Spillover: Animal Infections & The Next Human Pandemic

Among the very first postings to ProMED-mail,  the listserve for the Program for Monitoring Emerging Diseases now reaching more than 60,000 animal and human health experts per day,  was an October 1994 letter to The New York Times by Barbara Hatch Rosenberg,  then director of the Federation of American Scientists Biological Program.

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Opened Rosenberg,  “The next global epidemic, which may be more devastating than AIDS,  is waiting to strike, and we are pitifully unprepared to fend it off.   In recent years new diseases have been emerging and old ones reappearing in all parts of the world,  spurred by environmental disruption,  population movements,  urban crowding,  and the intrusion of commerce into once-isolated corners of the earth.”

. After detailing her case for several paragraphs,  Rosenberg finished,  “The human population risks crashing as gypsy moth populations crash periodically,  through the uncontrollable spread of infectious diseases.”

. Though starting from the same premise and concluding with the same example,  Spillover author David Quammen neither mentions Rosenberg in his 530-page text,  nor cites her in many pages of footnotes and acknowledgements.  Quammen does not mention or cite ProMED either,  though he does mention and cite many ProMED contributors.

. Yet Spillover is a detailed if unaware expansion of Rosenberg’s 1994 warning,  exploring many more recent examples of emerging disease in depth and detail.  Hendra virus,  SARS (short for Sudden Acute Respiratory Syndrome),  Nipah virus, Ebola virus,  and the H5N1 avian flu are among the diseases that Quammen singles out for special attention,  along with AIDS.  Pointing out that each of these diseases is zoonotic in origin, meaning that it crossed into humans from animals, Quammen tracks each disease back to whenever and wherever the “spillover” occurred,  as indicated by the best available historical and genetic evidence.

. This takes Quammen,  a longtime National Geographic correspondent,  far afield with research teams in Africa and Southeast Asia,  and into biologically secure U.S. laboratories where even angels might fear to tread without HazMat suits.

. Quammen’s previous blockbuster book, among several,  was Monster of God:  The man-eating predator in the jungles of history and the mind (2003).   Quammen observes in Spillover that parasites and disease-carrying microbes and viruses are predators too,  but instead of eating smaller prey from the outside in,  they tend to eat larger prey from the inside out.  Parasites and pathogens,  however,  usually cannot survive if they kill their hosts before reproducing successfully in a manner that enables offspring to invade new hosts.  Therefore,  the host species for zoonotic diseases tend to be animals who have co-evolved with the disease-transmitting agents,  so as to develop a high tolerance for the infection,  if not actual immunity.

. Often the host species have harbored diseases for millions of years before infecting other species sufficiently to start a pandemic. Then,  however,  a disease may race rapidly through a population of animals–including humans–who have not evolved any resistance,  but whose bodies prove vulnerable to the specific characteristics of the pathogen.  Usually outbreaks that jump from one species to another hit a biological dead end,  either because they kill their new hosts before reproducing and spreading,  or because they simply don’t find opportunities to spread further. Sometimes, though,  the pathogen mutates,  enabling a new form to establish itself within a new host, and/or finding new ways to infect vulnerable species.

. Bats are disproportionately often the hosts for diseases that become pandemic in other species,  Quammen explains,  because there are perhaps more bat species than species of all other mammals;  probably only humans are more numerous and broadly distributed;  bats had already emerged in almost their present form and diversity more than 50 million years ago,  and might actually be much older than that;  and until relatively recently,  humans and species kept by humans had relatively little exposure to bats.  Humans,  livestock,  and dogs are mostly diurnal,  dwelling on the ground;  bats are noctural,  dwelling either in caves or high places,  rarely coming to ground except to die. Dogs,  foxes,  raccoons,  and skunks,  all curious creatures who might investigate dying bats too closely and be bitten,  each eventually came to incubate an endemic rabies strain evolved from bat rabies,  but even after thousands of years of exposure to rabid dogs,  in particular, there is no form of rabies known to be incubated and transmitted by humans or most other mammals, except when the victims are already in extremis.

