July 21, 2010
Category: Inside the Outbreaks • public health
Mark Pendergrast writes: It's time to wrap up this ScienceBlog Book Club on my book, Inside the Outbreaks. I want to thank Liz Borkowski, Steve Schoenbaum, and Karen Starko for their excellent, insightful commentaries, and thanks too to those who commented here. I assume that you can continue to do so, and you can also contact me through my website at www.markpendergrast.com. While you're there, on the Outbreaks page, take a look at the YouTube link to the children of Niger singing. It's quite wonderful, and it also has an important message at the end.
I don't regard this as the end of the blog but as the beginning of your reading and thinking about public health and the impact of the Epidemic Intelligence Service. So, as food for thought, here are three sections of the book involving EIS officer Richard Levine, who was a bit of a troublemaker. These sections all involve important issues: environmental toxins, politics and business, mass psychosomatic illness, and iatrogenic illness (cholera spread by the cholera treatment center itself):
Read on »
Posted by Mark Pendergrast at 5:17 PM • 0 Comments • 0 TrackBacks
July 9, 2010
Category:
In this post I want to address disease control opportunities for EIS officers, many of which are detailed in "Inside the Outbreaks: One of the first things we learned about on joining the EIS was John Snow's determination that an outbreak of cholera in London was attributable to contamination of the water from the Broad St. pump and his stopping the epidemic by removing the pump handle. On reading "Inside the Outbreaks" one is struck with the number of EIS officers whose efforts have removed pump handles....
Read on »
Posted by Steve Schoenbaum at 11:54 AM • 3 Comments • 0 TrackBacks
July 8, 2010
Category: Bioterrorism • Inside the Outbreaks • Public Health • epidemiology
Mark Pendergrast writes: Instead of responding to last week's commentaries on this book club blog about my book, Inside the Outbreaks, I want to throw out a controversial idea that runs counter to what many public health commentators apparently believe. So I expect some disagreement here. (I will post responses to the commentaries as "comments" on each commentary. So go back and take a look at what I wrote there, please.)
Fears of bioterrorism are overblown. We should be spending much more money, time, effort, and print (including e-print) on naturally occurring outbreaks, epidemics, and human behavioral risk factors. At least, that is one of my conclusions after researching and writing the history of the Epidemic Intelligence Service, which is a kind of microcosm of public health events over the past half century.
Read on »
Posted by Mark Pendergrast at 12:43 PM • 7 Comments • 0 TrackBacks
July 7, 2010
Category: Inside the Outbreaks
Karen Starko writes: Several basic questions related to Reye's syndrome (RS) have come to me from readers of Mark's book, Inside the Outbreaks. These show the importance of continued education on health issues. (For example, some physicians thought that fever was essential to getting RS). Again, thanks to Mark Pendergrast for a wonderful addition to our public health knowledge.
Is an influenza or chickenpox infection necessary to acquire RS?
The answer is no. RS generally has two phases: the antecedent illness and usually, within a few days of this, the syndrome of vomiting and encephalopathy. While viruses are the most common antecedent event, other illnesses may precede RS such as teething and connective tissue diseases. Some antecedent viruses are influenza A and B, adenovirus, Coxsackie virus, Epstein-Barr virus, ECHO virus, polio, parinfluenza, reovirus, rubella virus, measles, herpes simplex. (Corey, Am J Med, 1975)
Is fever in the antecedent illness necessary to acquire RS?
No. In the U.S. Public Health Service Study (Hurwitz, NEJM, 1985) fever was reported less often by RS cases (54%) than by any of the four control groups (59% to 89%).
Was RS truly more common after influenza B than other viruses?
Currently available data are not sufficient to answer this question. (Any data on this would be welcome). Outbreaks of RS associated with influenza B infection were reported to CDC starting in 1967 when 6 cases were reported from Tampa, Florida. Other subsequent outbreaks included: Oklahoma 1969 (6 cases), Atlanta 1969 (6 cases), Massachusetts and Vermont 1970 (24 cases), and Guam 1971(6 cases). (Hochberg, JAMA, 1975)
The largest study (Corey, Am J Med, 1975) addressing the association was performed between December 15, 1973 and June 30, 1974. In anticipation of substantial influenza B activity after identification of a new variant of influenza B, both CDC through state health departments and the American Academy of Pediatrics urged physicians to report cases. 379 cases fitting the CDC case definition were reported. While it was hoped that laboratory evidence of the type of infection would be obtained from many, attempts at viral isolation or properly spaced serology were conducted in only 21%. However, many cases did cluster temporally and geographically with influenza B. 340 cases reported an upper respiratory infection. 58 (17%) had evidence of influenza B infection. Serology or viral isolation identified influenza A/Port Chalmers (2 cases), adenovirus (1 case), parainfluenza virus (1 case), double virus infections (3 cases), and no evidence for a virus (5 cases). 28 patients had an antecedent varicella infection and 15 patients had a gastrointestinal infection.
