Maryn McKenna

Journalist and Author

New CDC flu numbers: This may not go well

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(Constant readers: Apologies for the slow blogging. Casa Superbug’s little medical crisis from a week ago has recurred, and things are a bit distracting. Back to normal soon, I hope.)

In public health, one of the numbers you hear most often — and especially so the past few years — is 36,000. That’s the number of deaths that the CDC estimates occur in an average year from influenza.

Or rather, estimated. Because today, in its weekly bulletin MMWR and also in a teleconference for the press, the CDC announced that it is discarding that widely used number, in favor of newer numbers from newer studies that take into account the wide variation in illness and death from one flu season to the next.

The new estimate is: 23,607. Or, a range that goes from 3,349 to 48,614. Or, in the language recommended by a CDC scientist and a communications specialist in the press call, “tens of thousands of people [who] may die each year in an average flu season.”

If that sounds difficult to communicate in a concise manner, well, the reporters on the CDC call today clearly thought so too. And while reporting study results forthrightly is transparent, and more precise numbers are almost always better, I can’t help but wonder whether this attempt at precision and transparency will not be received well. After all, we are only a few months (or a few weeks, depending whose end date you accept) away from the dribbling conclusion of a worldwide pandemic that was taken so not-seriously by the public that, in the US, 71 million doses of H1N1 vaccine went unused — and in Europe, some public representatives alleged that the entire emergency was a concoction by pharmaceutical companies.

Given that history, putting out a public message that flu kills fewer people than we thought — but is, still, a serious disease that should be planned for and vaccinated against — sounds like a hard sell.

Here’s how today’s new numbers came about:

The mortality rate from flu has always been difficult to assess: People die of influenza directly, but they also die of underlying conditions — heart disease or chronic obstructive pulmonary disease, among others — that might not kill the person if influenza were not putting an extra strain on the system. In either case, but especially in the latter, the death may not be attributed to flu, particularly if the victim has not been tested for the presence of the flu virus.

So, to arrive at an estimate, the CDC has used a statistical model. As explained in the briefing today by Dr. David Shay of the CDC’s Influenza Division:

We have two categories that we look at… One is death certificates that have an underlying diagnosis of pneumonia or influenza. 99% of those deaths are actually coded as pneumonia. So, that’s to make an estimate of deaths in a particular season from pneumonia that are associated with flu. And typically, that’s about 8.5% of deaths over the time period that we looked at…  The broader category of respiratory and circulatory deaths we think encompasses the full picture of influenza-associated deaths, including things such as people who might die because of worsening chronic obstructive pulmonary disease or worsening congestive heart failure that results in death after an infection. And we estimate that about 2% of that broader category in any typical year is associated with influenza.

One other factor affects flu mortality: Which flu strain type is dominant in the season being measures. Flu is generally taken to cause the most severe disease, and the greatest number of deaths, in the elderly; but some strains cause more severe disease than others, and some (H1N1 “swine” flu, for instance) attack the young, who are healthier and less likely to die, more than they do the old. Again, Shay:

[I]t’s important to keep in context, which we don’t really describe in this article because of space, that there’s at least four factors that affect sort of flu mortality in any particular year, and those four would be the specific strain or influenza strains that are in circulation, sort of the length of the season or how long influenza is circulating in the united states, how many people get sick, because of course, the more people get sick, there is more likely to be more serious outcomes, and finally, who gets sick.

In the study released today, the CDC did two things: It broadened the range of flu seasons from which it took data to feed into the statistical model, and it took a second look at the years on which the previous model, the one that produced the 36,000-death estimate, was based.

When the range of years was broadened to 31 flu seasons (1976-77 to 2006-07), here’s what shook out:

  • For deaths from influenza and pneumonia: from 961 in 1986-87 to 14,715 in 2003-04, an average of 6,309
  • For deaths from respiratory and circulatory complications: from 3,349 in 1986-87 to 48,614 in 2003-04, an average of 23,607.

(When asked which number should be used for shorthand, Shay said: “The broader category of respiratory and circulatory deaths we think encompasses the full picture of influenza-associated deaths.”)

