TWiV 109: Virologia en México

Hosts: Vincent Racaniello, Rosa Maria del Angel, and Ana Lorena Gutiérrez

On episode #109 of the podcast This Week in Virology, Vincent visits Mexico City and speaks with Rosa Maria del Angel and Ana Lorena Gutiérrez about virology in Mexico, and their work on dengue and caliciviruses.

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Influenza A/Mexico/2009 (H1N1) update

There are some interesting statistics on influenza in the current issue of CDC’s Morbidity and Mortality Weekly Report. The first is this map showing the number of confirmed cases (N = 1,882) of novel influenza A (H1N1) virus infection worldwide as of May 6, 2009:


With the exception of a few countries, the vast majority of confirmed cases have been in the northern hemisphere. I suspect this situation will change rapidly – flu season is winding down in the northern hemisphere, and is about to begin in the south. The fact that there are already confirmed cases in the southern hemisphere means the virus is already there, and likely to spread further. CDC says as much, although with considerably more uncertainty:

Summertime influenza outbreaks in temperate climates have been reported in closed communities such as prisons, nursing homes, cruise ships, and other settings with close contact. Such outbreaks typically do not result in community-wide transmission, but they can be important indicators of viruses likely to circulate in the upcoming influenza season. The novel influenza A (H1N1) virus has been circulating in North America largely after the peak influenza transmission season. For that reason, the epidemiology and severity of the upcoming influenza season in the southern hemisphere or in the northern hemisphere cannot be predicted. The imminent onset of the season for influenza virus transmission in the southern hemisphere, coupled with detection of confirmed cases in several countries in the southern zone, raise concern that spread of novel influenza A (H1N1) virus might result in large-scale outbreaks during upcoming months. Countries in the southern hemisphere that are entering the influenza season should anticipate outbreaks and enhance surveillance accordingly. Influenza virus can circulate year round in tropical regions; therefore, these countries should maintain enhanced surveillance for novel influenza A (H1N1) virus.

Also shown in bar graph form are the number of confirmed (N = 822) and suspected (N = 11,356) cases of novel influenza A (H1N1) virus infection, by date of illness onset in Mexico, from March 11 – May 3, 2009:


These data suggest several interesting possibilities. Infection with the new H1N1 strain might have begun as early as March 11, although the early cases are suspected, not laboratory confirmed. After a period of relatively few infections, the number of cases rapidly climbed to a peak and then quickly declined. Of course, new outbreaks are still possible. If we take the number of deaths in Mexico (42) and divide them by the number of laboratory confirmed cases (949), the mortality rate is 4.4% – higher than the 2.5% observed during the 1918-19 pandemic. However, if we divide the number of deaths by the number of suspected cases (11,932), the fatality rate is more in line with typical seasonal influenza – 0.4%. Which number is correct awaits determination of the actual number of cases.

It is also informative to examine CDC’s case definition for influenza – fever plus cough or sore throat. This definition is very broad and could easily include infections caused by other respiratory viruses, such as rhinoviruses, coronaviruses, adenoviruses, and paramyxoviruses. Indeed, I have heard that some of the suspected cases of H1N1 influenza in New York are in fact a consequence of rhinovirus infection. Analyzing an outbreak by using the suspected number of cases is dangerous – akin to a scientist ‘wasting clean thoughts on dirty data’.

Nucleotide sequences of influenza A/Mexico/2009 (H1N1) viruses available

Here at virology blog we have been speculating for a week why sequences of the Mexican influenza virus isolates have not been available. Today we received a comment from Dr. Ruben Donis, who we quoted in a previous post. Dr. Donis wrote:

Thank you for the nice vignette about the ScienceInsider interview. I would like to point out that full genome sequences of Mexican viruses have been available in the public domain at the GISAID database since April 24, 2009. Sequences were posted in the public domain as soon as they were completed and curated. The availability of sequences at GISAID was also posted at the WHO website (pdf)

I thank Dr. Donis for clarifying this situation. Clearly I and many readers of virology blog had missed the original WHO statement, and unfortunately we took the lack of sequence information as a sign of greed or evil intent. My apologies to all who were offended.

GISAID is the Global Initiative on Sharing Influenza Data, established in 2006 to help sharing data on influenza virus:

Several countries and international agencies have recently taken steps to improve sharing of influenza data following the initiative of leading veterinary virologists in the field of avian influenza. However, the current level of collection and sharing of data is inadequate given the magnitude of the threat. We propose to expand and complement existing efforts with the creation of a global consortium – the Global Initiative on Sharing Avian Influenza Data (GISAID) – that would foster international sharing of avian influenza isolates and data.

