s health and safety. Health care workers have a profound effect on patients’ health. Although they have the same rights as all private citizens, it is likely that courts will continue to make the health and safety of patients the priority in permitting exceptions to individual rights.

No potential conflict of interest relevant to this article was reported.

Source Information: From George Washington University Medical Center and George Washington University School of Public Health and Health Services, Washington, DC.
This article (10.1056/NEJMp0910151) was published on November 4, 2009, at NEJM.org.

References

Open letter to health care workers from NY State Health Commissioner Richard F. Daines, M.D., September 24, 2009. (Accessed November 2, 2009, at http://www.health.state.ny.us/press/releases/2009/2009-09-24_health_care_worker_vaccine_daines_oped.htm.)

Williamson v. Lee Optical Co., 348 U.S. 483 (1955).

West Coast Hotel Co. v. Parrish, 300 U.S. 379 (1937).

Muller v. Oregon, 208 U.S. 412 (1908).

Cruzan v. Director, Missouri Department of Health, 497 U.S. 261 (1990

Unintended Consequences of Clinical Trials Regulations

PLoS Medicine
(Accessed 22 November 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 17 Nov 2009
The Unintended Consequences of Clinical Trials Regulations
Alex D. McMahon, David I. Conway, Tom M. MacDonald, Gordon T. McInnes

Summary Points
– Trial regulations are damaging noncommercial research and patients.
– The International Conference on Harmonisation (ICH) version of Good Clinical Practice (GCP) is inapplicable to most noncommercial research.
– ICH GCP is not usually legally binding (as conceded by the regulatory authorities in the UK).
– Other parts of the world should learn a lesson from the misguided trial regulations that have been created in Europe.

Medical Patents in Developing Countries

Science
20 November 2009  Vol 326, Issue 5956, Pages 1029-1148
http://www.sciencemag.org/current.dtl

Intellectual Property:
Research Centers Promise a Break on Medical Patents in Developing Countries
Sam Kean

More than a half-dozen major U.S. universities and institutes pledged last week to lean on biotech companies when licensing intellectual property to secure more favorable terms for countries in the developing world. Harvard, Yale, and Brown universities, the University of Pennsylvania, and the state universities of Oregon and Illinois, as well as the National Institutes of Health and Centers for Disease Control and Prevention, have signed the pledge, which is sponsored by the Association of University Technology Managers.

WHO: Pandemic (H1N1) 2009 – update 74: 13 November 2009

Pandemic (H1N1) 2009 – update 74
Weekly update

13 November 2009 — As of 8 November 2009, worldwide more than 206 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6250 deaths. As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data. More discussion at:

http://www.who.int/csr/don/2009_11_13/en/index.html

WHO: Revised guidance: Clinical management of H1N1

Clinical management of human infection with pandemic (H1N1) 2009: revised guidance
November 2009
Full document (15 pages) available at: http://www.who.int/csr/resources/publications/swineflu/clinical_management_h1n1.pdf

Summary
This guidance provides updated information for health care providers managing patients with suspected or confirmed pandemic (H1N1) 2009. It incorporates knowledge gained about clinical features of pandemic influenza through international consultations.

Key topics:
– risk factors for severe disease
– signs and symptoms of progressive disease
– diagnosis
– treatment, both outpatient and in hospitals, and
– clinical care for resource-poor settings.

http://www.who.int/csr/resources/publications/swineflu/clinical_management/en/index.html

WHO: Interim planning considerations for mass gatherings in H1N1 context

CDC Estimates of 2009 H1N1 Cases and Related Hospitalizations and Deaths from April-October 17, 2009, By Age Group

Interim planning considerations for mass gatherings in the context of pandemic (H1N1) 2009 influenza

November 2009

Introduction

Mass gatherings are highly visible events with the potential for serious public health and political consequences if they are not planned and managed carefully. There is ample documentation that mass gatherings can amplify and spread infectious diseases.

Respiratory infections, including influenza, have been frequently associated with mass

gatherings. Such infections can be transmitted during the mass gathering, during transit

to and from the event, and in participants’ home communities upon their return.

Planners of mass gatherings face special challenges during a global influenza

pandemic. The purpose of this document is to outline key planning considerations

for organizers of mass gatherings in the context of pandemic (H1N1) 2009 influenza. It

should be used in conjunction with WHO’s Communicable disease alert and response

for mass gatherings.

This document was prepared during September – October 2009 by WHO staff. It was

reviewed by WHO’s Virtual Interdisciplinary Advisory Group on Mass Gatherings. It is

based on currently available information about pandemic (H1N1) 2009 influenza. As the

pandemic situation evolves and additional information becomes available, it may be

necessary to revise the document. Review of the document is planned in the first quarter of 2010.

http://www.who.int/csr/resources/publications/swineflu/cp002_2009-0511_planning_considerations_for_mass_gatherings.pdf

FDA Commissioner letter to America’s healthcare professionals on H1N1 Vaccine

FDA Commissioner Dr. Margaret Hamburg sent “a letter to America’s healthcare professionals thanking them for their efforts during the 2009 H1N1 influenza outbreak and providing information on the safety of the 2009 H1N1 vaccines.” The letter provides an overview of the manufacturing and approval process for these vaccines as a way to help address issues around the delays in availability of the vaccine and public confidence about this vaccine overall. The letter does not address the vaccination of healthcare professionals. The letter can be viewed at: http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm189691.htm

WHO REport: Women and health: today’s evidence tomorrow’s agenda

The WHO released a new report: Women and health: today’s evidence tomorrow’s agenda. The foreword of the 111-page report is written by WHO Director-General Margaret Chan as below:

Foreword

When I took office in 2007, I asked that my performance be judged by results as measured by the health of women and of the people of Africa. My commitment to these populations is a reaffirmation of WHO’s long history of reaching out to those in greatest need and to redressing health inequalities and their determinants.