When the 36,000-death estimate was re-examined, Shay said:

The 36,000 number that’s often used pertains to a very specific time period from 1990 to 1999. And in that decade, where we had prominent circulation of H3N2 viruses, they were prominent in eight of the nine seasons that are contained within the data that were used to make that estimate, and those are, as you know, typically more severe seasons. We had a high mortality for that nine-year period.

According to the MMWR analysis, mortality rates in the H3N2 years were 2.7 times higher than in years when other types were dominant.

So that’s the rationale behind today’s dialed-down numbers. Here’s the potential problem with it: It just took me about 1,000 words to (somewhat talkily) explain. It requires patience and detail to impart, which in the current media environment are in very short supply. As one of the participants on the call said today:

I’m really scratching my head here wondering what I’m going to use, because we really don’t have a lot of time … to present a lot of numbers, and I think in a sense to say that the range is 3,000 or 3,300 to 49,000 raises a lot of questions, and I think we don’t have time to answer those questions in every report. And I also wonder if it’s not a bit misleading to use 3,300 as the bottom number since it’s been 20 years since it was that low, and even in the last 20 years, the mortality has never been much below 12,000.

You see the problem.

To repeat: This is an effort at transparency and accountability; those are worth applauding. But it’s also a nuanced and difficult health-communication message, launched into a zeitgeist already tuned toward conspiracy theories and a media marketplace with little time or expertise to counter them.

Pessimistically, I wonder how long it will be before this message gets transformed into something like, “See? I told you so. Flu isn’t that big a deal after all.” I hope the CDC is prepared when it does.

(Here’s today’s MMWR article, the transcript of the press briefing, and a Q&A on the new calculation. The cite is: Morbidity and Mortality Weekly Report, “Estimates of Deaths Associated with Seasonal Influenza — United States, 1976–2007.” August 27, 2010. 59(33);1057-1062)

A great blog leaves the ‘sphere

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Constant readers: Well, the bug finally got me, or one of its close cousins did. I’ve been on the road almost nonstop, and after a book event at University of Wisconsin last week, was felled by a violent bout of foodborne illness that was almost certainly staph — not MRSA, but the related strain of staph that causes very rapid food poisoning. (And, umm, thorough. Ick.) So I’ve been out of commission both physically and mentally. And on a plane again tonight. Back soon in both ways, promise.

But there’s important sad news today that I want you all to know about. Revere, the peerless author of the marvelous public health blog Effect Measure, is bowing out of the blogosphere. For more than 5 years now, Revere (a collective voice of an unknown number of public health experts —for simplicity, let’s say “he”) has been a reliable, thoughtful, expert, humorous and deeply knowledgeable guide to the intricacies of public health and public health politics. He has taken a particular interest in the possibility of pandemic flu and has been the unofficial leader of the loosely knit but fiercely loyal group of bloggers and crowdsourcers who call themselves Flublogia. And though few would admit it, Revere’s posts have been consistent agenda-setters in newsrooms all across the planet; insiders knew that, if Revere said something, it would start showing up in newspapers and on wires about 12 hours later.

If you are a Revere reader and missed this news, get over there and leave a note in the quickly lengthening comment string. If you never made the blog’s acquaintance, now would not be too soon.

Once again, flu and bacterial co-infection

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With the H1N1 pandemic trending down, it may seem that the question of how much bacterial co-infection affects the outcome of flu is less important than it was. But though the pandemic is subsiding — for ever, for this season, or just until a third wave, who can say — researchers are just now getting enough good data to be able to make solid observations about what happened during the past 10 months.

Case in point: Writing in the journal Public Library of Science (PLoS) ONE, a team of researchers from Australia has pinpointed the incidence of MRSA co-infection during flu in two hospitals in Perth last summer, which was the Australian winter and the height of their flu season. Of 252 patients admitted for H1N1 infection, 3 were identified during treatment as having MRSA pneumonia. They survived, but two other patients who died were found to have MRSA pneumonia during post-mortem exams.