Registration is required for access to the site.

Influenza A/Mexico/2009 (H1N1): Questions and answers

questionHere are my answers to questions about the currently circulating influenza H1N1 strain (formerly swine flu) sent by readers of virology blog.

A reader from Mexico shared the following numbers with virology blog, then asked a question about hog cholera.

Q: There are 312 confirmed cases of swine virus here in Mexico and 12 of them have died. This means 3.8%. In the rest of the world there are 159 confirmed cases of swine virus infection, but no deaths. It gets even worse, there have been reported 176 deaths by pneumonia in this past two weeks, but only 12 are positive for the swine virus, this means that only 6.8% of the fatalities can be blamed on the swine virus. Three states San Luis Potosi, Oaxaca and Aguascalientes have together reported 195 cases of pneumonia with 24 deaths, that is 12.3% die. While three other states (Tlaxcala, Veracruz and Coahuila) have together reported 154 cases of pneumonia with no deaths…(a similar situation as the rest of the world).

I have read that hog cholera can increase the death toll of influenza virus above 10%. What is hog cholera and why does this worsen flu?

A: Hog cholera is an infectious disease of pigs caused by a virus known as classical swine fever virus. Infection with this virus leads to fever, skin lesions, convulsions and often death. It is also immunosuppressive, therefore worsening influenza in swine.

Q: How risky is it to travel internationally (to places other than Mexico) at this time? How likely is one to pick up a flu on an airplane, in an airport, while staying at a hotel or hostel, etc? I am supposed to be visiting Spain for a month – my travel insurance company says they won’t cover any cancellation costs because no one has issued a travel advisory against Spain. Does this mean that it is more or less safe to visit Spain, although there are cases reported there as well? I am confused. How likely is one to become sick while travelling? Would it be better to stay home at this point?

A:At this point the new influenza virus strain seems to be nearly everywhere, even in the US, based on suspected cases. Therefore travel poses no increased risk. However, travel is a good way to become infected – airports, hotels, airplane, are all good venues for transmission by aerosol or contact (see an earlier virology blog post on transmission – the airplane transmission story is particularly interesting). So in my view, you probably have a higher risk of being infected because you will be in contact with more people while traveling than if you stayed at home. But if you take precautions like cleaning hands with an alcohol-based cleaner, refrain from touching mouth/eyes/nose, you can minimize the likelihood of exposure. I doubt there will be travel advisories issued for Spain because by the time there are many cases there, the virus will be elsewhere as well. If your trip is not imminent, you can delay and make a decision later.

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

A: It has been hypothesized that vitamin D was effective against influenza (see this paper), but this has never been rigorously proven. Seasonality better correlates with temperature and humidity.

Q: Your note that CDC does not recommend use of face masks for reducing viral spread is somewhat inaccurate. In addition, the posted article titled “Influenza Viral Transmission” does not take transmission through contact with GI substances into account. In CDC’s Interim Recommendations for Facemask and Respirator Use in Certain Community Settings Where Swine Influenza A (H!N!) Virus Transmission has been detected, it is stated, “When crowded settings and close contact with others cannot be avoided, the use of facemasks or respirators in areas where transmission of swine influenza A (H1N1) virus has been confirmed should be considered. The documents then gives three circumstances.

A: Thank you for your comments and support. I understand that in some cases facemasks/respirators are recommended. As I pointed out in virology blog, on the front page of CDC, which most laypersons will see, there is no recommendation for the use of such protection. As you know, when not use properly, face masks do not function as intended and most laypersons will not have the opportunity to use respirators (by layperson I mean someone not involved in health care). As for GI spread, influenza cannot and does not replicate in the GI tract of humans (although it does so in birds). Concurrent infections with other pathogens (e.g. norovirus) may lead to GI symptoms.

Q: Our elite team of news reporters (who still refer to this as Swine flu) listed vomiting and diarrhea as symptoms. This seems peculiar for flu. During the regular flu season, I remember telling patients to look out for fever, arthralgias, cough etc…never anything about vomiting and diarrhea. Is this a legitimate symptom, or just the media being as vague as possible?

A: Influenza cannot and does not replicate in the GI tract of humans (although it does so in birds). Concurrent infections with other pathogens (e.g. norovirus) may lead to GI symptoms.


A: Do not attempt to become infected now; the outcome of influenza infection may not be benign.

Q: I’d like to know the potential lethality of swine influenza  as compared with other types of influenza viruses. IS THERE ANY REFERENCE ABOUT THE RISK OF INFECTION IN OPEN OR CLOSED SPACES??