The Millennium Development Goals and other global commitments have focused primarily on the entitlements and needs of women. The current financial crisis and economic downturn make this focus even more urgent; protecting and promoting the health of women is crucial to health and development – not only for the citizens of today but also for those of future generations.

This report reviews evidence on the health issues that particularly affect girls and women throughout their life course. Despite considerable progress over the past two decades, societies are still failing women at key moments in their lives. These failures are most acute in poor countries, and among the poorest women in all countries. Not everyone has benefited equally from recent progress and too many girls and women are still unable to reach their full potential because of persistent health, social and gender inequalities and health system inadequacies.

This report does not offer a comprehensive analysis of the state of women and health in the world. The data and evidence that are available are too patchy and incomplete for this to be possible. Indeed, one of the striking findings of the report is the paucity of statistics on key health issues that affect girls and women. But the report does bring together what is currently known and identifies areas where new data need to be generated, available data compiled and analysed, and research undertaken to fill critical gaps in the evidence base.

In presenting this report, it is my hope that it will serve to stimulate policy dialogue at

country, regional and global levels, to inform actions by countries, agencies, and development partners, and to draw attention to innovative strategies that will lead to real improvements in the health and lives of girls and women around the world.

There is a single instance of the “vaccine” in the report. The passage in which it occurs follow: “Cervical cancer is globally the second most common type of cancer among women and virtually all cases are linked to genital infection with HPV. There were more than 500 000 new cases of cervical cancer and 250 000 deaths from it worldwide in 2005. Almost 80% of cases today occur in low-income countries, where access to cervical cancer screening and prevention services is almost non-existent. A highly effective vaccine against HPV is now available but cost and accessibility limit its use in less developed countries. Cervical cancer can also be prevented through regular screening coupled with treatment, but this is rarely available in most developing countries.

http://www.gavialliance.org/resources/Womenandhealthreport.pdf

CDC: H1N1 disease estimates in U.S.: April – October 17, 2009

The CDC released a single-page set of estimates associates with H1N1 in the U.S. The summary points are below:

– CDC estimates that between 14 million and 34 million cases of 2009 H1N1 occurred between April and October 17, 2009. The mid-level in this range is about 22 million people infected with 2009 H1N1.

– CDC estimates that between about 63,000 and 153,000 2009 H1N1-related hospitalizations occurred between April and October 17, 2009. The mid-level in this range is about 98,000 H1N1-related hospitalizations.

– CDC estimates that between about 2,500 and 6,000 2009 H1N1-related deaths occurred between April and October 17, 2009. The mid-level in this range is about 3,900 2009 H1N1-related deaths.

http://www.cdc.gov/h1n1flu/pdf/Table_CDC_Est_2009_H1N1_Cases_Related_%20Hosp_Deaths_April.pdf

Comment: Affordable cholera vaccine

The Lancet
Nov 14, 2009   Volume 374  Number 9702 Pages 1653 – 1722
http://www.thelancet.com/journals/lancet/issue/current

Comment
An affordable cholera vaccine: an important step forward
Saranya Sridhar

The cholera epidemic in Zimbabwe, which has claimed over 4000 lives since August, 2008,1 has refocused the world’s attention on strategies to prevent cholera. Such devastating cholera outbreaks, increasingly common as a result of sudden movements of populations and natural disasters, represent the tip of the iceberg and add to the regular burden of endemic cholera. WHO reported 236 896 cholera cases worldwide in 2006, an increase of 79% over the previous year, although these figures are thought to represent only 5–10% of actual cases.

A H1N1 and public health security in Saudi Arabia for the 2009 Hajj

The Lancet
Online First
http://www.thelancet.com/journals/lancet/onlinefirst

Nov 14, 2009
Public Health
Establishment of public health security in Saudi Arabia for the 2009 Hajj in response to pandemic influenza A H1N1
ZA Memish, SJN McNabb, F Mahoney, F Alrabiah, N Marano, QA Ahmed, J Mahjour, RA Hajjeh, P Formenty, FH Harmanci, H El Bushra, TM Uyeki, M Nunn, N Isla, M Barbeschi

Summary
Mass gatherings of people challenge public health capacities at host locations and the visitors’ places of origin. Hajj—the yearly pilgrimage by Muslims to Saudi Arabia—is one of the largest, most culturally and geographically diverse mass gatherings in the world. With the 2009 pandemic influenza A H1N1 and upcoming Hajj, the Saudi Arabian Ministry of Health (MoH) convened a preparedness consultation in June, 2009. Consultants from global public health agencies met in their official capacities with their Saudi Arabian counterparts. The MoH aimed to pool and share public health knowledge about mass gatherings, and review the country’s preparedness plans, focusing on the prevention and control of pandemic influenza. This process resulted in several practical recommendations, many to be put into practice before the start of Hajj and the rest during Hajj. These preparedness plans should ensure the optimum provision of health services for pilgrims to Saudi Arabia, and minimum disease transmission on their return home. Review of the implementation of these recommendations and their effect will not only inform future mass gatherings in Saudi Arabia, but will also strengthen preparedness efforts in other settings.

