A New American Epidemic: Dengue Fever

Ok, that's a bit of an alarmist and slightly misleading header - but there's frightful news out this weekend about a new influx of hemorrhagic dengue fever in Mexico. At least it appears frightful. "Hemorrhagic" is a terrifying word, giving rise to visions of ebola virus - and the idea that this exotic disease is on the US's doorstep is enough to spark fears of it crossing over. Indeed, dengue is quite at home in the Americas, contrary to popular perception that all virulent exotic diseases roost in Africa or Asia - and it has been known to cross our border into the Texas.

But let's look at the facts here: The article talks about a "600 percent increase" of dengue in Mexico. I always hate the construction that presents increases more than double in percent terms; it's illogical and not at all helpful. why not say "six-fold" or "six times"? In this case, the reporter seems to have got the math wrong: cases increased from 1,781 in 2001 to 27,000 cases in 2006. That's a 15 fold increase, not 600 percent. But of those 27,000 cases, there were only 20 deaths. That figure gives a more realistic look at the true nature of dengue, even in the hemorrhagic form - as the article mentions, properly treated, there's a fatality rate of 1 percent. That's it - and a long way from an ebola.

That's not to say that the rise of dengue infection isn't something to reckon with. But from what I've read, dengue seems less like a terrifying superbug and more of a beacon disease, one that we can face with common sense precautions; as the CDC notes, the virus takes advantage of human carelessness.

In most countries the public health infrastructure has deteriorated. Limited financial and human resources and competing priorities have resulted in a "crisis mentality" with emphasis on implementing so-called emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission. This approach has been particularly detrimental to dengue control because, in most countries, surveillance is (just as in the U.S.) passive; the system to detect increased transmission normally relies on reports by local physicians who often do not consider dengue in their differential diagnoses. As a result, an epidemic has often reached or passed its peak before it is recognized.

So that implies that this epidemic may be already on the way out. For those who want to get past the AP article, here's the CDC's backgrounder.

HPV Vaccine & the Christian Right

A pretty good backgrounder from HealthDay (Forbes uses their feed on their site) on the controversy of the HPV vaccine and why it sparks debate. And relatedly, an informed friend writes:

I have been following the HPV story for a while. The Conservative Movement has always been inordinately preoccupied with it. Christian conservatives talked about HPV much more than anyone else did long before the Merck vaccine. The reason is that HPV is a sexually transmitted disease against which a condom is almost no help. So they could say only abstinence truly protects you against sexually transmitted disease, which can lead to cervical cancer. That is one reason why they were ready to hate the Merck vaccine. HPV was such a good argument for abstinence, even though the main reason culturally conservatives favor abstinence is social/moral rather than medical.

For an example, here's an interesting article from an interesting evangelical news magazine...

Our Genetic Future

Nice round up of genetic news, mostly new biomarker research, at Genetics & Health blog. Honestly, you could do these things every day - the research is pouring out all over - and it signals two things to me.

1) We're only getting started here: all these 'associations' and 'possible targets' need to get borne out in future research several times over before any real therapies might emerge.

2) But that doesn't mean something hasn't shifted. No doubt we're well on the road to this 'third era' of medicine that I wrote about last week. It's going to be all risks, all the time.

The End of Disease: Guinea Worm Edition

Just saw this story that the WHO announced this week that it could eradicate guinea worm from the globe in two years. Pretty incredible feat, eliminating disease altogether. And this one in particular will be nice to see disappear: More specifically known as dracunculiasis, guinea worm infections are particularly nasty. Here's how it works: Worm larvae live in water, and wait for a host-human to drink - then the larvae make their way from the intestines towards the lower extremities (usually the feet). In a nefarious bit of evolution, the worm festers just below the skin, causing a blister which is characterized by a burning sensation. The burning causes the host to, often enough, soak their foot in water - which is just what the worm has been waiting for. Once in contact with water, the worm releases thousands of larvae and the cycle starts all over again. The treatment is usually to draw the worm out of the body by twisting it around a stick - a grusome method that's been practiced for centuries and may be the source for the symbol of medicine, shown above, the Caduceus (though there's some debate about this).

