Tamiflu Cited in 2 Teen Deaths – Global Plan for Influenza Action – Lancet

Tamiflu Cited in 2 Teen Deaths – Global Plan for Influenza Action – Lancet

Monday, November 14, 2005

Japanese newspapers report that two teenage boys – one 14 the other 17 – died after taking one dose of the antiviral drug, Tamiflu, the drug being stockpiled in the event that the Avian flu crosses from birds to humans. The boys became disoriented "exhibited abnormal behavior that led to their deaths." According to reports, neither had exhibited any psychological abnormalities before taking the drug. The Japanese Ministry of Health requires disclosure of adverse side effects:

“the literature accompanying the drug a list of side effects such as impaired consciousness, abnormal behavior and hallucinations and has called doctors’ attention to the possible side effects…there were 64 cases of psychological disorders linked to the drug between fiscal 2000 and 2004.”

An article in The Lancet surveyed experts around the globe about what steps are needed to avert or prepare for a flu pandemic. The report notes that "escalation in political rhetoric about avian influenza has led all countries to recognise the importance of the five essential action strategies put forward by WHO [World Health Organization] to reduce the risk of a pandemic. These are: reducing human exposure; intensifying capacity for rapid containment; strengthening early warning systems; rapid investigation of cases and clusters; and building general capacity for health."

The consensus for dealing with this global problem emphasizes the need for a coordinated global plan of action requiring ready communication – which is believed to be the key to successful management of a pandemic.

Samuel Jutzi, Director of the Division of Animal Production and Health, emphasizes that avian flu remains a disease of birds: "and this fact buys the international community some valuable time." "The way to stop avian influenza in its tracks is rapid containment of outbreaks by widespread culling of birds in infected areas."

Jutzi believes that too much emphasis has been given to the stockpiling of antiviral drugs while the battle against bird flu in animals remains under-funded. For example, he says, FAO and WHO together have just 40 veterinarians. Jutzi asserts that addressing this issue is "the only way by which the likelihood of the H5N1 virus acquiring human-to-human transmissibility can be influenced".

Everyone agrees that:  "The costs of panic to nations are magnified by misinformation and loss of trust among the public. Governments need to establish credibility and trust from the start."

Instead, US officials who lack credibility and public trust are using public anxiety about the potential flu pandemic and bioterrorism as an opportunity for submerging medical research on infectious diseases and biological-weapons in deep freeze. Senator Richard Burr¹s proposed legislation – S. 1873 (Biomedical Advanced Research and Development Agency, BARDA) – that would preclude public oversight and accountability.

The model for this legislation is the military forced anthrax vaccine debacle, a model grounded in tainted science, the disregard for medicine¹s foremost principle, "First, do no harm," which gave way to contractual deals between government and vaccine / drug manufacturers. Drug and vaccine manufacturers stand to gain huge profits from government stockpiling of drugs and vaccines – whether these have undergone adequate safety tests or not, whether evidence of their effectiveness is credible.

If passed into law, S. 1873 would spell the end of the American democratic process and preclude the following FDA public advisory committee hearing from taking place:

Flu Vaccine Manufacturing Shift:

Will influenza vaccine production go to the dogs?

Nov. 16-17: FDA’s Vaccines & Related Biological Products Advisory Committee will discuss whether canine kidney cells may be used for the manufacture of inactivated influenza vaccines.

How safe are cells from the tumorigenic canine cell lines with regard to cancer risk from residual cell DNA and unrecognized oncogenic viruses?

Will Solvay and Chiron be given the green light for continuing their clinical development of influenza vaccines using Madin Darby canine kidney cells?

CBER – Nov 16 -17 (Wed-Thur) 8:30 a.m.

Holiday Inn Select – Bethesda, MD

8120 Wisconsin Ave

A curtain of secrecy around contentious public health policies will only generate mistrust and further alienate the public from government. If enacted, Sen. Burr¹s legislation would effectively strip Americans of the right to say no to an experimental or unlicensed drug or vaccine.  [See analysis by Dr. Karen Effrem.]

Contact: Vera Hassner Sharav
212-595-8974

Chugai says two deaths have possible Tamiflu link
November 14, 2005

TOKYO (Reuters) – Japan’s Chugai Pharmaceutical Co. said on Monday it has reported to the government that two teenage boys exhibited abnormal behavior that led to their deaths after taking the anti-flu drug Tamiflu, made by Chugai’s Swiss parent Roche Holding AG.

The comments come in response to weekend news reports that Japan’s health ministry is investigating the deaths of two teenage boys who died in accidents linked to odd behavior shortly after taking the drug. Health ministry officials were not available for comment.

