Philip Alcabes discusses myths of health, disease and risk.

Plague Did Not Begin in China. And Why Should Anyone Think It Did?

Nicholas Wade, the NY Times‘s science writer, jumps the gun with a story today asserting that plague began in China.  Maybe it’s understandable:  you don’t often get a front-page story if you’re a science reporter, so once in a while you take some shaky science and turn it into an international incident.

But to understand why the story is wrong means recognizing a weakness of science as it’s often practiced today.

Wade’s claim is based on two papers published this month.  A relatively well done study by Haensch et al. in PLoS Pathogens earlier in October tested human remains from well-identified plague pits — burial sites for medieval plague victims — in different parts of Europe.  Researchers amplified DNA sequences of the plague bacterium, Yersinia pestis, at specific genetic loci, and tested to see whether the DNA matched known sequences of contemporary Y. pestis genes.

The findings published in PLoS suggest that the Black Death and perhaps subsequent waves of plague in Europe were indeed caused by Y. pestis — which would tend to debunk the theory proposed by some British researchers that the Black Death was some kind of viral hemorrhagic fever outbreak.  And they suggest that there were at least two widely different Y. pestis strains involved in different parts of Europe.  Here’s a bit of the abstract:

[O]n the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route.

The main weakness here is that DNA could not be amplified from all of the plague pits the researchers studied, but after using alternative means to test the DNA debris against contemporary gene sequences the investigators concluded that the absence of genetic material reminiscent of one strain of Y. pestis was evidence that that strain was not in play in that part of Europe at the time.  Probably right, but stretching the available evidence.

It’s a common mistake, alas.  To paraphrase Karl Popper:  just because you see DNA from white swans and don’t see any DNA from black swans, doesn’t mean that black swans don’t exist.

Still, the PLoS paper is persuasive that more than one strain of the plague bacterium was circulating, and probably causing deaths, in the plague period in Europe.  Of course, it says nothing about China.

So where does the NYT reporter get his headline-grabbing story?  A paper to be published in Nature Genetics online (still embargoed at the time I’m writing, but a summary appears here) states that the sequences of plague DNA amplified from plague pit remains, as well as contemporary isolates, can be placed on a molecular clock because of the occurrence of unique mutations.  Winding the clock backward, the researchers conclude that the Ur plague organism, ancestor of all Y. pestis, came from the far east.

The molecular biology may be unimpeachable, but the inferences about history aren’t supportable by molecular evidence.  That might explain why they’re almost certainly wrong.

The problem (scientists, I hope you’re listening!) is that you may know very well what you know, but you can never know what you haven’t seen.  The hereditary tree has its roots in China.  Here is one proposed by some of the same authors in a 2004 PNAS paper:

In this set-up, isolates of Y. pestis from China seem closest to the primordial strains.

But of course, the molecular clock doesn’t take account of strains that are no longer extant.  And ones that haven’t been unearthed.  The contemporary researchers don’t see them (or don’t know how to look), so they don’t exist.

It’s a bad mistake, inferentially.  And historically.  It’s where the NYT writer goes wrong.  Almost certainly, plague did not begin in China.  It began as an enzootic infection of small mammals in the uplands of central Asia.  This is the story convincingly relayed by William H. McNeill in Plagues and Peoples a generation ago, and none of the many accounts I’ve read since then has debunked it.

Plague would have had to begin in an ecosystem in which it could circulate at moderate transmission rates with little pathogenicity among small mammals (the natural host of the bacterium).  Exactly where it started remains open to question, but it was probably in the area that is now Turkestan/Uzbekistan.  With the development of trade between that region and China, intermixing of local (central-Asian) animals with caravan-accompanying rats would have allowed Y. pestis to adapt to the latter.

Quite possibly China was the source of the first human outbreaks of plague — because the river valleys of China were settled and agricultural (therefore offering feeding opportunities for rats as well as multiple opportunities for rat-human interaction) long before Europe was.  That fact probably accounts for the biologists’ (mistaken) belief that their early samples show that Y. pestis started out in China.

But plague began as — and remains — a disease of animals.  To acknowledge that human outbreaks in China preceded the human outbreaks in Europe (the Justinian plague that began in the mid-sixth century, the Black Death that began in the 1340s, and subsequent visitations) is not the same as saying that plague originated in China.

Which it didn’t.  Plague is an animal disease from Central Asia.  Plague’s long history is the usual one:  ecosystem change, trade, animal-human interactions, alterations in climate and economic conditions, and occasional opportunities for mass human illness.   (One world, one health.)

Above all, remember that science is only capable of drawing conclusions about what scientists can observe.  Don’t be taken in by hair-raising stories.  Even in the NY Times.

Bed Bug Worry, Mosquito Mayhem

You hear a lot about bed bugs these days, here in New York City.   The bed bug infestation has become part of New York angst, the newest of our plagues.  The NY Times had its top infectious disease writer cover the recent CDC-EPA joint statement on bed bug control.  There’s even an iPhone app with GPS-enabled bed bug maps of New York and other big cities.

