Pandemic Flu Update - June 6, 2007

 A pandemic is a global disease outbreak. A flu pandemic occurs when a new influenza virus emerges for which people have little or no immunity, and for which there is no vaccine.  The disease spreads easily person-to-person, it causes serious illness, and can sweep across the country and around the world in a very short time.  It is difficult to predict when the next influenza pandemic will occur or how severe it will be. Wherever and whenever a pandemic starts, everyone around the world is at risk. Countries might, through measures such as border closures and travel restrictions, delay arrival of the virus, but cannot stop it.

Health professionals are concerned that the continued spread of a highly pathogenic avian H5N1 virus across eastern Asia and other countries represents a significant threat to human health.  Influenza A (H5N1) virus  has raised concerns about a potential human pandemic because it is especially virulent;

• it is being spread by migratory birds;
• it can be transmitted from birds to mammals and in some limited circumstances to humans, and
• like other influenza viruses, it continues to evolve(mutate)

 H5N1 virus does not usually infect people, but infections with these viruses have occurred in humans. Most of these cases have resulted from people having direct or close contact with H5N1-infected poultry or H5N1-contaminated surfaces.  Of the few avian influenza viruses that have crossed the species barrier to infect humans, H5N1 has caused the largest number of detected cases of severe disease and death in humans. However, it is possible that those cases in the most severely ill people are more likely to be diagnosed and reported, while milder cases go unreported.

UPDATE ITEMS:

• Indonesia suspects ominous H5N1 mutations
• Physician survey shows mixed views on pandemic risk
• Labor Says OSHA Flu Pandemic Guidance Is Contradictory, Standard Needed
• Vietnam reports H5N1 case; Chinese patient dies
• FDA issues guidance on flu vaccine development
• Indonesian teen is latest H5N1 victim; Chinese samples reach WHO
• Indonesia reports fatal H5N1 case
• Baxter denies report of vaccine trial in Indonesia

Indonesia suspects ominous H5N1 mutations

Lisa Schnirring, Staff Writer

Jun 6, 2007 (CIDRAP News) – Officials from Indonesia's avian flu commission said today that the H5N1 avian influenza virus may have mutated in a way that makes it more transmissible from birds to humans, but a World Health Organization (WHO) official said the WHO had seen no evidence of such a change, according to news services.

Bayu Krisnamurthi, chief executive for Indonesia's National Committee for Avian Influenza Control and Pandemic Influenza Preparedness, told reporters that in the past, human infections required high-intensity and high-density exposure to the H5N1 virus, according to a Reuters report today. "There are now suspicions that this [infection] has become easier," he said, adding that a mutation has not been confirmed yet.

Wayan Teguh Wibawan, a microbiologist from Indonesia's avian flu commission, told Reuters that the suspicions are based on preliminary results of genetic tests at laboratories in Indonesia. The amino acid structure of poultry H5N1 samples is becoming increasingly similar to that seen in human H5N1 samples, he said.

The similarity in amino acid structure makes it easier for the virus to attach to receptors on cells that line the throat and lungs, Wibawan told Reuters. The virus would have to attach readily to human cell receptors in order to easily pass from birds to humans, he said.

Wibawan told Reuters he had noted "gradual changes" in the virus samples he receives each month, but he gave no other details.

However, Gregory Hartl, a WHO spokesman, told Reuters that the WHO has not seen any evidence that the virus has become more transmissible to humans.

The WHO has received very few H5N1 isolates from Indonesia recently. Hartl told CIDRAP News today that the agency has received just three Indonesian H5N1 samples, gathered from two patients, this year. "Without virus characterization, we cannot say whether the virus has changed or not," he said.

Indonesia withheld H5N1 samples from the WHO for about 5 months, starting last December, as a protest against the country's lack of access to pandemic vaccines and other pandemic medications. In mid-May, during the WHO's annual meeting in Geneva, the country's health minister announced that Indonesia had resumed sending samples to the agency. News reports at the time said the country had submitted three H5N1 samples to a WHO-affiliated laboratory.

Lo Wing-Iok, an infectious disease expert in Hong Kong, said the suspected changes in the virus show how important it is for Indonesia to share its samples with the global community, according to the Reuters report today.

