Zeno Swijtink
04-30-2009, 10:14 PM
https://www.sciencemag.org/cgi/content/full/324/5927/572?sa_campaign=Email/sntw/1-May-2009/10.1126/science.324_572]
Science 1 May 2009:
Vol. 324. no. 5927, pp. 572 - 573
NEWS OF THE WEEK
INFECTIOUS DISEASES
Jon Cohen and Martin Enserink
On 27 April, 6 days after the U.S. Centers for Disease Control and Prevention (CDC) first reported an unusual swine flu outbreak in humans, international agencies were still struggling to determine how serious a threat the virus posed. "Every new strain of the flu virus is unique," CDC acting Director Richard Besser said at a press conference, "and until the outbreak has progressed, you don't know what it is going to do."
Shortly after CDC rang the alarm bell on 21 April in a Morbidity and Mortality Weekly Report dispatch about two cases of swine flu in southern California, scientists and health officials around the world went on alert, concerned that this never-before-seen virus could lead to a killer pandemic. They quickly determined the genetic sequence of the virus, linked the U.S. cases to an apparently much larger outbreak in Mexico, and began fashioning international and local responses.
"On the bright side, this event was widely expected," says Julio Frenk, the former secretary of health in Mexico who now heads Harvard School of Public Health in Boston. In the wake of outbreaks of avian influenza, "there have been good efforts to prepare."
But others say the world hasn't done nearly enough over the past 10 years to prepare for a pandemic. They worry that most countries will find themselves without access to vaccines or antiviral drugs, which could become especially dangerous if the virus causes severe disease in many people—which is still uncertain—or evolves to do so. Some also question why the disease wasn't recognized as an international emergency several weeks earlier, which might have offered a chance to stop it at the source instead of battling it around the planet.
Much confusion surrounds the origins of the virus, why it seems to cause severe disease in Mexico and not elsewhere, and the overall threat it poses to the world. "Right now, there's more unknown than there is known," says microbiologist Francis Plummer, who heads the National Microbiology Laboratory in Winnipeg, part of the Public Health Agency of Canada (PHAC) and a key player in unraveling the Mexican link.
By 28 April, Mexico had connected this swine flu to 152 deaths (most of which have yet to be confirmed). But in the United States and Canada, "it doesn't seem to be anything different than seasonal flu," says Plummer. Solving that riddle will require tests on the suspected cases in Mexico, which totaled nearly 2000, to see whether they indeed are swine flu. But CDC and PHAC—the only two labs that initially had all the reagents necessary to test for the virus—had confirmed a mere two dozen cases as the new H1N1 at the time. Each had scientists in Mexico helping officials build the capacity to do the tests themselves.
As to the virus's spread, newspaper headlines seem to speak volumes. But what's needed to predict spread, says epidemiologist and disease modeler Ira Longini of the University of Washington, Seattle, is an estimate of the virus's basic reproductive number, or R0, a variable that denotes the number of new infections caused by each infected person. Longini and others are trying to get their hands on as much data as they can from the first outbreak clusters to make that estimate.
The outbreak's discovery underscores the axiom that luck comes to those who are prepared. Although Mexico began to experience an unusually high number of hospitalizations with respiratory problems in late March, no special investigation took place, in part because the cases overlapped with the end of flu season. The disease also spared young children and the elderly, the two groups most vulnerable to severe cases of flu, which some researchers say should have triggered suspicions that an altogether new pathogen was responsible. The answer came when two respiratory cases, both of which looked like run-of-the-mill flu, came to the lab at the Naval Health Research Center (NHRC) in San Diego, California, which is conducting sophisticated tests for influenza as part of other studies.
Most people who have the flu never see a doctor, and the virus is rarely analyzed. But the Navy is developing better influenza diagnostics along with CDC's Border Infectious Disease Surveillance project and the Department of Defense's Global Emerging Infections Surveillance and Response System. The standard rapid test for influenza determines whether the virus is strain A or B. The tests under development analyze specific subtypes based on two proteins on the viral surface, hemagglutinin (H) and neuraminidase (N). When the naval lab could not subtype two patient samples, they rushed the samples to CDC, which had determined by 17 April that both were from a novel H1N1 swine flu virus.