There were 3 female and 2 males, aged between 34 and 79 years… Two patients lived at the same long-term care facility, whilst the other patients lived independently in the community. Four of the 5 patients had conditions that may have increased their risk of pneumonia, including quadriplegia (two patients) asthma (one patient), cirrhosis (one patient) and diabetes mellitus (one patient). Two of the 5 cases (patients 3 and 4) had known MRSA infection/colonization prior to the onset of their illness (with the same cMRSA clone that subsequently caused their co-infection).

 There are some interesting points embedded here. First, incidence: In the Australian patients, MRSA pneumonia was much more common. The Perth researchers found 5 MRSA cases out of 252 flu patients. When the CDC analyzed the occurrence of MRSA pneumonia in flu last summer, it found only 1 case out of 272. Second, treatment: None of the 5 patients got antibiotics that would have affected MRSA — even though two of them were already known to be MRSA carriers. The possibility of MRSA pneumonia subsequent to flu seems not to have occurred to the health professionals taking care of them.

And third, the pathogen: The 5 Australian cases were caused by 3 community MRSA strains that are common in Australia — but only one of the 3 made PVL, the toxin that has so frequently been associated with MRSA pneumonia. That is interesting, and troubling at the same time. At this point, the association of PVL and necrotizing pneumonia has become practically taken for granted; and yet here are two strains that did not make PVL and yet caused severe and fatal pneumonia. It may be an indication that the inflammation that flu causes in the lung can open the door to more severe damage even when PVL is not present; it’s certainly an indication that the absence of PVL does not signal a mild or not-dangerous strain.

The cite is: Murray RJ, Robinson JO, White JN, et al. 2010 Community-Acquired Pneumonia Due to Pandemic A(H1N1)2009 Influenzavirus and Methicillin Resistant Staphylococcus aureus Co-Infection. PLoS ONE 5(1): e8705. doi:10.1371/journal.pone.0008705.
Simultaneously, a new paper in the American Journal of Pathology seeks to clarify how often and in what circumstances bacterial superinfection becomes a risk during flu. Using a range of mice — both healthy ones, and “knockout” mice bred to be without particular immune-system components — researchers from San Diego confirmed that infections with flu and with Haemophilus influenzae can be lethal when the flu infection precedes the bacterial one. That was true even for infections that, if experienced separately, would not have been lethal; it was the synergy of the two infections, flu first followed by the bacterial infection, that caused the high mortality rate. The results may not be directly applicable to human medicine (Do you all know the old flu-research saying, “Mice lie and ferrets mislead?”), but they are an important indicator both of the seriousness of bacterial infection after flu, and also of the potential vulnerability of even healthy beings to that one-two punch.
The cite is: Lee LN, Dias P, Han D, et al.: A mouse model of lethal synergism between influenza virus and Haemophilus influenzae. Am J Pathol 176: 800-811.

NEJM: Antibiotics for pneumonia in H1N1

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The New England Journal of Medicine has been running an open-access blog on H1N1 flu, and they’ve put up a post on when to give antibiotics to prevent secondary bacterial pneumonia, including MRSA pneumonia, in flu patients.

There’s a table of key clinical points to consider, and these important points are made:

For the child or adult admitted to a hospital intensive care unit in respiratory distress, we believe that empirical initial therapy with broad-spectrum antibiotics to include coverage for MRSA, as well as Streptococcus pneumoniae and other common respiratory pathogens, is appropriate.
For the previously healthy child or adult with influenza who requires admission to a community hospital and has features that suggest a secondary pneumonia (Table 1), we would recommend empirical treatment with a drug such as intravenous second- or third-generation cephalosporin, after an effort has been made to prove the association with influenza and to get adequate lower respiratory tract specimens for Gram’s stain and bacterial culture.
If the Gram’s stain suggests the presence of staphylococci or if there is a rapidly progressive or necrotizing pneumonia, an additional antimicrobial agent to cover MRSA is appropriate. …
We do not believe that initial coverage for MRSA is indicated in all patients who are thought to have secondary bacterial pneumonia.

So, to recap:

  • Development of apparent pneumonia in the presence of flu should be met with antibiotics that will treat drug-sensitive bacteria, along with a test to show which bacteria are causing the illness.
  • If staph is present (or the pneumonia appears very serious), then the antibiotics should be upped to one that can control MRSA.
  • But if the pneumonia is serious enough to send a patient straight to the ICU, then drugs that can quell MRSA should be started right away.

