Swine flu: Questions and answers

29 April 2009

questionHere are my answers to questions about swine flu sent by readers of virology blog:

Q: Can you please tell me why there is a flu “season”.

Influenza is seasonal in temperate climates because conditions found during winter, low temperature and humidity, favor spread of the infection. In the dry conditions of winter, virus-laden respiratory droplets remain small and travel further. When humidity is high, these droplets take on water and hence do not move well through the air, limiting transmission. However, influenza can be isolated all year round from most large cities. Furthermore, influenza occurs throughout the year in tropical climates. Finally, influenza in swine is not seasonal. These observations indicate that other modes of influenza transmission – via direct contact or contaminated objects – may play important roles under some conditions.

Q: So far, people aren’t even dying in New York. What about Dengue Fever, spread by mosquito like Malaria, but with only a 1% fatality rate? With CDC estimates at about 100,000,000 cases a year, that’s 100,000 dying people worldwide. (It might be higher, because the fatality rate in developing countries is about 5%). In Puerto Rico, about 2-3 people a week die from Dengue….each year 350-500 million cases of malaria occur worldwide, and over one million people die, most of them young children in sub-Saharan Africa. In areas of Africa with high malaria transmission, an estimated 990,000 people died of malaria in 1995 – over 2700 deaths per day, or 2 deaths per minute. Apparently, unless people are dying in New York, a disease is not our problem….again from the Centers for Disease Control and Prevention, the number of alcohol-induced deaths in the U.S., excluding accidents and homicides, in 2005 was 21,634. Here’s another statistic, the number of Lyme Disease infections in the U.S. for 2005 were 23,305.

Now I realize these questions are short sighted and have made my own responses based on my limited knowledge but I would like to hear an answer from someone like yourself who is more knowledgeable on the subject.

A: Influenza is a serious disease, and if the current swine flu virus sparks a pandemic, it could lead to millions of deaths. Influenza is a preventable disease – an effective vaccine and antiviral drugs are available. This is why the outbreak is receiving much attention, so health officials can decide whether to produce a vaccine against this new strain. Some of the infectious diseases that you mention are not at the moment preventable, but they might be one day. Vaccines against dengue and malaria are under development – they have not been as straightforward to devise as an influenza vaccine. And a vaccine against Lyme disease was licensed but recently removed from the US market.

Q: Should we actively seek exposure to this wave of a relatively mild flu in hopes that some immunity protection will be afforded to a possible more deadly mutation in the fall?

A: Absolutely not. First, it is not certain that infection with the past season’s human H1N1 strain would confer any protection – I have not yet see data to answer the question one way or the other. Second, the infection might not result in mild disease – for any number of reasons it could be more severe than you think.

Q: Can we be absolutely metaphysically certain this is not a genetically engineered virus/viruses? Dr. Marie Gramer at the University of Minnesota, who has actually examined this virus first hand, and has probably the largest swine flu virus library in the US at the University of Minnesota, states that this virus isn’t even close to being serially homologous with any others in her library. It is a radically different entity. There has never been a virus with two swine flu, one avian and one human component. Are there sufficient grounds, in light of all this, to be absolutely positive these have not been genetically engineered?

A: The A/California/09/2009 (H1N1) strain, and related viruses from other parts of the world, were not genetically engineered. Sequences of the viral RNAs reveal that they are very similar to viruses currently circulating in pigs. The particular combination of RNA segments has not been previously observed, but the sequence of each viral RNA is recognizable as derived from swine. More importantly – no one on earth would know how to engineer a swine influenza virus that could be transmitted among humans and cause respiratory disease and death. Only evolution can select viruses with this property.

Q: There are reports of large corporate hog farms in the district where the first case of the flu originated. Anything between 50,000 to 950,000 hogs are supposed to be reared and processed in these farms. Could there be a link? Would it statistically increase the possibility of reassortants emerging from these farms?

