PEP, PrEP, or even PeEP?

I finally got around to reading the paper in the New England Journal on the use of daily antiretroviral therapy for the prevention of HIV infection (full text here). In hospital epidemiology we're very familiar with post-exposure prophylaxis (PEP) for healthcare workers who sustain percutaneous exposures or blood/body fluid exposures to mucous membranes. This paper evaluated pre-exposure prophylaxis (PrEP) for men who have sex with men by having the study subjects take a daily dose of truvada. New HIV infections were compared in the treatment group to men who were assigned to take a placebo daily. There were roughly 1200 men in each study arm. On average the men were in their late 20s, had more than 1 sex partner weekly, about 60% reported unprotected anal intercourse, and they were followed for roughly 1 year. There were 36 new HIV infections in the Truvada group (2.9%) and 64 new infections in the placebo group (5.3%). This represents a 44% relative risk reduction. Sounds pretty good, but that translates to only a 2.4% absolute risk reduction (the infection rate in the treated group subtracted from the infection rate in the placebo group). When the subset of men with detectable drugs levels (i.e., those who were compliant with Truvada) were compared to those without detectable drug levels, the relative risk reduction was 92%. "That's huge," exclaimed Dr. Anthony Fauci, the head of the National Institutes of Allergy and Infectious Diseases, in the New York Times.

So here we have an intervention that appears to be efficacious but not effective (that is, it works when you take the drug, but in the real world many people just won't take it--we've talked about this before). By my calculations, compliance appeared to be about 38% in the study. However, I think we can be sure that compliance would have been even less in the real world if the study subjects had to pay for the Truvada at the retail price of $13,000 yearly. We're also not told whether those who took the drug faithfully may have also been highly compliant with condom use, which may make the drug appear to be more effective than it actually is. So, in the end, I don't think that the impact of this study will be huge. In fact, I doubt it will have much impact at all. The real issue, it seems to me, is helping people to reduce risk the old fashioned way (fewer sexual partners and consistent use of condoms), until the day finally arrives when we have an effective vaccine for HIV.

Switching gears, as a hospital epidemiologist, I wondered if there is a role for PrEP in the hospital. Let's consider the case of a an untreated HIV infected patient with a high viral load who needs cardiac or orthopedic surgery soon. Should the operative team be given PrEP or perhaps peri-exposure prophylaxis (PeEP), with dosing the day before, the day of the procedure, and the day after? If I were the surgeon, I would be interested in that.

Why we can't work at work

In my previous post, I mentioned what I was going to read during my quiet time this weekend.  We all have to work like this now, since it has become increasingly difficult for us to get work done at work. Our homes are now our offices. What we need is no-talk Thursdays or something like that. This Jason Fried TED video explains:

link for non-flash devices (iPhone etc)

Thanksgiving Reading List

I just ripped out a few articles to read over the upcoming holiday.  I may have more things to say on these subjects in the future; however, I didn't want you to lack good reading material for the long weekend.

1) Hospital-acquired C. difficile is associated with 3-fold risk of death which diminishes as baseline severity increases. (source: Oake N et al, Archive Intern Med. Nov 8, 2010)

2) The 7th Edition Mandell, Douglas and Bennet's Principles and Practive of Infectious Diseases is bigger and better than ever- Book Review by Preeti Malani. (source: Malani P JAMA Nov 10, 2010) the book is only 4328 pages, so you can have until Dec 31 to read this one. (Note: I did not specify a specific year)

3) Intentional infection with STDs (GC, chlamydia and syphilis) in vulnerable populations. A new unethical study from 1946-48 has been recently uncovered by Susan Reverby. The CDC Director Dr. Thomas Frieden and NIH Director Dr. Francis Collins report on her findings in JAMA, Nov 20, 2010). A copy of Dr. Reverby's forthcoming article is available on her Wellsley College webpage.  I read her amazing history of nursing in America, Ordered to Care: The Dilemma of American Nursing (New York: Cambridge University Press, 1987) when I was an undergrad at the University of Michigan.  I highly recommend this book as it explores the dilemma of a nursing profession that must care for people in a society that 'doesn't value caring.'  There are general lessons there for public health in the US since it remains unclear how the country values public health resources.

4) Potential opportunities to steamline IRB approval. Millum and Menikoff in Nov 16, 2010 Annals of Internal Medicine offer several under-utilized options for improving the efficiency of ethical review.

5) Significant direct (recipient) and indirect (herd immunity) protection secondary to LAIV vaccination of 4-11 year olds was evident even when there was a mismatch between the vaccine and epidemic strains.  (Source: Glezen WP et al JID Dec 1 2010 and Editorial by EB Lewin - both are free full text)

Happy Thanksgiving, safe travels and may your God go with you.

E. coli 0157:H7 and hypertension, renal and cardiac disease

Text-size doesn't correlate with population size

Another not exactly HAI prevention post, but as Mike just told us, we don't have much evidence in ID, so anything can be exciting, no?  This report out of BMJ tells of a May 2000 E. coli O157:H7 and Campylobacter outbreak that arose in the Walkerton, Ontario municipal water system after heavy rainfall drove livestock faecal matter into water supply. The outbreak resulted in 2300 cases of GI illness, at least 27 cases of haemolytic-uraemic syndrome, and seven deaths.  Amazingly, the government created a Walkerton Health Study to monitor individuals for the possible long-term consequences associated with the infection.  After 4-years, there was a 28% increase in hypertension associated with the exposure.  The BMJ report tells of the impact out to 2008.