For anyone concerned about pneumonia in the aftermath of H1N1, this is worth bookmarking.

CDC warns of deaths from H1N1 flu + bacterial infections

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Over at CIDRAP, my colleague Lisa Schnirring writes tonight about the CDC’s concern over increasing numbers of deaths from bacterial pneumonia in people who have come down with H1N1 flu.

We’ve talked about this before here. Our concern of course has been MRSA, and there is good evidence that there have been fatal MRSA infections in flu victims. But the primary culprit now is not MRSA but pneumococcus (S. pneumoniae):

Anne Schuchat, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, told reporters at a press briefing that the CDC is seeing an increasing number of invasive pneumococcal disease cases around the country, but the numbers were particularly high in Denver at a time when pandemic H1N1 activity was peaking in the area.
Over the past 5 years the Denver area averaged 20 pneumococcal disease cases in October, but this year the area recorded 58, and most were in adults between the ages of 20 and 59, many of whom had underlying medical conditions.
Health officials expect to see more pneumococcal disease when seasonal flu circulates, but the infections typically strike people who are older than 65. In past pandemics secondary bacterial pneumonia infections, particularly those involving Streptococcus pneumoniae, frequently contributed to illnesses and deaths.

This is particularly troubling and sad because we have good vaccines for pneumococcus, one for adults and a different one for children. Only, people are not taking them: Uptake is only about 25% in high-risk groups and much lower in the general population, despite urgings from CDC and other health advisory boards.

Perhaps it’s not surprising that people have not heeded advice to get the pneumococcus vaccine as a protection against flu’s worst effects, given that uptake of the flu vaccine itself has been so low. But if you or someone you love is in a high-risk group, it would be a really good idea to rethink that.

It’s World Pneumonia Day

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Readers, we talk all the time here about the unexpected and deadly attack of MRSA pneumonia, both on its own and as a sequela of influenza infection. But we should acknowledge that MRSA pneumonia is part of an epidemic of pneumonia, an under-appreciated disease of severe lung inflammation that takes the lives of 2 million children each year around the world.

Today, Nov. 2, has been declared World Pneumonia Day by an enormous coalition of global health organizations that includes UNICEF and Save the Children. (Mis amigos Latinos sabrán que está hoy también Dia de los Muertos. Fitting, no?) From their press release: “Pneumonia takes the lives of more children under 5 than measles, malaria and AIDS combined. The disease takes the life of one child every 15 seconds, and accounts for 20% of all deaths of children under 5 worldwide.“

World Pneumonia Day is being marked by events around the globe (here’s a clickable map) and by the release of a World Health Organization report, the Global Action Plan for Prevention and Control of Pneumonia. The plan has three main goals, aimed at the recourse-poor countries where most pneumonia deaths occur:

  • promote breastfeeding to ensure children’s nutrition and good immune status
  • protect immunity by guaranteeing the distribution in the developing world of the pneumonia vaccines we take for granted in the industrialized world, against Haemophilus influenzae and Strep pneumoniae (pneumococcus)
  • treat children when they need it by making sure that there is adequate, local primary care and — important for our purposes especially — also making sure that antibiotics are used appropriately, but not overused.

The international organization GAVI (formerly known as the Global Alliance for Vaccines and Immunization, now going just by its acronym) has announced plans to immunize 130 million children worldwide against pneumonia and other diseases by 2015.

I want to underline that pneumonia is of interest to us for several reasons: not just because we are concerned for MRSA pneumonia, but also because we are in the midst of the H1N1 pandemic, and as we have talked about before, bacterial infections appear to be playing a role in a significant percentage of the deaths. There is no MRSA vaccine, but there are Hib and pneumo vaccines, which might have prevented some of those deaths. So increasing the administration of pneumonia vaccines could affect the course of this pandemic right now, as well as the fates of children all over the world who have not contracted this flu but will be in danger of bacterial pneumonia in the future.

