"When public health works, it's invisible"

Caitlin Rivers' post on the "public health paradox: why people don't get flu shots" hits the nail on the head:

Unfortunately, the root of this problem is deep. The problem is that when public health works, it is invisible. It's an insidious, persistent public relations issue that plagues public health. Nobody sees when a chain of disease transmission is broken, or when contaminated food is prevented from reaching the market, or when toxic pollutants don't enter the environment. That's the point: the goal of public health is prevention, not reaction....

What then can be done to counteract these misperceptions? First, public health needs to be more vocal about its successes. This graphic of crude death rates for infectious diseases during the 19th century, for example, should be widely disseminated. A little self-promotion could go a long ways.

That's one reason I like Millions Saved, from the Center for Global Development -- it highlights "proven success in global health." One of the things that struck me when reading it was that most of the people who benefited from these interventions and programs would have no way of knowing that they benefited.

For another positive take, check out Charles Kenny's book Getting Better.

 

This beautiful graphic is not really that useful

This beautiful infographic from the excellent blog Information is Beautiful has been making the rounds. You can see a bigger version here, and it's worth poking around for a bit. The creators take all deaths from the 20th century (drawing from several sources) and represent their relative contribution with circles:

I appreciate their footnote that says the graphic has "some inevitable double-counting, broad estimation and ball-park figures." That's certainly true, but the inevitably approximate nature of these numbers isn't my beef.

The problem is that I don't think raw numbers of deaths tell us very much, and can actually be quite misleading. Someone who saw only this infographic might well end up less well-informed than if they didn't see it. Looking at the red circles you get the impression that non-communicable and infectious diseases were roughly equivalent in importance in the 20th century, followed by "humanity" (war, murder, etc) and cancer.

The root problem is that mortality is inevitable for everyone, everywhere. This graphic lumps together pneumonia deaths at age 1 with car accidents at age 20, and cancer deaths at 50 with heart disease deaths at 80. We typically don't  (and I would argue should't) assign the same weight to a death in childhood or the prime of life with one that comes at the end of a long, satisfying life.  The end result is that this graphic greatly overemphasizes the importance of non-communicable diseases in the 20th century -- that's the impression most laypeople will walk away with.

A more useful graphic might use the same circles to show the years of life lost (or something like DALYs or QALYs) because those get a bit closer at what we care about. No single number is actually  all that great, so we can get a better understanding if we look at several different outcomes (which is one problem with any visualization). But I think raw mortality numbers are particularly misleading.

To be fair, this graphic was commissioned by Wellcome as "artwork" for a London exhibition, so maybe it should be judged by a different standard...

Biological warfare: malaria edition

Did you know Germany used malaria as a biological weapon during World War II? I'm a bit of a WWII history buff, but wasn't aware of this at all until I dove into Richard Evans' excellent three-part history of Nazi Germany, which concludes with The Third Reich at War. Here's an excerpt, with paragraph breaks and some explanations and emphasis added:

Meanwhile, Allied troops continued to fight their way slowly up the [Italian] peninsula. In their path lay the Pontine marshes, which Mussolini had drained at huge expense during the 1930s, converting them into farmland, settling them with 100,000 First World War veterans and their families, and building five new towns and eighteen villages on the site. The Germans determined to return them to their earlier state, to slow the Allied advance and at the same time wreak further revenge on the treacherous [for turning against Mussolini and surrendering to the Allies] Italians.

Not long after the Italian surrender, the area was visited by Erich Martini and Ernst Rodenwaldt, two medical specialists in malaria who worked at the Military Medical Academy in Berlin. Both men were backed by Himmler’s Ancestral Heritage research organization in the SS; Martini was on the advisory board of its research institute at Dachau. The two men directed the German army to turn off the pumps that kept the former marshes dry, so that by the end of the winter they were covered in water to a depth of 30 centimetres once more. Then, ignoring the appeals of Italian medical scientists, they put the pumps into reverse, drawing sea-water into the area, and destroyed the tidal gates keeping the sea out at high tide.