Early this month, a couple of friends, thinking they might splurge on a downtown hotel to celebrate their tenth wedding anniversary, were soliciting bed bug reports before choosing where to stay.  And at a family gathering last week, one young man — recently graduated from an elite college, an intellectual usually given to ironic mockery of the nuttier trends evident in the generation that still uses e-mail — told me that while he’s afraid of bees and doesn’t like mosquitoes, bed bugs really terrify him.

Bed bugs are unpleasant.  Their bites can itch.  Their feces and molted shells can set off asthma attacks or other allergies.  It’s sensible to avoid them, and get rid of them if they’re in your home.  I wrote a few months ago that it makes perfect sense that health authorities do something to limit bed bug woes.

But if you ask me what insects worry me most as a public health professional, I certainly wouldn’t say “bed bugs.”  Ticks, especially as Lyme disease spreads geographically.  Phlebotomine (sand) flies, as leishmaniasis becomes a more serious problem.  Mosquitoes, always.   Bed bugs are far from the top of my list.

The Aedes mosquitoes that carry yellow fever, dengue, rift valley fever, and chikungunya viruses, are most troubling right now.  Ae. aegyptii most of all, of course, but increasingly Ae. albopictus.

An extensive outbreak of rift valley fever in South Africa produced dozens of human cases earlier this year, and seems to be continuing among livestock.  An epidemiologist friend in Europe told me a few weeks back that he and other European disease control specialists, already concerned about dengue and yellow fever, are looking at RVF exposures in the southern part of the continent — a worrisome finding for a virus that has primarily been African.   The European Center for Disease Control is, appropriately, concerned about the establishment of Ae. albopictus in Europe.

Ditto chikungunya, which as produced 33 cases in Delhi, India, this year, possibly including an illness in the city’s mayor.

Dengue  demands control most pressingly of all.  Although the CDC is busily advising Americans not to worry (“Nearly all dengue cases reported in the 48 continental states were acquired elsewhere by travelers or immigrants,” its info page reads), there is active spread through much of the Caribbean basin — see the map at Dengue Watch, for instance.  The Mexican ministry of health reports dengue transmission in areas bordering the U.S.  There has already been an outbreak in Texas (in 2005).  And other highly industrialized countries with strong surveillance and control systems are experiencing dengue cases, including the first report of domestic transmission within France this summer.

(Hats off to Crof at H5N1, who has been following both chikungunya and dengue assiduously.)

The expansion of the range of Ae. albopictus, a secondary but by no means ignorable vector for dengue, makes the geographic extension of these pathogens worthy of concern.

With climate changing, trade routes always in flux, area spraying of insecticide disfavored because of environmental considerations, and of course mosquitoes evolving to take advantage of new niches, it seems unlikely that North Americans can go on counting on the mere improbability that virus and vector will coincide.

Mosquito control programs are in place, and U.S. authorities expend considerable effort at controlling Ae. aegyptii in Puerto Rico.  But the West Nile fever outbreak of 1999 and its subsequent extension in North America reveals the porousness of mosquito control.

Mosquitoes are much more worrisome than bed bugs.

In the mouth of death

The Miami Herald‘s article yesterday on cholera reaching Port-au-Prince quotes a homeless resident of the Haitian capital, fearful at the approach of the disease:  “Of course I’m scared — we’re in the mouth of death.”

Haiti today: in the mouth of death.  Not just Haiti, of course.  Deadly, gruesome, and hard to stop, cholera seems emblematic of the many failures that preceded the earthquake and have been exacerbated since.  We Americans are paying attention to Haiti lately — because of the earthquake; because of proximity; or because however bad things are here, what with high unemployment and poor economic prospects, Haiti conveniently reminds us of what we’re not.  But really much of the world, of the dollar-a-day world, is in the mouth of death much of the time.

With cholera, the relief agencies are hard at work.  Ansel Herz, a freelance journalist who blogs at Mediahacker, writes that there have been five cholera deaths in Port-au-Prince as of this morning, although the authorities say those people came to the capital from elsewhere and that cholera isn’t yet spreading in Port-au-Prince.  Still, cholera mortality is over 200 nationally.   Herz describes the earnest efforts of aid workers.  But his reportage, along with that of the Miami Herald, the NY Times, and others, also reveals the shortcomings of relying on aid organizations to contain the complex problems — of which cholera is the latest.

Partners in Health, to my mind the most earnest and committed of the aid organizations, is compiling reports on the spread of cholera and, of course, trying to do something about it.  But here’s the problem: if it’s the aid workers who are trying to stop cholera, it’s too late.  I don’t mean that they’ll fail; I mean that there should have been infrastructure in place to make sure cholera doesn’t break out at all.  And if there’s no such infrastructure, cholera will happen again, however well it’s halted this time.