Despite the crush of activity since CDC first identified this H1N1, we are still "making decisions with incomplete information," Besser said. Part of the problem is that swine flu infections of humans have rarely been documented. Virologist Christopher Olsen of the University of Wisconsin, Madison, School of Veterinary Medicine co-authored a study in 2007 that found only 50 cases in the biomedical literature dating back to 1958. During the past 12 years, several new influenza genotypes surfaced in swine, making for "a very confusing picture," says Olsen.
Researchers would like to know whether a virus must mutate to move from pigs to humans and whether, as is the case with bird flu in humans, a specific mutation makes it more virulent. "There is a feeling that once you know the sequence, you know everything about a virus, and you really don't," says virologist Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee.
CDC and PHAC have found that the current H1N1 combines pieces of influenza from North American swine and avian viruses, with human and swine sequences from Europe and Asia. "It's really a grand old mix-up," says Webster.
Webster and Olsen also emphasize that just because the first cases surfaced in Mexico, the outbreak did not necessarily originate there. The pig that transmitted the virus may have been imported into the country, or the first transmission to a human may have occurred elsewhere.
Déjà vu. A hospital worker in Singapore, a country hit hard by SARS in 2003, stands ready to assess patients with respiratory illnesses.
CREDIT: VIVEK PRAKASH/REUTERS/LANDOV
[Larger version of this image]
Early on, CDC began to brew a "seed" strain for a possible vaccine against swine H1N1, and by 27 April the World Health Organization in Geneva, Switzerland, was already talking to vaccine manufacturers. One key problem is that the world's influenza vaccine production capacity—which still relies on growing the vaccine virus in chicken eggs—is limited to some 400 million vaccine doses a year and is impossible to expand quickly. Manufacturing swine flu vaccine would thus come at the expense of seasonal vaccine production, says retired pharma executive and flu vaccine expert David Fedson, and might lead to higher mortality and morbidity from the three seasonal strains.
For now, WHO says manufacturers should continue preparing vaccine for the 2009–10 flu season. But that could change if swine flu proves particularly severe. "We're in a casino now, and we're placing our bets," says Fedson.
As to drugs, many countries began stockpiling oseltamivir after avian influenza put the pandemic threat on the political agenda in 2003. Individual governments, mostly in Western countries, have at least 220 million treatment courses in stock, says Martina Rupp, a spokesperson for Roche, the main producer of Tamiflu. Roche could ramp up its production capacity to some 400 million treatment courses annually fairly rapidly, she says; in addition, there are at least 10 generic manufacturers, four of them working under license from Roche, that produce oseltamivir. But the drug's complex manufacturing process makes it too pricey for many poor nations, says Fedson.
From pigs to people. Swine flu has occasionally jumped the species barrier before but was never known to transmit easily between humans.
CREDIT: PHOTOS.COM
[Larger version of this image]
Both CDC and WHO have made clear that the careful plans developed over the past 5 years to squelch pandemics at their source don't play a role at all now because the virus is already too widely dispersed. In papers published in 2005 in Science and Nature, scientists concluded that it might be possible to stop a budding pandemic locally by aggressive, targeted use of antivirals and measures such as shutting down transport and schools. WHO had stashed away some 5 million treatment courses of oseltamivir that could be used to that end.
The scenario might have worked for swine flu, says Longini—if it had been tried much earlier. "There were 800 or 900 [suspected] cases before it hit the global radar screen; that's way beyond a containable outbreak," Longini says.
Why it took so long to garner attention has many scientists puzzled. John Brownstein, the director of HealthMap, one of several systems set up recently to provide the world with realtime information about suspicious disease activity by having software scour news sources around the globe, says the first reports about a respiratory illness appeared in a Mexican newspaper on 1 April. "But there were 300 outbreaks at the same time, so what made this one different?" Brownstein asks. "We have to go back and see if there was a signature that we should have picked up here."