Overall, people who had acute gastroenteritis were 1.3 times more likely to develop hypertension, 3.4 times more likely to develop both structural and functional renal impairment, and 2.1 times more likely to report a physician-diagnosed cardiac disease. The authors do an excellent job discussing the potential limitations of the study including recall bias and confounding. They also explain away the impact of Campylobacter coinfection by saying that the infectious dose of 0157:H7 is 10 bacteria, while it is 500 for Campylobacter, so people were unlikely to have avoided 0157:H7 exposure.

This is a very unique study.  Most studies that have assessed infections as risk factors for chronic diseases were case-control studies that identified patients with specific outcomes and looked back for certain risk factors.  You would imagine that recall bias would play a much larger role in remembering certain distant and unremarkable exposures like GI illness in a case-control study. With this cohort study, exposures and outcomes were well characterized and measured.  I wonder what this study's impact will be in ascertaining the causes of hypertension, renal and cardiac disease in the general population?  Their recommendation that patients who are post-exposure from E coli 0157:H7 should be carefully monitored for hypertension and renal disease seems prudent.


Clark WF et al. BMJ Nov. 17, 2010 (open access)

Occupational transmission of meningococcal disease

This week's MMWR has a report on transmission of meningococcal disease from an infected patient to a police officer who responded to the patient's home and a respiratory therapist who cared for the patient in the Emergency Department. Neither of the secondary cases were offered postexposure prophylaxis. CDC recommends prophylaxis for HCWs with direct exposure to the patient's oral secretions (e.g., performacne of endotracheal intubation). In this case the police officer was not evaluated for prophylaxis because of a delay in contact tracing. However, the MMWR report admits that if the CDC recommendations were followed the police officer may have not been offerred prophylaxis. What's surprising is that CDC didn't revise the recommendation. Given the severity of meningococcal disease I think we need to be more flexible than CDC's recommendation. We offer prophylaxis to any unprotected HCW within 3 feet of the patient.

Listeria: Safety-based date labels, cheese and the FDA

As I've written before, I spent several years on the USDA's National Advisory Committee on Microbiological Criteria For Foods (NACMCF).  We spent several years writing scientific briefs on a variety of topics. During 2002-2004, I worked on a subcommittee looking at "Criteria for Refrigerated Shelf-life Based on Safety."  For someone who didn't spend 100% of my time on food-safety issues, I was initially surprised that the dates on foods were not at all related to safety.  Dates on that yogurt you are about to eat are based on palatability, FYI.

The document we produced and then published in 2005 in the Journal of Food Protection was predominately a Listeria control document even though we considered four psychrotrophic pathogens: L. monocytogenes, nonproteolytic C. botulinum, Y. enterocolitica, and B. cereus. The hope was that a safety-date on refrigerated foods, when combined with education about proper storage and handling of these foods, could reduce the health risk in the very young, very old, immunocompromised and pregnant women, who are at increased risk for miscarriages and stillbirths after Listeria infection.  Of course, any safety-based date label would have little impact if the food is highly contaminated during production. 

One thing I noticed serving on NACMCF was the hard work and honest efforts of the others on the committee. Even though some members worked for industry, some worked for the government and some had worked for both, they all tried hard to produce a good document. There was no evidence of some conspiracy to harm the public.  Outbreaks of foodborne illness are bad for everybody. Producers looked to government to set standards and then helped determine the best ways to meet those standards.

With that background, I was shocked to read recently in the NY Times about an artisanal cheese producer from Washington state who was defying a recall order from the FDA. Her cheeses were found to be contaminated with Listeria.  She and others are claiming that the FDA is going after the little producers - a David vs Goliath story.  Senators and others are rallying to modify the food safety bill in the Senate that I blogged about last week, in an effort to exempt these types of small producers.  They suggest that the real risk is in the big producers since they make the most foods, but I think they are making a very poor decision.  If you had the choice to buy cheese that was subject to regulation and unlikely to be contaminated or some cheese that wasn't tested for safety, which would you buy?  I agree with William Marler, a Seattle food safety lawyer, who said he just doesn't "know how they make the leap from the government trying to do the right thing for public health to ‘they’re food Nazis in the pocket of big agribusiness.’ ”

What if we had that situation in HAI prevention? What if big hospitals had to publicly report CLABSIs and follow Joint Commission standards and small hospitals got a free pass? Wouldn't that be the quickest path for bankruptcy for small hospitals? It would be hard to imagine small hospitals claiming that they only take care of a few patients so a few excess deaths don't matter, but that is exactly what the small food producers are claiming in the NY Times article.

Falsum in uno, falsum in omnibus
It seems that we currently live under a logical fallacy, where the government is evil and people claim that the government is bad at everything. Sure, government has its faults and could improve its efficiency, but when we get to a point where we are saying that small food producers shouldn't have to be regulated and thus produce safe food, we have gone too far. I would love to support local producers and serve fresh produce in my home, but I won't do it if they get a free pass on safety.  I hope they can work out a compromise where the FDA and small producers can work together.

NY Times article: Small Cheesemaker Defies F.D.A. Over Recall - November 19, 2010

The specialty of Infectious Diseases: More art than science?

The November 15 issue of Clinical Infectious Diseases has an interesting paper that evaluates the quality of the IDSA clinical practice guielines. The authors reviewed 44 current guidelines available at the time of the study, which consisted of 4,182 component recommendations. Over half (55%) of the recommendations were based on level III evidence (expert opinion or descriptive studies), and only 15% were based on level I evidence (at least 1 randomized controlled trial). Of note, when revised guidelines were compared to their corresponding original versions, there was a 12% relative increase in recommendations backed by level I evidence, though that was only a 1.6% absolute increase. Just goes to show you that infectious diseases is still in its infancy as a specialty and the unknown remains vast. This must be why I often feel like I am flying by the seat of my pants.