On their orders German troops dynamited many of the pumps and carted off the rest to Germany, wrecked the equipment used to keep the drainage channels free of vegetation and mined the area around them, ensuring that the damage they caused would be long-lasting.

The purpose of these measures was above all to reintroduce malaria into the marshes, for Martini himself had discovered in 1931 that only one kind of mosquito could survive and breed equally well in salt, fresh or brackish water, namely anopheles labranchiae, the vector of malaria. As a result of the flooding, the freshwater species of mosquito in the Pontine marshes were destroyed; virtually all of the mosquitoes now breeding furiously in the 98,000 acres of flooded land were carriers of the disease, in contrast to the situation in 1940, when they were on the way to being eradicated.

Just to make sure the disease took hold, Martini and Rodenwaldt’s team had all the available stocks of quinine, the drug used to combat it, confiscated and taken to a secret location in Tuscany, far away from the marshes. In order to minimize the number of eyewitnesses, the Germans had evacuated the entire population of the marshlands, allowing them back only when their work had been completed. With their homes flooded or destroyed, many had to sleep in the open, where they quickly fell victim to the vast swarms of anopheles mosquitoes now breeding in the clogged drainage canals and bomb-craters of the area.

Officially registered cases of malaria spiralled from just over 1,200 in 1943 to nearly 55,000 the following year, and 43,000 in 1945: the true number in the area in 1944 was later reckoned to be nearly double the officially recorded figure. With no quinine available, and medical services in disarray because of the war and the effective collapse of the Italian state, the impoverished inhabitants of the area, now suffering from malnutrition as well because of the destruction of their farmland and food supplies, fell victim to malaria. It had been deliberately reintroduced as an act of biological warfare, directed not only at Allied troops who might pass through the region, but also against the quarter of a million Italians who lived there, people now treated by the Germans no longer as allies but as racial inferiors whose act of treachery in deserting the Axis cause deserved the severest possible punishment.

Infectious history

The late Joshua Lederberg, a Nobel-winning molecular biologist (at the age of 33!), wrote an essay on the history of our fight against microbes titled "Infectious History." It's readable and covers a lot of ground fairly succinctly, and there's a non-paywalled version here. (The formatting isn't great, so it's a great excuse to install the Readability plugin if you haven't already.) One of my favorite excerpts:

Bacteriology's slow acceptance was partly due to the minuscule dimensions of microbes. The microscopes of the 19th and early 20th centuries could not resolve internal microbial anatomy with any detail. Only with the advent of electron microscopy in the 1930s did these structures (nucleoids, ribosomes, cell walls and membranes, flagella) become discernible. Prior to that instrumental breakthrough, most biologists had little, if anything, to do with bacteria and viruses. When they did, they viewed such organisms as mysteriously precellular. It was still an audacious leap for René Dubos to entitle his famous 1945 monograph "The Bacterial Cell."

And on diminishing returns on extending life expectancy (at least in industrialized countries) since 1950:

Other statistics reveal that the decline in mortality ascribable to infectious disease accounted for almost all of the improvement in longevity up to 1950, when life expectancy had reached 68. The additional decade of life expectancy for babies born today took the rest of the century to gain. Further improvements now appear to be on an asymptotic trajectory: Each new gain is ever harder to come by, at least pending unpredictable breakthroughs in the biology of aging.

Read the rest. I came across Lederberg's article in a footnote to Adel Mahmoud's article "A global road map is needed for vaccine research, development, and deployment."

Genesis

I highly recommend Patient Zero, the  latest episode of the podcast RadioLab. It covers Typhoid Mary, the origin of HIV, and the diffusion of ideas. Evocative as always, but what I like the most is how they add new information to stories you think you know. For one, you really feel sorry for Mary. And I've read quite a bit on the origin of HIV (a great way to learn more about phylogenetics!) but RadioLab takes it back even further and highlights some research I hadn't seen. Related: I haven't read it yet, but Tyler Cowen really likes Jacques Pepin's new book, The Origin of AIDS -- more happy reading for Christmas break.