Science 1 May 2009:
Vol. 324. no. 5927, pp. 572 - 573
NEWS OF THE WEEK
INFECTIOUS DISEASES
Jon Cohen and Martin Enserink
On 27 April, 6 days after the U.S. Centers for Disease Control and Prevention (CDC) first reported an unusual swine flu outbreak in humans, international agencies were still struggling to determine how serious a threat the virus posed. "Every new strain of the flu virus is unique," CDC acting Director Richard Besser said at a press conference, "and until the outbreak has progressed, you don't know what it is going to do."
Shortly after CDC rang the alarm bell on 21 April in a Morbidity and Mortality Weekly Report dispatch about two cases of swine flu in southern California, scientists and health officials around the world went on alert, concerned that this never-before-seen virus could lead to a killer pandemic. They quickly determined the genetic sequence of the virus, linked the U.S. cases to an apparently much larger outbreak in Mexico, and began fashioning international and local responses.
"On the bright side, this event was widely expected," says Julio Frenk, the former secretary of health in Mexico who now heads Harvard School of Public Health in Boston. In the wake of outbreaks of avian influenza, "there have been good efforts to prepare."
But others say the world hasn't done nearly enough over the past 10 years to prepare for a pandemic. They worry that most countries will find themselves without access to vaccines or antiviral drugs, which could become especially dangerous if the virus causes severe disease in many people—which is still uncertain—or evolves to do so. Some also question why the disease wasn't recognized as an international emergency several weeks earlier, which might have offered a chance to stop it at the source instead of battling it around the planet.
Much confusion surrounds the origins of the virus, why it seems to cause severe disease in Mexico and not elsewhere, and the overall threat it poses to the world. "Right now, there's more unknown than there is known," says microbiologist Francis Plummer, who heads the National Microbiology Laboratory in Winnipeg, part of the Public Health Agency of Canada (PHAC) and a key player in unraveling the Mexican link.
By 28 April, Mexico had connected this swine flu to 152 deaths (most of which have yet to be confirmed). But in the United States and Canada, "it doesn't seem to be anything different than seasonal flu," says Plummer. Solving that riddle will require tests on the suspected cases in Mexico, which totaled nearly 2000, to see whether they indeed are swine flu. But CDC and PHAC—the only two labs that initially had all the reagents necessary to test for the virus—had confirmed a mere two dozen cases as the new H1N1 at the time. Each had scientists in Mexico helping officials build the capacity to do the tests themselves.
As to the virus's spread, newspaper headlines seem to speak volumes. But what's needed to predict spread, says epidemiologist and disease modeler Ira Longini of the University of Washington, Seattle, is an estimate of the virus's basic reproductive number, or R0, a variable that denotes the number of new infections caused by each infected person. Longini and others are trying to get their hands on as much data as they can from the first outbreak clusters to make that estimate.
The outbreak's discovery underscores the axiom that luck comes to those who are prepared. Although Mexico began to experience an unusually high number of hospitalizations with respiratory problems in late March, no special investigation took place, in part because the cases overlapped with the end of flu season. The disease also spared young children and the elderly, the two groups most vulnerable to severe cases of flu, which some researchers say should have triggered suspicions that an altogether new pathogen was responsible. The answer came when two respiratory cases, both of which looked like run-of-the-mill flu, came to the lab at the Naval Health Research Center (NHRC) in San Diego, California, which is conducting sophisticated tests for influenza as part of other studies.
Most people who have the flu never see a doctor, and the virus is rarely analyzed. But the Navy is developing better influenza diagnostics along with CDC's Border Infectious Disease Surveillance project and the Department of Defense's Global Emerging Infections Surveillance and Response System. The standard rapid test for influenza determines whether the virus is strain A or B. The tests under development analyze specific subtypes based on two proteins on the viral surface, hemagglutinin (H) and neuraminidase (N). When the naval lab could not subtype two patient samples, they rushed the samples to CDC, which had determined by 17 April that both were from a novel H1N1 swine flu virus.