More evidence of MRSA involvement in H1N1 flu

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When the H1N1 pandemic started at the end of last April, few of the case-patients seemed to have any secondary bacterial infections. This was unusual: In the 3 20th-c pandemics, the only ones for which there are good records, bacterial pneumonias seem to have accounted for a high percentage of illness and death. But H1N1 was unusual in a number of ways, and so health authorities wrote down the lack of bacterial infections as one more quirk of this novel strain.

Comes now the CDC to say that while that may have been the case in the spring, it is not now. In a conference call conducted Monday for doctors, which I covered for CIDRAP, the agency said that out of 77 deaths for which it had excellent autopsy data (a small subset of the deaths so far), 22, or 29%, had some bacterial co-involvement. Among the 22, the leading bacterium was S. pneumoniae (or Pneumococcus), but S. aureus was the second leading cause, with 7 cases, and 5 of those cases were MRSA.

(There is not yet anything online from that call to link to. A transcript is promised, and the CDC reps conducting the call said the data will be out soon in the MMWR. I’ll update when possible.)

In fact, there is an emerging literature on the role of bacterial infections in illness and deaths in this flu, and an emerging consensus that bacterial infections are playing a bigger and more serious role than was thought at first. At the ICAAC meeting two weeks ago (more on that soon), KK Johnson et al of the Women’s and Children’s Hospital of Buffalo, N.Y., along with researchers from two other institutions, described two severe and ultimately fatal infections with H1N1 complicated by community-strain MRSA. The victims were children, a 9-year-old girl and a 15-year-old boy, who arrived at the emergency room several days after being seen for mild flu symptoms. Both children died of necrotizing pneumonia, one 11 days after being hospitalized and one 3 days. Cite (no link available): K.K. Johnson, H. Faden, P. Joshi, J. F. Fasanello, L. J. Hernan, B.P.Fuhrman, R.C.Welliver, J.K. Sharp and J. J. Schentag, “Two Fatal Pediatric Cases of Pandemic H1N1/09 Influenza Complicated by Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA),” poster G1-1558a.

Finally, there is one recent paper that is online, and it describes MRSA necrotizing pneumonia plus flu in an adult, not a child. It comes from Hong Kong, from a group that were the first to describe SARS pneumonia and thus have a lot of experience in surfing the early wave sof a pandemic. In this new paper in the Journal of Infection, they describe the death from necrotizing pneumonia of a healthy 42-year-old man who was in the hospital only 48 hours. They believe this is the first H1N1+MRSA death to be recorded in the medical literature, and so they use the opportunity to issue a warning to doctors: If a flu patient arrives with what appears to be secondary pneumonia, drugs that can treat MRSA must be prescribed, or the infection will flourish unchecked and death will result. The cite is: Cheng VCC, et al., Fatal co-infection with swine origin influenza virus A/H1N1 and community-acquired methicillin-resistant Staphylococcus aureus, J Infect (2009), doi:10.1016/j.jinf.2009.08.021.

We’ve been talking since the beginning of this pandemic, and before that, about the unique hazards of MRSA + flu coinfection. (Archive of posts here.) It’s important ot understand that the bacterial pneumonias now being recorded are not only due to MRSA; Pneumococcus is playing a role as well. That is important because, unlike MRSA, we have vaccines against Pneumococcus; in the United States, one vaccine is approved for children and a second related one for adults. With no MRSA vaccine anywhere, and no H1N1 vaccine yet, it is worth considering whether to take a pneumococcal vaccine for additional protection as this pandemic unfolds.

A parent’s plea and confusion

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I want to highlight a comment that was left on Labor Day by a woman named Valorie in Arkansas (thank you for reading, Valorie). She said:

