John Oliver on Vaccines

Of course, how could we not share another great John Oliver video that covers an ID topic even if it's NSFW. One of the more insightful sections starts around 6:00, where he admits he understands why people are afraid of vaccines, since they are "getting injected by a needle filled with science juice." He also describes antibiotics as "poison used to murder things living in you." Now wouldn't antimicrobial stewardship be easier if patients and physicians thought of antibiotics as poisons and not just magical pills that have few side effects? What if we treated antibiotics like cancer chemotherapies?

Clarification: I'm in favor of mandating influenza vaccination of healthcare workers (for now)

There's been some misunderstanding of the motivation behind my recent posts offering suggestions for improving the implementation of compulsory influenza vaccination policies and acknowledging the limitations of the existing data supporting vaccine mandates. Most of the snark was on twitter where folks challenged my commitment to infection prevention and my interpretation of the data. If I can dish it, I better be able to take it. With that being said, however, I still feel a need to clarify my support for mandatory influenza vaccination policies in both acute care and long-term care settings. But...

1) I will only support such policies for 4-5 years. If those that push these policies can't come up with better clinical trial data during that time, I'm going to call BS. There is simply no excuse for stretching the existing data to drive change now and not validating your claims. Recommend the mandate, but then do the proper studies.

2) CDC and others must fund studies evaluating the benefits of mandatory vaccine policies in acute care settings. There is never going to be a better time than now, when hospitals are implementing mandatory vaccination programs, to fund the necessary cluster-randomized and quasi-experimental studies. Wouldn't it be great if we could find 50 or more hospitals planning to implement an influenza vaccine mandate and then fund a mixed-methods, stepped-wedge cluster randomized trial as those hospitals implemented the policy over the next 3-4 years? I think it can happen and SHEA, IDSA, PIDS and APIC need to demand such a study.

3) As Sara Cosgrove and I wrote in the 2007 SHEA Business-Case Guideline: "Most hospital epidemiologists or infection control specialists want to increase the resources available for infection control activities, but it is important to avoid overestimating benefits or underestimating staff and time costs. Overestimation in an initial analysis may improve the situation in the short term, but it will hinder efforts and necessary trust in the long term after actual resource audits are performed." There's simply no excuse for hand waiving and over promising the benefits of healthcare worker influenza vaccination. It erodes trust and prevents the necessary validation studies from being funded. Please take the long view and don't be afraid to challenge dogma.

Happy holidays!

No spring break for measles

If you’re a regular reader, you may have noticed the blog has been on break for a little while. While I was trying to relax with my morning coffee last week in Sarasota, I kept running across reports of measles outbreaks in New York City, British Columbia, and California. As usual, these outbreaks can be sourced to those who refuse immunizations, perhaps because of long-discredited fears about autism, or (as in the case of the BC outbreak) because they are getting confusing messages from the person who speaks for their deity. 

I have nothing to add to this commentary by a New England pediatrician, which refers to a depressing study out of Dartmouth that suggests our current messaging around vaccine acceptance is ineffective. For a great recent example of good messaging, see this post by Tara Smith, entitled, “Why I vaccinate my kids”.

But if factual, rational messages fail to sway vaccine deniers, what other options are available? How to respond, for example, to those who base their vaccine denial on religion? So I spent the better part of my time away in prayer and meditation, seeking revelations from all the major deities. I’m happy to announce that they all were in favor of immunization. The main point each of them made to me (aside from pointing out that all the others I communicated with were false deities, not worthy of my time), was that they gave humans an astonishing intelligence and reasoning capacity for a purpose. 

Thus I implore you to go forth and get immunized. The only true god of your choice commands it.

Now here's something to be thankful for...

Personalize funny videos and birthday eCards at JibJab!

Vaccines! This week's New England Journal of Medicine has a study from the University of Pittsburgh that analyzed 125 years of weekly surveillance reports for infectious diseases, and today's New York Times has an article about the study. By analyzing time periods before and after introduction of vaccines, the investigators were able to estimate that in the last decade 99% of cases of childhood diseases have been prevented. Quick, someone please call Jenny McCarthy!

Another Staph aureus vaccine failure

The April 3rd JAMA contains the results of a wonderfully designed and executed study by Fowler and colleagues assessing the benefits of a novel (V710) vaccine targeting S. aureus infection in cardiothoracic surgery. The study was negative (i.e. the vaccine didn't work) and highlights how little we know in 2013 about how humoral immunity works for this important human commensal. But first the study and results...

