Gettin'r'round
12-05-2009, 02:15 PM
Expert analysis: Mexican swine flu – the story so far
* Updated 18:42 29 April 2009 by Wendy Barclay
* For similar stories, visit the Epidemics and Pandemics and Comment and Analysis Topic Guides
http://www.newscientist.com/data/images/ns/cms/dn17049/dn17049-1_300.jpg
Computer artwork of an H1N1 influenza A (flu) virus. In the particle's lipid envelope (purple) are two types of protein spike, haemagglutinin (H) and neuraminidase (N), which determine the strain of virus. These are used for recognising and binding to the host cell (Image: PASIEKA / SPL)
Out of the blue, a novel influenza virus has emerged in Mexico. The virus seems to have been born from the combination of at least two pig viruses, that themselves carried gene segments that originated in viruses of other species such as birds or humans. The combination of elements from three species is called "triple reassortment".
This new virus, although dubbed "swine flu", has not been identified from pigs in Mexico, nor is it caught directly from pigs, but has the ability to infect and transmit efficiently between humans. This led the World Health Organization to increase its pandemic alert to level 4.
So far there seem to have been around 159 fatalities among perhaps 2000 cases in Mexico, although only a small number of these have been confirmed in the laboratory as influenza infections. Although this suggests a scary fatality rate of around 10%, there has so far been just one death outside of Mexico – of a 23-month-old Mexican child in Texas, who had recently been in Mexico. The "case fatality" of the virus is not yet known.
This is the key point that scientists are now investigating. Travellers returning to their home countries after acquiring the virus in Mexico have experienced mild influenza-like illness. What might explain this apparent discrepancy in disease outcome?
A matter of numbers
One simple answer is that there have been many more mild cases in Mexico than counted so far and that the true case fatality rate is more like 1 to 2%. This would be akin to that seen during previous pandemics such as the 1957 (H2N2) Asian influenza or the 1968 (H3N2) Hong Kong flu. Even with the 1918 Spanish influenza, which killed tens of millions, the case fatality rate is estimated at between only 2.5 and 5%.
In other words, as cases outside of Mexico increase, we may expect a small number of fatalities from what is otherwise a rather mild virus. Increased epidemiology – for example, monitoring the spread of the virus and the strain type in the affected areas in Mexico – will shed light on this issue.
Another possibility is that the Mexican fatal cases have been due to co-infections with other pathogens that together lead to a worse outcome, or that somehow the indigenous population of Mexico is genetically predisposed to fare badly with this particular influenza strain. There is no evidence to support either of these possibilities, but then so far we have few clinical details of any of the cases.
Something about Mexico?
Neither does the limited data available suggest that the viruses in Mexico differ genetically from those that have caused mild symptoms in the US. The outcome of any influenza infection likely depends on the dose to which an individual was exposed. It may be that travellers unwittingly exposed to swine influenza have experienced a lower dose than some of the Mexican victims whose circumstances have not as yet been described.
Moreover in Europe and North America we are well outside the influenza season and the climatic conditions may be unfavourable for high-dose transmission. Contacts of returning travellers may have acquired the infection at a lower dose than individuals in Mexico. What is certain is that, as the number of cases outside of Mexico rise, we will have a much better idea of what sort of influenza virus this is.
Analysis of the viral genome indicates that it does not carry any of the genetic determinants associated with high virulence in other influenza viruses like H5N1. Genetic analysis suggests that the virus is unable to grow in areas beyond the respiratory tract, although it is already well adapted for binding to the upper respiratory tract of humans.
Evolution of a virus
However, until real biology begins in earnest with this virus in relevant model systems, coupled with careful descriptions of clinical courses in those infected, we cannot be sure what to expect.
Furthermore, this is a novel influenza virus, fresh from a cross-species jump. The virus might be expected to change within the coming months in ways that adapt it to its new host. If the virus persists until the advent of the next influenza season, or takes hold in the southern hemisphere where influenza season is getting underway right now, we might also have to look out for further reassortment events between this virus and the currently circulating human influenza A H3N2 or H1N1 strains.
The biological consequences of such changes are unpredictable at present, but for many reasons the "second wave" of this virus may not follow the characteristics of the first.
Wendy Barclay is professor of influenza virology at Imperial College London
First analysis of swine flu spread supports pandemic plan
* 19:00 11 May 2009 by Andy Coghlan
* For similar stories, visit the Epidemics and Pandemics Topic Guide
H1N1 swine flu is spreading fast enough to justify the preparations for a pandemic, say epidemiologists who've analysed the pattern of spread so far.
"The message is that the epidemic is spreading very much as expected based on past flu epidemics," says Christophe Fraser of Imperial College London, and co-leader of the analysis team.
The results suggest that the H1N1 virus is showing "sustained human-to-human transmission", thereby justifying the WHO's pandemic phase 5 rating, one short of the most severe.
By analysing the pattern of spread within and beyond Mexico, where the epidemic emergedMovie Camera in February, the researchers estimate that on average, each person who contracts flu passes it on to between 1.4 and 1.6 other people.
