Swine flu A/Mexico/2009 (H1N1): Questions and answers

30 April 2009

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

Q: Am I missing something?  How can a summer pandemic be unprecedented?  You cited a pretty famous example of one.  In fact nearly all of your examples seem to have occurred partly or mostly “out of season”.

A: You are correct; it is true that there were cases of influenza over the summer of 1918, even in the northern hemisphere. These were mainly in troops; I believe this situation was anomalous due to massive troop movements. But in 1968 the seasonal pattern was clear.

Q: I haven’t seen anyone address death rates for cases treated with antivirals vs. cases not treated with antivirals. For that matter, reporting of the cases in the US has been rather unclear about the extent to which confirmed and suspected cases are being treated with antivirals. Couldn’t it be that Mexico has only relatively recently started to consistently treat suspected cases with antivirals within the short window of effectiveness, and that most US cases have received treatment? This would explain a leveling off of the increase in number of deaths in Mexico and the “mild” cases we’re seeing in the U.S.  If this is not made clear, the public will mistakenly believe this flu to be benign and will not take the appropriate steps to mitigate its spread. And couldn’t this turn political as countries have different incentives to shut down their economies with quarantines and bans on public gatherings given their respective antiviral stockpiles?

A: I don’t have any information on the extent of use of antivirals anywhere. There are still so few confirmed cases that it would be premature to speculate, although it’s a good point.

Q: 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?

A: 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.

Q: I found these statistics on the newspaper “Reforma” so I have added the population for each state (in thousands) and calculated morbidity and mortality by adding all up (deaths, proven cases and probable (maybe) cases) and it turns out that the states with the highest morbidity do not have the highest mortality… for instance Tlaxcala has the highest morbidity for such a small state and San Luis Potosi has the highest mortality with a much lower morbidity….Could be that we are dealing with two different types of H1N1 viruses? one is the California that is not too virulent and a mutated one that is highly virulent and is not spreading that much….

A: These are certainly possible scenarios. Until we have sequences from the Mexican isolates we won’t know the answers. I do think the absence of sequence information from Mexico is exacerbating the panic.

Q: What are the chances of swine flu developing resistance against Tamiflu and other currently available antiviral drugs ?  Do you think that the distribution of Tamiflu and other drugs over the course of the last few years have been a mistake that leaves us less well-prepared in front of the current epidemic ?

A: The chance of swine flu becoming resistant to Tamiflu is very high; last season a high proportion of all circulating H1N1 viruses were resistant to the drug. Remember, the current H1N1 viruses are already resistant to adamantanes. I don’t think distribution of the drugs was a mistake; their use probably saved lives. What is a mistake is not having a deeper arsenal of antiviral drugs. We need to have at least 6 drugs for an effective antiviral approach.

Q: I live in Mexico and we are very confused here about the measures the government is taking against the flu. I have heard that it is not possible in the first 7 days passing the virus person-person, but only in the moment that the symptoms are already visible. Is that true?

A: Peak virus shedding occurs about a day before peak symptoms. I would not say it is not impossible to shed virus without symptoms, but in most cases, shedding is quickly followed by symptoms.

Q: I read somewhere that this new strain is one that contains parts of the H5N1 virus (bird flu) and other flues, including the H1N1 strain (human), and some genetic material from swine flu, but they’re just calling it the H1N1 virus. This is all very confusing, because that would have had to be genetically engineered in a lab and then released into the general public. They (the media) is also saying that it is a rapidly mutating virus (RNA, obviously, because they are unstable). Could this be genetically engineered? If someone could explain, that would be great.

A: Pigs are infected with many different influenza virus subtypes (H1N1, H3N2) and viruses with different sets of RNA segments can emerge. It does not have to be engineered in a lab to have RNAs from so many different viruses. This is not a virus anyone has seen before, and no scientist is smart enough to have made it so that it would be transmitted among humans.

We receive quite a few anxious emails from Mexico. Following is an example:

Q: I am living in Baja, Mèxico. This  swine influenza issue is getting really scary. And I suspect authorities  give one information then they give contradictory information, I think they don´t want people to panic. As we already are anyway.

a) La Paz, is really  hot weathered, unfortunately… and the hot weather hasn`t come yet, do you think hot weather would help to attenuate the spreading of the virus?

A: Yes, hot weather should interfere with aerosol transmission. But it is possible that the virus might continue to spread through contact.

b) How long do you think it would take to make a vaccine?

Six months. I have read that some companies feel it can be done faster, but the vaccines we have used successfully in the past require six months.

c) Now it is really difficult to find the Relenza or Tamiflu, but I have heard that some natural products sometimes help reinforced the inmunological system , like the onion, would you recommend to eat something in particular?

I am not aware of natural antiviral sources, but I would caution you against using natural products that might contain other dangerous materials (not onions, of course).