Shares in Chugai were down 3.1 percent at 2,630 yen on Monday afternoon, compared with a 1.3 percent fall in the Tokyo Stock Exchange’s pharmaceutical sector subindex. Tamiflu, considered one of the best defences against bird flu in humans, might help slow the spread of a much-feared pandemic should the H5N1 flu virus become able to spread from person to person.

The Mainichi newspaper and Kyodo News agency reported on Saturday that a 17-year-old high school student jumped in front of a truck in February last year shortly after taking the medicine, while a junior high school student is believed to have fallen from the ninth floor of his apartment building this February.

“We reported these cases to the health ministry as a link between the deaths and the drug could not be ruled out,” a Chugai spokesman said. The reports were made separately after each incident, he said. He said Chugai has included in the literature accompanying the drug a list of side effects such as impaired consciousness, abnormal behavior and hallucinations and has called doctors’ attention to the possible side effects.

Kyodo said the ministry is considering issuing a fresh warning about the side effects, following its decision to increase stockpiles of the drug amid growing fears about a possible pandemic.The Pharmaceuticals and Medical Devices Agency said there were 64 cases of psychological disorders linked to the drug between fiscal 2000 and 2004, according to Kyodo.

Chugai launched Tamiflu in Japan in 2001. During the last flu season it shipped the drug to more than 10 million people.

The Japanese government is planning to boost its target stockpile of Tamiflu to 250 million capsules, up 70 percent from its previous target, to cover treatment for 25 million people.

© Copyright 2005 The New York Times Company

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http://download.thelancet.com/pdfs/journals/0140-6736/PIIS0140673605676799.pdf

The Lancet 2005; 366:1684-1685
Nations set out a global plan for influenza action
Hannah Brown

A pandemic of human influenza is coming. That was the warning last week from WHO Director-General Lee Jong-wook, who called for an urgent global consensus on how to combat avian influenza. Reporting from Geneva, Hannah Brown finds out if the world is up to the challenge.

Warning of the "incalculable human misery" that will inevitably accompany the next influenza pandemic, WHO Director-General Lee Jong-wook opened the international meeting on avian and pandemic human influenza in Geneva last week with a single request: that delegates should use the 3-day meeting to build a global consensus on what should be done to halt the relentless spread of avian influenza. The hope is that action now will delay, or perhaps even avert, a global crisis.

During the past few months, the threat of a human pandemic of influenza has catapulted the issue of global preparedness into a political priority in almost all nations. Since the end of August, there have been high-level meetings in Paris, New York, Washington, DC, and Ottawa, to forge links between national representatives at the highest echelons of government and across the political spectrum.

Lee told delegates on Monday that now, for the first time, there is "a truly global awareness of the importance of pandemic preparedness and the role of international cooperation in responding to the pandemic threat". Without international cooperation, he warned, no nation can consider itself safe.

Encouragingly, on the big issues at least, consensus on what needs to be done has not been difficult to achieve. The escalation in political rhetoric about avian influenza has led all countries to recognise the importance of the five essential action strategies put forward by WHO to reduce the risk of a pandemic. These are: reducing human exposure; intensifying capacity for rapid containment; strengthening early warning systems; rapid investigation of cases and clusters; and building general capacity for health. But implementation of these policies is far from easy.

Cultural change

Reducing human exposure requires education about handling poultry and a fundamental change in cultural attitudes towards human-animal interactions and husbandry in many parts of the world. In some African countries, people sleep in the same places as poultry. In southeast Asia, "wet markets", where live poultry are traded and slaughtered on the spot, pose a risk of human transmission. And in central Asia and eastern Europe, hunting of wild birds may have played a major part in the spread of avian influenza.

Countries such as Vietnam and China have begun to tackle these problems with new laws limiting poultry rearing and live trade. And the Ukraine, whose new laws came into force on Nov 11, is among several nations to issue restrictions on hunting. But all these governments fear that local authorities will not abide by the regulations, thus limiting their effectiveness. UN Secretary-General Kofi Annan has said that the threat of avian influenza may make it necessary for humanity to fundamentally review its ways of close co-habitation with animals.

The second point in WHO’s urgent action list – rapid containment of the first human cases – requires stockpiles of antiviral drugs that can be quickly distributed to infected individuals and people living nearby. But according to Margaret Chan, Representative of the Director-General of WHO for Pandemic Influenza, current stockpiles are not sufficient in even the richest countries. And the existence of just two drugs to use against H5N1 infection, according to Dennis Carroll, Director of USAID’s Avian and Pandemic Preparedness and Response Unit, makes us especially vulnerable. "We need an urgent increase in antiviral drug production and availability", he says.

