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EINet Alert ~ Jul 17, 2009
*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- ***This bulletin was supplemented with information provided by Veratect***
1. Influenza News
- Weekly APEC update of pandemic influenza H1N1
- Cumulative number of human cases of avian influenza A/H5N1
- Global: WHO suspends reporting of pandemic influenza H1N1 case counts
- Global: WHO says healthcare workers should get first pandemic H1N1 vaccine
- Global: Obesity emerges as new risk factor for severe pandemic influenza H1N1 infection
- Global: Another study suggests greater pandemic influenza H1N1 pathogenicity
- Global: Vaccine contracts could be broken in severe pandemic, experts say
- UK: Prepares to launch phone service to supply antivirals
- Australia: Vaccine manufacturer announces launch of human trial for pandemic H1N1 vaccine
- China (Hunan): China confirms 27th H5N1 avian influenza fatality
- South America: Ministers meet to coordinate response to pandemic influenza H1N1
- USA: An additional $1 billion will be used to procure pandemic H1N1 influenza vaccine
- USA (California): Nurses file complaint alleging lack of protective gear
- INFLUENZA A/H1N1
- AVIAN INFLUENZA
- Dating the emergence of pandemic influenza viruses
- Pandemic influenza response: CDC guidance for medical offices and outpatient facilities
- CDC Health Alert Network Info Service Message: Three Reports of Oseltamivir Resistant Novel Influenza A (H1N1) Viruses
- Influenza in the Asia-Pacific
1. Influenza News
Weekly APEC update of pandemic influenza H1N1
Australia and Chile exceed 10,000 cases of pandemic H1N1 influenza. Five thousand surgeries were postponed in Chile last week to free up hospital beds for patients with H1N1 influenza. The number of delayed procedures could rise to over 20,000 over the next few weeks. Thailand reports continued spread of pandemic H1N1 infection with over 3800 cases and 21 deaths as of 13 July 2009.
(AP 7/13/09; CIDRAP 7/14/09, 7/15/09)
***For data on human cases of avian influenza prior to 2009, go to:
Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 436 (262)
Avian influenza age distribution data from WHO/WPRO:
WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 5/10/09): http://gamapserver.who.int/mapLibrary/
WHO’s timeline of important H5N1-related events (last updated 3/23/09):
Global: WHO suspends reporting of pandemic influenza H1N1 case counts
In a 16 Jul 2009 statement, the WHO said countries with sustained community transmission are having an extremely difficult time confirming cases through laboratory testing. In addition, counting individual cases isn't essential for monitoring the level or nature of risk posed by the virus or implementing response measures. Detecting and confirming all possible cases is highly resource-intensive, the WHO said. "In some countries, this strategy is absorbing most national laboratory and resource capacity, leaving little capacity for the monitoring and investigation of severe cases and other exceptional events."
For these reasons, the WHO said it will no longer issue reports of confirmed cases. However, it said it will provide regular updates on the spread of pandemic flu in newly affected countries. The focus of surveillance activities in countries where the virus is already established will shift to existing systems for monitoring seasonal flu, the WHO said. Countries are no longer required to submit regular reports of individual confirmed cases and deaths to the WHO. Monitoring for unusual events such as clusters of severe or fatal cases or changes in clinical patterns is important and should continue, the agency said. It added that countries should maintain vigilance for changes in transmission patterns, such as rising rates of school or work absenteeism, and also surges in emergency department visits, which could foreshadow increasing numbers of severe cases.
US CDC says change is no surprise
Specific case counts were once needed to help characterize the early spread of the disease, he said. Now that the virus is widespread and poised for a potential surge in the fall, "specific case counts are no longer needed, and since they don't represent the true picture of the situation, they are not necessary," Skinner said. The CDC will likely make a similar move to downplay the number of confirmed cases, but it will maintain, if not expand, surveillance to gauge the health impact of the pandemic and the severity of the illness, he said.
