Effect Measure

The California swine flu cases

Late yesterday afternoon a Morbidity and Mortality Weekly Report (MMWR) Dispatch appeared on CDC’s website that is unique in my experience. MMWR is usually heavily vetted and edited and nothing gets out of there fast. Indeed, in recent years, nothing at all got out of CDC very fast. And yet here is this Dispatch, with text referring to the same day of issue (April 21), reporting on two young patients with febrile respiratory illnesses, one of whose cases CDC only learned about on April 13, 8 days earlier. April 17 CDC determined that the two children, both from the San Diego, California area, were infected with a swine flu virus of a novel kind. That was five days ago. The extremely rapid publication of this MMWR is apparently a consequence of the new International Health Regulations. It’s good to see CDC take them so seriously. Are you listening Indonesia?

Both patients recovered uneventfully. Neither had been around pigs. CDC therefore considered it likely that human to human transmission was involved, although investigations are still taking place. The Dispatch was also a heads up to clinicians and health departments to be on the lookout for influenza like illnesses in patients who resided in, or had recently traveled to, southern California, or who had had recent exposure to pigs.

The discovery in both cases seems to have involved an element of luck. The first patient was seen at a clinic where some kind of investigational diagnostic device was in use. It detected influenza/A but was negative for the two subtypes of seasonal flu (H1N1 and H3N2) and for bird flu (H5N1). This made it a novel influenza virus, requiring notification of the San Diego County Health Department and further testing in more specialized laboratories, which verified it was an unsubtypable influenza A strain. The next day (April 14) CDC identified it as an H1N1 swine flu virus. Three days later (April 17) CDC received a second specimen from a 9 year old girl who had been seen at an outpatient facility that was part of an influenza surveillance project. This virus, too, had been initially unsubtypable.

Further genetic tests showed the two viruses to be similar, although not identical, pig influenza viruses. Pigs get influenza fairly often but rarely pass it on to humans. Diagnosed human swine flu infection is rarely recognized, although the one or two cases a year has increased slightly since 2005. It is usually a relatively mild illness, and almost patients give some history of contact with or proximity to pigs. So the lack of pig contact in these cases was unusual. Moreover the viruses weren’t the usual swine flu viruses, either. Most of the genes, including the hemagglutinin (HA) gene, were of the same family as seen in US pigs in the last decade, but the neuriminidase (NA) and matrix (M) protein genes were like swine flu viruses seen in Eurasia. This particular genetic combination has not previously been described and it raised the question whether a new reassortant was appearing that might become a public health problem if it could spread easily from pigs to humans and then human to human. There is no systematic surveillance of pigs in the US, however, so how new and how novel it is remains uncertain. Both of the novel isolates are resistant to the older antiviral adamantane class of drugs (M2 inhibitors). Interestingly, this year’s seasonal version of H1N1 is sensitive to the adamantanes. Resistance testing for the more recent neuriminidase inhibitors (oseltamivir/Tamiflu and zanamivir/Relenza) is in process.

Investigations so far have turned up no link between the two patients, who reside in adjacent counties. CDC and state and local health departments are making an unusually aggressive contact tracing effort. The first patient traveled with his family to Texas shortly after his illness and an AP story reports that CDC is trying to locate air crew and nearby passengers on the same flight. Family members of both patients had also been sick with respiratory symptoms on or around the same time, although no diagnostic tests were done.

Human to human spread of swine flu is unusual but not unprecedented. The most famous example was the 1976 outbreak of flu amongst army recruits at Fort Dix, NJ. Four cases and one death occurred, with evidence of person-to-person transmission both within the recruit population and outside it. After a month, the outbreak burned itself out. We still don’t know the source of the swine flu H1N1 virus, now called A/New Jersey/76 (Hsw1N1). In 1988 a pregnant woman died of influenza later determined to be a swine flu. She had visited a pig exhibition at a county fair four days before the onset of her illness. 76% of the exhibitors in the swine building developed antibodies to the virus, and several health care personnel in contact with the patient developed mild flu-like symptoms and later showed antibody evidence of infection.

However this turns out, it illustrates the value of a surveillance system. While these two cases were fortuitously caught, there was still something there to catch them. Novel influenza infections are notifiable diseases and in this case the system worked just as it should and in a timely manner. The lack of pig exposure in these two cases is clearly worrying to CDC, suggesting human to human transmission might be taking place.

So far it’s not an emergency, but it’s not business as usual, either. Hence the priority and the heads up to the medical and public health community.

Comments

  1. #1 SusanC
    April 22, 2009

    Makes you wonder how much else we are missing. Probably many orders of magnitude more than what we are catching, in the surveillance.

  2. #2 sdepi
    April 22, 2009

    CDC’s level of concern could be related to the need to finalize vaccine components for the next flu season.

  3. #3 revere
    April 22, 2009

    sdepi: I doubt it. That decision has already been made, and not by CDC. Clearly, however, if this stuff starts circulating, it will result in a mismatch next year.

  4. #4 maryn
    April 22, 2009

    It’s interesting to me that they were both caught by the San Diego HD. That HD department seems to me particularly nimble and alert; I know of some other stuff that they have caught, that they tested and dxd very rapidly. (It turned out to be MRSA necrotizing pneumonia post-flu, but had surrounding circumstances that made it look like a nasty zoonosis.)

  5. #6 paiwan
    April 22, 2009

    Perhaps SusanC’s speculation that “.. many orders of magnitude more than what we are catching, in the surveillance” has a point; especially the area of the transmission between animals and humans.