"These must be confirmed and the world must be forewarned if there has been such an important change," he told Reuters. "If there is such a change, it would not only mean that the virus can jump more easily from bird to man, but from human to human, too."

Indonesia has had 99 human H5N1 cases with 79 deaths, more than any other country. WHO data show that from January through May of this year, the country had 26 cases with 21 deaths, versus 31 cases and 24 deaths for the same period in 2006. Indonesia is one of three countries, along with Egypt and Vietnam, where the H5N1 virus is endemic in poultry.

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Physician survey shows mixed views on pandemic risk

Lisa Schnirring, Staff Writer

Jun 6, 2007 (CIDRAP News) – Fewer than half of physicians who responded to a survey at a recent conference in Europe said they thought an influenza pandemic was very likely in the next few years, according to a report in the journal Archives of Disease in Childhood.

The survey was an anonymous electronic poll conducted at a pediatric infectious disease course at Oxford University in England. The group included 161 physicians, mostly from Europe, with half from the United Kingdom. The poll was conducted by Nigel Curtis of the University of Melbourne (Australia) and Andrew Pollard of Oxford.

The findings, published early online, revealed that only 72 (44.7%) of respondents took the view that an avian influenza pandemic is "almost inevitable" or "very likely" within "the next few years."

Seventy-three physicians, or 45.4%, thought a pandemic was "possible" in that time span, while 16 (9.9%) viewed such an event as unlikely or very unlikely.

The researchers also asked if attendees had gathered a supply of the antiviral drug oseltamivir for personal or family use. Only 11 (7.9%) of 139 respondents said they had. By training level, only 1 of 27 infectious disease specialists reported having acquired the antiviral, but among those in infectious disease training, 5 of 24 (17.2%) had their own supply.

The authors concluded that the survey contains some mixed messages about physicians' perceptions of pandemic risk. Despite widely publicized evidence that the world faces a serious threat of a pandemic, more than half of the respondents "did not believe the risk of an imminent influenza pandemic was more than a possibility," the report says. However, a "significant minority" of the doctors believed the risk was high enough to warrant gathering their own antiviral supply, despite recommendations against personal stockpiling.

"If the perceived risk of an influenza pandemic observed in our survey is reflected in the wider medical community then it is perhaps not surprising that doctors are largely silent about this issue," the authors write. They add that the reasons for physicians' attitudes warrant further investigation if they are to help alert the world to the threat of a pandemic.

Sarah Long, MD, chief of infectious diseases at St Christopher's Hospital for Children in Philadelphia, said she has spoken at the same Oxford conference before and knows the audience. "It's a very educated group, with a lot of doctors in training," she told CIDRAP News.

Long wasn't surprised by the survey results, but she said they may give a false impression that physicians don't take the pandemic threat seriously, because qualifiers such as "possible" may not accurately gauge what people think. "Some might think 'probably' is associated with inevitable in the next 2 or 3 years," she said. "Some of us are lumpers, and some of us are splitters."

Concerning antiviral stockpiling, Long said, "I'm pleased that such a small number [of survey respondents] have their own stockpile." Antiviral supplies should be reserved for early responders and patients who need them, but other countries may have different views on physicians' keeping their own supply, Long added.

Peter M. Sandman, PhD, a risk communication expert from Princeton, N.J., and a columnist for the CIDRAP Business Source Weekly Briefing, questioned the authors' interpretation of their survey findings, saying they equated pandemic inevitability with pandemic imminence. "We are on solid ground when we say another flu pandemic is nearly inevitable. We are on extremely weak ground when we say that it's probably imminent, and we are doing terrible science and terrible risk communication when we conflate the two claims," he told CIDRAP News.

Sandman said that in the face of a dramatic decline in media coverage of H5N1 avian flu, the finding that 45% of physicians thought a pandemic was inevitable or very likely represents a sustained concern, rather than complacency. "The data suggest, if anything, that European physicians share the hunch that H5N1 makes a pandemic likelier than usual," he added.

"It is good news that many of Curtis and Pollard's respondents still think a pandemic may well be imminent," Sandman said. "But it would be better news if they realized that nobody has a clue whether a pandemic is imminent or not, and if they understood that preparedness doesn't depend on whether a pandemic is imminent or not."

