Flu: Georgia on CDC's mind

A day or two after CDC's Morbidity and Mortality Weekly Reports (MMWR) released a report about risks to pregnant women from pandemic 2009 flu, CDC held a suddenly announced press briefing about the current H1N1 situation (I listened in but a transcript should be up on the site by the time you read this; check this page). The occasion for the briefing was a worrisome increase in hospitalizations and deaths in CDC's Georgia backyard. Despite housing CDC, Georgia has one of the lower flu vaccination rates in the country and now is experiencing an unexpected recrudescence of H1N1 flu, with numbers of hospitalizations not seen in the state since the height of the pandemic last October. The cases were described as "adults," many with pre-existing medical conditions, with a geographic distribution that, on a preliminary view, might be hitting areas less hard hit than the fall wave of cases. Since late February, Georgia was seeing more hospitalizations (in numbers) than any other state in the union and the reason isn't known. What we know so far is that it is the 2009 H1N1 pandemic, laboratory confirmed and said not to be different than before. What that is based on we don't know. It is not either of the previous seasonal flu strains, seasonal H1N1 or seasonal H3N2, nor influenza B, which is circulating at many locations at very low levels.

Is this the harbinger of a third wave that will spread more generally? It is uncharacteristically late in the usual flu season for this to happen, although this particular flu did poke its head above water just about this time of year last year. Maybe there is something about the virus that makes its seasonal pattern different. Perhaps it's because Georgia citizens have less herd immunity than elsewhere, a not too thinly veiled suggestion by CDC's Dr. Anne Schuchat on the conference call. She did use the opportunity to urge reporters to remind their readers that a flu vaccine, which she noted has an excellent safety record, is the best protection against influenza. This is a CDC Talking Point that has the added virtue of being true. At one point she suggested many of the seriously ill had not been vaccinated, although she gave not data. Back to the question, What does this mean, the truthful answer is, "We don't know."

Asked why the estimated 12,000 deaths for pandemic 2009 H1N1 didn't indicate that this was a much milder flu season than the usual estimate of 36,000 flu deaths in other years, Schuchat made the observation that 11,000 of the 12,000 deaths were in people under the age of 65, a much higher number (not just proportion) than usual. This is another way of saying that the difference is in the epidemiology, i.e., the pattern of disease and death in the population. It's also true, however, that the 36,000 death figure is not just an average, but an estimate of excess mortality calculated in a particular way and that it represents the estimated excess averaged over 30 seasons. Calculated that way, in some seasons the excess is essentially zero, even though in those years many people's deaths would not have happened had they not had the flu (if you want to know more, here's one of a number of posts we wrote on the subject).

And it's true, too, that whatever the numbers, some people are at much more risk than others. Like pregnant women with no other risk factors. The MMWR Report has a vignette of one tragic case. It could have been titled, Why you should get your flu shot:

A woman aged 27 years who was at 32 weeks' gestation (Table) went to her primary care physician during May 2009 after 1 day of fever and cough (Figure). She was treated with antibiotics for 3 days without improvement. Five days after symptom onset, she went to the emergency department, reporting persistent fevers, chills, cough, wheezing, and an episode of near-syncope. On admission she was afebrile, with a respiratory rate of 22 breaths per minute, a heart rate of 96 beats per minute, blood pressure of 100/70 mmHg, and oxygen saturation of 99% on room air. A chest radiograph revealed bilateral lobar pneumonia, and she was treated for community-acquired pneumonia. On hospital day 2, she developed fever to 102.9°F (39.4°C), tachycardia (141 beats per minute) and severe respiratory distress. ARDS was diagnosed, and the patient was transferred to the ICU for mechanical ventilation and treated empirically with oseltamivir, 75 mg twice daily. Rapid influenza diagnostic tests performed on nasopharyngeal specimens 1 day before hospital admission and on hospital day 3 were negative for influenza.