NEJM: 2009 H1N1 Influenza Overview

New England Journal of Medicine
Volume 361 — November 12, 2009 — Number 20
http://content.nejm.org/current.shtml

Editorial
Preparing for 2009 H1N1 Influenza
Richard P. Wenzel, M.D., and Michael B. Edmond, M.D., M.P.H. http://content.nejm.org/cgi/content/full/361/20/1991

Original Articles
Critical Care Services and 2009 H1N1 Influenza in Australia and New Zealand
The ANZIC Influenza Investigators
Abstract | FREE Full Text |

Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009
S. Jain and Others
Abstract | FREE Full Text |

Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
K. Hancock and Others
Abstract | FREE Full Text |

Europe Reconsiders H1N1 Flu Shots for Children

CDC Estimates of 2009 H1N1 Cases and Related Hospitalizations and Deaths from April-October 17, 2009, By Age Group
Science
13 November 2009  Vol 326, Issue 5955, Pages 905-1028
http://www.sciencemag.org/current.dtl

News of the Week
Pandemic Influenza: Europe Reconsiders H1N1 Flu Shots for Children
Martin Enserink*

Until recently, no European country had included healthy children in the priority groups targeted for vaccination against the H1N1 pandemic virus. But as the outbreak gathers speed and more vaccine becomes available, some countries are now telling families that healthy children—or at least infants—are candidates for vaccination after all. The change of mind did not reassure a jittery public. How many European children will eventually be vaccinated remains to be seen, partly because distrust of the new vaccines is running high.

Pandemic H1N1 and the 2009 Hajj

CDC Estimates of 2009 H1N1 Cases and Related Hospitalizations and Deaths from April-October 17, 2009, By Age Group
Science
13 November 2009  Vol 326, Issue 5955, Pages 905-1028
http://www.sciencemag.org/current.dtl

Policy Forum
Public Health: Pandemic H1N1 and the 2009 Hajj
Shahul H. Ebrahim,1,* Ziad A. Memish,2 Timothy M. Uyeki,1 Tawfik A. M. Khoja,3 Nina Marano,1 Scott J. N. McNabb1

The annual Hajj pilgrimage of more than 2.5 million pilgrims from more than 160 countries is held in the Kingdom of Saudi Arabia (KSA) (1) (see the figure). Hajj is a deeply spiritual journey undertaken by Muslims at least once in their lifetimes. Hajj-related infectious disease outbreaks in recent decades have focused attention on Hajj as a global public health security challenge of extraordinary dimensions (1–5). This past summer, a KSA–World Health Organization (WHO) consultation process developed the Jeddah recommendations on mitigation for the effects of the current pandemic influenza A (H1N1) virus during the 2009 Hajj, which is the last week of November (6). Here, we outline some of the realities associated with meeting those recommendations and the most recent plans to help mitigate the transmission burden.

1 Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
2 Ministry of Health, Riyadh, Saudi Arabia.
3 Executive Board, Health Ministers’ Council for Cooperation, Council of Gulf States, Riyadh, Saudi Arabia.

WHO: Pandemic (H1N1) 2009 – update 73

The WHO continues to issue weekly “updates” and briefing notes as below:
Pandemic (H1N1) 2009 – update 73
Weekly update

As of 1 November 2009, worldwide more than 199 countries and overseas territories/communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6000 deaths.

As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

Situation update:

Intense and persistent influenza transmission continues to be reported in North America without evidence of a peak in activity. The proportion of sentinel physician visits due to influenza-like-illness (ILI)(8%) has exceeded levels seen over the past 6 influenza seasons; 42% of respiratory samples tested were positive for influenza and 100% of subtyped influenza A viruses were pandemic H1N1 2009. Rates of ILI, proportions of respiratory samples testing positive for influenza, and numbers of outbreaks in educational settings continues to increase sharply in Canada as activity spreads eastward. Significantly more cases of pandemic H1N1 have been recorded in Mexico since September than were observed during the initial springtime epidemic.

In Europe and Central and Western Asia, pandemic influenza activity continues to increase across many countries, signalling an unusually early start to the winter influenza season. Active circulation of virus marked by high proportions of sentinel respiratory samples testing positive for influenza has been reported in Belgium (69%), Ireland (55%), Netherlands (51%), Norway (66%), Spain (46%), Sweden (33%), the United Kingdom (Northern Ireland:81%), and Germany (27%). In addition, there is evidence of increasing and active transmission of pandemic influenza virus across Northern and Eastern Europe (including Ukraine and Belarus), and eastern Russia. For details on the situation in Ukraine please refer to the Disease Outbreak News update below. In Western Asia and the Eastern Mediterranean Region, increasing activity has been reported in Oman and Afghanistan.

Pandemic (H1N1) 2009, Ukraine – update 1

In East Asia, intense and increasing influenza activity continues to be reported in Mongolia. In China, after an earlier wave of mixed influenza activity (seasonal H3N2 and pandemic H1N1), pandemic H1N1 influenza activity now predominates and is increasing. Sharp increases in pandemic influenza activity continue to be reported throughout Japan with highest rates of illness being reported on the northern island.

Active influenza transmission and increasing levels of respiratory diseases continues to be reported in parts of the Caribbean, including in Cuba, Haiti, and other Caribbean Epidemiology Centre (CAREC) countries. Most other countries in the tropical region of Central and South America continue to report declining influenza activity. With the exception of Nepal, Sri Lanka, and Cambodia, overall transmission continues to decline in most but not all parts of tropical South and Southeast Asia. Influenza virus isolates from sub-Saharan Africa are predominantly pandemic H1N1 virus but some seasonal H3N2 has been detected even in recent weeks. Unconfirmed media reports from the area indicate that disease activity has increased in recent weeks.

