CDC warns of deaths from H1N1 flu + bacterial infections

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

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.

MRSA involvement in H1N1 flu: UPDATE

The CDC's MMWR report on their analysis of bacterial co-infections in H1N1 flu deaths has been placed online here.

And there are two excellent analyses of it by the marvelous blogs Effect Measure and Mike the Mad Biologist.

More evidence of MRSA involvement in H1N1 flu

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.

Catching up on some reading: health care reform, food bugs, vaccine, MRSA+flu

Folks, while I was caught in travel hell, some excellent stories and blogposts were released. Here's a quick round-up of recommendations for a rainy weekend:

• At Roll Call (covers Congress like a blanket), Ramanan Laxminarayan, PhD MPH, of the rational-use-of-antibiotics project Extending the Cure and infection-control physician Ed Septimus, MD make a strong argument for including control of hospital infections in health care reform. Hard to argue against when you realize that HAIs cost the United States more than $33 billion each year.
• At Meat Wagon, a blog of the online magazine Grist, the always-excellent Tom Philpott digs into the ongoing outbreak of antibiotic-resistant Salmonella in hamburger meat. Key quote: "Outbreaks of [antibiotic-resistant foodborne illnesses] are really ecological markers — feedback that our way of producing meat is deeply unsustainable and really quite dangerous."
• The Associated Press reports that the long-in-development staph vaccine made by Nabi Pharmaceuticals may have received a second life: It's been purchased by international pharma giant GlaxoSmithKline in a $46-million deal.
• And finally and sadly, the Sacramento Bee reports that a California nurse who died of H1N1/swine flu also had MRSA pneumonia. Karen Ann Hays, 51, died despite being extremely healthy: she was a triathlete, skydiver and marathon runner. No one yet has been able to say whether she caught the flu — or MRSA — at work (though her partner believes that to be true), but her death has fueled disquiet among members of the California Nurses Association, who are protesting a lack of protective equipment for nurses.

For those of us concerned about MRSA pneumonia — and we have been talking here since the start of the H1N1 pandemic about the danger of MRSA co-infection — that last item about Hays' very sad death should underline a vital point. Public health authorities have been stressing that H1N1 is most deadly when the infected person has a pre-existing condition: pregnancy, heart disease, obesity, diabetes, cystic fibrosis. It is possible that MRSA infection is also a pre-existing condition that will put anyone infected with flu at risk of deadly complications.

If you have had MRSA, even a minor skin infection — and especially if you have experienced recurrent infections — you should probably discuss with your personal physician whether you should take the H1N1 vaccine when or if it becomes available. It could be the step that prevents a minor case of flu from tipping over into something much more serious.

MRSA in space

No, really — but not quite the way you think. The weekly geekfest that is Aviation Week and Space Technology reports that the payload of the space shuttle Atlantis includes a MRSA experiment. The goal is to investigate whether bacteria held in the microgravity of space become more virulent — this was done earlier with salmonella — and then to determine whether any new virulence markers suggest targets for a potential staph vaccine.

A vaccine of course, is the Holy Grail of MRSA research — and it has remained frustratingly out of reach. For a great review of past research and future challenges, see this review article from March.

Prevention v. treatment (1st Global Health Blog Carnival!)

Constant readers, about a dozen of us who are interested in global health are co-blogging today in a Global Health Blog Carnival. If you are on Twitter, search the hashtag #ghnews. If you're not, we will try to get them all linked somewhere. This was organized (to the degree that blogger organize, which as you can guess is like herding small felines) by reporter and blogger Christine Gorman, formerly of TIME Magazine.

Our theme for today is prevention v. treatment. Fortuitously, the New England Journal of Medicine today is publishing an editorial (for which they have posted the free full text) that reminds us of the full burden and cost of MRSA. Drs. Cesar A. Arias and Barbara E. Murray say:

Faced with this gloomy picture, 21st-century clinicians must turn to compounds developed decades ago and previously abandoned because of toxicity — or test everything they can think of and use whatever looks active. ...
It is more difficult than ever to eradicate infections caused by antibiotic-resistant "superbugs," and the problem is exacerbated by a dry pipeline for new antimicrobials with bactericidal activity against gram-negative bacteria and enterococci. A concerted effort on the part of academic researchers and their institutions, industry, and government is crucial if humans are to maintain the upper hand in this battle against bacteria — a fight with global consequences. (NEJM 360(5):439-443)

As we've discussed time and time again, MRSA is increasingly common worldwide and increasingly costly to treat. Moreover, what has been presented by some as the first line of prevention for hospital-acquired MRSA — active surveillance and testing programs, also called "search and destroy" — is deeply controversial.