The Gates Foundation has helped the WHO attack guinea worm, and this accomplishment nicely vindicates their stated mission of eradicating - not just containing or alleviating - the worst infectious diseases on earth. I should note that it's not clear to me whether they are actually on the way to eradicating the very worm itself - ie, elimate the species from the face of the earth, which is kinda remarkable (didn't even need DDT!) - or simply make it so rare as to be effectively eliminated from endemic areas. Either way, it's an amazing achievement - and is likely to give much encouragement to the folks at Gates and elsewhere that disease is, indeed, something we can target and eliminate, given the resources, ambition, and sustained effort. That was certainly the conviction of Pasteur and Koch back in the late 19th century, as I wrote recently. But it hasn't been a realistic target, many would say, for decades now.

As it happens, I had an interesting conversation a few days ago with D.A. Henderson, who ran the WHO's project to eliminate smallpox in the 60s and 70s, and is widely credited with eliminating that scourge from the face of the earth. I asked him what he made of the ambition of Gates and others to eliminate, rather than contain, disease. You might think that, given his own success, Henderson would be one to encourage others to pursue the path of eradication. In fact, he said entirely the opposite: smallpox was the exception, he said, and making 'eradication' your benchmark is a dangerously high goal. He shared a funny story about the idea: "In 1980 I was invited to speak at a meeting to identify what to go after for eradication after smallpox," he said. His answer: Given the technology and resources available, he said, he saw no realistic targets on the horizon. "They never invited me to another one of those meetings," he said with a smile.

What to Eat & Why

Another day, another report on how a certain diet wards off certain diseases/conditions; this time, it's diets high in flavonoids - a kind of antioxidant - reducing heart disease. My interest here isn't in the fact that contary results that came out last month that purportedly refuted the worth of antioxidants - that sort of back/forth on research, especially dietary research, iswellcommented on elsewhere.

My question is: Why doesn't someone come up with a spreadsheet or database of all the possible benefits of various nutritional components? It wouldn't take too much work to compile, and would be a great resource; link-bait if there ever was such a thing. Me, I'm too busy, but someone should...

What's In Your Food?

Food has long been seen as a delivery vehicle for public health - mostly for kids. We add vitamin D to milk to prevent rickets, iodine to salt, even flouride to water - all as a way to get certain substances into the diets of the maximum amount of people. It's always been an intriguing bit of paternalism - a government (usually) mandating an addition for the benefit of the people, whether they want it or not. Typically, the added ingredients are simple, almost benign vitamins and minerals. And the additions have little to do with the actual substance they're bolstering: Folic acid was first added to flour and cereal in 1998 not because iron makes sense as a baking ingredient, nor because most Americans want more iron, but rather as a way to raise the folic acid level in prenatal women, thus preventing neural tube defects (which afflict 2,500 newborns a year). Why cereal? No real reason – the acid is found in leafy green vegetables in nature – except that cereal is widely eaten, and therefore a good vector for the additive.

That's all backstory to a recommendation out of Oxford University today that we start adding deuterium and other isotopes to food as a way of lengthening our lifespans. These are stable isotopes - they're not radioactive - but the basic idea is that the isotope prevents cancer cells from replicating. This one seems like a longshot - it's only been tested on nematode worms so far - but it's a pretty remarkable idea, and a relatively predictable progression of the drug-delivery-through-the-food-supply idea. But boy, it's a long way from vitamin D.

The End of Disease, pt. 1

I've been tooling around with this idea that 1) may be brilliant in its simplicity and clarity or 2) may be totally obvious to everyone but me. It goes something like this: We are entering a Third Phase of medicine - one that spots disease and illness based on risks rather than one that responds to symptoms (phase 1, from pre-history to the mid 19th c), or one that seeks out the causes (phase 2, from circa-1850 to just about now).

These three phases closely parallel our technological capacity to spot disease: Phase 1 was primed to spot symptoms because humans relied on our senses - and nothing more - to recognize illness. If we couldn't see it (or smell it), it wasn't yet evident. Phase 2 emerged with the perfection of the microscope and the discovery of the germ theory of disease: finally we could see disease in its pathogenic form - bacteria, mostly - and thus began a race to find the little buggers that were causing disease. The late 19th century saw a flurry of diagnosis, as the cause of one disease after another was identified, and the Pasteurs and Kochs went about devising antibodies or vaccines to vanquish them. So it went for a century, culminating in the eradication of smallpox in the 1970s, when it seemed possible that we could not only treat causes, but eliminate them from the face of the earth (turns out smallpox was an exception, not a harbinger, but that's another story).