Since the new pandemic H1N1 2009 virus emerged, infections in different species of susceptible animals (pig, turkey, ferret, and cat) have been reported. Limited evidence suggests that these infections occurred following direct transmission of the virus from infected humans. These isolated events have had no impact on the dynamics of the pandemic, which is spreading readily via human-to-human transmission. As human infections become increasingly widespread, transmission of the virus from humans to other animals is likely to occur with greater frequency. Unless the epidemiology of the pandemic changes, these will continue to pose no special risks to human health.

http://www.who.int/csr/don/2009_11_06/en/index.html

H1N1 Vaccine Allocation: CDC letter to state and local health officials

[Editor’s Note: The following letter to state and local health officials followed media reports last week about potential diversion of H1N1 vaccine stocks to non-priority groups]

November 5, 2009

Dear State/Local Health Officer:

Today we have 35.6 million doses of 2009 H1N1 vaccine allocated for ordering, with more coming every day. As you know all too well, at present, demand for the vaccine in your communities still exceeds the supply we have received from manufacturers. That means it is more important than ever to focus on ensuring equitable access to the vaccine for the priority groups identified by the Advisory Committee on Immunization Practices: pregnant women, caretakers of infants less than 6 months of age, health care workers, children and adults with health conditions such as asthma or diabetes, and people under the age of 25. These are the people who are most vulnerable to 2009 H1N1 influenza, and it’s our job to do everything we can to keep them safe this flu season.

I know you have been working hard to distribute vaccine to the people who need it most. You are on the front lines of the fight, and no one knows better than you how to reach people in your communities. I especially appreciate the many innovative ways you’ve found to reach them, including school-located vaccine clinics, special clinics for pregnant women, outreach to children with special needs, and making vaccine available to community- and faith-based organizations serving these high-risk populations.

The goal of the H1N1 vaccination program is to protect our population – focusing first on these high-risk groups and ensuring equitable access to the vaccine. While vaccine supplies are still limited, any vaccine distribution decisions that appear to direct vaccine to people outside the identified priority groups have the potential to undermine the credibility of the program.

It is important to make it clear to the public that we are all committed to the science-based vaccination recommendations established by the Advisory Committee on Immunization Practices. This may include making clear to the public as well as health care providers how the vaccine available to you is being targeted, and the basis for targeting. CDC expects all grantees to ensure that all vaccinators chosen by state and local health departments adhere to those recommendations. Toward that end, and in light of changing projections of vaccine availability, I ask each of you to review your plans immediately and work to ensure that the maximum number of doses is delivered to those at greatest risk as rapidly as possible.

I know how difficult your jobs are; we are ready and willing to help you any way we can.

Sincerely,

Thomas R. Frieden, M.D., M.P.H.
Director, Centers for Disease Control and
Prevention, and
Administrator, Agency for Toxic Substances
and Disease Registry

http://www.cdc.gov/media/pdf/Final-H1N1-Letter-to-State-Officials–CDC-Director.pdf

NIAID funds infectious disease research, including bioterrorism-induced events

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, said it awarded approximately US$208 million to two programs that support research “to better understand the human immune response to emerging and re-emerging infectious diseases, including those that may be introduced into a community through acts of bioterrorism.” The grants were awarded to the Cooperative Centers for Translational Research on Human Immunology and Biodefense (CCHI) and the Immune Mechanisms of Virus Control (IMVC). NIAID said it also received approximately US$21 million under the American Recovery and Reinvestment Act to supplement these two programs and fund some additional researchers. This funding is part of the US$5 billion awarded by NIH in FY 2009 for research projects under the Recovery Act. The long-term goal of the CCHI and IMVC programs is to identify new vaccines and drug targets.

Daniel Rotrosen, M.D., director of the NIAID Division of Allergy, Immunology and Transplantation, said, “Developing vaccines and treatments for emerging pathogens continues to be a priority for NIAID. The CCHI and IMVC programs will foster collaboration among many talented investigators working toward the common goal of understanding the human immune response to infectious diseases and developing more effective measures to prevent and treat infection.”

http://www.nih.gov/news/health/nov2009/niaid-04a.htm

PATH and PharmaJet to evaluate new generation of needle-free injection technologies

PATH and PharmaJet, a privately held company, said they are collaborating “to bring developing countries safe, effective, and affordable injections without using needles.” The new partnership “will evaluate a new generation of needle-free injection technologies, including PharmaJet’s needle-free, disposable-syringe jet injectors. These vaccine delivery technologies could reduce health risks and costs associated with traditional needle injections.” Starting in Brazil, where clinical studies are scheduled to begin in early 2010, PATH will evaluate needle-free delivery of a variety of vaccines compared to delivery by needle and syringe. Vaccines to be tested include those to prevent measles-mumps-rubella and yellow fever. PATH and its Brazilian partners also plan to conduct pilot introduction studies and other activities to facilitate adoption of needle-free technologies like the PharmaJet system. Darin Zehrung, team leader for vaccine delivery technologies at PATH, said, “Disposable-syringe jet injector technology has the potential to provide safer and more affordable vaccines to millions of people around the world. This collaboration is an important step in our work to explore the regulatory pathway, commercial viability, and sustainability of this class of jet injectors in the developing world and share that knowledge with the entire global health community.”