So what's the next step? Well, in the past, when medicine has wanted to nullify an infectious disease threat, it did not rely only on surveillance or asepsis; it developed a vaccine. And there have been a few efforts to develop a MRSA vaccine, which are recapped in a new article in Infectious Disease Clinics of North America (yes, that's a journal):

The most extensively tested vaccine against S aureus, which is a capsular polysaccharide-based vaccine known as StaphVAX, showed promise in an initial phase 3 trial, but was found to be ineffective in a confirmatory trial, leading to its development being halted. Likewise, a human IgG preparation known as INH-A21 (Veronate) with elevated levels of antibodies to the staphylococcal surface adhesins ClfA and SdrG made it into phase 3 testing, where it failed to show a clinical benefit. ... Given the multiple and sometimes redundant virulence factors of S aureus that enable it to be such a crafty pathogen, if a vaccine is to prove effective, it will have to be multicomponent, incorporating several surface proteins, toxoids, and surface polysaccharides. (23 (1): 153-171)

Several longtime MRSA researchers, including Dr. Robert S. Daum of the University of Chicago, who wrote the first paper calling attention to community-associated MRSA in 1998, have called for a vaccine to be made a research priority.

Any thoughts, constant readers? In the public mind, right now, vaccines are at a low point: People are turning away from them, manufacturing problems have led to shortages, and pharma no longer finds vaccine manufacturing a lucrative business sector. If a MRSA vaccine were developed, would you take it yourself before surgery, or give one to your children?

A staph vaccine: How much would it help?

One more post on research from the meeting of the Society for Healthcare Epidemiology of America: Many MRSA researchers believe that the only way to truly control the pathogen — especially out in the community — will be through a vaccine.

Lay aside for the moment how problematic introducing a new vaccine can be these days, since the cost issues, along with shifts in the public's willingness to accept new vaccines, are ferocious hurdles. And lay aside also the difficulties that pharma companies have already faced in attempting to develop a staph vaccine.

But if such a vaccine were achieved, how many people could it help? Researchers from the Centers for Disease Control and Prevention attempted to answer that question in research presented at SHEA.

Background assumptions, part 1: The number of invasive MRSA infections now tops an estimated 105,000/year (a recalculation of the 94,000/year estimate from last October); more than 40% of invasive infections occur in those over 65; more than 50% are associated with a recent hospitalization; and 15% of MRSA infections recur at least once. And background assumptions part 2: A vaccine would have an efficacy rate of 40-75%, and an acceptance rate similar to flu-vaccine uptake: 20-50% among those 15-44, 35-70% among those 45-64, and 50-70% among those 65 and older.

Given those assumptions, Cynthia Lucero, MD and colleague predicted:

• If given only to those 65 and older, a vaccine would prevent from 12,720 to 32,270 invasive MRSA infections;
• If given to those over 65 and also those 15 and older who have already had an invasive infection, a vaccine would prevent 14,130 to 38,310 invasive MRSA infections;
• And if given to those over 65 and also anyone over 15 who is being discharged from a hospital, a vaccine would prevent from 17,240 to 49,940 invasive MRSA infections.

The best bang for the buck, the agency said, would be the middle strategy: It would prevent from 660 to 1,170 cases for every million doses of vaccine used. And since the vaccine would also cover methicillin-sensitive staph, it would likely prevent an equal number of serious MSSA cases as well.

The CDC is not by law allowed to lobby — or even, for the most part, allowed to offer a professional opinion unless Congress has asked it to do so. So these numbers are purely a thought experiment. But they're also a strong argument for the broad usefulness of a staph vaccine if one could be achieved.