Despite the crush of activity since CDC first identified this H1N1, we are still "making decisions with incomplete information," Besser said. Part of the problem is that swine flu infections of humans have rarely been documented. Virologist Christopher Olsen of the University of Wisconsin, Madison, School of Veterinary Medicine co-authored a study in 2007 that found only 50 cases in the biomedical literature dating back to 1958. During the past 12 years, several new influenza genotypes surfaced in swine, making for "a very confusing picture," says Olsen.
Researchers would like to know whether a virus must mutate to move from pigs to humans and whether, as is the case with bird flu in humans, a specific mutation makes it more virulent. "There is a feeling that once you know the sequence, you know everything about a virus, and you really don't," says virologist Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee.
CDC and PHAC have found that the current H1N1 combines pieces of influenza from North American swine and avian viruses, with human and swine sequences from Europe and Asia. "It's really a grand old mix-up," says Webster.
Webster and Olsen also emphasize that just because the first cases surfaced in Mexico, the outbreak did not necessarily originate there. The pig that transmitted the virus may have been imported into the country, or the first transmission to a human may have occurred elsewhere.
Déjà vu. A hospital worker in Singapore, a country hit hard by SARS in 2003, stands ready to assess patients with respiratory illnesses.
CREDIT: VIVEK PRAKASH/REUTERS/LANDOV
[Larger version of this image]
Early on, CDC began to brew a "seed" strain for a possible vaccine against swine H1N1, and by 27 April the World Health Organization in Geneva, Switzerland, was already talking to vaccine manufacturers. One key problem is that the world's influenza vaccine production capacity—which still relies on growing the vaccine virus in chicken eggs—is limited to some 400 million vaccine doses a year and is impossible to expand quickly. Manufacturing swine flu vaccine would thus come at the expense of seasonal vaccine production, says retired pharma executive and flu vaccine expert David Fedson, and might lead to higher mortality and morbidity from the three seasonal strains.
For now, WHO says manufacturers should continue preparing vaccine for the 2009–10 flu season. But that could change if swine flu proves particularly severe. "We're in a casino now, and we're placing our bets," says Fedson.
As to drugs, many countries began stockpiling oseltamivir after avian influenza put the pandemic threat on the political agenda in 2003. Individual governments, mostly in Western countries, have at least 220 million treatment courses in stock, says Martina Rupp, a spokesperson for Roche, the main producer of Tamiflu. Roche could ramp up its production capacity to some 400 million treatment courses annually fairly rapidly, she says; in addition, there are at least 10 generic manufacturers, four of them working under license from Roche, that produce oseltamivir. But the drug's complex manufacturing process makes it too pricey for many poor nations, says Fedson.
From pigs to people. Swine flu has occasionally jumped the species barrier before but was never known to transmit easily between humans.
CREDIT: PHOTOS.COM
[Larger version of this image]
Both CDC and WHO have made clear that the careful plans developed over the past 5 years to squelch pandemics at their source don't play a role at all now because the virus is already too widely dispersed. In papers published in 2005 in Science and Nature, scientists concluded that it might be possible to stop a budding pandemic locally by aggressive, targeted use of antivirals and measures such as shutting down transport and schools. WHO had stashed away some 5 million treatment courses of oseltamivir that could be used to that end.
The scenario might have worked for swine flu, says Longini—if it had been tried much earlier. "There were 800 or 900 [suspected] cases before it hit the global radar screen; that's way beyond a containable outbreak," Longini says.
Why it took so long to garner attention has many scientists puzzled. John Brownstein, the director of HealthMap, one of several systems set up recently to provide the world with realtime information about suspicious disease activity by having software scour news sources around the globe, says the first reports about a respiratory illness appeared in a Mexican newspaper on 1 April. "But there were 300 outbreaks at the same time, so what made this one different?" Brownstein asks. "We have to go back and see if there was a signature that we should have picked up here."