Miscellany: Epidemic City and life expectancy

In 8 days I'll be done with my first year of graduate studies and will have a chance to write a bit more. I've been keeping notes all year on things to write about when I have more time, so I should have no shortage of material! In the meantime, two links to share: 1) Just in time for my summer working with the New York City Department of Health comes Epidemic City: The Politics of Public Health in New York. The Amazon / publisher's blurb:

The first permanent Board of Health in the United States was created in response to a cholera outbreak in New York City in 1866. By the mid-twentieth century, thanks to landmark achievements in vaccinations, medical data collection, and community health, the NYC Department of Health had become the nation's gold standard for public health. However, as the city's population grew in number and diversity, new epidemics emerged, and the department struggled to balance its efforts between the treatment of diseases such as AIDS, multi-drug resistant tuberculosis, and West Nile Virus and the prevention of illness-causing factors like lead paint, heroin addiction, homelessness, smoking, and unhealthy foods. In Epidemic City, historian of public health James Colgrove chronicles the challenges faced by the health department in the four decades following New York City's mid-twentieth-century peak in public health provision.

This insightful volume draws on archival research and oral histories to examine how the provision of public health has adapted to the competing demands of diverse public needs, public perceptions, and political pressure.

Epidemic City delves beyond a simple narrative of the NYC Department of Health's decline and rebirth to analyze the perspectives and efforts of the people responsible for the city's public health from the 1960s to the present. The second half of the twentieth century brought new challenges, such as budget and staffing shortages, and new threats like bioterrorism. Faced with controversies such as needle exchange programs and AIDS reporting, the health department struggled to maintain a delicate balance between its primary focus on illness prevention and the need to ensure public and political support for its activities.

In the past decade, after the 9/11 attacks and bioterrorism scares partially diverted public health efforts from illness prevention to threat response, Mayor Michael Bloomberg and Department of Health Commissioner Thomas Frieden were still able to work together to pass New York's Clean Indoor Air Act restricting smoking and significant regulations on trans-fats used by restaurants. Because of Bloomberg's willingness to exert his political clout, both laws passed despite opposition from business owners fearing reduced revenues and activist groups who decried the laws' infringement upon personal freedoms. This legislation preventative in nature much like the 1960s lead paint laws and the department's original sanitary code reflects a return to the 19th century roots of public health, when public health measures were often overtly paternalistic. The assertive laws conceived by Frieden and executed by Bloomberg demonstrate how far the mandate of public health can extend when backed by committed government officials.

Epidemic City provides a compelling historical analysis of the individuals and groups tasked with negotiating the fine line between public health and political considerations during the latter half of the twentieth century. By examining the department's successes and failures during the ambitious social programs of the 1960s, the fiscal crisis of the 1970s, the struggles with poverty and homelessness in the 1980s and 1990s, and in the post-9/11 era, Epidemic City shows how the NYC Department of Health has defined the role and scope of public health services, not only in New York, but for the entire nation.

2) Aaron Carroll at the Incidental Economist writes about the subtleties of life expectancy. His main point is that infant mortality skews life expectancy figures so much that if you're talking about end-of-life expectations for adults who have already passed those (historically) most perilous times as a youngster, you really need to look at different data altogether.

The blue points on the graph below show life expectancy for all races in the US at birth, while the red line shows life expectancy amongst those who have reached the age of 65. Ie, if you're a 65-year-old who wants to know your chances of dying (on average!) in a certain period of time, it's best to consult a more complete life table rather than life expectancy at birth, because you've already dodged the bullet for 65 years.

(from the Incidental Economist)

History refresh: AZT and ethics

A professor pointed me to this online history and ethics lesson from the Harvard Kennedy School's Program on Ethical Issues in International Research: The Debate Over Clinical Trials of AZT to Prevent Mother-to-Infant Transmission of HIV in Developing Nations. It's surprisingly readable, and the issues debated are surprisingly current.

