Links to Pneumonia, Rapid Effects on Young Noted

By Rob Stein
Washington Post Staff Writer
Saturday, October 17, 2009
http://www.washingtonpost.com/wp-dyn/content/article/2009/10/16/AR2009101601384.html

As swine flu continues to spread around the globe, a clearer and in some ways more unnerving picture of the most serious cases has started to emerge, indicating that the virus could pose a greater threat to some young, otherwise vibrant people.

The virus can cause life-threatening viral pneumonia much more commonly than the typical flu, prompting the World Health Organization on Friday to warn hospitals to prepare for a possible wave of very sick patients and to urge doctors to treat suspected cases quickly with antiviral drugs.

Experts stress that most people who get the H1N1 virus either never get sick or recover easily. But some young adults, possibly especially women, are falling seriously ill at an unexpectedly rapid pace and are showing up in intensive care units and dying in unusually high numbers, they say.

Although why a minority of patients become so sick remains a mystery, new research indicates that H1N1 is different from typical seasonal flu viruses in crucial ways -- most notably in its ability to penetrate deep into the lungs and cause viral pneumonia.

"It's not like seasonal influenza," Nikki Shindo of the World Health Organization said at the conclusion of a three-day meeting of more than 100 experts the WHO convened in Washington to review swine flu. "It can cause very severe disease in previously healthy young adults."

Meanwhile, the Centers for Disease Control and Prevention reported Friday that vaccine production was proceeding more slowly than hoped. Officials had predicted that about 40 million doses would be available by the end of October, but that projection will probably fall short by about 10 million to 12 million doses, said Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases.

"Eventually, anyone who wants to be vaccinated will be able to be, but the next couple of weeks will continue to be a slow start," she said. So far, 11.4 million doses have become available and states have ordered about 8 million doses, but the vaccine will not become available in large amounts until November, she said.

The WHO's warning came as U.S. health officials reported that the number of states reporting widespread flu activity was up to 41, including Maryland and Virginia, and that the death toll among children had climbed to 86. Maryland has reported 10 deaths and Virginia health officials say eight people, including one child, have died. There have been no reports of deaths among District residents.

So far, the virus does not seem to sicken or kill people more often than the typical flu. But the pattern of people getting seriously ill is far different than in typical flu seasons. The elderly, who are usually most vulnerable, are generally spared; children, teenagers, pregnant women and young adults are the most common victims.

Officials have been closely monitoring the virus for signs it has mutated into a more dangerous form, and they have also been testing animals for the virus because of fears that infected livestock could cause more-lethal mutations.

Federal agriculture officials said Friday that pigs from the Minnesota State Fair had tested positive for H1N1, which would make them the first documented pig infections in the United States, if follow-up tests confirm the results. But there are no signs that the pigs were sick or that the animals had infected any humans. Children staying near the fair had gotten the virus, but there was no sign they were infected by the pigs.

Seasonal flu viruses tend to infect primarily the upper respiratory system. But recent animal studies and autopsies on about 100 swine flu victims show that H1N1 infects both the upper respiratory tract, which makes it relatively easy to transmit, and also the lungs, which is more similar to the avian flu virus that has been circulating in Asia.

"It's like the avian flu on steroids," said Sherif Zaki, chief of Infectious Disease Pathology at the CDC. He noted that unusually large concentrations of the swine flu virus have been found in the lungs of victims: "It really is a new beast, so to speak."

About a third of patients who required intensive care had bacterial pneumonia, but H1N1's proclivity to infect lung cells makes it more likely than seasonal flu to cause viral pneumonia, which can lead to life-threatening lung damage.

"Remarkably different is this small subset of patients that presents very severe viral pneumonia," Shindo said.

One of those patients was Karen Ann Hays of Sacramento, Calif., an otherwise healthy nurse whose hobby was tackling grueling triathlons. Despite desperate measures to keep her alive, Hays, 51, died in July within days of coming down with swine flu.