A: There is no reason to believe that the current H1N1 virus, which originated in swine, is any more lethal than any other influenza virus, with the exception of avian H5N1 strains and the 1918-19 strain. Transmission is likely to be more efficient in closed spaces (such as an airline cabin; see this post).

Q: How long would you expect human immunity to exist within an individual infected with H1N1 virus?

A: I would expect immunity to be lifelong against that specific strain. However, immunity will not completely protect agains future antigenically drifted viruses of the same lineage.

Q: One small correction. N-95s are respirators, not face masks. Respirators must meet specifications for filtering out specific types and sizes of particles. An N-95 is a particulate respirator that when fitted properly filters 95% of particles 0.3 microns or larger. Face masks generally refer to medical and surgical masks that need only provide a physical barrier.

Thank you.

Q: At the end of a recent interview with Science magazine, Dr. Donis of the CDC states that the USA has received 300 samples of this virus from Mexico. Why has the CDC failed to publish the sequences of any of these 300 Mexican samples Dr. Donis says have been received from Mexico? Doesn’t this seem to be an intentional act?

A: I’m not sure. It’s been suggested that the Mexican government wants to keep rights to the use of the viruses as a vaccine and therefore do not want the sequence released. I suspect we’ll find out in the coming week.

Q: Regarding Dr. Schuchat’s statement, could it be that if you trace the lineage of certain viral genome segments that their origin could be avian, for example? i.e., perhaps the A/swine/Indiana/P12439/00 isolate was/is a reassortant originally containing some segments of avian origin? Just a thought, I have not personally looked closely at these sequences…

and also:

Q: But you still agree that this virus appears to contain genetic pieces from from four virus sources, correct? (one avian influenza viruses, one human influenza viruses, and two swine influenza viruses).

A: In 1998, recombinant viruses arose in pigs that were a combination of human, pig, and avian influenza virus RNAs. See Dr. Donis’ statement in yesterday’s Science interview. Today they look like swine viruses because they have been evolving in this animal for so many years.

Q: How do we account for the April 24 comments of Dr. Marie Gramer below, who has perhaps the largest library of swine flu virus isolates in the nation the day after Schuchat’s comments? “There have been no reports of this virus in pigs, said Dr. Marie Gramer, a swine flu expert with the University of Minnesota’s college of veterinary medicine. “It doesn’t seem to be very similar to anything that is currently circulating, from what I have,” said Gramer, who has an extensive library of swine flu virus isolates.”

A: I believe she is wrong.

Q: I do not understand why you are morally certain that the German and New York isolates arose from Mexico.

A: I am not certain, I only assume that because the New York and German tourists visited Mexico, that there were infected there and returned with the virus. However the point is moot if the Mexican viruses are very similar to all the others.

Q: Mexico’s chief epidemiologist insists this virus did not begin in a Mexican pig farm. “Miguel Angel Lezana, Mexico’s chief epidemiologist, told reporters…. the presence of Eurasian swine flu genes in the H1N1 virus makes it unlikely that the disease originated in a Mexican pig farm.”

A: Chief Epidemiologist? He should be fired. The fact that Eurasian swine flu genes are present in no way makes a Mexican origin more unlikely than any other.

Q: It’s taken me a while to digest the fact that the Mexican flu viruses haven’t been sequences. Shouldn’t this be bigger news? Why is it confined to a relatively obscure blog? (No offense, Dr. Racaniello.)

(I could not resist printing the preceding question. Not offended at all!)

Q: Canine influenza emerged a few years ago in Florida in greyhounds, and was found to have come from an equine influenza strain.  However, after entering the canine population, the virus is no longer able to infect horses.  Perhaps a similar thing is occurring here.

A: Swine are readily infected with human influenza viruses. So there is no reason to believe that the new human H1N1 virus would not be able to go back into pigs. We’ll see.

Q: Fucoidan is a sulfated polysaccharide primarily found in brown seaweeds.  Although the specific shape/sugar to sulfate compositions vary from seaweed to seaweed, the fucoidan used in this paper is from Undaria pinnatifida, one of the most popular dietary seaweeds consumed in Japan and Korea.  The sporophyll contains 8-12% fucoidan (the part of the Undaria used in this study, also called Mekabu in Japanese).  Is it possible that people in Japan will be protected from H1N1 if they eat Mekabu?

A: The concentrations of fucoidan used in the studies you provided are rather high and would not be present at such levels in Mekabu. Therefore eating the seaweed would not likely be of value in preventing infection.

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

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.

Swine flu: Questions and answers

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.