So now this third phase dovetails with the bevy of new diagnostics emerging - devices and techniques that look for certain molecules and DNA strands to not only detect the presence of disease, but predispositions towards certain conditions as well. This what's behind announcements like this one today, that they've found another gene that may be linked to a certain condition (in this case, colon cancer).

This third phase contains elements of what many are calling "personalized medicine," but I hate that term - it sounds too servicey and implies that this is simply regular medicine/clinical practice that's been tailored for you, as if we have a computer watching our health (it's "personalized!"). To my mind, what's happening now is much more than simply a move to personalization; it's an entirely new way of relating to disease and illness, one that's as impactful and as new as the realization that germs - not bad air or bad luck - caused disease. What's happening now makes disease/illness an optional state, one that can be opted out of (ideally) or engineered against (more likely). It's the same sort of thing that's going on by our treatment of high cholesterol - which is, after all, not a disease at all but a natural substance in the body, large amounts of which simply indicate a likelihood to develop heart disease sometime in the future. Or to put it another way: high cholesterol is a "risk factor" for heart disease, not a disease itself. But it's one that we now treat to the tune of $30 billion a year.

What's significant, then, is that with the dawn of genetics - specifically, the emergence of "biomarkers" like certain genes or antibodies that testify to the current or potential presence of disease - we'll be dealing with illness in an entirely different way than ever before in history. For one, we'll be treating disease before it happens, which creates all sorts of ethical issues (when to intervene? How aggressively to treat?). And secondly, we'll be oftentimes "diseased" even when we aren't (using current understanding of the term). This is already picking up heat as "genetic profiling," which can be good - we'll know what our profile holds - and bad - insurance companies, employers, and potential mates could discriminate against us for what our profile shows. It's going to be a messy and remarkable future, to put it mildly.

I'll be posting more about this idea in the weeks to come - but want to get it out there in case anybody has any ideas.

Waking Up to Organ Donation

There's an interesting trend story in the Washington Post about a new early-harvest technique with organ donors - called "donation after cardiac death," it basically means getting the organs as soon as possible, which in some cases means getting close to that vague line between life and death. A few things strike me here: First, implicit in the story - and in all organ transplant stories - is the incredible imbalance between those who need organs and the available supply of organs. Getting better sources and more efficient about supplying organs to those who need them can only be a good thing.

Second, it raises the issue - still verboten in many circles - about creating real, honest markets for organs. Present ethics of organ donation make selling organs impossible. But that only gives rise to black markets, favoritism, and other creepy stuff. Create real, legal opportunities for organ markets - with ample regulatory oversight - and we might better serve those who would otherwise die for want of an organ.

Last, we're only on the tip of the iceberg with these sorts of issues. As organ transplants become easier and more dependable, and as transportation systems make the rapid long-distance transport of organs more feasible, like it or not this is an emerging market that will be served (if I was an investor and amoral and you could invest in such things, I'd say it has all the makings for promsing longterm speculation). Better we face this sort of thing sooner rather than later.

HPV: Consider the Man

Following up on my post last week about the HPV vaccine, and the question of prevalence among men - the LATimes has a story (reg required) that discusses the idea of a male vaccine, and has a prevalence figure. Curiously, they put it at 60% - which is significantly less than the 75% prevalence among women. They don't discuss the discrepancy, however.

Making Drugs That Count

The pharmaceutical industry gets a bad rap for spotting profit opportunities with better skill than medical opportunities. No doubt profit is their primary motive - their public companies, after all - but pharma probably doesn't get enough credit for its overall record at creating medicines that help us live better lives. Sure, they don't do everything we'd ask of them (see the orphan disease problem), but that's the bargain we've made in asking the free market to do the bulk of our medical research. That backdrop makes a new paper at Nature Medicine especially interesting - Carl Nathan is arguing for new ways to align drug research with medical needs. He has two principal recommendations:

First, open-access drug companies—fee-for-service sites within drug companies for collaborations among academics and biotechnology and pharmaceutical professionals, funded by users and government—would bring new ideas and expertise to the development of drugs inde- pendent of market drivers. Second, a patent track that rewards innovation in proportion to its impact on the global burden of disease would provide an incentive for pricing near the cost of production and commit govern- ment and business to improving health care delivery.

I find the open-access suggestion particularly intriguing - and not a little ironic, since he's publishing at Nature, which has struggled with open-access publishing of late. Funny he didn't decide to publish at PLoS Medicine instead...