"I have seen more cases like this in the last three months than I have in the last 30 years," said Peter Murphy, director of intensive care at the Mercy San Juan Medical Center in Carmichael, Calif., who tried to save Hays.

Although it remains unclear how frequently the virus makes people seriously ill, recent reports from Mexico, Canada, the United States, Australia and New Zealand indicate that perhaps 1 percent of patients who get infected require hospitalization. Between 12 to 30 percent of those hospitalized need intensive care, and 15 to 40 percent of those in intensive care die.

While about two-thirds of U.S. patients who were hospitalized in the spring had other medical conditions, the CDC reported this week that an analysis of more than 1,400 hospitalized victims found perhaps half had no serious health problems.

About one-third of those around the world who have died or became seriously ill from swine flu appear to have been vulnerable because they had heart or lung disease, chronic kidney problems, or other ailments that usually put people at risk. But others had conditions that many may not immediately associate with frailness, such as mild asthma, high blood pressure, high cholesterol and obesity.

"Many of these people look just like you or me," said Anand Kumar, an associate professor of critical care and infectious disease at the University of Manitoba in Winnipeg, Canada, which was hit hard by the pandemic's first wave last spring.

There appears to be no way to predict with certainty who may suffer serious, life-threatening complications, since some victims have had no other health problems.

For instance, Stacey Hernandez Speegle, 30, of Madison, Calif., who died in July, "was in great shape. She was on the softball team. She had two young children. She was renovating her house," said her mother, Tamara Brooks. "It's just so hard to believe."

Although it has been well publicized that pregnant women appear to be at increased risk, some evidence has started to suggest that being female may itself be a risk factor, for reasons that remain unclear.

"There's no question that women, and particularly young women, are getting hit disproportionately," said Kumar. He noted that women tend to have more fat tissue, which can help stimulate a dangerous inflammatory response to infections.

And some of those who develop serious illness deteriorate soon after starting to feel ill. They require oxygen masks, ventilator machines to pump oxygen into their lungs to keep them alive, and drastic, often rarely used measures to try to save them within days of the first fever, ache or cough.

"The rapidity of it is striking," said Andrew R. Davies, deputy director of intensive care at Alfred Hospital in Melbourne, Australia.

Some of the cases in Australia and New Zealand were so severe that doctors resorted to a much more aggressive, less commonly used treatment known as extracorporeal membrane oxygenation (ECMO). It involves siphoning patients' blood into a machine to remove carbon dioxide and then infuse it with oxygen before returning it to their bodies.

"It's quite an extreme form of treatment," said Steve Webb, a clinical associate professor at the Royal Perth Hospital in Australia.

Other doctors have tried administering nitric oxide and putting patients in a bed that turns them upside down to help their lungs work better. "Our back was against the wall," Murphy said, adding that after the deaths of patients such as Hays his hospital is working to make ECMO available.

"It's very difficult to get this double-barreled message out that: 'Yes, most cases are mild, but in a small percentage of cases these cases are disastrous,' " Vanderbilt University's William Schaffner said. "But the message is: Don't underestimate H1N1."

Of the at least 86 Americans younger than 18 who have died from H1N1, 11 deaths were reported in the past week. About half of the deaths in the past month were among teenagers, Schuchat said. Since Aug. 30, 43 pediatric deaths have been reported, including three in those younger than age 2, five among those ages 2 to 4, 16 in those ages 5 to 11, and 19 among those ages 12 to 17, she said.

"These are very sobering statistics," Schuchat said, noting that only about 40 or 50 children usually die during an entire flu season.

Virginia Health Commissioner Karen Remley said Friday that although the majority of H1N1 cases in the state are "mild and moderate," significant numbers have become seriously ill.

In Maryland, at least 257 people have been hospitalized with confirmed cases of H1N1 since June, health officials said.

At least 2,914 Americans have died from flu-related illnesses since the H1N1 began, the CDC said.