A: It is my understanding that pigs on commercial farms in Mexico are vaccinated; although it is not the same strain this might confer some protection. The private pig farms, however, do not use the vaccine, and could be the source of the virus. The larger the farm, the more swine viruses are present, and the more chance for contact between pigs and humans, leading to more likely virus transfer from pig to human.

Q: What, if any, is the structural comparison of the current H1N1 strain with a swine flu outbreak in 1998 in the US?

A: In 1998 an H3N2 influenza virus was introduced into pigs in the US. This virus is very different from the current swine flu strain (H1N1) which resembles more recently circulating H1N1 swine viruses.

Q: It is said that human, avian and swine flu viruses have got shuffled together to produce the current type. How does that happen – meaning how do these three get together? Why are pigs needed for this? Can it happen in other organisms too?

A: Pigs are good hosts for influenza viruses because their respiratory tract can be infected with both human and avian influenza viruses (as well as swine flu of course). One reason why pigs are so susceptible is that their cells bear receptors for both human and avian influenza viruses. When two influenza viruses infect a cell, the viral genes mix and the new viruses produced can have genes from both infecting viruses. Influenza viruses infect many other animals, including birds, horses, dogs, cats, whales, and seals. Aquatic birds are the natural reservoir of the virus; they harbor all known HA and NA subtypes and may also serve to produce new strains.

Q: Should this be considered a prime candidate for next winters flu season?

A: It depends on the extent of spread of the virus in the southern hemisphere. A decision to make a vaccine must be made very soon, so that the vaccine can be deployed in the fall. If the virus continues to spread in the next week I would presume that vaccine production will go forward. It probably already is.

Many readers are perplexed by the unusual severity of the outbreak in Mexico. The following readers wonder what non-viral conditions might impact on disease severity:

Q: You mentioned in a TWiV that a theory about the mortality in the 1918 influenza stemmed from a concurrent infection with a bacteria that weakened the bodies immune response. Is that a possibility here? I only ask because you mentioned people living in such close proximity–already present flora in the lungs+pollution+new viral infection? Or could there be another virus, in addition to H1N1, causing an additional immunological insult?

Q: How about the delay in access to quality health care or laxity on the part of patients to seek treatment as they ignore the symptoms of early disease just as another case of “cold”? Combine it with secondary bacterial infections and/or high pollutant levels and low immunity levels, hence high mortality!

Q: I have a third theory about why fatalities could be higher in Mexico City: that town has some of the worst air quality in the world. I’m just speculating here, but it seems at least plausible that high smog and particulate pollution levels could tip some patients over the edge, turning an unpleasant but otherwise survivable case of the flu into a deadly viral pneumonia.

Q: It is too early to fully understand the current situation, but I would nevertheless draw your attention to the possibility that the very important pollution level and the high altitude of Mexico City (2,250 meters) can be partly responsible for the severity of swine influenza cases reported in Mexico. Remember that to date, all cases reported elsewhere in the world seem rather benign, or at least non-fatal. If this hypothesis is true, the severity of a pandemic outbreak may well be less severe than that suggests by the seriousness of the cases observed in Mexico City. Indeed, polluted cities such as Mexico City or located more than 2,000 meters are not numerous. I obviously do not know the nature of complications that resulted in the death of Mexican patients, but this knowledge could lead to a better understanding of how pollution and altitude should be considered as aggravating factors in the evolution of infection. Obviously, it is possible that the global death toll increase, but if, in the coming days, the severity of cases seen outside Mexico remains similar to what it is today and if it is confirmed that it is really the same viral strain, pollution and altitude could be important explanations of the current differential severity observed.