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Labor Says OSHA Flu Pandemic Guidance Is Contradictory, Standard Needed

Inside OSHA , June 5, 2007

Organized labor advocates applaud OSHA for issuing a flu pandemic guidance for healthcare workers that emphasizes concerns about airborne flu transmission, but complain the wording of the non-binding guidance is contradictory on the use of face masks and not mandatory.

The new OSHA guidelines, unveiled May 21, recommend ways health care workers can plan for a pandemic, and, in the event of a pandemic, prevent it from spreading and get supplies that may be in short supply. The agency issued the non-binding guidance in lieu of issuing an emergency temporary flu pandemic standard called for by organized labor and key lawmakers.

Bill Borwegen, health and safety director for the Service Employees International Union, said the flu pandemic document is better than what SEIU expected from OSHA, but expressed concern it is not mandatory and is confusing and contradictory on the use of face masks.

A discussion of personal protective equipment on page 23 of the guidance says, “healthcare workers transporting patients should use a respirator (N95 or higher). If respirators are not available, healthcare workers should wear a surgical mask.”

Yet on page 28, the guidance says, “In comparison (to respirators), surgical masks are not designed to prevent inhalation of airborne contaminants. Their ability to filter small particles varies greatly and cannot be assured to protect healthcare workers against airborne infectious agents.”

Another labor advocate complains hospitals will have a hard time following the guidance because of its confusing and non-binding nature.

Lawmakers have also questioned why OSHA is not issuing binding requirements. Rep. James Walsh (NY), ranking GOP member of the Appropriations labor subcommittee, questioned OSHA chief Edwin Foulke during a House appropriations hearing in March about the agency’s denial of organized labor’s petition for such an emergency temporary standard. Lawmakers also quizzed Labor Secretary Elaine Chao in a separate hearing on why OSHA opted against a formal standard.

But an American Hospital Association spokesperson disagrees on the need for a formal standard, saying most hospitals already follow many of the recommendations in the guidance.

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Vietnam reports H5N1 case; Chinese patient dies

Jun 4, 2007 (CIDRAP News) – Vietnam's health ministry announced over the weekend that a poultry slaughterhouse worker was being treated for H5N1 avian influenza, and the World Health Organization (WHO) confirmed today that China's most recent H5N1 patient has died.

Vietnam's health ministry said the man, from the northern province of Thai Nguyen, worked in a Hanoi slaughterhouse on May 14, got sick 5 days later, and was admitted to Hanoi's Tropical Disease Hospital, according to a Jun 2 report from Xinhua, China's state news agency.

After a nearly 18-month lull in Vietnamese H5N1 cases, the man's case is the country's second in a little more than a week. In the previous case, a 30-year-old farmer fell ill after he helped slaughter chickens for a wedding. He was recovering at Hanoi's Bach Mai Hospital, according to the Xinhua report.

The WHO has not yet confirmed either case. If the agency confirms both infections, they will be listed as Vietnam's 94th and 95th H5N1 cases. For now, Vietnam's H5N1 case count stands at 93 cases and 42 deaths.

In other avian flu developments, China's health ministry announced that a 19-year-old soldier who was recently listed as the country's 25th H5N1 case-patient died yesterday, according to a WHO statement today. The man had been receiving treatment at a military hospital, according to Reuters. He becomes China's 16th avian flu fatality.

The man had been serving in southeastern China's Fujian province when he became ill, though he had had no reported contact with infected birds, according to the WHO. A WHO official recently pointed out that only one of China's 25 H5N1 patients had reported contact with sick birds, according to an Associated Press report.

The lack of apparent links to infected birds raises questions about how effectively the Chinese government is monitoring the disease in birds, WHO spokesperson Gregory Hartl told Reuters. "This would suggest that the monitoring of H5N1 in poultry in China needs to be strengthened," he said.

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FDA issues guidance on flu vaccine development

Jun 4, 2007 (CIDRAP News) – The US Food and Drug Administration recently released separate documents outlining the kinds of clinical data required for licensing of new seasonal and pandemic influenza vaccines.

In a May 31 news release, the agency said the guidance documents were designed to facilitate the rapid development and approval of new vaccines by outlining the regulatory pathways for companies.