Staff researcher Madonna Lebling and staff writer Michael Laris contributed to this report.
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Swine Flu Causes Unprecedented Amount Of Illness Early In Season

LAURAN NEERGAARD, AP Medical Writer
October 16, 2009

WASHINGTON -- The swine flu is causing an unprecedented amount of illness for this early in the fall, with the deaths of 11 more children reported in the past week. And less vaccine than expected will be ready by month's end, federal health officials said Friday.

Of the 86 children who have died since the new swine flu arose last spring, 43 deaths have been reported in September and early October alone, the Centers for Disease Control and Prevention reported. That's a startling number because in some past winters, the CDC has counted 40 or 50 child deaths for the entire flu season -- and no one knows how long this swine flu outbreak will last.

"These are very sobering statistics," said the CDC's Dr. Anne Schuchat.

Also surprising, about half of the child deaths reported since Sept. 1 have been teenagers. Until now, much of the attention has focused on younger children.

Overall, what CDC calls the 2009 H1N1 flu is causing widespread disease in 41 states, and about 6 percent of all doctor visits are for flu-like illnesses, levels not normally seen until much later in the fall.

There may be only 28 million to 30 million vaccine doses dispersed around the country by month's end, Schuchat said, short of the 40 million-plus the government had hoped. But more will continue to arrive weekly, and she urged patience as people await their turn.

As of Wednesday, states had ordered 8 million of the 11.4 million doses of swine flu vaccine the government has ready to ship.

Initial vaccine shipments were only of FluMist, the nasal spray version that can be used by only certain people -- those ages 2 to 49 who aren't pregnant and have no chronic illnesses such as asthma. But swine flu shots now are shipping, too, accounting for a bit more than half of the vaccine available today, Schuchat said.
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Canada: Young man is first in Ontario with swine flu that doesn't respond to drug

Canada:

Tamiflu-resistant H1N1 in Hamilton


October 16, 2009

Joanna Frketich
The Hamilton Spectator
(Oct 16, 2009)

A young Hamilton man was infected with Ontario's first case of Tamiflu-resistant H1N1.

Only a few dozen people worldwide have been reported to have pandemic influenza resistant to the antiviral treatment. They include a 60-year-old Quebec man and an Alberta woman. Both recovered without being hospitalized.

The Hamilton man is in his 20s. Public health officials don't believe he spread it because no one he had contact with has become sick.

"People should take this seriously, but not panic," said Dr. Chris Mackie, Hamilton's associate medical officer of health.

The emergence of Tamiflu-resistant H1N1 comes at the same time local doctors have reported to the public health department that at least one company tried to pay for its staff to get prescriptions for the antiviral to prevent the flu.

"It sent a letter with all of their employees out to doctors saying we'll pay you $60 to give a 60-day prescription to prophylactics," Mackie said.
"This is exactly the sort of thing that generates resistance."

Tamiflu is only to be used as a treatment for high-risk patients with symptoms and not for prevention.

The H1N1 flu shot is the best way to protect against the pandemic and Mackie says he's hoping to announce today when it will be available and where.

He refused to provide any details about the young man who caught the Tamiflu-resistant strain. He wouldn't even say whether the man is dead or alive.

Normally, public health provides details about whether the person is in hospital or at home and how ill.

"For reasons of confidentiality, I'm afraid we can't say anything more about this individual case and I really apologize about that," said Mackie.

The Ministry of Health is confident it's an isolated case.

"At the moment there is no evidence of widespread resistance to Tamiflu anywhere," said ministry spokesperson David Jensen.

There are other antiviral treatments available when H1N1 is resistant to Tamiflu. However, it can take weeks to determine the strain is resistant. Often, the patient's illness gets worse and that's what prompts doctors to try other antiviral treatments.

So far, it hasn't been a big concern because there have been so few cases.

