http://www.baltimoresun.com/health/bal-md.hs.lungs01nov01,0,2790600,full.story
Unraveling swine flu’s greater toll on children
By Meredith Cohn | meredith.cohn@baltsun.com
November 1, 2009
When Jasmine Cadavid’s parents took her to the emergency room near their Abingdon home nearly two weeks ago, the normally playful 2-year-old was lethargic, feverish and struggling to breathe.
She not only had swine flu, but her right lung was so filled with fluid from pneumonia that it was getting no air. Soon she was headed to an intensive-care unit at the University of Maryland Hospital for Children, where doctors scrambled to halt the damage; she’s still in the hospital, recovering, today.
Doctors still can’t say why Jasmine got so sick, but what happened so quickly to her young lungs is a subject of intense interest for doctors nationwide who are seeing the same pattern in a small number of children severely sickened by swine flu.
Young people have been disproportionately hit. So far, two children in Maryland and 114 across the country have died from the H1N1 strain – about the standard toll for an entire year of seasonal flu. Half of the approximately 20,000 people hospitalized have been under 18.
Their lungs also seem to respond in a way that’s different, and may trigger more damage, than in adults. That might make them less able to ward off secondary infections such as pneumonia, the most common complication.
Health officials stress that cases like Jasmine’s are uncommon. There have been millions of cases of swine flu, and the vast majority of children and adults get better at home within a week without so much as a prescription. Two-thirds of those hospitalized had underlying health problems.
But a small number of cases have proceeded much like Jasmine’s – making seemingly healthy young people severely ill – and it is the unpredictability of those cases that researchers and clinicians are studying closely so they can better prepare for the next pandemic.
The little girl who likes to play with her two bigger sisters got sick Oct. 15 and her parents took her the next day to the doctor, who did what most doctors would do. He sent her home with ibuprofen for the fever.
That’s a sign that a secondary infection has begun, doctors say. And when her breathing became labored, her parents took her to the emergency room at Upper Chesapeake Medical Center, which sent her to intensive care at Maryland.
There, Dr. John Straumanis, head of the Hospital for Children’s pediatric intensive-care unit, put her on antibiotics and oxygen and inserted a tube to remove the infected fluid from her lungs. A full 8 ounces of fluid was drained the first day.
The Cadavids do not know where Jasmine, who is cared for at home by her mother, caught the flu, and why neither they nor their other children, ages 4 and 7, have gotten sick.
Neither does Straumanis. About the pneumonia, he said: "It’s luck, bad luck. Organisms are in the environment. Washing your hands isn’t going to stop them."
He said the lungs become inflamed as the body’s immune system works to fight off flu. In children, the temporary lung damage can be worse because their systems work harder than adults’. Respiratory troubles can become so bad that patients need to be put on a ventilator.
When the lungs are vulnerable, secondary infections can strike. Various bacteria, including Streptococcus pneumoniae and Staphylococcus aureus, are to blame. They live in the nose and throat and on the skin and can cause infections in the lungs, or pneumonia. The infection can be treated with antibiotics, though some have become resistant.
Jasmine’s infection in her right lung, which did respond to antibiotics, never completely stopped her from breathing because her left lung was largely unaffected.
"It’s a harder question about why some kids do fine and some get sicker," said Straumanis, who said he’s at least 50 percent busier in the pediatric unit because of swine flu. "But most kids are fine in a few days."
The federal Centers for Disease Control and Prevention does not have accurate data on the number of H1N1 cases because many people have not been tested for the strain. Dr. Thomas R. Frieden, the CDC’s director, said at a news conference Friday that, in a few weeks, the agency will have better counts of those with influenza-like illnesses, or estimates of those with flu. He said 90 percent of the confirmed deaths from swine flu are among people under age 65 and that two-thirds of the victims had pre-existing health problems.
While more children are getting sick from swine flu in the region and across the nation, it might be that the percentage who suffer complications is no greater, said Dr. Aaron Milstone, a pediatric infectious disease specialist at the Johns Hopkins Children’s Center and an assistant professor at the Johns Hopkins University School of Medicine.
"I think it’s good for parents to recognize that the majority of those who get really sick were not healthy to begin with," he said. "For the others, we’re still trying to figure out why some kids get more sick. Right now, we haven’t been able to pinpoint it."
Milstone said the H1N1 strain seems to "have a predilection to go to the lower lungs," causing a lot of coughing, and extra trouble for those with underlying lung disease such as asthma, which is common in Baltimore.
Pneumonia is a common complication of flu. During the 1918 influenza pandemic, more than 90 percent of the fatal cases were tied to secondary bacterial pneumonia. Then and now, most who died had a harder time fighting infection because they had underlying illnesses such as cardiac problems or respiratory diseases such as asthma and emphysema, or suppressed immune systems, said Dr. Jeffery K. Taubenberger, who investigates infectious diseases for the National Institutes of Health.