Whenever this value, called the reproductive number or Ro, is more than 1, it means that a disease is transmissible, and the higher the number, the easier it's transmitted.
The values found match or are less than those for previous flu epidemics, in 1918, 1957 and 1968.
But while the speed of spread is now better understood, researchers say they need more data to assess how dangerous the new virus is.
"Our early analysis would suggest this is going to be an outbreak comparable to that of 20th century pandemics regarding the extent of its spread," says Neil Ferguson, co-leader of the team.
"However, it's very difficult to quantify the human health impact at this stage," he said.
Case fatalities
Their best estimate from the Mexican fatalities is that the virus kills 0.4 per cent of those it infects on average, ranging from 0.3 to 1.5.
"So while substantial uncertainty remains, clinical severity appears less than that seen in 1918, but comparable with that seen in 1957," says the journal report. However, this is the "first wave" of the virus – scientists don't yet know whether the virus will become more dangerous.
Ferguson and his colleagues reached their latest estimates by assuming that cases in visitors to Mexico were much better investigated than those in Mexico itself, where the virus circulated invisibly for months before fuller surveillance was introduced.
"We used indirect detective measures to work it out," says co-leader of the team, Christophe Fraser, also at Imperial. "We had good data on people crossing in and out of Mexico, and assumed they were representative of the numbers of people originally infected in Mexico," he explained.
So from the figures, they estimate that between 6000 and 32,000 individuals in Mexico have had the virus, with a central estimate of 22,000.
From this, they worked out the Ro estimates.
Virus mutations
They reached a similar Ro figure, 1.2, when they worked backwards by tracking genetic mutations in the virus since the epidemic originated.
But the team says there's more uncertainty about how lethal the virus is, because there have been relatively few deaths so far. "That's the tricky one," says Fraser.
Figures released today by the WHO reveal that there have been 4694 cases worldwide, with 48 deaths in Mexico, three in the US, and 1 each in Canada and Costa Rica.
"Much remains to estimate the clinical severity of infection," say the researchers.
Equally difficult is to predict how the virus will evolve. But they warn that as the flu season gets underway in the southern hemisphere, it will need to be carefully monitored to find out whether climatic conditions make things better or worse, whether the virus develops resistance to anti-flu drugs, and whether vaccination makes any difference to survival.
"The key trade-off remains the balancing of the economic and societal cost of interventions, such as school closure, against the numbers of lives saved through use of such measures," they say. "Where substantial antiviral stockpiles are available, a secondary trade-off is the extent to which large-scale prophylaxis is justified, given the potential of high level resistance developing."
Journal reference: Science DOI: 10.1126/science.1176062
* Updated 18:42 29 April 2009 by Wendy Barclay
* For similar stories, visit the Epidemics and Pandemics and Comment and Analysis Topic Guides
http://www.newscientist.com/data/images/ns/cms/dn17049/dn17049-1_300.jpg
Computer artwork of an H1N1 influenza A (flu) virus. In the particle's lipid envelope (purple) are two types of protein spike, haemagglutinin (H) and neuraminidase (N), which determine the strain of virus. These are used for recognising and binding to the host cell (Image: PASIEKA / SPL)
Out of the blue, a novel influenza virus has emerged in Mexico. The virus seems to have been born from the combination of at least two pig viruses, that themselves carried gene segments that originated in viruses of other species such as birds or humans. The combination of elements from three species is called "triple reassortment".
This new virus, although dubbed "swine flu", has not been identified from pigs in Mexico, nor is it caught directly from pigs, but has the ability to infect and transmit efficiently between humans. This led the World Health Organization to increase its pandemic alert to level 4.
So far there seem to have been around 159 fatalities among perhaps 2000 cases in Mexico, although only a small number of these have been confirmed in the laboratory as influenza infections. Although this suggests a scary fatality rate of around 10%, there has so far been just one death outside of Mexico – of a 23-month-old Mexican child in Texas, who had recently been in Mexico. The "case fatality" of the virus is not yet known.
This is the key point that scientists are now investigating. Travellers returning to their home countries after acquiring the virus in Mexico have experienced mild influenza-like illness. What might explain this apparent discrepancy in disease outcome?
A matter of numbers
One simple answer is that there have been many more mild cases in Mexico than counted so far and that the true case fatality rate is more like 1 to 2%. This would be akin to that seen during previous pandemics such as the 1957 (H2N2) Asian influenza or the 1968 (H3N2) Hong Kong flu. Even with the 1918 Spanish influenza, which killed tens of millions, the case fatality rate is estimated at between only 2.5 and 5%.
In other words, as cases outside of Mexico increase, we may expect a small number of fatalities from what is otherwise a rather mild virus. Increased epidemiology – for example, monitoring the spread of the virus and the strain type in the affected areas in Mexico – will shed light on this issue.
Another possibility is that the Mexican fatal cases have been due to co-infections with other pathogens that together lead to a worse outcome, or that somehow the indigenous population of Mexico is genetically predisposed to fare badly with this particular influenza strain. There is no evidence to support either of these possibilities, but then so far we have few clinical details of any of the cases.