Case counts give wrong impression
The downside of the focus on the confirmed case numbers has been that the public perceives the pandemic as less pervasive than experts know it to be, Sandman said. When a public health official makes a reasonable extrapolation of the burden of disease, the number of confirmed cases seems puny by comparison. "Reputable experts are dismissed as nuts," he added.
Sandman said another problem is that an emphasis on the number of confirmed cases, along with the number of deaths, gives the public—and even some government and public health officials—an inflated impression of the case fatality rate.
"The pandemic H1N1 virus could get more deadly at any time," Sandman said. "But if you compare the number of pandemic deaths in the US to the CDC estimates of how many people have already had the disease, it calculates out that the pandemic is less deadly than seasonal flu so far." However, most people don't do that calculation, he said. "People compare the number of deaths to the number of confirmed cases, and that makes the pandemic look much more deadly, because all the cases that never got confirmatory testing are missing from the denominator."
Global: WHO says healthcare workers should get first pandemic H1N1 vaccine
The agency said it's important to vaccinate health workers first in order to keep health systems functioning. After that, governments should consider other groups that are most vulnerable to severe H1N1 infections, such as pregnant women, people with chronic health problems, and young adults. At the same time, the WHO reported that vaccine manufacturers growing the candidate H1N1 vaccine viruses are getting relatively poor yields—only about 25% to 50% as much antigen as with seasonal H1N1 vaccine viruses. That suggests it may take longer for manufacturers to fulfill their existing vaccine contracts and to begin making vaccine for countries that have not yet ordered doses.
Dr. Marie-Paule Kieny, director of the WHO's initiative for vaccine research, said the low yields are not yet considered a major concern and that the agency's collaborating laboratories are working to develop better-yielding strains.
Last week, US Health and Human Services Secretary (HHS) Kathleen Sebelius said priority groups for H1N1 vaccine would include schoolchildren, non-elderly adults with health problems, pregnant women, and healthcare and emergency workers, but she did not put any one of those ahead of the others. Elderly adults are believed to have some protection from the novel virus because of past exposure to H1N1 viruses and vaccines.
Kieny said vaccine allocation plans will depend on how countries balance the three major objectives of immunization: reducing transmission, reducing sickness and death, and protecting the healthcare system. If a country's primary aim is to limit spread of the virus, authorities might put children ahead of other groups, she observed.
Seasonal vaccine nearly all made
Further, because some pandemic vaccines involve new technologies, the best possible post-marketing surveillance will be important, SAGE said. The group said findings should be shared with the world quickly so that countries can adjust their immunization strategies. The advisory panel also said that the production and use of vaccines containing oil-in-water adjuvants and of live attenuated vaccines should be encouraged, since initial vaccine supplies will be limited and there is a potential for drifted strains of the H1N1 virus.
Low yields with current candidates
"For the first series of [vaccine] strains that were generated, we unfortunately didn't come up with a good yielder," she said. "In order to remedy that, the WHO laboratory network is trying to generate new vaccine viruses from wild type viruses generated from patients."
Kieny asserted that the low yields are not a big problem for the timing of vaccine production now. Using the current strains, manufacturers are harvesting enough antigen for clinical trials, she said. Also, regulatory authorities have said that when new candidate strains become available, it won't be necessary to conduct "bridging studies" to compare them with the current strains, because they will differ only in yield, not in antigenicity, she said.
However, in slides that Kieny presented at the SAGE meeting, she stated that a lower-yielding vaccine "would considerably push back the timelines." The presentation, which is available online, suggests that poor yields could delay manufacturers' fulfillment of current vaccine orders by two to six months.
The presentation says existing government orders for H1N1 vaccines total 850 million to 900 million doses. On average, governments have ordered one dose per person, but most have options for, or are considering ordering, two doses per person, which would increase total orders to about 1.8 billion doses. If vaccine yields are normal, if a relatively low dose of 8 micrograms (mcg) is sufficient, and if governments order an average of one dose person, vaccine manufacturers in the wealthy countries could fulfill their current vaccine orders in November, according to Kieny's estimate.