This flu strain, however, could be producing more pneumonia.
"I think the available data supports the hypothesis that more virulent influenza viruses are more likely to induce more bacterial pneumonias – perhaps by causing more initial damage in the lungs during the primary viral infection, leaving the patient at a higher risk of developing a secondary pneumonia, often from bacteria carried in their throats," Taubenberger said.
NIH researchers are looking at swine flu from all angles in an attempt to discover new diagnostic and treatment tools. Another NIH researcher has been looking at images, such as CT scans.
In an article published in the American Journal of Roentgenology, researchers say they have found that H1N1 flu patients’ lungs seem to have certain characteristics. The article focuses on a man who died of swine flu. Doctors had immediately begun treatment for H1N1 because of his symptoms, though he initially tested negative for the virus. Doctors also had taken a CT scan of his lungs.
Chief author Dr. Daniel J. Mollura, a radiologist and staff scientist at the National Institutes of Health Clinical Center, viewed the CT scan and identified "ground glass opacities," similar to small, hazy-looking pingpong balls.
In an interview, he said lungs have branching air tunnels called bronchi, and along the tunnels are areas of gas exchanges or air sacs. In H1N1 cases, the tunnels have the abnormalities, while healthy lungs are clear. Mollura says study of more early images of patients with swine flu could help determine who is likely to become more severely ill.
Further research is needed to determine what other infectious diseases may produce the same hazy images or whether they are different in children and adults with H1N1. Lung images from patients with seasonal flu are not widely available for comparison because doctors do not always take X-rays of those patients.
But Mollura said further research eventually could mean that doctors would have an effective tool to predict which high-risk patients are headed for potentially fatal complications.
"Early diagnosis is the goal," he said. "Perhaps this will lead to new ways to determine who will have a mild illness and those who might progress and have more complications."
In the meantime, the CDC will continue to dole out H1N1 vaccine, considered the best defense against the strain.
There were 26.5 million doses available for order Friday. And officials also said they have made about 250,000 more doses of pediatric Tamiflu, the best treatment, available from the nation’s strategic stockpile.
When to get help
Most children and adults recover at home from the flu without a prescription. The U.S. Centers for Disease Control and Prevention recommends that health care providers be contacted if children under 5, pregnant women or those with underlying health conditions get the flu.
Anyone with these symptoms should seek medical attention immediately:
•In children: Fast breathing or trouble breathing, bluish skin color, not drinking enough fluids, not waking up or not interacting, being so irritable that the child does not want to be held, flu-like symptoms improve but then return with fever and worse cough, fever with a rash.
•In adults: Difficulty breathing or shortness of breath, pain or pressure in the chest or abdomen, sudden dizziness, confusion, severe or persistent vomiting. Their lungs also seem to respond in a way that’s different, and may trigger more damage, than in adults. That might make them less able to ward off secondary infections such as pneumonia, the most common complication.
Health officials stress that cases like Jasmine’s are uncommon. There have been millions of cases of swine flu, and the vast majority of children and adults get better at home within a week without so much as a prescription. Two-thirds of those hospitalized had underlying health problems.
But a small number of cases have proceeded much like Jasmine’s – making seemingly healthy young people severely ill – and it is the unpredictability of those cases that researchers and clinicians are studying closely so they can better prepare for the next pandemic.
"I hope they learn from Jasmine, because no one should have to go through this with their child," said Jacqueline Cadavid, who hopes to take her daughter home this week.
The little girl who likes to play with her two bigger sisters got sick Oct. 15 and her parents took her the next day to the doctor, who did what most doctors would do. He sent her home with ibuprofen for the fever.
Jasmine did get a little better. But a few days later she got worse, said her father, Fred Cadavid.
That’s a sign that a secondary infection has begun, doctors say. And when her breathing became labored, her parents took her to the emergency room at Upper Chesapeake Medical Center, which sent her to intensive care at Maryland.
There, Dr. John Straumanis, head of the Hospital for Children’s pediatric intensive-care unit, put her on antibiotics and oxygen and inserted a tube to remove the infected fluid from her lungs. A full 8 ounces of fluid was drained the first day.
"It’s amazing what this flu can do," said Fred Cadavid, who has been alternating eight-hour shifts with his wife to make sure Jasmine is not alone. "Within two or three days, it can take a healthy kid and put them in the hospital. It’s been very stressful."
The Cadavids do not know where Jasmine, who is cared for at home by her mother, caught the flu, and why neither they nor their other children, ages 4 and 7, have gotten sick.
Neither does Straumanis. About the pneumonia, he said: "It’s luck, bad luck. Organisms are in the environment. Washing your hands isn’t going to stop them."