Representatives of several low-income countries speaking in Geneva last week expressed concerns about the lack of action to promote equitable distribution of drug stockpiles and vaccines in the event of a pandemic. Many countries are too poor to buy drug stockpiles and have no capacity for manufacturing vaccine or generic versions of drugs. India challenged the international meeting delegates to resolve this problem; whether they did so remains to be seen.

Common to all the main preparedness strategies is the problem of coordination across government departments, and between governments and international organisations. Shigeru Omi, WHO Regional Director for the Western Pacific, says there remains little communication between agriculture and health sectors in most of the countries affected by avian influenza. This issue is not easily solved. In Indonesia, for instance, where several people have died from H5N1 infection this year, while avian influenza has been spreading in the country, pro-democracy changes in government have boosted decentralisation. And, since two of the key areas of devolved power are health and agriculture, this change has made national-level coordination for preparedness planning difficult. Resolving this problem will take months of negotiations about where state and local responsibilities lie.

Worrisome though these issues are, Samuel Jutzi, Director of the Division of Animal Production and Health at FAO, emphasises that avian influenza remains a disease of birds – and this fact buys the international community some valuable time. Jutzi believes that too much emphasis has been given to the stockpiling of antiviral drugs while the battle against bird flu in animals remains under-funded. For example, he says, FAO and WHO together have just 40 veterinarians. Jutzi asserts that addressing this issue is "the only way by which the likelihood of the H5N1 virus acquiring human-to-human transmissibility can be influenced".

The way to stop avian influenza in its tracks is rapid containment of outbreaks by widespread culling of birds in infected areas. But this strategy has a huge impact on the poorest people in affected countries, who often depend on poultry for their livelihoods. Farmers may also resist culling unless there is an appropriate level of compensation. "Too little and farmers will not have sufficient incentive to report disease in their animals; too much and the money will be an incentive to deliberately infect their flocks", says Milan Brahmbhatt, World Bank Lead Economist for East Asia and Pacific Region.

WHO’s Omi, however, is confident that a coordinated, concerted effort to solve these problems will work. "I firmly believe it is not impossible to avert or at least delay the outbreak of a human pandemic", he says.

Testing and action

So how prepared are we? 6 months ago, less than 50 countries had preparedness plans for pandemic influenza. Now, over 60% have at least some sort of plan in place. FAO, WHO, and OIE (the International Organisation for Animal Health) have helped achieve this mark by providing clear guidance and offering technical support while countries are working to build up surveillance infrastructure. But, says WHO’s pandemic influenza representative Chan, some plans are little more than single sheets of paper. What is needed now is testing and action. "A plan is a plan. Until you test it and use it you will not know the gaps", she says.

Countries affected by outbreaks of H5 influenza in animals and human beings

There is a mild optimism among international health experts about the likely success of a global response. The experience of countries that have already battled human and animal cases has refined preparedness plans and improved recommended actions. However, according to David Nabarro, Senior UN System Coordinator, Avian and Human Influenza, if a pandemic occurs this winter, the world will certainly not be able to cope. "The more I find out about the potential impact of a pandemic and about the general preparedness of the world to deal with it, the more concerned I am", he says. And the fact remains that we know very little about H5N1. "Neither our knowledge or our tools are currently adequate", adds USAID’s Carroll.

Worryingly, this immediate gap remains unaddressed. While preparedness planning focuses on the long-term goals of boosting capacity for surveillance and response, the issues that would become immediate priorities for individual nations in the event of a pandemic – drug and vaccine distribution, civil unrest, and economic disruption – are virtually untouched. Nabarro says these issues will feature in his discussions with humanitarian agencies over the coming months.

World Bank economist Brahmbhatt believes that the most immediate problems caused by a pandemic will probably arise not from death or sickness, but from uncoordinated efforts of individuals to avoid infection, as happened with SARS. Communication is the key to mitigating this type of crisis. Governments must have effective mechanisms for communicating with the public, to make sure they understand the real risk. They must talk with other countries and international organisations to share information necessary for disease control. And they must communicate within themselves to ensure preparedness plans can be effectively acted upon.

The costs of panic to nations are magnified by misinformation and loss of trust among the public, warns Brahmbhatt. "Governments need to establish credibility and trust from the start."

Copyright © 2005 Elsevier Limited – http://www.elsevier.com – All rights reserved.

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