Among 8031 patients entered into the study, the vaccine was given between 14 and 60 days pre-op to 3981 randomly-selected patients prior to surgery while 3982 received saline placebo. The study was powered to detect a 20% reduction in S. aureus bacteremia or deep surgical site infection through 90-days post-op. Secondary outcomes were any invasive S. aureus infection. Three interim analyses were planned but the data monitoring committee terminated the study after the second interim analysis. Thus, only around ~5100 patients completed the full study with 90-day endpoints. Of note, 67% were male, 24% had diabetes, 18% were S. aureus colonized and 2% were MRSA colonized. Randomization appears excellent.

As I suggested, the results are sobering. The primary outcome (deep SSI or bacteremia) occurred in 2.6% of vaccinated patients and 3.2% of controls, p=0.58. There were more adverse events at 14 days in the vaccinated group (31% vs 22% ) and a greater incidence of multiorgan failure. Depressingly, there was far higher mortality secondary to S. aureus infection in the vaccinated group, 23 vs 4.2 per 100 person-years. The overall comparison between vaccinated and unvaccinated for S. aureus related outcomes is striking and humbling. I've pasted Table 4 from the study below, for your review (click on it to enlarge).

The authors of the study point out that their study isn't the first to find worse outcomes in a vaccinated group and also that MRSA infections were more common in the vaccinated arm of the trial. But I don't buy their suggestion that MRSA was a significant contributor to the poorer S. aureus related outcomes in the vaccinated group. There just wasn't enough MRSA disparity between the vaccinated and control groups. I wonder if part of the answer to higher mortality in the vaccinated group could be explained by this old paper by Heiman Wertheim and colleagues that I discussed several years ago. Wertheim report significantly lower mortality among S. aureus carriers vs. non-carriers. Could the vaccine be upsetting the delicate protective effect of pre-existing S. aureus colonization?

There is an excellent accompanying editorial by Preeti Malani and I urge you to read it. She does a wonderful job putting this study in historical context and pointing a path forward for HAI prevention research. The money quote from her editorial is: "Ultimately, the results of the study by Fowler et al say more about the need to rigorously study infection prevention in general than about S aureus per se." I couldn't agree more.

Image source: Vance Fowler, MD MHS from Duke

Things is gettin' worser - Pediatric Undervaccination

The typical trajectory of public health over the past several centuries has pointed upwards towards improvements including longer life-expectency. However, as we've entered the post-scientific era, where our country receives its medical advice from celebrities, it's not at all surprising that things can move in the wrong direction. Of course, vaccines are a victim of their own successes since absence of a terrible diseases like measles convinces people they don't need to vaccinate their children and also more susceptible to false claims of vaccine side-effects, but I digress.

Authors Jason Glanz and colleagues recently published a matched-cohort study of healthcare utilization in vaccinated vs. under-vaccinated children less than 3 years old. Their primary findings were that undervaccinated children had lower rates of outpatient visits but higher rates of inpatient admissions.  There are also some interesting findings about how parental choice in vaccination is associated with healthcare utilization. What was more interesting to me is how things have changed gotten worse in the birth cohorts over the 5 years studied (2004 to 2008).  In the figure below, time to first vaccination has increased greatly over the 5 years (solid shapes), as have the rates of 'no vaccination'. So things are moving upward, but in this case, that's the wrong direction.

Reference: Glanz JM, Newcomer SR, Narwaney KJ, et al. A Population-Based Cohort Study of Undervaccination in 8 Managed Care Organizations Across the United States. JAMA Pediatr. 2013;():1-8. doi:10.1001/jamapediatrics.2013.502.

Blowback

Remember how U.S. intelligence used a physician who was running an immunization campaign as a covert agent, in an attempt to determine if a high value target was living in Pakistan?

Well, this is why aid workers, and others, were so upset about it. There has been great progress toward the goal of polio eradication. Widespread belief that immunization campaigns could be used as a cover for espionage now threatens to stall progress in one of the few countries where polio still has a foothold.

(Twinrix x 2) x 3 = (0.95) HBsAb+

I recently had a dentist referred to me for treatment of an infection and in reviewing her chart incidentally noted that her hepatitis B surface antibody was negative. In taking her history I learned that after receiving the hepatitis B vaccine series twice (6 doses), she still had a negative hepatitis B surface antibody, which indicates no protection against hepatitis B, a major occupational hazard for dentists.