But if vaccine yield is only half of normal, with other conditions the same, it would take until January 2010 for the manufacturers to fulfill their vaccine orders, she projects. An even lower yield, such as one third of normal, could delay the completion of production until April 2010, according to her presentation. Other factors could also slow production, according to Kieny's estimates. For example, using a dose of 15 mcg instead of 8 mcg could delay the fulfillment of vaccine orders from November 2009 until February 2010 (still assuming one dose per person).
In other comments at the press conference, Kieny said the manufacturers of live attenuated H1N1 vaccines have not had a problem with yield so far. The appropriate dose for these vaccines is not yet known, but "in terms of growth they seem to be behaving normally," she said.
SAGE meeting documents are available at http://www.who.int/immunization/sage/previous_july2009/en/index.html. In addition, Kieny’s slide presentation can be accessed at http://www.who.int/immunization/sage/3.MPK-SAGE_7_July.pdf.
Global: Obesity emerges as new risk factor for severe pandemic influenza H1N1 infection
The study, published in advance in the Centers for Disease Control and Prevention's (CDC) weekly report on death and disease, also suggests doctors can safely double the usual dose of oseltamivir, the antiviral drug sold under the Tamiflu brand name.
"What this suggests is that there can be severe complications associated with this virus infection, especially in severely obese patients," said CDC virus expert Dr. Tim Uyeki. "And five of these patients had. . .evidence of blood clots in the lungs. This has not been previously known to occur in patients with severe influenza virus infections," Uyeki said.
Dr. Lena Napolitano of the University of Michigan Medical Center and colleagues studied the cases of 10 patients admitted to the university's intensive care unit with severe acute respiratory distress syndrome caused by infection with H1N1.
Their study was not designed to see if obesity or anything else poses a special risk factor for flu. But the researchers were surprised to see that seven of the 10 patients were extremely obese. Nine had multiple organ failure, which can be seen in influenza, but five had blood clots in the lungs, and six had kidney failure. None has fully recovered, the researchers said.
"The high prevalence of obesity in this case series is striking," the CDC's commentary accompanying the researchers’ report reads. "Whether obesity is an independent risk factor for severe complications of novel influenza A (H1N1) virus infection is unknown. Obesity has not been identified previously as a risk factor for severe complications of seasonal influenza."
Global: Another study suggests greater pandemic influenza H1N1 pathogenicity
In a multifaceted study that appears in an early online edition of Nature, the group, from Japan and the University of Wisconsin, conducted a host of other experiments—both in vitro and in vivo—to better characterize the risks of the new virus.
Yoshihiro Kawaoka, PhD, a researcher from the University of Wisconsin-Madison who led the Nature study, said that the study may help clear up misunderstandings people have about the new virus. "People think this pathogen may be similar to seasonal influenza," he said. "This study shows that is not the case. There is clear evidence the virus is different than seasonal influenza."
Animal models show pathogenicity trends
In macaques, animals infected with the pandemic H1N1 virus had greater body temperature increases, but body weight loss wasn't different from animals that were infected with the seasonal flu virus. The new virus replicated efficiently in the lungs and other respiratory organs, similar to highly pathogenic influenza viruses. Pathological examination revealed that the novel virus caused more severe lung lesions that contained type 2 pneumocytes—a finding that has been reported with H5N1 avian influenza viruses.
In the ferret model, the group found more severe bronchopneumonia in the animals infected with the pandemic H1N1 virus. Researchers also used ferrets to test transmission, a key factor in human-to-human spread of the virus. They placed ferrets infected with either the pandemic or seasonal flu virus in perforated cages next to, but not touching, cages housing uninfected ferrets.