Also, more RS cases were reported to CDC during influenza B years as follows: (Hurwitz, Pediatrics, 1982)
Year Major influenza activity Number of RS Cases
1973-74 B 379
1976-77 B 454
1977-78 A 237
1978-79 A 389
1979-80 B 548
Thus, the association with influenza B is a descriptive one. It may be real (influenza B is an independent risk factor), a confounder (influenza B is a reason to give aspirin), or an artifact of surveillance. Reporting RS to CDC was for the most part voluntary. Once the early small outbreaks associated with influenza B were reported and CDC and the AAP called for RS cases during an influenza B year (and found them!) the impression that the illness was associated with influenza B was furthered. Interestingly, after 1990, although the number of RS cases had fallen, no association was noted with influenza B (Belay, NEJM, 1999). Thus the question of whether or not influenza B predisposed to RS is still up in the air. To my knowledge, there are no data addressing the question of whether children with influenza B are at greater risk of RS than children with influenza A or other viral illnesses.
Are influenza and chicken pox independent risk factors for RS or are they simply a trigger for the administration of aspirin?
Unfortunately, this question has not been addressed directly. While temporal and geographic associations with viruses have been identified, these are only descriptive. It remains unclear if these viruses possess some characteristic that promotes the development of RS or whether they are simply the trigger for the administration of aspirin.
On the other hand, there is pharmacology evidence that aspirin alone can accumulate to toxic levels at the doses recommended at the time in children. In 1906 Langmead (Lancet, 1906) reported a child hospitalized with rheumatic fever who received 325mg of a salicylate every 6 hours and on day 4 developed vomiting, fever, dyspnea, cyanosis, and coma and died. He suggested the salicylate might have accumulated. Yet, it wasn't until 1947 and the development of a test to measure salicylate in the blood that Erganian (J Pediatrics, 1947) showed that indeed salicylate levels progressively increased over several days in some children given commonly recommended doses. In 1965 Levy showed that when the body level of salicylate reaches 360 mg, metabolism changes from first order (when the body can metabolize whatever amount of drug it is given) to zero order (when only a certain amount can be metabolized at a time). In other words, metabolism becomes rate limited and the drug can easily accumulate. Any one of a number of factors will predispose to salicylate accumulation: too much, doses too close together, dehydration (as with fever), reduced renal excretion, low urine pH, and individual variation in speed of metabolism. Other factors such as acidosis and hypoproteinemia increase brain uptake. In addition, individual differences in level at which toxicity occurs have been noted. (Reviewed in Starko, CID, 2009)
Pinsky and colleagues (JAMA, 1988) at the CDC provided evidence that suggests that accumulation happens in RS. They showed that RS cases generally took more salicylate than did controls (although for the most part within recommended amounts) and more importantly that RS cases continued to take salicylate for more days than controls. On day 3 for example, 18 (78%) of 23 RS cases were still taking aspirin whereas only 12 (9%) of 134 controls were doing so. This pattern is consistent with accumulation similar to that reported by Langmead in 1906 and Erganian in 1947.
Posted by Karen Starko at 8:49 AM • 0 Comments • 0 TrackBacks
July 6, 2010
Category: Inside the Outbreaks • Public Health
Liz Borkowski writes: I wrote last week about how federal agencies can solve the problems that create conditions for disease outbreaks - or fail to solve them, as is too often the case. This week, I wanted to focus on the role Congress plays in public health agencies' effectiveness, because that's another angle that crops up repeatedly in Inside the Outbreaks.
Congress's creation of federal agencies is clearly a huge achievement, and they've also periodically given new powers to already existing agencies. For instance, Mark Pendergrast tells the story of the Dalkon Shield, an IUD that turned out to cause infections while failing to prevent pregnancy in many of the women who used it; at least 17 pregnant women died with IUDs in their uteruses. The manufacturer, facing lawsuits, eventually took the product off the market, but the episode demonstrated the need to prevent similar problems in the future. Congress responded by passing the Medical Devices Amendment Act, which mandates that medical devices receive FDA approval before being marketed.