In 1994, researchers in the US and France announced stunning news of a rare victory in the battle against the AIDS pandemic. Studies conducted in both countries had shown conclusively that a regimen of the drug AZT, administered prenatally to HIV-positive pregnant women and then to their babies after birth, reduced the rate of mother-to-infant transmission of HIV by fully two-thirds. The results of the clinical trials constituted "one of the most dramatic discoveries of the AIDS epidemic," the New York Times declared, and one of the most heartening as well.

The new regimen--known by its study name, AIDS Clinical Trials Group (ACTG) 076 or, often, simply "076"--offered the epidemic's most vulnerable targets, newborns, their best hope thus far of a healthy childhood and a normal life span. The number of infants who might benefit from this research was significant: according to World Health Organization (WHO) figures, as many as five to ten million children born between 1990-2000 would be infected with HIV. In the mid-1990s, it was estimated that HIV-infected infants were being born at the rate of 1,000 a day worldwide.

So impressive were the findings of ACTG 076--and so substantial the difference in the transmission rate between subjects given AZT and those given a placebo (eight percent versus 25 percent)--that the clinical trials, which were still ongoing, were stopped early, and all participants in the studies were treated with AZT. In June 1994, after reviewing the study results, the US Public Health Service recommended that the 076 regimen be administered to HIV-infected pregnant women in the US as standard treatment to prevent transmission of the virus.

But while 076 was hailed as a major breakthrough, the celebration was somewhat muted. For a variety of reasons, the new treatment regimen would not likely reach those who most desperately needed it: pregnant women in the developing nations of the world and, most particularly, sub-Saharan Africa, where AIDS was wreaking devastation on a scale unimagined in the West.

I think one reason why graduate school can be so overwhelming is that you're trying to learn the basic technical skills of a field or subfield, and also playing catch-up on everything that's been written on your field, ever. True, some of it's outdated, and there are reviews that bring you up to speed on questions that are basically settled. But there's a lot of history that gets lost in the shuttle, and it's easy to forget that something was once controversial. Something as universally agreed upon today as using antiretrovirals to prevent mother-to-child transmission of HIV was once the subject of massive, heart-wrenching debate. I tend to wax pessimistic and think we're doomed to repeat the mistakes of the past regardless of whether we know our history, because we either can't agree on what the mistakes of the past were, or because past conflicts represent unavoidable differences of opinion, certainty, and power. But getting a quick refresher on the history of a is valuable because it puts current debates in perspective.

Review: "The Panic Virus"

Review of The Panic Virus, by Seth Mnookin. Simon & Schuster Jan 2011 (Available at Amazon) [Disclosure: I got a free copy of the Panic Virus from a friend who has a friend that works at the publisher -- I wasn't given the copy specifically to write a review, but it's still probably better to disclose I didn't pay for the book.]

Seth Mnookin's The Panic Virus starts and ends with two stories of parents whose seemingly normal children come down with a serious illness. He describes their children before the episodes, and then their dread as they go downhill, are hospitalized, and fight for their lives. These stories intentionally parallel the narrative of the vaccines-cause-autism movement -- "our child was normal, then he got the vaccine, and then he got autism, so it must have been the vaccine." However, Mnookin's carefully chosen stories don't support the anti-vaccine movement; they do just the opposite and make you feel heartsick for the children affected by vaccine-preventable diseases.

Mnookin knows how to tug on heart strings, and how to get his readers riled up, so it's a good thing that he comes down strongly pro-vaccine. His case studies are selected for emotional value, and they illustrate how a thoughtfully written narrative can humanize statistics about disease outbreaks and the danger of the anti-vaccine movement. But I approve of Mnookin's tactics ultimately because his stories are true -- vaccines save lives, and much harm has been done by the spread of unfounded fear.

That said, Mnookin's book isn't at all a fearmongering tale of what will happen if you don't vaccinate your child -- the bookend stories are just that, and he could probably have included a few more narratives throughout without stretching it. For the most part his book is a sober narrative of a social movement that goes back to the earliest vaccines, but has only come to nationwide fruition with the rise of the Internet.