He said the lungs become inflamed as the body’s immune system works to fight off flu. In children, the temporary lung damage can be worse because their systems work harder than adults’. Respiratory troubles can become so bad that patients need to be put on a ventilator.
When the lungs are vulnerable, secondary infections can strike. Various bacteria, including Streptococcus pneumoniae and Staphylococcus aureus, are to blame. They live in the nose and throat and on the skin and can cause infections in the lungs, or pneumonia. The infection can be treated with antibiotics, though some have become resistant.
Jasmine’s infection in her right lung, which did respond to antibiotics, never completely stopped her from breathing because her left lung was largely unaffected.
"It’s a harder question about why some kids do fine and some get sicker," said Straumanis, who said he’s at least 50 percent busier in the pediatric unit because of swine flu. "But most kids are fine in a few days."
The federal Centers for Disease Control and Prevention does not have accurate data on the number of H1N1 cases because many people have not been tested for the strain. Dr. Thomas R. Frieden, the CDC’s director, said at a news conference Friday that, in a few weeks, the agency will have better counts of those with influenza-like illnesses, or estimates of those with flu. He said 90 percent of the confirmed deaths from swine flu are among people under age 65 and that two-thirds of the victims had pre-existing health problems.
While more children are getting sick from swine flu in the region and across the nation, it might be that the percentage who suffer complications is no greater, said Dr. Aaron Milstone, a pediatric infectious disease specialist at the Johns Hopkins Children’s Center and an assistant professor at the Johns Hopkins University School of Medicine.
"I think it’s good for parents to recognize that the majority of those who get really sick were not healthy to begin with," he said. "For the others, we’re still trying to figure out why some kids get more sick. Right now, we haven’t been able to pinpoint it."
Milstone said the H1N1 strain seems to "have a predilection to go to the lower lungs," causing a lot of coughing, and extra trouble for those with underlying lung disease such as asthma, which is common in Baltimore.
Pneumonia is a common complication of flu. During the 1918 influenza pandemic, more than 90 percent of the fatal cases were tied to secondary bacterial pneumonia. Then and now, most who died had a harder time fighting infection because they had underlying illnesses such as cardiac problems or respiratory diseases such as asthma and emphysema, or suppressed immune systems, said Dr. Jeffery K. Taubenberger, who investigates infectious diseases for the National Institutes of Health.
This flu strain, however, could be producing more pneumonia.
"I think the available data supports the hypothesis that more virulent influenza viruses are more likely to induce more bacterial pneumonias – perhaps by causing more initial damage in the lungs during the primary viral infection, leaving the patient at a higher risk of developing a secondary pneumonia, often from bacteria carried in their throats," Taubenberger said.
NIH researchers are looking at swine flu from all angles in an attempt to discover new diagnostic and treatment tools. Another NIH researcher has been looking at images, such as CT scans.
In an article published in the American Journal of Roentgenology, researchers say they have found that H1N1 flu patients’ lungs seem to have certain characteristics. The article focuses on a man who died of swine flu. Doctors had immediately begun treatment for H1N1 because of his symptoms, though he initially tested negative for the virus. Doctors also had taken a CT scan of his lungs.
Chief author Dr. Daniel J. Mollura, a radiologist and staff scientist at the National Institutes of Health Clinical Center, viewed the CT scan and identified "ground glass opacities," similar to small, hazy-looking pingpong balls.
In an interview, he said lungs have branching air tunnels called bronchi, and along the tunnels are areas of gas exchanges or air sacs. In H1N1 cases, the tunnels have the abnormalities, while healthy lungs are clear. Mollura says study of more early images of patients with swine flu could help determine who is likely to become more severely ill.
Further research is needed to determine what other infectious diseases may produce the same hazy images or whether they are different in children and adults with H1N1. Lung images from patients with seasonal flu are not widely available for comparison because doctors do not always take X-rays of those patients.
But Mollura said further research eventually could mean that doctors would have an effective tool to predict which high-risk patients are headed for potentially fatal complications.
"Early diagnosis is the goal," he said. "Perhaps this will lead to new ways to determine who will have a mild illness and those who might progress and have more complications."
In the meantime, the CDC will continue to dole out H1N1 vaccine, considered the best defense against the strain.
There were 26.5 million doses available for order Friday. And officials also said they have made about 250,000 more doses of pediatric Tamiflu, the best treatment, available from the nation’s strategic stockpile.
When to get help
Most children and adults recover at home from the flu without a prescription. The U.S. Centers for Disease Control and Prevention recommends that health care providers be contacted if children under 5, pregnant women or those with underlying health conditions get the flu.