PATH noted WHO estimates that at least 16 billion injections are given in developing and transitional countries each year. Prior to the introduction of autodisable syringes and a worldwide emphasis on injection safety, “health officials estimated that at least 50 percent of injections in developing countries were considered to be unsafe.” Unsafe injections can expose individuals to the risk of infections such as HIV, hepatitis B, or hepatitis C. Infection can occur when health workers or patients reuse syringes, contaminate medications with used syringes, or accidentally injure the patient or themselves with a used needle. While developing countries have begun extensive efforts to improve injection safety, the costs and difficulty of managing ever-growing volumes of vaccine and sharps waste remain an obstacle to safety, PATH noted.

http://www.path.org/news/pr091105-pharmajet.php

Editorials: Influenza

JAMA
Vol. 302 No. 17, pp. 1839-1926, November 4, 2009
http://jama.ama-assn.org/current.dtl

Editorials

Respiratory Protection Against Influenza
Arjun Srinivasan; Trish M. Perl
JAMA. 2009;302(17):1903-1904. Published online October 1, 2009

Preparing for the Sickest Patients With 2009 Influenza A(H1N1)
Douglas B. White; Derek C. Angus

Influenza in 2009: New Solutions, Same Old Problems
Julie Louise Gerberding

Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers

JAMA
Vol. 302 No. 17, pp. 1839-1926, November 4, 2009
http://jama.ama-assn.org/current.dtl

Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers: A Randomized Trial
Mark Loeb, MD, MSc; Nancy Dafoe, RN; James Mahony, PhD; Michael John, MD; Alicia Sarabia, MD; Verne Glavin, MD; Richard Webby, PhD; Marek Smieja, MD; David J. D. Earn, PhD; Sylvia Chong, BSc; Ashley Webb, BS; Stephen D. Walter, PhD

Context  Data about the effectiveness of the surgical mask compared with the N95 respirator for protecting health care workers against influenza are sparse. Given the likelihood that N95 respirators will be in short supply during a pandemic and not available in many countries, knowing the effectiveness of the surgical mask is of public health importance.

Objective  To compare the surgical mask with the N95 respirator in protecting health care workers against influenza.

Design, Setting, and Participants  Noninferiority randomized controlled trial of 446 nurses in emergency departments, medical units, and pediatric units in 8 tertiary care Ontario hospitals.

Intervention  Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008-2009 influenza season.

Main Outcome Measures  The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers. Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator. The criterion for noninferiority was met if the lower limit of the 95% confidence interval (CI) for the reduction in incidence (N95 respirator minus surgical group) was greater than –9%.

Results  Between September 23, 2008, and December 8, 2008, 478 nurses were assessed for eligibility and 446 nurses were enrolled and randomly assigned the intervention; 225 were allocated to receive surgical masks and 221 to N95 respirators. Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, –0.73%; 95% CI, –8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of –9%.

Conclusion  Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza.

Trial Registration  clinicaltrials.gov Identifier: NCT00756574

Author Affiliations: Departments of Pathology and Molecular Medicine (Drs Loeb, Mahony, and Smieja and Ms Dafoe), Medicine (Dr Loeb), Clinical Epidemiology and Biostatistics (Drs Loeb, Smieja, Earn, and Walter), and Mathematics and Statistics (Dr Earn), Michael G. DeGroote Institute for Infectious Disease Research (Drs Loeb, Mahony, Smieja, and Earn), McMaster University, Hamilton, Ontario, Canada; St Joseph’s Hospital Regional Virology Laboratory, Hamilton (Dr Mahony and Ms Chong); Departments of Pathology and Microbiology and Immunology, University of Western Ontario, London (Dr John); Department of Microbiology, Credit Valley Hospital, Mississauga, Ontario (Dr Sarabia); Joseph Brant Memorial Hospital, Burlington, Ontario (Dr Glavin); and World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds, St Judes Children’s Hospital, Memphis, Tennessee (Dr Webby and Ms Webb).

Novel H1N1 Influenza and Respiratory Protection for Health Care Workers

New England Journal of Medicine
Volume 361 — November 5, 2009 — Number 19
http://content.nejm.org/current.shtml

Novel H1N1 Influenza and Respiratory Protection for Health Care Workers
Kenneth I. Shine, M.D., Bonnie Rogers, Dr.P.H., R.N., and Lewis R. Goldfrank, M.D.

[Initial language]
Your hospital has been seeing a large number of patients with influenza-like symptoms, many of whom turn out to be infected with the novel H1N1 influenza A virus. You have been asked to consult on the case of a 28-year-old woman who is in an isolation room because of an influenza-like presentation and shortness of breath. You put on a gown, carefully clean your hands with hand soap or an alcoholic gel, pull on gloves, and reach for a mask. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend the use of an N95 filtering facepiece respirator. Some states and many professional groups have suggested that a standard surgical mask is satisfactory in this situation, except when a clinician is performing high-risk procedures, such as airway suctioning, in which case the N95 is still recommended. What should the hospital and its infection-control officer provide when you reach into the box for a respiratory protective device? What should be available to others who will enter this room, including nurses, respiratory technicians, cleaners, and food servers?….