Something about Mexico?
Neither does the limited data available suggest that the viruses in Mexico differ genetically from those that have caused mild symptoms in the US. The outcome of any influenza infection likely depends on the dose to which an individual was exposed. It may be that travellers unwittingly exposed to swine influenza have experienced a lower dose than some of the Mexican victims whose circumstances have not as yet been described.
Moreover in Europe and North America we are well outside the influenza season and the climatic conditions may be unfavourable for high-dose transmission. Contacts of returning travellers may have acquired the infection at a lower dose than individuals in Mexico. What is certain is that, as the number of cases outside of Mexico rise, we will have a much better idea of what sort of influenza virus this is.
Analysis of the viral genome indicates that it does not carry any of the genetic determinants associated with high virulence in other influenza viruses like H5N1. Genetic analysis suggests that the virus is unable to grow in areas beyond the respiratory tract, although it is already well adapted for binding to the upper respiratory tract of humans.
Evolution of a virus
However, until real biology begins in earnest with this virus in relevant model systems, coupled with careful descriptions of clinical courses in those infected, we cannot be sure what to expect.
Furthermore, this is a novel influenza virus, fresh from a cross-species jump. The virus might be expected to change within the coming months in ways that adapt it to its new host. If the virus persists until the advent of the next influenza season, or takes hold in the southern hemisphere where influenza season is getting underway right now, we might also have to look out for further reassortment events between this virus and the currently circulating human influenza A H3N2 or H1N1 strains.
The biological consequences of such changes are unpredictable at present, but for many reasons the "second wave" of this virus may not follow the characteristics of the first.
Wendy Barclay is professor of influenza virology at Imperial College London
First analysis of swine flu spread supports pandemic plan
* 19:00 11 May 2009 by Andy Coghlan
* For similar stories, visit the Epidemics and Pandemics Topic Guide
H1N1 swine flu is spreading fast enough to justify the preparations for a pandemic, say epidemiologists who've analysed the pattern of spread so far.
"The message is that the epidemic is spreading very much as expected based on past flu epidemics," says Christophe Fraser of Imperial College London, and co-leader of the analysis team.
The results suggest that the H1N1 virus is showing "sustained human-to-human transmission", thereby justifying the WHO's pandemic phase 5 rating, one short of the most severe.
By analysing the pattern of spread within and beyond Mexico, where the epidemic emergedMovie Camera in February, the researchers estimate that on average, each person who contracts flu passes it on to between 1.4 and 1.6 other people.
Whenever this value, called the reproductive number or Ro, is more than 1, it means that a disease is transmissible, and the higher the number, the easier it's transmitted.
The values found match or are less than those for previous flu epidemics, in 1918, 1957 and 1968.
But while the speed of spread is now better understood, researchers say they need more data to assess how dangerous the new virus is.
"Our early analysis would suggest this is going to be an outbreak comparable to that of 20th century pandemics regarding the extent of its spread," says Neil Ferguson, co-leader of the team.
"However, it's very difficult to quantify the human health impact at this stage," he said.
Case fatalities
Their best estimate from the Mexican fatalities is that the virus kills 0.4 per cent of those it infects on average, ranging from 0.3 to 1.5.
"So while substantial uncertainty remains, clinical severity appears less than that seen in 1918, but comparable with that seen in 1957," says the journal report. However, this is the "first wave" of the virus – scientists don't yet know whether the virus will become more dangerous.
Ferguson and his colleagues reached their latest estimates by assuming that cases in visitors to Mexico were much better investigated than those in Mexico itself, where the virus circulated invisibly for months before fuller surveillance was introduced.
"We used indirect detective measures to work it out," says co-leader of the team, Christophe Fraser, also at Imperial. "We had good data on people crossing in and out of Mexico, and assumed they were representative of the numbers of people originally infected in Mexico," he explained.
So from the figures, they estimate that between 6000 and 32,000 individuals in Mexico have had the virus, with a central estimate of 22,000.
From this, they worked out the Ro estimates.
Virus mutations
They reached a similar Ro figure, 1.2, when they worked backwards by tracking genetic mutations in the virus since the epidemic originated.
But the team says there's more uncertainty about how lethal the virus is, because there have been relatively few deaths so far. "That's the tricky one," says Fraser.
Figures released today by the WHO reveal that there have been 4694 cases worldwide, with 48 deaths in Mexico, three in the US, and 1 each in Canada and Costa Rica.
"Much remains to estimate the clinical severity of infection," say the researchers.
Equally difficult is to predict how the virus will evolve. But they warn that as the flu season gets underway in the southern hemisphere, it will need to be carefully monitored to find out whether climatic conditions make things better or worse, whether the virus develops resistance to anti-flu drugs, and whether vaccination makes any difference to survival.
"The key trade-off remains the balancing of the economic and societal cost of interventions, such as school closure, against the numbers of lives saved through use of such measures," they say. "Where substantial antiviral stockpiles are available, a secondary trade-off is the extent to which large-scale prophylaxis is justified, given the potential of high level resistance developing."
Journal reference: Science DOI: 10.1126/science.1176062