Q: I would appreciate your thoughts on how likely you think it is that the higher incidence of hospitilization and death (confirmed cases) in Mexico are simply reflective of the fact that a lot more people have been infected there than in the U.S., rather than that the isolates circulating in Mexico are more virulent to humans than the isolates circulating in the U.S. If getting very sick or dying after exposure to this strain of H1N1 is primarily a function of a hyperactive cytokine response (which I assume is related to human genetics), then I am wondering if whether a person gets very sick or dies after exposure to an isolate is more related to the genetics of the person (i.e. the intensity of their cytokine response) than to the genetics of the isolate.  If only a very small percentage of people have an immune response that is sufficient to make them very sick or kill them after exposure to the virus, then perhaps we simply have not had enough people in the U.S infected yet for the virus to “find” these hyper-responsive individuals.

A: These are all reasonable and possible scenarios, but there is no evidence yet to support any of them. I am waiting for the viral RNA sequence for the Mexican strains to determine if they differ in any way from other isolates. However, there are few differences between the New York strains and those from other parts of the US. If the NY virus came from Mexico, this would imply that the differences in the virus do not account for the lethality in Mexico. The small amount of sequence available from a German isolate, from a tourist who visited Mexico, also shows that it is nearly identical to the US strains.

There has now been a laboratory confirmed fatal case in Texas, in a Mexican toddler visiting the US with his family. This should be viewed as part of the Mexican statistics but since the child died in Texas it goes into the US case count.

A comment from Mystery Rays:

I still think the most likely reason for the apparent difference in Mexico and the US is the missing denominator, rather than any host or environmental factor. That is, I suspect that the virus is much more widespread in Mexico City than the authorities know. Because they almost entirely tested severely ill hospitalized patients, it’s not surprising that they found high mortality rates; if they were also testing mild cases (as is happening in the US and elsewhere) I think they would likely find a very widespread infection with a low mortality rate.

A: I agree that it is still too early in the epidemic, and the numbers needed to determine the percent fatality are not yet available. Remember that the fatality of seasonal influenza is about 0.1%; for the 1918-19 pandemic it was about 2.5%. Considering the laboratory confirmed cases in Mexico, there have been 7 deaths out of  26 cases which would be a fatality rate of 30% – anomalously high and probably incorrect for the reasons above.

Q: With respect to differences in mortality/pathogenesis between Mexico and the US, what about the extent of vaccination? Certainly there’s a big push in the US to get regular vaccinations. Those who have been vaccinated have had multiple exposures to other H1N1 viruses.

A: I am not aware of how immunization rates in Mexico compare to those in the US, nor of the extent of circulation of other human H1N1 strains. This could play a role if such immunization or exposure lead to protection against the new influenza strain. CDC asserts that “Vaccination with seasonal influenza vaccine containing human influenza A (H1N1) would not be expected to provide protection against swine influenza A (H1N1) viruses”, but I have not seen the data on possible cross-protection.

Q: There has been no mention, save a passing comment from the media on pneumonia, of the pathology associated with this influenza pandemic.  Could it be necrotizing bronchial interstitial pneumonia or is that only associated with H5N1?  What about MODS or Cyanosis? What, essentially, is killing our Mexican neighbors?

A: I have not seen any information on the type of pathology observed in the Mexican victims. To date interstitial fibrosis has only been a feature of infection with H5N1 viruses. If anyone has such information, please share it with us.

Q: Regarding your first theory of why the non-Mexican cases are milder: “…infection with the current circulating human H1N1 strain might confer some protection…” I’m just a layman, and so I’m wondering exactly how something like that would work.  What percentage of (say) American victims would likely have this benefit?  Enough to explain the discrepancy?  Why wouldn’t we expect a similar number of “protected” persons in Mexico? Also, regarding the “air pollution theory”, haven’t their been deaths inside Mexico, but outside Mexico City?  Perhaps in locales with comparatively pristine air?

A: Virus infection stimulates the production of host proteins called antibodies, which bind to the virus and prevent its from infecting cells. Each year, influenza virus strains change so as to avoid binding by such antibodies. However, some of the antibodies produced by infection with the previous year’s strain confer some protection against the new strain, and hence disease may be milder. A pandemic strain is completely different and not affected at all by existing antibodies in the population. Antibodies produced in response to infection with previous human H1N1 strains might recognize the swine influenza virus and block infection. Whether or not this is the case is not known.