"This virus has been remarkably stable," said Dr. Michael Gardam, director of infectious disease prevention and control at Ontario's Agency for Health Protection and Promotion. "It hasn't shown any propensity at this point to easily develop resistance and then for those resistant strains to spread."
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Shortage of shots as more kids die of swine flu

Oct. 16, 2009

CDC: H1N1 virus causing unprecedented number of infections for early fall

WASHINGTON - Even as swine flu infections are causing an unprecedented amount of illness for this time of year — and a growing number of deaths, particularly among children — supplies of vaccine to protect against it will be delayed, government health officials said Friday.

In the past week, 11 more children have died from H1N1 influenza infections, an official from the Centers for Disease Control and Prevention said, bringing the total to 86 children since April. That's a startling number because in some past winters, the CDC has counted 40 or 50 child deaths for the entire flu season — and no one knows how long this swine flu outbreak will last.

"These are very sobering statistics," said Dr. Anne Schuchat, the CDC's director of immunization and respiratory diseases.

At the same time, drug manufacturers have told health officials to expect at least 25 percent less vaccine by the end of the month than anticipated. Instead of the 40 million doses projected by the end of October, only 28 million to 30 million doses may be available, said Schuchat.

"We aren't expecting widespread availability until the end of the month or until November," Schuchat said. "It will be pretty challenging to find vaccine."

She urged people anxious to get immunized to check back with their state and local health departments.

"Keep looking," Schuchat said.

Initial vaccine shipments were only of FluMist, the nasal spray version that can be used by only certain people — those ages 2 to 49 who aren't pregnant and have no chronic illnesses such as asthma. But swine flu shots now are shipping, too, accounting for a bit more than half of the vaccine available today, Schuchat said.

Vaccine manufacturers have told CDC that the yield of H1N1 antigen, the substance that produces infection-fighting antibodies, has been lower than expected.

Swine flu is now widespread in 41 states, CDC reported. And overall for the country, deaths from pneumonia and flu-like illnesses have passed what CDC considers an epidemic level. About 6 percent of all doctor visits are for flu-like illnesses, levels not normally seen until later in the fall. Half of the all the child deaths have been in teenagers.

Earlier this week, health officials said that almost half of the hospitalized adult swine flu patients had been healthy people who did not have asthma or any other chronic illnesses before they got sick.

Unpredictable nature
Separately, the World Health Organization said Friday although the H1N1 virus has killed fewer than 5,000 people so far this year worldwide, the influenza remains a cause for concern because of its unpredictable nature.

Most people who catch the H1N1 virus suffer mild symptoms.

But in contrast to seasonal flu strains which can be serious for elderly people, H1N1 can turn dangerous for some people with existing health conditions or otherwise healthy young adults.

"There is a small subset of cases that do and can progress quite rapidly to severe disease and this is sometimes in the space of less than 24 hours and it then becomes a big, big challenge to save the people," said WHO spokesman Gregory Hartl.

"This disease continues to cause concern because it doesn't act exactly like seasonal influenza and because it doesn't affect the same groups who are affected by seasonal influenza."
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Australia: Piggery quarantined after swine flu outbreak

October 14, 2009

A PIGGERY near Toowoomba has been placed under quarantine after test results came back positive for swine flu.

Biosecurity Queensland chief veterinary officer Ron Glanville said given the widespread presence of H1N1 in the human population, the occasional case in piggeries was to be expected.

"Fortunately, influenza A H1N1 in piggeries can be managed relatively easily through routine biosecurity measures,'' Dr Glanville said.

Biosecurity officers are working with the owners in the latest case to implement on-site biosecurity measures to ensure the virus remains contained.

"This is not a human health issue and food authorities maintain that pork and pork products are safe to eat,'' he said.

"The infection should be self-limiting within the piggery and the response is designed to allow the disease to burn out as quickly as possible.''

Dr Glanville said this was only the second case of human pandemic (H1N1) 2009 influenza detected at a piggery in Queensland following the quarantine of a piggery near Dalby in August.