Human Papillomavirus Vaccine for Cancer Prevention

New England Journal of Medicine
Volume 361 — November 5, 2009 — Number 19
http://content.nejm.org/current.shtml

Human Papillomavirus Vaccine for Cancer Prevention
O. J. Finn and R. P. Edwards

[First 100 words per NEJM convention]
Cancer immunoprevention has become synonymous with the vaccines that have been approved for the prevention of infection with highly transmissible strains of human papillomavirus (HPV) that establish chronic infection and cause cervical and other cancers.1 Although many cancers may have a viral origin,2 only a small number of viruses have been implicated as causes of human cancer. Cancer having a viral origin provides an opportunity to develop virus-specific vaccines that lower infection rates and consequently lower the incidence of cancer; this is what the HPV vaccine is expected to do for cervical cancer and what the hepatitis B vaccine has . . .

Developing Countries to Get Some H1N1 Vaccine—But When?

Science
6 November 2009  Vol 326, Issue 5954, Pages 757-904
http://www.sciencemag.org/current.dtl

Swine Flu Pandemic:
Developing Countries to Get Some H1N1 Vaccine—But When?
Martin Enserink

The World Health Organization has said that about a month from now, it will begin supplying developing countries with H1N1 vaccine donated by manufacturers and rich countries. But it has secured only about 200 million doses for 95 countries that together are home to a third of the world’s population, compared with the 250 million doses that the United States has purchased, Germany’s 50 million, and France’s 94 million. Moreover, much of that vaccine won’t arrive for several months, and the pandemic marches on…

WHO: Pandemic (H1N1) 2009 briefing note 14; 30 October 2009

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

Pandemic (H1N1) 2009 briefing note 14

Experts advise WHO on pandemic vaccine policies and strategies

30 OCTOBER 2009 | GENEVA

The Strategic Advisory Group of Experts (SAGE) on Immunization, which advises WHO on policies and strategies for vaccines and immunization, devoted a session of its 27–29 October meeting to pandemic influenza vaccines. The experts reviewed the current epidemiological situation of the pandemic worldwide and considered issues and options from a public health perspective.

Items on the agenda included the status of vaccine availability, results from clinical trials on vaccine immunogenicity, and early results from safety monitoring in countries where administration of the H1N1 pandemic vaccine is currently under way.

The experts also advised WHO on the number of doses of vaccine needed to confer protection, also in different age groups, the co-administration of seasonal and pandemic vaccines, and vaccines for use in pregnant women. Recommendations on the formulation of seasonal influenza vaccines for the southern hemisphere in 2010 were also provided.

Current situation

Globally, teenagers and young adults continue to account for the majority of cases, with rates of hospitalization highest in very young children. Between 1% to 10% of patients with clinical illness require hospitalization. Of hospitalized patients, from 10% to 25% require admission to an intensive care unit, and from 2% to 9% have a fatal outcome.

Overall, from 7% to 10% of all hospitalized patients are pregnant women in their second or third trimester of pregnancy. Pregnant women are ten times more likely to need care in an intensive care unit when compared with the general population.

Based on these and other current findings, the experts made a number of recommendations.

Single dose recommended

The experts noted that a variety of pandemic vaccines, including live attenuated and both adjuvanted and non-adjuvanted inactivated vaccines, have now been licensed for use by regulatory authorities. SAGE recommended the use of a single dose of vaccine in adults and adolescents, beginning at the age of 10 years, provided such use is consistent with indications from regulatory authorities.

Data on immunogenicity in children older than 6 months and younger than 10 years are limited and more studies are needed. Where national authorities have made children a priority for early vaccination, SAGE recommended that priority be given to the administration of one dose of vaccine to as many children as possible. SAGE further stressed the need for studies to determine dosage regimens effective in immunocompromised persons.

Co-administration of vaccines

Clinical trials investigating the co-administration of seasonal and pandemic vaccines are ongoing, but SAGE acknowledged the recommendation, from the US Centers for Disease Control and Prevention, that live attenuated seasonal and live attenuated pandemic vaccines should not be co-administered.

The experts recommended that seasonal and pandemic vaccines can be administered simultaneously, provided both vaccines are inactivated, or one is inactivated and the other is live attenuated. The experts found no evidence that co-administration of vaccines, as recommended, would increase the risk of adverse events.

Vaccine safety

The experts reviewed early results from the monitoring of people who have received pandemic vaccines and found no indication of unusual adverse reactions. Some adverse events following vaccination have been notified, but these are well within the range of those seen with seasonal vaccines, which have an excellent safety profile. Although early results are reassuring, monitoring for adverse events should continue.

Vaccines for pregnant women

Concerning vaccines for pregnant women, SAGE noted that studies in experimental animals using live attenuated vaccines and non-adjuvanted or adjuvanted inactivated vaccines found no evidence of direct or indirect harmful effects on fertility, pregnancy, development of the embryo or fetus, birthing, or post-natal development.

Based on these data and the substantially elevated risk for a severe outcome in pregnant women infected with the pandemic virus, SAGE recommended that any licensed vaccine can be used in pregnant women, provided no specific contraindication has been identified by the regulatory authority.

Vaccines for the southern hemisphere in 2010

SAGE also considered vaccines for use in the southern hemisphere during the 2010 winter season. Two options were assessed: a trivalent vaccine, effective against the H1N1 pandemic virus, the seasonal H3N2 virus, and influenza B viruses, and a bivalent seasonal vaccine, effective against H3N2 and influenza B viruses, which might need to be supplemented with a separate monovalent H1N1 pandemic vaccine.