The two documents reflect public input on draft versions that were released in March 2006, the FDA said. They outline approaches for developing vaccines that are "safe, pure, and potent."

"Both guidances recommend using recent technologies such as cell culture and recombinant manufacturing to enhance the development and evaluation of vaccines," the FDA statement said. "They also recommend adding substances that improve the immune response from the vaccine (adjuvants)."

The recommendations describe conventional and accelerated approaches to vaccine licensing. Companies that choose the conventional pathway must provide clinical evidence that the vaccine actually prevents flu.

With the accelerated pathway, a company still must conduct clinical trials but can use a biological indicator, such as antibody response, to predict the effectiveness of the vaccine, the FDA said. Companies will be expected to conduct additional clinical studies if and when the vaccine is used.

The guidance documents are part of the FDA's ongoing efforts to reduce the time it takes to translate scientific advances, such as cell culture–derived and recombinant vaccine technologies, into approved medical products, the agency said.

In April the FDA approved the nation's first human vaccine aimed at the pandemic threat posed by the H5N1 avian influenza virus. In a clinical trial, two doses of the vaccine, made by Sanofi Pasteur, yielded what was believed to be a protective immune response in 45% of volunteers. The vaccine is based on a 2004 strain of H5N1 virus from a human patient in Vietnam.

Despite the vaccine's limited efficacy as predicted by the clinical trial, federal officials hope that in the event of a pandemic involving an H5N1 virus, it would buy some time to develop a vaccine closely matched to the emerging pandemic strain. The Department of Health and Human Services is stockpiling the vaccine and had 13 million doses, or enough to vaccine 6.5 million people, on hand when the FDA approved it.

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Indonesian teen is latest H5N1 victim; Chinese samples reach WHO

Jun 1, 2007 (CIDRAP News) – Indonesian officials announced today that a 15-year-old girl from Central Java died of H5N1 avian influenza this week, as the World Health Organization (WHO) confirmed that it received two human H5N1 samples from China, ending a nearly year-long delay in sharing promised samples.

An official named Tondro from Indonesia's bird flu center said the girl got sick on May 21 and was treated at a local hospital, but was transferred to Karyadi hospital in the Central Java capital of Samarang 4 days later and died there on May 29, the Chinese news agency Xinhua reported today.

The girl was reported to have had contact with sick birds, Reuters and Xinhua reported. Muhammad Nadirin, another official from Indonesia's bird flu center, told Reuters the girl handled a dead chicken when preparing to cook it. Several chickens died at her home and that of a neighbor, the Xinhua report said.

Her death marks Indonesia's third fatal H5N1 case, with all three cases from Central Java, in less than 2 weeks.

If the WHO confirms her case, Indonesia's H5N1 toll will be 99 cases with 79 deaths. The country's latest previous case, in a 45-year-old man who was reported to have slaughtered and eaten a sick chicken, was confirmed by the WHO yesterday, bringing the agency's count for Indonesia to 98 cases and 78 deaths, the most of any country. The global WHO count is 309 cases with 187 deaths.

Meanwhile, a shipment containing two human H5N1 samples from China arrived at the US Centers for Disease Control and Prevention (CDC) last night, a WHO official said today, according to Reuters. The CDC is a WHO collaborating center.

"We welcome it, it shows China is working with the international system of virus sharing," WHO spokesman Gregory Hartl told Reuters. Last week another WHO official told the Associated Press (AP) that the specimens were from a 2006 case from Xinjiang province in far western China and a 2007 case from Fujian province in the south.

Researchers use samples of both seasonal flu viruses and novel strains like H5N1 to monitor viral evolution and drug resistance and to develop vaccines. The WHO has coordinated the international flu surveillance system for more than 50 years.

In other avian flu news, a veterinary official in Vietnam said an H5N1 outbreak has been confirmed in another province, bringing the number of provinces with recent outbreaks to 13 out of 64, the AP reported today.

Pham Ngoc Anh, director of animal health for Quang Nam province, said an outbreak killed 300 unvaccinated ducks at a farm in the province, and tests confirmed the birds were infected with H5N1 avian flu, the AP report said. The remaining 400 birds were culled and the site was disinfected.