On hospital day 4, because her oxygen saturations worsened to approximately 75% despite maximal ventilation settings, an emergency cesarean delivery was performed. During the procedure, the patient was hypotensive and required multiple blood transfusions. Cultures from bronchoalveolar lavage collected the previous day grew Acinetobacter baumanii. On hospital day 11, diagnosis of 2009 H1N1 was confirmed from a nasopharyngeal swab specimen submitted to the DOHMH Public Health Laboratory on hospital day 3. On hospital day 16, because of refractory hypoxemia and severe ARDS, the woman was transferred to another hospital ICU for extracorporeal membrane oxygenation (ECMO), and oseltamivir was increased to 150 mg, twice daily. Her subsequent hospital course was complicated by volume overload, septic shock, and ventilator-associated pneumonia with Klebsiella pneumoniae and A. baumanii. She died on hospital day 38, a total of 42 days after symptom onset (Figure). At birth, her infant weighed 1,500 g and had Apgar scores of 1 at 1 minute and 1 at 5 minutes after birth; the infant stopped breathing, and neonatal resuscitation efforts were unsuccessful. (MMWR, CDC)

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Well yes, we have known a recrudescence in this spring was not an unlikely scenario. Wonder if the age range is now moving up (if, as she stated, mostly "adults") and how well those vaccinated are doing against it.

Despite the CDC's presence, Georgia has terrible public health services, even within the Atlanta area. Absent some detail about the cases, I wouldn't be surprised if the mobility of greater Atlanta's population (lots of relatively young people from elsewhere) and the recent collapse of real estate may have contributed.

I was wondering, can some one explain, or point me in the direction of, why pregnancy is a risk factor for flu? That story is tragic, but I still don't understand why this vunerability exists. Thanks.

Robin: Presumably it's because pregnant women have both altered immune status (they are carrying a foreign body) and altered physiology. That's the big picture. The details need to be filled in and I don't think we know them.


One piece of the puzzle for why pregnant women are more likely to get severe disease from this flu appears to be that they are more likely to have lower IgG2 levels. For some reason, that seems to be important with this flu. The data showing this is from Australia and is from a fairly small number of people, and the finding needs to be reproduced elsewhere, but I think the finding gives us a toe in the door towards figuring out exactly what is going on. If IgG2 (and/or other antibody deficiencies) do turn out to be very significant, though, that will just beg the question, What exactly is IgG2 doing with this flu? We don't know the answer to that. (One idea: IgG2 is important for dealing with S. pneumoniae, which can cause a secondary bacterial infection; is IgG2 protecting from secondary infections, and is this flu just much worse at making us susceptible to them? One counter-argument to that idea, though, is that it would seem unlikely that all or nearly all of the severe, IgG deficient patients were severe due to secondary infections.) Look up "IgG2 deficiency flu" in google and you'll find a bunch of news reports describing the finding. The research paper itself isn't free to the general public.

By biologist (not verified) on 30 Mar 2010 #permalink

Biologist, thanks for your reader posting. There are so many unknown aspects of viral flu infection requiring investigation. The research you are referring to is available via CID journal subscription or an online credit card payment of US $15 per article contract.

Like you, I really want to know more about this... Can IgG2 deficiency explain why some healthy people fail to respond to antivirals and end up on mechanical respirators, for example!?! Or is that disease phenomenon an aspect of viral mutations such as Tamiflu resistance and/or hemagglutinin (HA) receptor binding domain mutations written about by A Kilander, R Rykkvin, S G Dudman, et. al in "Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009-2010."!?!

Clinical Infectious Diseases (Vol. 50 , pp. 672-678, 1 March 2010) -- "Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency" By C. L. Gordon, P. D. R. Johnson, M. Permezel, et. al. http://www.journals.uchicago.edu/doi/abs/10.1086/650462

Abstract Excerpt: "Severe H1N1 infection is associated with IgG2 deficiency, which appears to persist in a majority of patients. Pregnancyârelated reductions in IgG2 level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG2 deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications..."

One of the authors of this paper, Prof M. Lindsay Grayson, Infectious Diseases Dept, Austin Hospital, Austin Health, Victoria, Australia, said this regarding the relationship between low IgG2 levels and viral susceptibility and disease severity, ''For the first time, we may be able to explain why pregnant women are more likely to get swine flu, why some healthy people get severe swine flu and others don't." (The Age, February 04, 2010)

Nick Miller, the journalist of this Age article, 'Eureka moment' may unlock swine flu mystery" wrote about the future work of Professor Grayson's research team, "The team's next step is to determine if an IgG2 injection is a genuine ''cure'' for swine flu. Several other Melbourne hospitals have been recruited into the trial, and results will be published later in the year. They will also examine whether there is a particular relationship between swine flu and the IgG2 protein - or whether it has wider implications for treating other influenza types."

By Jonathon Singleton (not verified) on 30 Mar 2010 #permalink

what revere doesn't mention (why ?) :
ILI is not up in Georgia.
People presenting at sentinal providers with
flu-like illness.
Can there be a "wave" without ILI going up ?
Has it ever happened ?