Mnookin chronicles the development of early vaccines, and, to his credit, spends a good deal of time on what was done badly by the scientists and advocates. The Cutter Incident is there,  along with the 1976 swine flu vaccine. Mnookin doesn't mince words in describing injuries that have been caused by vaccines, and at many times I found myself cringing and thinking "why weren't better systems in place earlier?" and "they really should have done more".

This willingness to confront unpleasant truths is a strong point for the Panic Virus, and it also gives Mnookin an opportunity to introduce the safety innovations that stemmed from each incident, all while setting the stage for the anti-vaccine movement. Another strength is that The Panic Virus also offers compelling humanizations of many of the parents of autistic children who have been involved in the anti-vaccine movement. Their despair at seeing their children suffer, their ostracization in a society where autism is not accepted, their occasionally callous treatment by physicians who have no easy answers to offer -- all of this makes it impossible not to sympathize with them.

For the most part, Mnookin doesn't present parents as the villains of his story. That role is reserved for shoddy physicians, scientists and pseuodoscientists, and most of all for journalists. Andrew Wakefield, Mark and David Geier, and journalist/author David Kirby all come in for harsh reckonings, along with many other "expert witnesses" for anti-vaccine lawsuits. This book left me quite depressed regarding the role of journalists and TV personalities in the whole fiasco. There has been so much bad reporting, and so little good.

While reading The Panic Virus, I kept thinking that its major shortcoming is a lingering uncertainty about its target audience. Is Mnookin writing for the uninitiated who want an introduction to where the anti-vaccine movement? Or is he writing a broadside for those already staunchly in the pro-vaccine community? There are sections where the rhetoric made me think it was the latter, while the majority of the book seems to be for those with little outside knowledge of vaccine science. Since Mnookin cautions so much against being led astray by charlatans who peddle fear with a thin veneer of scientific-sounding verbiage, I wish he had done a bit more to explain the science done in recent years on vaccine safety, thiomersal, MMR, and autism. I understand why an author writing a popular narrative would avoid trying to describe these subjects: they are incredibly complicated and divert the reader from the narrative. [Note that I haven't read Paul Offit's Autism's False Prophets, which I understand might have a bit more of that.] And it's not like good science writing is entirely missing from The Panic Virus. Some things are explained well, but overall there's just a bit too much deference to the authority of  science and scientists for my tastes, especially for a book intended for lay audiences. It's a good book, but not a great book.

I also wish Mnookin had provided a better counter-narrative in the second half of the book. Broadly speaking, the first half follows the development of vaccines and early vaccine injury scares (founded and unfounded), and the second half explores the rise of the anti-vaccine social movement. The second half is missing strong pro-vaccine characters, such as one or two scientists or policymakers who have been working to combat the anti-vaccine crowd. A lot of good research has been done to disprove fallacious claims, and to look for policy solutions aimed at decreasing opt-out rates on a state level, but none of that is here.

To date the anti-vaccine crowd has really won the narrative war: their message is simpler, and scarier, and has the added perk of being anti-establishment in appealing ways. The Panic Virus didn't give me much hope that that would change soon -- although the book itself is mostly a step in the right direction, combining a pro-science view with a few emotional narratives about vaccine-preventable diseases.

Our best hope is that eventually our scientific explanations of autism etiology will solidify a bit more, and coupled with much more demonstrably effective treatments, the snake oil appeal of the "cures" sold by the anti-vaccine movement will lose their charm. One theme of the Panic Virus is that the anti-vaccine movement arose because parents of autistic children weren't getting the sympathy, explanations, and help they needed. Many factors including a lack of understanding by doctors and communities, isolation, weak scientific explanations, and a lack of viable treatments all created a situation like a field of dry grass. When a powerful idea -- "vaccines cause autism" -- arose and was amplified by the echo chambers of Internet communities, it ripped through the dry field like a wildfire, sowing panic and fear. And the fire still hasn't been put out.