On May 25 an official from Vietnam's National Institute of Epidemiology confirmed that a 30-year-old farmer from Vinh Phuc province who got sick after slaughtering chickens for a wedding had tested positive for H5N1, according to previous media reports.

He was reported to be hospitalized in critical condition. The WHO, however, has not yet confirmed the man's case, so Vietnam's case count remains at 93 cases and 42 deaths.

In the past, Vietnam has been praised by animal health experts for its tough avian flu prevention efforts after widespread outbreaks in 2004 and 2005 led to the culling of 66 million birds and triggered many human cases. The disease subsided through most of 2006, but late in the year it flared up at farms where poultry flocks had not been vaccinated and birds were hatched illegally.

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Indonesia reports fatal H5N1 case

May 30, 2007 (CIDRAP News) – Health officials in Indonesia reported today that a 45-year-old man from Central Java province died of H5N1 avian influenza, marking the country's second fatal case in less than 2 weeks.

Joko Suyono of the Indonesian health ministry's avian flu center said the man was hospitalized May 17 and died 2 days ago, Reuters reported today.

Investigators, saying dead poultry were found near the man's home, believe he slaughtered and ate a sick chicken, the Reuters report said.

If his case is confirmed by the World Health Organization (WHO), he will be listed as Indonesia's 98th case-patient and its 78th fatality. The latest previous case reported in Indonesia was in a 5-year-old girl who died May 17. The country leads the world in human H5N1 cases and deaths.

On May 16 the WHO announced it would accept H5N1 test results from Indonesia's newly accredited national laboratory. Before that, the agency had refused to confirm any cases reported by Indonesia since late January, because the country had stopped sending viruses to WHO collaborating labs in December.

Meanwhile, the WHO today confirmed China's latest H5N1 case, in a 19-year-old soldier who, according to media reports yesterday, was apparently being treated in a military hospital. China now has had 25 cases, 15 of them fatal.

The patient's H5N1 results were confirmed by China's national laboratory on May 23, a WHO statement said.

Before the soldier got sick, he was serving in Fujian province, the WHO said. He experienced fever and pneumonia-like symptoms on May 9 and was hospitalized May 14.

"There is no initial indication to suggest he had contact with sick birds prior to becoming unwell," the WHO reported, adding that the patient's close contacts are under medical supervision and remain well.

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Baxter denies report of vaccine trial in Indonesia

Lisa Schnirring, Staff Writer

May 30, 2007 (CIDRAP News) – Indonesia's health minister said yesterday that Baxter Healthcare Corp would launch a clinical trial of an H5N1 avian influenza vaccine in Indonesia in July, according to news reports, but a Baxter official said the company has not announced any clinical trials.

Siti Fadilah Supari, Indonesia's health minister, said the clinical trial would involve "hundreds of participants" and conclude in October, according to an Associated Press (AP) report published today. She also said Indonesia would initially stockpile 2 million doses of the vaccine.

In February, Indonesia revealed it had stopped sharing H5N1 virus samples with the World Health Organization (WHO) in a protest against drug companies' use of the samples to make vaccines seen as too costly for developing countries. Soon afterward Indonesia signed a memorandum of understanding with US-based Baxter International, owner of Baxter Healthcare, which laid the groundwork for future collaboration or supply agreements on H5N1 vaccines.

Chris Bona, a Baxter spokesman in Deerfield, Ill., told CIDRAP News today that the company has not announced any plans for a clinical trial of its vaccine in Indonesia and has not signed any new agreements with Indonesia beyond the initial memorandum of understanding in February.

Bona said there were no firm plans to produce the company's vaccine in Indonesia and no agreements about stockpiling. In addition, any Indonesian H5N1 samples Baxter would use to develop a vaccine would likely come directly from the WHO, Bona said.

On May 15 Indonesia announced it had resumed sharing its H5N1 samples with the WHO. A week later, during the annual meeting of WHO member countries, the WHO negotiated a preliminary agreement designed to maintain the international sharing of flu virus samples while ensuring that developing countries can obtain pandemic flu vaccines

Baxter has a cell culture–based H5N1 vaccine under development. Last October the company said the preliminary results of a phase I/II clinical trial showed a good immune response against drifted H5N1 strains. The vaccine was based on a 2004 strain of H5N1 from Vietnam.

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