It’s hard to escape the image, provided by Herz, of a new water tank installed near Cité Soleil by the International Organization for Migration — which stands empty, because nobody has provided clean water to fill it.

This is the problem with aid:  of course there must be organizations, like Partners in Health or MSF, that provide relief to the suffering.  But if there’s no support, or demand, for permanent public health infrastructure, the aid workers will always be scrambling to keep up with crises, and the crises won’t stop happening.

In the New Yorker this month, Philip Gourevitch takes a skeptical view of humanitarian aid (abstract here; full article requires subscription).  He summarizes the message of Dutch journalist Linda Polman sympathetically:

The scenes of suffering that we tend to call humanitarian crises are almost always symptoms of political circumstances and there’s no apolitical way of responding to them – no way to act without having a political effect.

Now, Gourevitch is talking specifically about crises created by political conflict.  But something of this dilemma pervades the problem of relief.  Public health is political.  It takes political will — not just oral rehydration therapy — to install water supplies and sewage systems, and housing with running water even for the poor.

Canada is going to send a million dollars to Haiti to help with the cholera problem (thanks to Crof at H5N1 for picking that up).  No doubt the U.S. will outdo its neighbor in looking mournful and concerned, and donating even more money.  But where’s the support for good government, and real public health, and necessary infrastructure?

What are we doing to promote the implementation of good public health? What are we doing to generate the political will to install even just the ordinary civil engineering works that we take for granted in America, but which would make a difference to the people who are living in the mouth of death?

Why Vaccinate Children Against Flu?

Scientists shill for vaccine manufacturers in doing routine research.  This week, HealthDay reports that University of Rochester researchers found lower flu-immunization coverage in states with less Medicaid coverage for vaccination.   Instead of asking whether pediatric flu immunization has any public health value, research like this assumes that flu immunization is useful.  It helps make sure the vaccine manufacturers sell more flu vaccine.

What is the value of mass immunization of children against flu?

CDC claims that flu is dangerous for children and recommends immunization.  This claim seems to be based on the 50 to 150 pediatric deaths attributed to flu each year.  Preventing children’s deaths is a good reason to immunize those who might get very sick were they to be exposed to influenza.

But to translate a small number of possibly preventable deaths into a national policy of mass immunization?  That takes a special relationship with the vaccine manufacturers (see here and here and here and here for my comments on the collusion of officials with pharmaceutical interests).

The evidence that flu vaccine is effective in children is shaky, as Dr. Tom Jefferson’s exhaustive scrutiny of study data reveals.  Immunization of children seems to be weakly effective at reducing influenza-like illnesses in a general population, as Ritzwoller et al. showed in a study published in Pediatrics in 2005.  Partial immunization was ineffective — an issue worth considering if more than a single dose is required.

A few studies suggest that mass immunization of children is a way to prevent flu among young adults.

A community trial of immunization of children against flu, published in Vaccine in 2005, showed the ineffectiveness of immunizing children:  there was no reduction in acute respiratory illnesses among children in the concurrent or subsequent flu seasons, compared to communities where kids were not immunized.  There were slight reductions in ARI incidences among adults in the community where children were immunized — but this study wasn’t designed to show whether it was the immunizing of kids that protected the adults, or something else.

Similarly, a 2000 study published in JAMA by Hurwitz et al. showed that flu immunization of children in day care had the effect of reducing acute febrile illnesses among household contacts, compared to household contacts of daycare attenders who were not immunized (abstract here, full article requires subscription).  So immunizing children in daycare might help their parents to avoid getting sick.

In general, there’s suggestive evidence that mass immunization of small children against flu lessens the impact of flu outbreaks among young adults.

But few young adults die of flu.  It’s an annoying and sometimes serious illness.  The reason the public health authorities are interested in preventing flu among young adults isn’t to reduce suffering; it’s to keep them from staying out of work.  Should we immunize children so that the nation’s economic machine doesn’t slow down?

To put it a little differently:  should we shift large amounts of taxpayer money into the hands of pharmaceutical and vaccine manufacturers for the purchase of flu vaccine for children, basically in order to spare employers the loss in profits that would arise when workers stay home?

The news from ProPublica this week, that they and associated journalists found many cases of physicians taking money from big pharmaceutical companies, is alarming but comes as no surprise.  ProPublica’s new searchable database shows that the seven pharmaceutical companies (collectively accounting for 36% of market share) that provided data together made $257.8 million in payments to physicians.

What’s more alarming is that pharmaceutical companies often don’t even have to bother paying to push their products.  That’s especially true when the product is a vaccine.  Even flu vaccine, despite its limited and highly variable effectiveness.  Policy decisions made by the Advisory Committee on Immunization Practices and CDC, practice decisions by medical organizations, research-grant funding, and so on are thoroughly organized around immunization.  Despite the evidence.