Agencies also rely on Congress for their annual appropriations, and public health isn't often the top Congressional priority when it comes to dividing a limited pool of revenue. There are times when Congress responds to a growing health threat by giving an agency more money to address the problem; for instance, after several outbreaks of food-borne illnesses, Congress gave FDA's FY 2010 budget a large increase to help it hire more food inspectors. It seems like more often, though, Congress makes funding decisions that run counter to the advice of public health professionals.
Read on »
Posted by Liz Borkowski at 8:28 AM • 0 Comments • 0 TrackBacks
July 2, 2010
Category:
Steve Schoenbaum writes: In his blog this week, Mark Pendergrast challenges someone/anyone to take on explaining the differences between case-control studies vs. cohort studies. As an EIS officer, back in late May/early June 1968, I did a case-control study as part of the investigation of a common source outbreak of hepatitis in Ogemaw County, Michigan, so I will try to pick up the challenge. I believe it was only the second time case-control methods were used in a CDC epidemic investigation. In using this method I learned about the power of comparison, not just that numerators need denominators, but cases need controls. I also learned about the factors influencing use of different types of epidemiologic investigation and elaborate on those below:
Read on »
Posted by Steve Schoenbaum at 11:11 AM • 1 Comments • 0 TrackBacks
June 30, 2010
Category: Inside the Outbreaks
Karen Starko writes: When the "financial crisis" started and the news media started throwing around numbers in the trillions and projected fixes in the billions, I realized I just didn't get it. So I got a little yellow post-it, labeled it "understanding trillions," and started a list of examples. And when I learned that the US GDP in 2006 was 13T and the derivative market, estimated in June 2007, was valued at 500T, I quickly got a sense of the potential drain of the derivative market (in which money is spent on items without real value...my definition, please correct me if I am wrong). I was scared. I thought of taking my cash from the bank and converting into something tangible, like food, but decided to hold on and hope the government would "save" us. We now all are learning that we didn't pay enough attention and what we lost is painfully real in terms of our financial health.
As I read Mark's book, I began thinking about whether we are in the same situation with our physical and mental health. Are we paying enough attention to that which produces real value, like prevention, a key strategy of the EIS and other prevention-oriented organizations?
First, a little perspective...CDC's budget request for 2010 was 10.1 billion. (http://www.cdc.gov/fmo/topic/Budget%20Information/index.html) including:
3.3 B for childhood vaccines
2.0 B for infectious diseases
1.5 B for terrorism
1.0 B for health promotion
In 2006, it was estimated that bringing a single drug to market costs 0.5 to 2 billion. (http://content.healthaffairs.org/cgi/content/full/25/2/420). A Reuters report in April 2010 (http://www.reuters.com/article/idUSLDE63C0BC20100413) indicated that consensus forecasts for sales figures for the top selling drugs ranged from 11.7 billion for Lipitor to 5.8 billion for Crestor with Plavix, Advair, Remicade, Enbrel Humira, Avastin, Rituxan, Diovan in between.
So we spend almost 12 B on our top selling drug and 10 B on the entire CDC budget. Is this how we want to spend our money? Now don't get me wrong I am all for drugs (medical). And I am not implying that a 12 billion for one drug isn't worth it. Rather, the relative amount spent for the prevention and health promotion work of CDC seems a bit low.
An important question then is: How do you understand the value of prevention efforts? While we do a pretty good job measuring the benefit we get from each drug in its formal clinical trials, can calculate cost benefit, and can use this information to make choices about how we spend our dollars, measuring what didn't happen (what we prevented) is much more difficult involving projections, assumptions, and discounting.
Here is where Mark's book comes in. Inside the Outbreaks is the first book chronicling the work of the EIS. Each sub-section tells a brief story and as you read through the book, you develop a growing knowledge and appreciation for what illnesses did and, importantly, didn't happen. For example, for each of these diseases, it is clear that many illnesses and deaths were prevented.
--In 1965, a Salmonella outbreak afflicted about 200,000 people in Riverside, California killing an infant and several others before the CDC team found that water was the source and stopped the outbreak.
-- In 1966, the World Health Organization passed a vote to fund a worldwide small pox elimination program. CDC played an important role in the subsequent eradication program.
--CDC was a leader in identifying infections that originated in hospitals and in instituting surveillance and preventive programs.
--Lead poisoning, vinyl chloride associated liver cancer, toxic shock syndrome and tampons, Accutane-associated birth defects, and many other links between an environmental cause and health were identified or characterized by CDC studies.
