Effect Measure

Swine flu: more on the cases

Late yesterday The New England Journal of Medicine published a number of papers on the recent swine flu outbreak. The first paper, “Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans” by large federal-state team of epidemiologists describes 642 confirmed cases in 41 states as of May 5, 2009, two days before publication. What I find remarkable is the speed the problem was recognized — literally days. Identification of the virus was first made in the CDC laboratory on April 15, just 3 weeks ago. Now we are already reading scientific papers providing a wealth of detail.

Among those details is a fuller account of the two epidemiologically unlinked US index cases, first reported in MMWR on April 21 and the subject of a post here shortly thereafter. This was just before it was determined the same virus was circulating in Mexico and causing substantial morbidity and worrying mortality:

On March 30, 2009, in San Diego County, California, a 10-year-old boy with asthma (Patient 1) had an onset of fever, cough, and vomiting. On April 1, he was evaluated in an urgent care clinic, where he received treatment for his symptoms. He recovered from the illness within approximately 1 week. An influenza A virus that could not be sub-typed was identified from a nasopharyngeal specimen that was collected from Patient 1 as part of a clinical trial to evaluate an experimental diagnostic test. As specified by the study protocol, the specimen was then sent to a reference laboratory for further testing and was found to be positive for influenza A virus but negative for both human H1 and H3 subtypes, with the use of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing. On April 15, the CDC received the clinical specimen and identified a novel influenza A (H1N1) virus of swine origin. On the same day, the CDC notified the California Department of Public Health, and an epidemiologic investigation was initiated by state and local health department officials and animal health officials. A viral isolate was found to contain genes from triple-reassortant swine influenza viruses that were known to circulate among swine herds in North America and two genes encoding the neuraminidase and matrix proteins that were most closely related to genes of viruses obtained from ill pigs in Eurasia, according to results available in GenBank.

On March 28, 2009, in Imperial County, California, a 9-year-old girl (Patient 2) without an epidemiologic link to Patient 1 had an onset of cough and fever. Two days later, she was taken to an outpatient clinic that was participating in an influenza surveillance project. A nasopharyngeal swab was collected at the clinic. Patient 2 was treated with amoxicillin-clavulanate, and she had an uneventful recovery. The nasopharyngeal specimen was sent to the Naval Health Research Center in San Diego, where an influenza A virus that could not be subtyped was identified. The specimen was shipped to the CDC, where it was received on April 17, and a novel influenza A (H1N1) virus of swine origin was identified. The genotype of the virus was similar to that of the virus isolated from the sample obtained from Patient 1. On April 17, both cases were reported to the World Health Organization (WHO), according to the provisions of the International Health Regulations.

Epidemiologic investigation of Patients 1 and 2 revealed that neither patient had a recent history of exposure to swine. According to protocol, the identification of these two epidemiologically unlinked patients with novel S-OIV infection prompted the CDC to notify state and local health departments, which initiated case investigations and implemented enhanced surveillance for influenza A viruses that could not be subtyped. The CDC issued recommendations to clinicians, asking that they consider the diagnosis of S-OIV infection in patients with an acute febrile respiratory illness who met the following criteria: residence in an area where confirmed cases of human infection with S-OIV had been identified, a history of travel to such areas, or contact with ill persons from these areas in the 7 days before the onset of illness. If S-OIV infection was suspected in a patient, clinicians were asked to obtain a nasopharyngeal swab from the patient and to contact their state and local health departments in order to facilitate initial testing of the specimen by RT-PCR assay at the state public health laboratory. State public health laboratories were asked to send all specimens identified as influenza A viruses that could not be subtyped to the CDC for further investigation. Additional cases were identified with the use of a nationally standardized case definition of confirmed swine influenza A (H1N1) virus infection, which was defined as an acute febrile respiratory illness with the presence of S-OIV confirmed by real-time RT-PCR, viral culture, or both. (Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, New England Journal of Medicine)

There were some lucky breaks in all this, including the enhanced surveillance in the border area, the evaluation of a new diagnostic test, and the fact that CDC had recently prepared PCR primers for swine influenza requiring only minor modification to identify the new strain. While both children recovered uneventfully, it is clear patient 1 was a pretty sick little boy. 60% of the cases reported in this paper were under 18 years of age. 18% had recently traveled to Mexico, although in yesterday’s CDC briefing it was said that the travel associated cases are now only 10% of the US total as sustained person to person transmission begins to take hold on US soil. The most common presenting symptom was fever (94%) followed by cough (92%) and sore throat (66%). Unusually for respiratory influenza, 25% had diarrhea and 25% vomiting.

Hospitalization status was known for 399 of the cases and amounted to 36 in the series (it has since increased). While this 9% prevalence is high, it is likely that more serious cases were preferentially tested, so we have yet to get a good fix on the severity of illness caused by this virus. Sufficient information on 22 hospitalized patients showed that 12, or about half, had underlying medical conditions that might have increased risk, but half did not, that is, they were previously healthy individuals, many of them young. There were 11 cases of pneumonia among the hospitalized. 8 wound up in intensive care, 4 had respiratory failure and 2 died.

All of these things happen with seasonal influenza, too, so it doesn’t mean this is an especially virulent version of flu. It may well qualify for the much used term, “mild,” in that regard, because real seasonal influenza is an inherently nasty illness.

But for these patients, half of them previously healthy and on average quite young, “mild” won’t cut it as a description of what they went through. Something to keep in mind.