The Changing Face of Epidemiology

Unlike many scientific disciplines, undergraduate training in epidemiology is fairly rare. I've met a lot of public health students over the past few months, but only a few majored as an undergrad in public health or something similar, and I haven't met anyone whose degree was in epidemiology. For the most part, people come to epidemiology from other fields: there are many physicians, and lots of pre-med student who decided they didn't want to be doctors (like me) or still want to be. This has many implications for the field, including a bias towards looking at problems primarily through a biomedical lens, rather than through sociological, political, economic, or anthropological ones. Another interesting consequence of this lack of (or only cursory) study of epidemiology before graduate school is that the introductory courses in epidemiology at most schools of public health are truly introductory. If you're a graduate student in biochemistry and molecular biology (my undergraduate field), my guess is that it's assumed you know something about the structure of nucleic acids, have drawn the Krebs cycle at some point, and may even have heard the PCR song.

In epidemiology we're essentially starting from scratch, so there's a need to move rapidly from having no common, shared knowledge, through learning basic vocabulary (odds ratios, relative risk differences, etc.), all the way to analyzing extremely complex research. This presents pedagogical difficulties, of course, and it also makes it easier to miss out on the "big picture" of the field of epidemiology.

For one of our earliest discussion labs in my epidemiologic methods course, we discussed a couple papers on smoking and lung cancer. While "everyone knows" today that smoking causes lung cancer, it's a useful exercise to go back and look at the papers that actually established that as a scientific fact. In terms of teaching, it's a great case-study for thinking about causality like an epidemiologist. After all,  most people who smoke never get lung cancer, and some people get lung cancer without ever smoking, so establishing causality requires a bit more thought. Two of the papers we read are great for illustrating some changes that have occurred as epidemiology has changed and matured over the last 50 years.

The first paper we looked at is "The Mortality of Doctors in Relation to Their Smoking Habits: A Preliminary Report," written by Richard Doll and Bradford Hill in the British Medical Journal in 1954. (Free PDF here)  Doll and Hill followed up their groundbreaking study with "Mortality in relation to smoking: 50 years' observations on male British doctors" in 2004 (available here).

A few observations: First, the 1954 paper is much shorter: around 4 1/2 pages of text compared to 8 1/2 in the 2004 article. The 1954 paper is much more readable as well: it's conversational and uses much less specialized vocabulary (possibly because some of that vocabulary simply didn't exist in 1954). The graphs are also crude and ugly compared to the computer-generated ones in 2004.

The 2004 paper also ends with this note: "Ethical approval: No relevant ethics committees existed in 1951, when the study began."

Beyond the differences in style, length, and external approval by an ethics committee, the changes in authorship are notable. The original paper was authored by merely two people: a physician and a statistician. The 2004 paper adds two additional authors for a total of 4 (still small compared to many papers) -- and notably, the two new authors are both female. During those 50 years there was of course great progress in terms of women's representation in scientific research.  While that record is still spotty in some areas, schools of public health today are producing many more female scholars than males -- for example, current public health students at Hopkins are 71% female.

There has been a definite shift from the small-scale collaboration resulting in a paper with an individual, conversational style to the large-scale collaboration resulting in an extremely institutional output. One excellent example of this is a paper I read for an assignment today: "Serum B Vitamin Levels and Risk of Lung Cancer" by Johansson et al. in JAMA, 2010 (available here).

The Johansson et al. paper has ~8 pages of text, 47 references, 2 tables and 2 figures (all of which are quite complicated) and a number of online supplements. Its 46 authors have between them (by my count) 33 PhDs, 27 MDs, 3 MPHs, and 6 other graduate degrees! It's hard to tell gender just by name, but by my count at least half of the authors are likely female.

Clearly, epidemiology has changed a lot in the last 50 years. Gone are the days of (at least explicit) male domination. Many of the problems with the field today are related to information management and large-scale collaborations. Gone are the days of one or two researchers publishing ground-breaking studies on their own -- many of the "easy" discoveries have been made. Yet many of the examples we learn from -- and role models young public health researchers may want to emulate -- are from an earlier era.