The experts concluded that both options should remain available for vaccine formulations in the southern hemisphere, subject to national needs.

http://www.who.int/csr/disease/swineflu/notes/briefing_20091030/en/index.html

WHO Briefing Note: Pandemic (H1N1) 2009, Ukraine

Pandemic (H1N1) 2009, Ukraine

On 28 October 2009, the Ministry of Health of the Ukraine informed WHO, through its Country Office in Ukraine, about an unusually high level of activity of acute respiratory illness in the western part of the country, associated with an increased number of hospital admissions and fatalities.

On 30 October 2009, the Ministry of Health of the Ukraine announced the confirmation of pandemic (H1N1) 2009 virus infection by RT-PCR in eleven out of 30 samples obtained from patients presenting with acute respiratory illness in two of the most affected regions. Tests were performed in two laboratories in Kyiv, including the National Influenza Centre. Confirmatory tests will be performed at one of the WHO Collaborating Centres for Influenza.

The situation is quickly changing with increasingly high levels of acute respiratory illness (ARI)/Influenza-like-illness (ILI) activity being observed in Ternopil, Lviv, Ivano-Frankivsk, and Chernivtsi regions. The higher levels of transmission in these regions corresponds to an increased number of hospital admissions and fatalities associated with severe manifestations of acute respiratory illness.

As of 30 October 2009, over 2,300 individuals have been admitted to hospital, including over 1,100 children. One hundred and thirty one (131) cases have required intensive care, including 32 children. As of 31 October 2009, a total of 38 fatalities associated with severe manifestations of ARI have been registered. Preliminary epidemiological data analysis indicates that severe cases and deaths primarily occur among previously healthy young adults aged 20 – 50 years. Fatal and severe cases are reported to have sought medical attention 5 to 7 days after onset of symptoms.

International experience of the (H1N1) 2009 pandemic to date, especially from the Southern Hemisphere, has shown that poor clinical outcomes are associated with delays in seeking health care and limited access to supportive care. In addition, this virus has also shown its ability to cause rapidly progressive overwhelming lung disease which is very difficult to treat.

Public health measures recommended by the Ministry of Health of the Ukraine across the entire country include: social distancing (school closures and cancellation of mass gatherings); enhancement of surveillance activities; increased respiratory hygiene; and continuation of the vaccination campaign against seasonal influenza targeting at risk groups.

The Government of the Ukraine has activated coordination mechanisms to respond to the rapidly evolving situation, including the harmonization of response plans across all administrative levels.

In response to the request from the Minister of Health of the Ukraine, WHO is deploying a multi-disciplinary team of experts to assist national authorities in mitigating the impact of the pandemic. The team comprises of the following expertise: health emergencies coordination, case management, epidemiology, laboratory diagnostics, logistics, and media/risk communications.

As per WHO’s communication in May 2009, there is no rationale for travel restrictions because such measures will not prevent the spread of the disease.

Travellers can protect themselves and others by following simple recommendations aimed at preventing the spread of infection such as attention to respiratory hygiene. Individuals who are ill should delay travel plans and returning travellers who fall ill should seek appropriate medical care. These recommendations are prudent measures which can limit the spread of many communicable diseases and not only the pandemic (H1N1) 2009 virus. http://www.who.int/csr/don/2009_11_01/en/index.html

WHO/UNICEF launch GAPP: avoiding 5.3 million pneumonia deaths by 2015

The WHO and UNICEF launched a “comprehensive action plan that can save up to 5.3 million children from dying of pneumonia by 2015.” The Global action plan for the prevention and control of pneumonia (GAPP) includes “recommendations on what needs to be done, specific goals and targets, and estimates of what it will cost and how many lives will be saved…its aim is to increase awareness of pneumonia as a major cause of child deaths, and it calls on global and national policy-makers, donor agencies and civil society to take immediate action to implement the plan.” The release of the GAPP strategy coincides with the first Global Pneumonia Summit being held in New York City on 2 November.

The GAPP has a three-pronged vision:

– Protecting every child by providing an environment where they are at low risk of pneumonia (with exclusive breastfeeding for six months, adequate nutrition, preventing low-birth-weight, reducing indoor air pollution, and increasing hand washing);

– Preventing children from becoming ill with pneumonia (with vaccination against its causes: measles, pertussis, Streptococcus pneumoniae and Haemophilus influenzae b, as well as preventing and treating HIV in children, and providing zinc for children with diarrhoea);

– Treating children who become ill with pneumonia with the right care and antibiotics (in communities, health centres and hospitals).

The cost of implementing the GAPP by scaling up the recommended measures in the 68 high burden countries is estimated at US$39 billion for 2010-2015. The costs are expected to double over the six-year period, rising from an annual need of US$ 3.8 billion in 2010 to US$ 8.0 billion by 2015.

Specific targets and goals to be reached by 2015 under the GAPP strategy are to expand coverage of all relevant vaccines and exclusive breastfeeding rates to 90%, and raise the level of access to appropriate pneumonia case management to 90%. This will lead to a reduction in child pneumonia deaths by 65% and cutting the number of severe pneumonia cases in children by 25%, compared to 2000 levels.

The GAPP strategy document is available at: http://whqlibdoc.who.int/hq/2009/WHO_FCH_CAH_NCH_09.04_eng.pdf

http://www.who.int/mediacentre/news/releases/2009/child_pneumonia_gapp_20091102/en/index.html

IVI: new low-cost killed whole-cell (WC) oral cholera vaccine

The International Vaccine Institute (IVI) said its new low-cost killed whole-cell (WC) oral cholera vaccine was found to be protective against clinically significant cholera in an endemic setting in a large-scale field trial conducted in nearly 70,000 residents of Kolkata, India. The new vaccine was found to be safe, and was effective in young children as well as older persons. IVI developed the vaccine “by modifying an inexpensive vaccine produced in Vietnam and said the new vaccine was licensed early this year in India. This major study was conducted by the IVI in collaboration with the National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, India. Based in Seoul, Korea, the IVI is a nonprofit international organization devoted exclusively to development and deployment of new vaccines primarily for people in developing countries.