Anyone with these symptoms should seek medical attention immediately:
•In children: Fast breathing or trouble breathing, bluish skin color, not drinking enough fluids, not waking up or not interacting, being so irritable that the child does not want to be held, flu-like symptoms improve but then return with fever and worse cough, fever with a rash.
•In adults: Difficulty breathing or shortness of breath, pain or pressure in the chest or abdomen, sudden dizziness, confusion, severe or persistent vomiting.
http://www.mercurynews.com/ci_13683182?source=most_emailed&nclick_check=1
UCSF scientists track swine flu virus for tiny changes that would cause big problems
By Lisa M. Krieger
SAN FRANCISCO — As the H1N1 flu virus spreads at breakneck speed, a team of local scientists are close behind. They are watching its evolution through a cutting-edge technology in hopes of answering the question: Where did it come from — and where is it going?
Their lab at the University of California-San Francisco holds a growing international collection of viral samples, including some from San Jose swabbed from the noses of sick people, since the first days of the swine flu epidemic. Genetic analysis of each sample will alert researchers to any tiny change that would create a giant problem.
So far, the swine flu virus seems to be evolving slowly. But a small mutation could create resistance to drugs.
The scientific sleuths are most worried about a big genetic leap — such as in 1918, when a mild virus turned deadly, killing 20 million to 40 million people. If such a leap does happen, the lab hopes to detect it early, triggering more aggressive treatment, quarantining and prevention measures.
Locked inside a large, $14,000 freezer, kept at 7 degrees below zero, are trays of plastic vials holding specimens of the H1N1 virus from California, Canada and Mexico. Some of the viruses came from dead patients; others caused merely an annoying cough.
"So far, we have no evidence that this virus is any more virulent than seasonal flu," said Dr. Charles Chiu, director of the Viral Detection and Discovery Center. Instead what seems to matter is the immune response of the infected person; while some people shrug it off, others go into lethal overdrive. There is also new evidence suggesting that co-infection with another virus, such as the common cold, may worsen illness.
 "What we’re worried about is the possibility, because it is a fundamentally new virus, that it may mutate into a strain that is more virulent," said Chiu.
The ambition of the new center, just a half block from AT&T Park, is to hunt down viruses whose identities and origins baffle doctors. And its team wants to understand these mystery viruses at the most essential level: the sequence of its genes.
Upon opening in January, one of the center’s first projects was to study H1N1. Its first specimen, from a young girl in Mexico, is now known to be one of the first cases of swine flu. Since then, the virus has spread to 190 countries
But its researchers have also detected a new virus linked to a rare type of prostate cancer and another virus that causes diarrheal disease in children. In yet another project, they are collecting unusual strains of HIV from Cameroon, Africa.
While at least 20 other labs are studying the genetic structure of the flu virus through conventional sequencing, the San Francisco lab is one of two in the entire nation engaged in viral discovery and "deep sequencing," seeking mutations that occur at very low frequencies. The other is the Center for Infection and Immunity at Columbia University in New York City. "They’re doing a great job. What they do is very important," said molecular virologist Paul Luciw of the University of California-Davis.
"The technology enables analysis of strain variation. If you find something very different, then you have to pay more attention — isolating that patient and looking at the patient’s contacts."
The collection now includes about 100 samples sent from the California Department of Health Services, 100 from Canada and 100 from various sites in Mexico.
More specimens arrive every day.
Long ago, scientists had to peer through microscopes to figure out what was killing people — a process that could take 10 to 20 years.
Modern surveillance is improved not only through use of "deep sequencing," but another novel detection tool called the virochip, designed by the center’s Joseph DeRisi.
The technology uses tiny glass slides dotted with thousands of fragments of DNA from 2,500 known viruses. The tool can study an entire genome at once — so experiments that used to be impossible are now being performed in days or hours.
All the viral sequences are stored in a huge computer database.
A flu virus is thought to reproduce about every eight hours. Within one day, it’s spawned several generations. As it breeds, it mixes and morphs.
By comparing H1N1’s genetic code with other influenzas, scientists have found a new combination of elements of previously known viruses. Three flu strains — from pigs, birds and humans — combined in one animal to create an unusual "triple re-assortment."
It’s not known how, when or where this happened. Then it jumped into humans.
Chiu’s team is watching its continued evolution, a gradual accretion of minor mutations called genetic "drift."
"There are changes," he said. "Not a lot of changes — but there are changes. Now we’re investigating the significance of these changes."
What he’s worried about is a big change called genetic "shift," when there’s a dramatic re-assortment and exchange of strands of genetic material that trigger hard-to-predict epidemic trajectories.
Such a shift could build a virus that is fast-growing, adept at infecting lungs, unfamiliar to the immune system — and highly contagious.
For now, they’re waiting and watching, so that a catastrophe like 1918 need never happen again
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