To the rescue is this important study (full text here). In this study, 48 hepatitis B vaccine nonresponders were given double doses of Twinrix vaccine (combined hepatitis A + hepatitis B vaccine) at 0, 1 and 6 months. At the end of that vaccine series, 95% of the nonresponders developed protective levels of antibody against hepatitis B. This is a very cool finding for healthcare workers who are hepatitis B vaccine nonresponders.

The study isn't new. Dan reviewed it for Journal Watch several years ago (full text here), but I wasn't aware of it and neither were my partners, so I thought it would be important to highlight this paper.

Herd Immunity in the Jet Age

By 2012, I thought we'd already be beyond the jet age. Although, if you go by the GOP debates, determining if a "moon-colony" could apply for U.S. statehood is now our top domestic concern, so maybe we're finally getting beyond the jet age?

An idea central to controlling infectious diseases is herd immunity. This is the idea that vaccinating a proportion of the population (e.g. 80% for mumps or 95% for measles) will protect the entire population, even the unvaccinated. In a paper presented recently at the meeting of the American Mathematical Society and the Mathematical Association of America and discussed in the Economist, Petra Klepac and colleagues wanted to know how increasingly mobile populations with varying vaccination rates would impact optimal vaccination targets for infectious diseases. That is, does it make economic sense to target a herd-immunity threshold? Also, how would high-levels of varicella vaccination in the US vs. low levels in Britain interact to impact chickenpox in both countries?

Dr. Klepac and her team used a susceptible-infected-removed (SIR) mathematical model, which we frequently use in analysis of infection-control interventions. Analysis of their model determined that targeting herd immunity makes sense for an isolated country. However, when international travel was added, she found that a small rate of unvaccinated travelers would reduce the optimal vaccination below the level of herd immunity, so that targeting herd immunity becomes too expensive. Thus, we have to be tolerant of more infections.

There are some other interesting implications of her study, so head on over to the Economist Babbage blog to read more.

"Young" doctors and vaccines

Vaccines these days can't catch a break.  Back in the day when people were dying from polio and measles, everyone (including physicians) could see the benefits of vaccines first hand. Now, with the success of vaccines in the bag, the ground has shifted against vaccines from "seeing is believing" to "what have you done for me lately." 

There is an abstract at IDSA that reports that young physicians are less supportive of vaccines. Sara Kliff at the Washington Post reports that Michelle Mergler (Emory) and Saad B. Omer (Johns Hopkins) found that recent medical school graduates were “more likely to believe immunizations do more harm than good" and were 15 percent less likely to believe vaccines work. Bummer.

see also: Shari Roan, LA Times 10/20/2011

Flu vaccine breakthrough

Influenza virus, A/Hong Kong/1/68

Yesterday, when commenting on Bill Gates' vaccine efforts, I wrote that a key breakthrough might be "an influenza vaccine that targets a conserved region of the virus, which would eliminate the need for costly annual vaccinations."  As if on cue...

The Guardian reports of an influenza vaccine breakthrough out of Oxford University. The new vaccine, developed by Dr Sarah Gilbert's team, targets proteins inside the flu virus that are common across all strains. The two proteins, Nucleoprotein and matrix protein 1, are more than 90% conserved across all influenza A strains and less liable to change over time.

In their initial human trial of 11 healthy vaccinated people and 11 non-vaccinated people, they exposed them to what I think is A/Wisconsin/67/2005 (H3N2). Fewer vaccinated people got the flu and vaccinated people had more T-cells and more activated T-cells. We will have to wait a bit for more details, since they have just submitted the paper for publication. Interesting that the Guardian is reporting this before a a medical journal. Given how dysfunctional the peer-review process is these days (STAR-ICU trial anyone?), I don't blame them for communicating the results in this time-efficient manner.

You can read about the initial vaccine creation and phase 1 safety trial of the Modified Vaccinia virus Ankara vector encoding nucleoprotein and matrix protein 1 in the January 1st CID.

Guardian article by Alok Jha

Berthoud et al Clin Infect Dis, January 1, 2011

Bill Gates pledges $10 billion to vaccinate children

Source: Gizmodo.com

Bill Gates spoke with Sanjay Gupta (CNN) recently and is pledging $10 billion over 10 years to vaccinate children worldwide.  Gates' plan:

"Over this decade, we believe unbelievable progress can be made, in both inventing new vaccines and making sure they get out to all the children who need them. We could cut the number of children who die every year from about 9 million to half of that, if we have success on it. We have to do three things in parallel: Eradicate the few that fit that profile -- ringworm and polio; get the coverage up for the vaccines we have; and then invent the vaccines -- and we only need about six or seven more -- and then you would have all the tools to reduce childhood death, reduce population growth, and everything -- the stability, the environment -- benefits from that."