IVI Director-General Dr. John Clemens said, “This interim analysis shows that the modified vaccine is safe and efficacious, providing nearly 70 percent protection against clinically significant cholera for at least two years after vaccination.” IVI noted that an internationally licensed, killed whole-cell vaccine containing the recombinant cholera toxin B subunit (rBS-WC) is currently available. IVI said that due to the high cost and requirement of buffer for administration of rBS-WC, it is not feasible for use in developing countries. In contrast, the new IVI vaccine does not require any buffer, making it easier to administer, and is cheaper to produce, making mass vaccination campaigns more feasible, IVI said. In order for the new vaccine to be purchased by United Nations organizations such as UNICEF, the IVI said it transferred its production technology to the vaccine manufacturer, Shantha Biotechnics, in India, where the national regulatory authority is approved by the WHO. Shantha obtained licensure for this vaccine (Shanchol) on February 24, 2009 from the Indian national regulatory authority, paving the way for the expanded use of the vaccine.

http://www.ivi.org/event_news/news_view.asp?enid=105

Long-Lasting Measles Outbreak Affecting Several Unrelated Networks of Unvaccinated Persons (Quebec)

Journal of Infectious Diseases
15 November 2009  Volume 200, Number 10
http://www.journals.uchicago.edu/toc/jid/current

Major Articles and Brief Reports
VIRUSES
LongLasting Measles Outbreak Affecting Several Unrelated Networks of Unvaccinated Persons

Frédéric Dallaire, Gaston De Serres, François-William Tremblay, France Markowski, and Graham Tipples

Abstract
Despite a population immunity level estimated at 95%, an outbreak of measles responsible for 94 cases occurred in Quebec, Canada. Unlike previous outbreaks in which most unvaccinated children belonged to a single community, this outbreak had cases coming from several unrelated networks of unvaccinated persons dispersed in the population. No epidemiological link was found for about one-third of laboratory-confirmed cases. This outbreak demonstrated that minimal changes in the level of aggregation of unvaccinated individuals can lead to sustained transmission in highly vaccinated populations. Mathematical work is needed regarding the level of aggregation of unvaccinated individuals that would jeopardize elimination.

Malaria: a research agenda for the eradication era

The Lancet
Oct 31, 2009  Volume 374  Number 9700  Pages 1473 – 1566
http://www.thelancet.com/journals/lancet/issue/current

Comment
Malaria: a research agenda for the eradication era

Wen Kilama, Francine Ntoumi
The world’s largest meeting on malaria, the 5th Multilateral Initiative on Malaria (MIM) Pan-African Malaria Conference, convenes in Nairobi, Kenya, on Nov 1–6.1 Since the last MIM meeting in 2005, the malaria landscape has transformed dramatically. Scientific progress and support from the highest levels of government galvanised the field, and the global community has begun to coalesce around the most ambitious goal possible—eradication.

Adoption of Rotavirus Vaccination by U.S. Pediatricians and Family Medicine Physicians

Pediatrics
November 2009 / VOLUME 124 / ISSUE 5
http://pediatrics.aappublications.org/current.shtml

Adoption of Rotavirus Vaccination by Pediatricians and Family Medicine Physicians in the United States
Allison Kempe, Manish M. Patel, Matthew F. Daley, Lori A. Crane, Brenda Beaty, Shannon Stokley, Jennifer Barrow, Christine Babbel, L. Miriam Dickinson, Jonathan L. Tempte, and Umesh D. Parashar

OBJECTIVES: The goals were to assess, among pediatricians and family medicine physicians, (1) rates of offering the vaccine in their office; (2) knowledge of Advisory Committee on Immunization Practices recommendations; (3) barriers to use; and (4) factors associated with offering the vaccine.

METHODS: Surveys of pediatricians and family medicine physicians were conducted in August to October 2007.

RESULTS: Response rates were 84% for pediatricians and 79% for family medicine physicians (N = 623). Proportions routinely offering the vaccine were 85% of pediatricians and 45% of family medicine physicians (P < .0001); 70% of pediatricians and 22% of family medicine strongly recommended the vaccine (P < .0001). Sixty-two percent of pediatricians and 32% of family medicine physicians (P < .0001) knew the age by which all 3 doses should be completed. Definite barriers to vaccine use included reported lack of coverage by insurance companies (family medicine physicians: 22%; pediatricians: 19%; not significant), costs of purchasing vaccine (family medicine physicians: 22%; pediatricians: 17%; not significant), lack of adequate reimbursement (family medicine physicians: 18%; pediatricians: 15%; not significant), concerns about safety (family medicine physicians: 25%; pediatricians: 9%; P < .0001), and concerns about adding another vaccine to the schedule (family medicine physicians: 22%; pediatricians: 5%; P < .0001).

CONCLUSIONS: Rates of offering the new rotavirus vaccine are high among pediatricians but <50% among family medicine physicians. Both specialties identified financial barriers to use of the vaccine, but family medicine physicians had significantly more concerns about safety and about adding another vaccine to the vaccination schedule.