  1. #1 alm
    May 8, 2009

    The epidemiologic curve (fig.1) in that paper (as well as those in the new article in mmwr) give to me the impression that the worst of this outbreak is (for now, at least in mexico and the northern hemisphere) behind us. Is that a fair conclusion? I also wonder if the decline isn’t a selection effect – people who get sick may wait a number of days before seeking medical attention, and then test results become available a number of days after that…

    The daily numbers from the cdc and w.h.o. continue to rise (but these obviously lag).

    What conclusions can fairly be made from these plots, and from the daily numbers released by the cdc and w.h.o?

  2. #2 revere
    May 8, 2009

    alm: We will have to wait for the reporting bias to shake itself out. CDC believes this outbreak is still in the acceleration phase, not plateau or decline, and so do I. Also be aware that there is a lot of unevenness in where this virus is at the moment. It doesn’t strike everywhere at once, so there will likely be hills and valleys in the epi curve. We’ll just have to keep looking and not draw premature conclusions.

  3. #3 Carolyn
    May 8, 2009

    My daughter and her friends had flu back in March. Is there any value in having them tested for antibodies to the novel virus? If so, my daughter took Tamiflu upon onset of fever and aches and was over the flu in 72 hrs, while her friends had it for 10 days. Is it likely that her immune system did not have a chance to respond, so not worth testing her. Just wondering if antibody testing of kids with flu in March would help CDC in figuring out the origin of the virus.

  4. #4 Jonathon Singleton
    May 8, 2009

    Note: I mentioned to a close friend some years ago that if genetically modified food had something to do with the evolutionary genesis of transgenic viruses (eg. H1N1/2009 and H5N1), then shouldn’t we have evidence occurring within the GM crop growing American environments (South America to Canada)!?!

    The paradigm of “horizontal gene transfer and recombination” (Google search) fits current South/North American events — indeed WHO Director General Margaret Chan has made mention of these two viruses (AP report) future-evolving into one viral strain…

    From: “Hazel.Mendonca@dh.gsi.gov.uk”
    Date: Friday, March 10, 2006

    Our ref: TO00000073916

    10 March 2006

    Dear Mr Singleton,

    Thank you for your email of 5 January to the Home Office about avian flu. As this is a health related matter, your email has been passed to the Department of Health for response. I have been asked to reply.

    With regard to a possible link between genetically modified food and avian flu, may I suggest that you address your concerns to the Food Standards Agency as they are best placed to comment on this matter…

    I hope the above information has been helpful and thank you again for writing.

    Yours sincerely,

    Hazel Mendonca
    Customer Service Directorate
    Department of Health

  5. #5 Erin
    May 8, 2009

    there are a lot of stories still going around about the swine flu. In fact, nurses are almost working double time trying to keep people healthy. Many of them share their stories and offer tips on general healthy living on this Nursing resource if anyone is interested.

  6. #6 Destiny
    May 8, 2009

    hi im 16 just wondering is there a chance i can get it i live in cantonment fl

  7. #7 MoM
    May 8, 2009

    Maybe the strengthening of the public health infrastructure that Bessler bragged about in yesterday’s press conference actually exists. If now we can now respond to an exercise of an anthrax attack at a Hannah Montana concert, maybe we can actually respond to a real event produced by that epitome of bioterrorists, Mother Nature.

  8. #8 pft
    May 8, 2009

    Your surprise over the speed of the response and quick identification is only valid if it was a surprise, and not planned.

    [removing tin foil hat] As for what the young people went through, it was worsened by the hysteria that was generated. It’s never fun getting the flu even without the hysteria and fear you have some deadly disease, and those who were hospitalized and without insurance, well, the flu they recovered from is far from the worst of it; they still have the bills that charged them 10 times what the insurance companies were charged.

  9. #9 caia
    May 9, 2009

    Destiny: I would say at this point it’s highly unlikely, but not impossible that you might get it. On the one hand, it’s popped up around the country. On the other hand, there have only been 896 confirmed cases in the U.S. as of Friday morning.

    Even there were really 8,960 cases, that would be out of more than 300,000,000 Americans. So currently, the chances are slight. But as the Reveres have pointed out repeatedly, we don’t know yet what the virus will do in the coming weeks and months. The only thing I see as certain is that the odds of any of us getting it will change — they will either increase or decrease, or do one and then the other, in the coming months.

    I’m not a medical professional or public health expert of any kind, so I will refrain from giving advice about what this means you should do.

  10. #10 Anja
    May 9, 2009

    I’d like to know if it would make sense to get a pneumonia vaccine for my sons ages 24 and 28. They are in good health – my thinking being why not proactively try to prevent one of the really dangerous possible complications – bacterial pneumonia. I am also considering the pneumonia vaccine at this point – I am almost 47 and in good health.
    Thank you for any thoughts on this,

  11. #11 revere
    May 9, 2009

    Anja: A good idea for your sons. I recommend it.

  12. #12 Anja
    May 9, 2009

    Thank you for responding so quickly. It just makes sense to get vaccinated as the pneumoniavaccine confers immunity against almost 90% of the bacteria that cause pneumonia as well as conferring immunity against bacterial meningitis. Perhaps this is an issue that ought to be at least considered by the medical community in the public interest of health. I know – my kids call me loony for stocking up on a month’s water and food but my first thought that came to mind at the initial reports of this flu was the memories of the hysteria, short tempers, mob mentality and shocking selfish attitudes I observe whenever a hurricane threatens or actually hits here in South Florida. I can recall my great-grandmother, grandparents and assorted other older relatives talk about the WWI flu as they mostly called it and the havoc it wreaked in Europe. So maybe I’m a little inoculated with vivid memories from the stories told to me when very young. I can only hope this pandemic has run it’s course and won’t return with a vengeance and much increased deadliness later this year.
    Keep up the excellent work!