How many thousands or millions of us are healthy today because of this work? And how many suffer because we didn't do more of this kind of work? I suggest that a general appreciation and awareness is a first step in placing value. Pendergrast's book goes a long way in providing this. Once we truly understand and appreciate, we can think about measuring value. Was the money we spent worth it? Could we have done more with more? If we have a dollar for our health today, where do we think we will get the most value? Would more funds toward prevention give us more of the health value we want?
Are we headed for another crisis, one caused by spending dollars on health products of lesser (or no) value rather than those of more value resulting in slowing improvements or decreases in our health...a health recession?
Posted by Karen Starko at 9:18 AM • 1 Comments • 0 TrackBacks
June 29, 2010
Category: Food • Inside the Outbreaks • Public Health
Liz Borkowski writes: Mark Pendergrast wrote yesterday about how politics plays into the work of the EIS, and it's something that I kept noticing as I read Inside the Outbreaks. As he points out, my post last week highlighted the solution to the Reye's Syndrome puzzle - which was solved by Karen Starko, who's also one of the Book Club bloggers! - but didn't get into the larger issue: there can be a big difference between solving the puzzle and solving the problem. In yesterday's post, Mark writes:
Although Karen's and subsequent CDC studies clearly demonstrated that giving children aspirin caused the vast majority of Reye syndrome cases, the CDC has no regulatory power. The FDA gave in to pressure from the aspirin industry and delayed a warning label on children's medicine containing aspirin for five years, during which nearly 300 more children died of Reye syndrome in the United States.
He follows up the Reye's Syndrome story by asking "Should the CDC have regulatory power?" In considering that question, it's instructive to look at some of the many episodes in the book where EIS officers either were or weren't able to use their discoveries about the source of disease outbreaks to get necessary large-scale changes made.
Read on »
Posted by Liz Borkowski at 12:28 PM • 1 Comments • 0 TrackBacks
June 28, 2010
Category: Inside the Outbreaks • Public Health • epidemiology
Mark Pendergrast writes: Thanks to commentators Liz Borkowski, Karen Starko, Steve Schoenbaum, and Mark Rosenberg for their thoughtful posts, though it appears that Mark Rosenberg's post got cut off after his first-paragraph query asking why anyone would go into the field of public health. I will wait to respond to his post once I see him answer his own question! In the meantime, there is much to talk about. I (Mark Pendergrast) will respond to parts of what Liz, Karen, and Steve wrote in order, along with other blogger comments.
Let me respond first to a blog comment from John Willis, who wrote: "This sounds like the basis for the show Medical Investigation, which is just the kind of superhero style TV show about the CDC that you imagine. I thought when I watched the show that it was far-fetched - a kind of House for epidemiologists with as much connection to the real world of outbreak investigation as House does to internal medicine - but perhaps I judged it too soon."
Well, Inside the Outbreaks has indeed been optioned for a television series, though that apparently doesn't mean that it will necessarily happen. I watched a few episodes of the short-lived Medical Investigation and was disappointed in the show, since it was, as Willis thought, pretty unrealistic. In fact, the Epidemic Intelligence Service folks told me that at first they were distressed that (for unknown reasons) the TV show placed the EIS-type officers at the National Institutes of Health instead of the CDC. But when they saw the show, they were relieved. My main problem with Medical Investigation was that they often presented the epidemiologists as superhero clinicians who were actively caring for the patients. While some EIS officers have helped to care for patients during the course of an investigation, that isn't their job, and it is rare.
The super-hero cover of Inside the Outbreaks is misleading as well, showing a Clark Kent/Superman look-alike dressed in a lab coat, triumphantly holding up a test tube in a Eureka moment. That too rarely happens, since most EIS officers do not do lab work. In fact, if they had shown a realistic cover, it would have perhaps featured a photo such as this picture of Brad Hersh during a 1991 measles outbreak in Colorado. He stayed up most of the night crunching data in his lonely motel room, with papers spread all over the bed.
As mundane as that sounds, such number-crunching ("grunt work," as Liz puts it) lies at the heart of disease detection and epidemiology in general, and it often is quite urgent and dramatic, as Karen points out - it can mean life or death for someone you have never met. Take, for instance, the story of E-Ferol. Here is an excerpt from Inside the Outbreaks:
Read on »
Posted by Mark Pendergrast at 3:56 PM • 0 Comments • 0 TrackBacks
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