I am just now learning about all of this and am very concerned about my 12 year old daughter. We were only 10 days into the school year, and she came down with the flu about a week ago. The rate at which it spread within her school as well as to me (her mother) and 2younger siblings was astonishing! We were all running high fevers within 24 hours of the onset of her first noticeable symptoms. Her junior high (which has approximately 500 students) had between 130 and 140 students absent last week due to flu like symptoms. However, the school is saying this is not H1N1 because it is too early in the season to be the actual flu. (This is absurd in my opinion.) Now, on our oldest daughter’s 5th day into the illness she has developed an MRSA infection from a small boil on her tummy. Within a day, it has swollen from a golf ball size to larger than a baseball in size. She now has 2 places of infection and is running a fever of about 101.7 on her 6th, almost 7th day of illness. Her doctor has placed her on a high powered antibiotic, but she is feeling so ill that I am scared to death for her, especially reading about the complications from having both the flu and MRSA. Do you think the oral antibiotics should take care of it, or do you think we need to have her admitted for IV antibiotics. I’ve just been surprised at how long this illness has lasted and how ill she still seems to be. No one seems to want to talk about the flu, much less any other possible complications in order to keep everyone else from panicking. I just want to get my daughter well and keep her safe. Any advice? Thanks so much for your time.

I wanted to highlight Valorie’s comment for a couple of reasons.

First, because it captures the way in which H1N1 has been ripping through schools in most places where school has returned to session. Schools in the Southeast tend to go back before the Northeast or the West; in Atlanta, where I used to live and where schools reopen long before Labor Day, H1N1 has gone through schools like a hot knife. Second, it shows how little the education about flu being pushed out by the CDC (and by others including my colleagues at CIDRAP) has penetrated: There has been H1N1 flu all over the place this summer, and it’s precisely because it is “too early in the season” that we know it is H1N1 and not the seasonal flu.

But what is most concerning and touching is Valorie’s confusion over which drugs her daughter should be taking, and whether her daughter’s physician is giving enough attention to her illness. Despite years of clinical experience, figuring out which drugs to give for MRSA is not easy. That’s first because many of them are old and now generic-only drugs for which clinical trials (in the context of this disease) were never done; and second because community MRSA’s resistance profile keeps changing as it picks up additional resistance factors.

The CDC dealt with this problem of what drugs to give in a meeting held in 2004 and a report issued in 2006. The report, going drug by drug, is here (caution, it’s 24 pages) and a flow chart summarizing the findings is here. Either is useful to have and to take to doctors if you feel uncomfortable about what is being prescribed or about a patient’s lack of progress.

Valorie, I hope your daughter does better. Keep us posted.

New England Journal editorial: MRSA, H1N1 parallels

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There’s a very interesting piece in a recent New England Journal of Medicine (unfortunately, only the abstract is online) that draws parallels between MRSA and public expectations for pandemic flu. Written by Dr. Kent Sepkowitz, chief of infection control at Memorial Sloan-Kettering Cancer Center in New York and one of the authors of the “Medical Examiner” column at Slate, it’s an exploration of microbial sleight of hand: We were looking in one direction for a problem to develop, and — like Wile E. Coyote staring after the Road Runner but missing the Acme anvil — the problem came around and socked us in the back of the head.

In the case of flu, Sepkowitz writes, we concentrated on the threat of H5N1 avian influenza — the focus, until H1N1/swine flu arrived, of billions of dollars and years of effort in pandemic preparation — but were surprised by the sudden catastrophic emergence of seasonal flu strains resistant to oseltamivir (Tamiflu), one of the few antiviral drugs that can reduce illness and death from flu if taken early enough. In the case of MRSA, medicine focused on containing the spread of hospital MRSA and its rare transformation into VRSA, vancomycin-resistant staph — and mostly discounted, until far too late, the enormous threat of community MRSA strains:

The intensity of our concern and the frequency of the doomsday dispatches were appropriate. We were simply chasing the wrong microbe. It is community-acquired MRSA, not VRSA… that now occupies the center of the public health stage. And just about everything predicted for VRSA has come true for community-acquired MRSA. It’s everywhere; it’s deadly; it has changed the day-to-day management of skin infections and pneumonia in clinics, emergency rooms and intensive care units. It’s a true public health disaster. It’s just a different disaster from the one we were exercised about.

As we wrangle the new threat of H1N1, Sepkowitz warns that it is vital to remember how many millennia of practice microbes have in foiling our expectations:

We should marvel at the raw, restless power of microbes. They have the numbers — trillions and quadrillions and more that replicate wildly, inaccurately and disinterestedly. Nothing microbes do, whether under the duress imposed by antimicrobials or from some less evident pressure, should surprise us. It’s their world; we only live in it.

(Image courtesy Sansceo Design)