"That piggery has since been released from quarantine after the illness ran its course,'' he said.

"The pigs at this site are now all in good health.''

All pig owners should maintain strict biosecurity procedures on their properties and report anything unusual in their herds to the Emergency Disease Watch Hotline on 1800 675 888.

BAMC to Use CombiMatrix Influenza Array to Study Genetic Drift of H1N1 Swine Flu

October 13, 2009 6:00 AM ET

MUKILTEO, Wash., Oct. 13, 2009 (GLOBE NEWSWIRE) -- CombiMatrix Corporation (Nasdaq:CBMX) announced today that Brooke Army Medical Center ("BAMC") is using the CombiMatrix Influenza-Detection System to analyze influenza cases including those involving H1N1 Swine flu. BAMC is a military hospital that is investigating the feasibility of screening all patients presenting in its emergency room with symptoms of respiratory distress and consenting to nasal swabs, by both electrochemical array-based diagnostics and bead-based multiplex fluorescent methods.

While there are other flu tests including the fluorescent test used at BAMC that can identify the presence or absence of H1N1 Swine flu, they do not provide information on genetic drift of the virus. It is important to understand the genetic drift of rapidly mutating pathogens in general and of Swine flu in particular because of the potential for increased pathogenicity of a mutated virus.

Recent estimates by the President's Council of Advisors on Science and Technology indicate that millions of U.S. citizens might contract Swine flu, and nearly 1.8 million individuals might be hospitalized, with up to 90,000 deaths in the U.S. during this flu season. World-wide, there are already several hundred thousand confirmed cases, and the World Health Organization has declared a pandemic. Although some of these estimates might be high, the numbers clearly indicate that this viral disease is a major public health concern. Because Swine flu can be a rapidly mutating virus, concerns exist about mutations that might make it more pathogenic while maintaining its highly infectious nature.

"We are pleased to be working with BAMC to evaluate the genetic drift of the Swine flu virus," stated Dr. Amit Kumar, President and CEO of CombiMatrix. "Our influenza array has demonstrated its ability to provide tremendous genetic information regarding numerous infectious agents including Bird Flu, Swine flu, and other infectious agents. It is especially significant to note that our Influenza-Detection System was developed with funding from the U.S. Department of Defense, and it is now being used to evaluate infections in military, former-military, and government personnel. Also, we encourage interested parties to review information on the website of the U.S. Centers for Disease Control and Prevention to get an understanding of the limitations of currently available flu tests, especially what we feel is poor performance of many rapid flu tests," concluded Dr Kumar. The link for this information is as follows: http://www.cdc.gov/h1n1flu/guidance/diagnostic_tests.htm

According to Dr. Gerald Merrill, Laboratory Director for the Department of Clinical Investigation at BAMC, "We are already seeing a high percentage of novel H1N1 flu cases in the San Antonio military community this season. The CombiMatrix system allows us to screen for Swine flu versus seasonal influenza A and influenza B. Samples analyzed using the CombiMatrix system from last season allowed us to look at clustering of genotypes and to see patterns suggesting genetic drift in both the novel H1N1 Swine flu virus and the seasonal influenza A virus in San Antonio. This can be useful in spotting divergence of strains and possibly in identifying problems earlier than if we did not screen for such divergence," concluded Dr. Merrill.

ABOUT COMBIMATRIX CORPORATION

CombiMatrix Corporation is a diversified biotechnology business that develops proprietary technologies, including products and services in the areas of drug development, genetic analysis, molecular diagnostics, nanotechnology and defense and homeland security markets, as well as in other potential markets where our products and services could be utilized. The technologies we have developed include a platform technology to rapidly produce user-defined, in-situ synthesized, oligonucleotide arrays for use in identifying and determining the roles of genes, gene mutations and proteins. This technology has a wide range of potential applications in the areas of genomics, proteomics, biosensors, drug discovery, drug development, diagnostics, combinatorial chemistry, material sciences and nanotechnology.
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