It is my understanding that most laboratory confirmed deaths have been in Mexico City (if anyone has more detailed information, please send it to virology blog). But with just seven laboratory confirmed deaths from swine influenza in Mexico, it is far too soon to reach a conclusion.

Q: A New Zealand blogger posits that getting swine flu now could be beneficial if this becomes a pandemic. (“How Swine Flu Could Save Your Life” – ) Clearly, he makes some poor leaps of logic, but he presents what seems to be a reasonable point re: cow pox and small pox….

Could getting the swine flu now help to weather future, more virulent strains?

A: Possibly; see the discussion above.

Since this flu also has a bird flu heritage, could catching (and surviving) it help with a possible H5N1 outbreak in the future?

No. As far as can be determined from examining the sequences of the viral RNAs, it does not appear that the virus has any genes from an avian strain. Furthermore, the  HA is very important for protective immunity, and the hemagglutinin (HA) subtypes are completely different: H1 vs H5.

  • http://www.pacfs.org Greg

    How are influenza viruses classified as H1, H2, etc? I had always thought it was serological, but that would imply that the seasonal H1N1 vaccine might have some efficacy against this H1N1 “swine” virus. Is there a more modern method for classification based on nucleotide sequence?

  • http://www.virology.ws profvrr

    The subtyping (H1, H2, etc) is done by serology, using a panel of
    antibodies against the 17 known HA subtypes. This would imply some
    cross-reactivity among the H1 HAs of the swine flu strain and the
    previous H1N1 strain. Such cross-reactivity might confer perhaps not
    protection against infection but could lead to milder disease. CDC
    asserts that “Vaccination with seasonal influenza vaccine containing
    human influenza A (H1N1) would not be expected to provide protection
    against swine influenza A (H1N1) viruses” but it could reduce disease
    severity.

  • Pingback: Swine flu, virulence, and jumping viruses | Mystery Rays from Outer Space()

  • emmanueluche

    what are the means of eradication of swine flu and avian influenza?
    am emmanuel .from nigeria.please i need your urgent reply now. i want to submit my term papper this morning.

  • http://www.virology.ws profvrr

    I'm sorry to tell you that influenza virus cannot be eradicated – the
    virus is in too many animal species to be able to do that. This is in
    contrast to other viruses such as polio and measles, for which there
    are no known animal reservoirs.

  • alikarami

    I did bioinformatics' analysis few month ago on genomic and Amino acid comparison of HA and NA sequence of strains in the 2009-1010 Vaccine with New H1N1 flu virus sequences and Identified strong antigenic similarities and postulated that there should be some protection from this seasonal vaccine against New Virus,

    I Think theoretical analysis shows that there is DNA and Protein similarity between these strains and I think further analysis will reveal these cross protection too

    Sincerely yours
    Dr. ali Karami
    Associate Professor of Molecular Biology
    Research Center of Molecular Biology
    Baqiyatallah University of Medical Science
    PO. Box 19945-581, Tehran- IRAN
    Telefax:0098-21- 88039883

  • DarkAngeal

    Whats the difference between the swine & normal flu?

  • sethkane68

    Every time the swine flu virus enters a host, it mutates. Now it does not always mutate into another “novel” virus but it does change. The swine flu viruses are killing people with pneumonia, especially in the immuno-compromised youth, who don't have a fully developed system and the older population who have weakened immune system. The swine flu vaccine will not work if H1N1 mutates into something else. Another great source of swine flu information is http://swineflureader.com

  • http://www.swineflureader.com Seth Kane

    Every time the swine flu virus enters a host, it mutates. Now it does not always mutate into another “novel” virus but it does change. The swine flu viruses are killing people with pneumonia, especially in the immuno-compromised youth, who don't have a fully developed system and the older population who have weakened immune system. The swine flu vaccine will not work if H1N1 mutates into something else. Another great source of swine flu information is http://swineflureader.com