    The swine flu is just a tip of the problem. If the mistreatment of pig by feeding them more antibiotics persists, then the pig farms will be the incubators of super bugs now and in the future. Maybe I am wrong, no evidence.

    I am not clear what the common cause of swine flu and MRSA which have transmitted to humans is. But it is really scaring to know that humans as the carriers of MRSA are increasing- only carriers without symptom.

    If you read the report from Nicholas Krisof from New York Times: “Now this same strain of MRSA ( which has been found in Netherlands) has also been found in the United States. A new study by Tara Smith, a University of Iowa epidemiologist, found that 45 percent of pig farmers she sampled carried MRSA, as did 49 percent of the hogs tested.”

    http://www.nytimes.com/2009/03/12/opinion/12kristof.html?_r=1&scp=2&sq=MRSA%20Nicholas%20Krisof&st=cse

    I suspect that swine flu carriers in human also exist; they may release the virus to the people who are immunity less mature people like children, and they are infected. Because the carriers have no symptom; so it has not seen as a case of human to human transmission.

  6. #7 Ren
    April 22, 2009

    As the Epi in charge of flu surveillance in a certain mid-Atlantic state, we are looking at this very carefully. Just last week, I advised my colleagues that the next pandemic might very well come from a swine flu variant. This is because of two things… Swine to human transmission, and human to human transmission. These swine flu viruses are easier to transmit both of these ways than birds. If you look at the recent bird flu cases, all of them have involved being in close proximity with the birds. Here, we have two kids removed at least one degree from the pigs.

    Are we ready for the next pandemic? Not by a long shot. Are we catching everything through surveillance? Not even close. (Show me a disease surveillance scheme that catches all cases, and I’ll show you a pot of gold at the end of a rainbow.)

    Am I excited by all this? Absolutely. (Epidemiologists, like lab techs, get all giddy about bugs.)

  7. #8 paiwan
    April 23, 2009

    How innocent is the swine!

    If the reports of MRSA carriers in Netherlands and the United States have happened in a short time difference, then, perhaps that human was the one that transmitted to swine in the first place. We are much more mobile than swine. ;-(

    The final solution is swine has to be slaughtered.

    Ren: “Am I excited by all this? Absolutely.” This a bit rants too far. Bug has no eye like bullet, whom will it hit first?

    But you are absolutely right that swine flu is much dangerous than bird flu. Please show your pot of gold first for merciful sake. :-)

  8. #9 sdepi
    April 23, 2009

    And of course we now have additional cases. The two initial cases have been joined by several more, two of these were from previous samples that were just now screened (subtyping is only done on random samples). And this is interesting but the virulence is still unknown.

  9. #10 Stephan
    April 24, 2009

    Since this is hitting people in the 25-44 age group, I am very curious if it is a strain of flu that creates a cytokine storm in the infected individual, like the highly deadly Spanish flu did.

  10. #11 Phillip Huggan
    April 24, 2009

    Obvious interpretations for the lower USA death rate (0/8 vs 60/1000 Mexico) are statistics, healthier population, better healthcare upon treatment, a greater percentage of infected cases receiving treatment or early treatment…the most insidious interpretation would be the virus has already mutated in the (I assume) later USA cases, luckily in a less lethal direction. A close analysis of human sample similiarities among different patient should or may have already ruled out the latter interpretation.

    Something that would be (maybe is) useful in assessing instances of further mutation would be accurate running daily tallies of new infections and death tolls. I wouldn’t expect this of Mexico’s healthcare system yet, but certainly USA should be able to output these stats in near real-time; maybe are but not publicly.

    We should be paying these healthcare costs at the butcher shop via taxes on markets and farms where difference species have the opportunity to mutate flus. Be nice to have local epidemic reports like a weather channel in place before these things become designer.

  11. #12 m
    April 25, 2009

    Health care and reporting in Mexico are inferior so the ill and death rate are probably higher. Mexico is also dealing with an undernourished population.

    Those who have health insurance in America will probably have much better health care. Most of us are not undernourished.

    http://www.rense.com has several articles about this swine flu situation. Some of them are very good.

    75 students at a Catholic prep school in NYC are sick and have been tested for swine. If 75 NYC kids have it, the situation has become a lot more dangerous.

    If this thing is on, stock up on food, drink and supplies. Start a garden. Buy a large freezer and use it. Learn to can the food you grow. Look into buying n95 – n100 face masks. PROTECT YOURSELVES.

    FOX News just announced that 200 kids probably have mild cases of swine flu.

  12. #13 Mark Gendreau
    April 25, 2009

    Anyone have a guess on the transmission dynamics of this agent-i.e: R0, generation time and theta value?-based upon Mexico’s experience.

  13. #14 revere
    April 25, 2009

    Mark: I don’t think there’s much data except that CDC is saying the serial interval is unusually short — 1 – 2 days, so it could spread fast. No idea about R0, although usual estimates for flu are around 2 – 3.

  14. #15 Linda
    April 28, 2009

    Two school districts in Texas that shut down for this week have now extended that until May 11. Seems a bit extreme, but parents are scared, I guess.

  15. #16 hastürk
    June 17, 2009

    “CDC’s level of concern could be related to the need to finalize vaccine components for the next flu season…thank you

  16. #17 hastürk
    June 17, 2009

    “CDC’s level of concern could be related to the need to finalize vaccine components for the next flu season…thank you

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