My favorite quote (the counterfactual):  "In fact, it is so simple, people often forget what a big deal this is. The 2 million people that would have died from smallpox now don't think, 'Wow, I'm alive today because of vaccinations,' but that's the case."

It will be interesting to see if this effort can lead to 6 or 7 new vaccines.  A key one would be an influenza vaccine that targets a conserved region of the virus, which would eliminate the need for costly annual vaccinations.  I think we will also need a similar effort to identify new antibacterials before too long.

Full transcript and video of Bill Gates interview (CNN.com)

h/t gizmodo

S. aureus vaccine breakthrough?

Researchers at the University of Rochester have just announced a potential breakthrough in S. aureus (MRSA) vaccine methods.  Edward Schwarz and John Varrone presented their new findings at the Orthopaedic Research Society annual meeting in Long Beach, Calif this past week.

Their work targets the S. aureus glucosaminidase (Gmd) protein, which is thought to act as a zipper by opening the bacterial cell wall during cell division. Importantly they discovered four anti-Gmd monoclonal antibodies that prevented growth in cell culture. They also demonstrated that mice treated with anti-Gmd antibody were half as likely to develop infection. Phase I human trials are planned for 2012.

References:
URMC Press Release

RSC Article

h/t Mark Vander Weg

The History of Vaccines (new website)

The College of Physicians of Philadelphia, the oldest professional society in the United States, has just launched a new educational website on the History of Vaccines. There is so much information available, that it literally will blow your mind. I should post a picture, it's not pretty. Topics include "The Development of the Immunization Schedule," a timeline of vaccination history from the year 1000, "History of the anti-Vaccination Movements," and "Top 20 Questions about Vaccines." There are already 424 images and videos for your use and education. Wow.

The site has been planned for several years and has been in development for a year. It will officially launch on November 3, 2010, when Stanley A. Plotkin, MD, developer of the current rubella vaccine, and emeritus professor of The Wistar Institute and The University of Pennsylvania, will give the Samuel X Radbill lecture entitled "Four Centuries of Vaccinology" in Philadelphia.

Check out the preview version of the website "The History of Vaccines" and related blog. Just fantastic.

h/t Tara Smith at Aetiology

Sunday reading

A couple recent New York Times articles relevant to infection prevention are worth a read. The first reports on an Annals of Internal Medicine paper describing how cost and reimbursement serve as barriers to the uptake of the adult varicella zoster virus (VZV, shingles) vaccine. The second is a fascinating story about the last of the old-time TB sanitariums. Although directly observed therapy (DOT) outside the hospital is the current model, there are some for whom prolonged inpatient care is needed, including those with dual diagnoses or extremely-drug resistant TB for whom simple outpatient DOT regimens are not feasible.

NY Times article on VZV vaccine
Annals paper describing barriers to vaccine uptake
NT Times article on A.G. Holley TB hospital

TB Vaccine effective in HIV+ with BCG history

This study, to be published in an upcoming issue of AIDS, tested the effect of an inactivated whole cell mycobacterial vaccine, Mycobacterium vaccae, in HIV+ (CD4+>200) outpatients in Tanzania who also had a history of childhood BCG vaccination. Ford von Reyn and his Dartmouth and Tanzanian colleagues completed a double-blind placebo controlled trial testing the effect of 5 intradermal injections on subsequent disseminated and definite TB. Vaccinated patients had reduced disseminated TB (HR=0.52, p = 0.16), and definite tuberculosis (HR=0.61, p = 0.03). The study was stopped early do to significant protective effect but it prevented the assessment of longer-term effects.

Genetically engineered viruses, distributed from the air by government officials!

Don’t be alarmed, it’s just the Department of Agriculture’s multi-state oral rabies vaccine program. Targeted to raccoons, foxes and coyotes, it involves spreading bait (fishmeal or dog food) containing hidden vaccine packets. The vaccine is a live recombinant vaccinia virus with a gene encoding rabies glycoprotein.

This MMWR report details the second human case of vaccinia infection from contact with vaccine bait. In both human cases, contact occurred after a dog got into the bait and punctured the vaccine packet. This particular case was pretty scary, given that the infected person was immunocompromised from treatment of inflammatory bowel disease.

A photo of the rash, from the MMWR report:

Anti-vaccine movement gaining strength

Click here to read a very interesting article in Wired.com about Dr. Paul Offit, the pediatric infectious diseases specialist and vaccine expert, who has been hounded by the anti-vaccine movement.