Experts say animal models have limits
"We have already had over a million—probably several million—human infections with the new strain, and all agree the symptoms are mild, similar to those of seasonal flu," Racaniello said. "So it's not clear to me why these results should suddenly make us all fear that the new virus is in fact more virulent than we think." Perhaps the results underscore the point that animal models are just models and don't reveal much about human infections, he added.
Racaniello cautioned against thinking of serious infections in patients with no known underlying conditions as evidence of pandemic H1N1's pathogenic potential. Subtle defects that can impair immune response, especially early in infection, can lead to lethal disease in otherwise healthy people, he said. "In other words, you don't have to have heart disease to have a bad outcome with influenza."
"I don't think the results of any of the three papers should be interpreted to mean that 2009 H1N1 is more virulent than we think it is," he said, pointing out that there are enough differences among the three studys' results to cast doubt on any virulence extrapolations in humans.
The article “In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses” by Itoh Y, Shinya K, Kiso M, et al. can be found in Nature early online edition 13 July 2009 at http://www.nature.com/nature/journal/vnfv/ncurrent/abs/nature08260.html.
Global: Vaccine contracts could be broken in severe pandemic, experts say
UK: Prepares to launch phone service to supply antivirals
Following a surge of flu-like illnesses, a British system that will allow people to report symptoms by phone and obtain antiviral drugs will be launched very soon. Data from general practitioners indicated that the rate of people reporting flu-like illnesses rose to 73 per 100,000 last week, from 50 per 100,000 the week before. Using the phone service, people will get reference numbers that friends can use to collect antivirals for them.
Australia: Vaccine manufacturer announces launch of human trial for pandemic H1N1 vaccine
Australia-based flu vaccine maker CSL Ltd said on 13 Jul 2009 that it expects to launch a human trial of its novel H1N1 vaccine on 22 Jul 2009, Bloomberg News reported. In a Jun 29 press release, CSL said it would undertake the trial with a research group in Adelaide and was seeking healthy adults aged 18 to 64 to enroll in the study to compare two injections of a standard dose, administered three weeks apart, with a higher dosage. The Australian government has ordered enough vaccine to immunize 10 million people.
China (Hunan): China confirms 27th H5N1 avian influenza fatality
On 18 Feb 2009, the Health Ministry confirmed a 22-year-old man in the central Hunan Province had tested positive for H5N1. He had died on 24 Jan 2009.
South America: Ministers meet to coordinate response to pandemic influenza H1N1
Health ministers from six South American countries met 15 Jul 2009 in Buenos Aires, Argentina, to coordinate responses to the H1N1 pandemic. Besides Argentina, the meeting included Bolivia, Brazil, Chile, Paraguay, and Uruguay. Ministers said the countries need to share medicine and supplies, and they voiced concern about access to vaccines. Argentina has had 137 deaths, second highest toll after the United States.
USA: An additional $1 billion will be used to procure pandemic H1N1 influenza vaccine
USA (California): Nurses file complaint alleging lack of protective gear
The following websites provide the most current information and advice.
- North America
- Other useful sources
Dating the emergence of pandemic influenza viruses
Smith GJD et al. PNAS. 13 July 2009. Available at http://www.pnas.org/content/early/2009/07/10/0904991106.abstract?etoc.
Pandemic influenza response: CDC guidance for medical offices and outpatient facilities
Available at http://www.cdc.gov/h1n1flu/10steps.htm.
CDC Health Alert Network Info Service Message: Three Reports of Oseltamivir Resistant Novel Influenza A (H1N1) Viruses
The Lancet and The Lancet Infectious Diseases have joined forces to develop a conference that will enable leaders in their fields to present and discuss management of influenza with key health administrators, experts from the medical and scientific communities, and industry representatives. We hope the meeting will provide valuable insight into fundamental public health and operation strategies to bring about change within the Asia-Pacific.
To register, go to http://mail.elsevier-alerts.com/go.asp?/bELA001/qUQEAS8/x8BATS8