Q: I was reading that some countries do not have the techniques for testing if a virus is of the present H1N1 type. Which exactly is the procedure for this test and why it is so complex/expensive?

A: It is true that some of the assays are complex, and several are used. One method is to isolate the virus in cell culture by inoculating a nasal swab or throat wash specimen into cultured cells. Then a panel of antibodies against the 16 known HA subtypes are used in a variety of assays, such as neutralization assays, in which the capacity of the antibody to block infection is determined. For example, if the virus is an H1 virus, only antibodies against the H1 HA would block infectivity. Other diagnostic methods include direct fluorescent antibody testing, immunoassays, real-time reverse transcription-polymerase chain reaction, nucleotide sequencing, and multiplex reverse transcriptase-polymerase chain reaction. Some of these assays can be done directly on the nasal swab or throat wash. Viral culture is the “gold standard” for typing and subtyping of influenza viruses, but takes 3 to 7 days to culture the virus. In experienced hands they are not complex, but they must be done properly to have confidence in them. Lab personnel need to be trained in the methods because clearly a great deal depends upon a reliable test.

Q: Why does the CDC recommend against face masks when the science clearly shows they are exceedingly beneficial at stopping the transmission of flu-like disease? Here’s a study I found on the CDC’s own site clearly demonstrating the efficacy of properly fitted N95 face masks during the SARS outbreak.

A: I did not mean to imply that CDC advises against using face masks. My statement was based on the fact that on the CDC’s swine flu page, there are no recommendations for face masks. This is the page that most of the public will see. Face masks will work if used properly; if not used according to directions, they will not prevent transmission or infection and will convey a false sense of security.

  • MS

    Is Vitamin D effective against influenza? And does this also help explain seasonality?

  • Pingback: Mexico fights swine flu with 'pandemic potential' - Page 11 - Gossip Rocks Forum

  • http://theswine.wordpress.com/ Trevor Snapp

    This is a great resource. For more on the human element here Mexico City, please check out my blog:
    http://theswine.wordpress.com/

  • http://www.swine-flu-pig-flu.blogspot.com/ Influenza A (H1N1)

    Although swine flu did originate from pigs not all pigs have the virus. In fact i believe that we will see other virus coming out of farm animals because this could have easily been avoided if farmers would stop trying to mass produce and leave animals huddled/sick/filthy. Its a shame that they are considering killing all those pigs in Egypt.

  • Melissa Kim

    I would imagine that the face masks that are commonly being worn in the streets across the globe may help to reduce the spread and reach of sneezes and other respiratory aerosols – true? I realize they are not protective but they may do some good in this respect perhaps?

  • http://www.virology.ws profvrr

    When used properly, by health care personnel, they will help
    significantly. But worn loosely on the street – minimal I think. But
    it's a difficult experimental study to conduct. Do you know of any
    controlled experiments with such masks worn outdoors?

  • Glen C

    I don’t know where I can find the answer to this question.
    Exposed to a patient who passed a FRI screening on Tuesday night.
    Wednesday patient developed signs and symptoms of the flu. Her nasopharyngeal swab showed influenza A.
    On Friday evening I developed signs and symptoms of the flu. Friday evening I started Tamiflu 75mg BID. By Sunday evening short of breath, x ray indicated pneumonia. Early Monday nasopharyngeal swab was done. I had asked the resident if it was possible for the swab to be a false negative since I already had 5 out of 10 doses of Tamiflu. She did not know. The swab came back today negative. Is it possible for the result to be wrong

  • http://www.virology.ws profvrr

    It depends what type of test was done. The rapid tests for influenza
    are notoriously inaccurate; up to 50% of negatives are actually
    positive. The PCR and viral isolation assays are much more accurate.
    See more here: http://www.cdc.gov/flu/professionals/diagnosis/….

  • Glen C

    It was a viral culture. Could the tamiflu effect the results? or anything else effect the results?

  • http://www.virology.ws profvrr

    Even viral culture isn't perfect, so yes, it could have been a false
    negative. Tamiflu reduces viral loads but would not eliminate virus,
    so I doubt it would influence the virus isolation assay. For example,
    tamiflu resistant strains are isolated from patients treated with the
    drug.

  • http://www.virology.ws profvrr

    It depends what type of test was done. The rapid tests for influenza
    are notoriously inaccurate; up to 50% of negatives are actually
    positive. The PCR and viral isolation assays are much more accurate.
    See more here: http://www.cdc.gov/flu/professionals/diagnosis/….

  • Glen C

    It was a viral culture. Could the tamiflu effect the results? or anything else effect the results?

  • http://www.virology.ws profvrr

    Even viral culture isn't perfect, so yes, it could have been a false
    negative. Tamiflu reduces viral loads but would not eliminate virus,
    so I doubt it would influence the virus isolation assay. For example,
    tamiflu resistant strains are isolated from patients treated with the
    drug.