. Other bat-borne diseases,  including Hendra virus,  Nipah virus,  SARS,  and Ebola, have recognizably afflicted humans only after humans replaced much forest bat habitat with structures and food production facilities that provide alternate habitat and sustenance–such as belfries,  the Australian stables where Hendra virus first infected humans,  and pig pens and date palm plantations,  where Nipah virus emerged in Malaysia and Bangladesh.

.Quammen refers often to the “SIR” model of epidemics published in 1927 by Anderson G, McKendrick,  a medical doctor,  and William Ogilvy Kermack,   a chemist who was blinded by an exploding experiment and turned to applying math to epidemiology.  “SIR” stands for “susceptible, infected,  and recovered.”  The progress of epidemics can be tracked by the movement of living beings through the three categories.  Much depends upon whether survivors of a disease in the “recovered” category become dead ends for the infection,  or remain capable of transmitting it, even after recovering from all the evident symptoms.

. Preventing emerging diseases from spreading is largely a matter of reducing the susceptible populations,  whether through vaccination,  changing habits and customs, or–as is often done with diseases in domestic species when public officials do not know what else to do–trying to kill the entire population at perceived risk.  This procedure is called “stamping out,”  in analogy to stamping out the sparks from a fire.  Quammen writes little about “stamping out,”  but the prevalence of “stamping out” is both central to humane concerns about zoonotic disease control and to understanding why the enormous wastes of life it entails seldom either promptly or demonstrably stop epidemics. Indeed,  “stamping out” may accelerate the likelihood that a disease will find a new host, albeit that it may not immediately re-emerge from the new host in a deadly form.

. Many millions of chickens and pigs have been killed in recent years,  often by live burning or live burial,  to try to stop the spread of SARS,  H5N1,  and other diseases, especially in Korea and southern Asia.  Some of the diseases,  notably foot-and-mouth,  rarely kill the infected animals and do not pass to humans,  but reduce the market value of the animals and are therefore handled as if they were actually deadly–most notoriously in Britain, where the authorities responded to foot-and-mouth disease in 2001-2002 as they belatedly had to “mad cow disease” five years earlier,  after discovering that it could could occasionally kill people who eat beef.  The most numerous victims of “mad cow disease,”  detected a decade earlier, were cattle and sheep who were fed the processed remains of other cattle and sheep.

. Sometimes mass killing spreads the “fire” instead of stopping it,  especially when the “stamping out” approach is attempted with free-roaming wildlife.  Thus,  though Quammen does not delve into raccoon rabies,  “stamping out” helped to spread raccoon rabies from Florida to Maine between 1976 and 1991.  The more aggressively raccoons were persecuted,  the farther the survivors roamed to find mates,  and the faster the pandemic moved.

. The raccoon purges repeated one of the best-known catastrophic mistakes in the annals of epidemiology,  the attempt to stop the Black Death in continental Europe and southern China during the Middle Ages,  and in London several centuries later,  by killing cats–who were the major biological control of the black rats who carried the Yersina pestis flea that carried bubonic plague.

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Centuries of efforts to prevent canine rabies by killing dogs have comparably failed,  but with less severe consequences for humans,  though dog purges did immediately precede an outbreak of bubonic plague that killed 56 people in Surat,  India,  in 1994.

. The badger massacre proposed in Britain to try to control bovine tuberculosis is yet another instance of trying to “stamp out” a population of wild,  free-roaming potential carriers.  Most epidemiologists who have looked at the badger “stamping out” strategy expect that it will only superficially and temporarily appear to do anything to control bovine TB;  some predict that persecuting badgers will spread bovine TB to previously uninfected habitat.

. While Quammen writes little about “stamping out,”  he devotes much attention to the role of “bush meat” hunting and consumption in spreading Ebola virus and AIDS.  The latter apparently crossed into humans from chimpanzees, to whom it is in original form also deadly, somewhere in southeastern Cameroon circa 1908, traveling down through tributaries to Sangha River,  then to the Congo River and to the small cities of Brazzaville and Leopoldville,  which is now the Kinshasa metropolis.

. Because AIDS develops slowly,  and–like rabies–requires blood contact to spread,  it required more than 50 years to kill patients from whom tissue samples were collected and stored, and took more than 20 years longer to come to medical attention as an emerging disease.  By then AIDS had become so widely distributed,  by several different avenues,  that it may now have killed approximately as many people as the 1918 swine flu pandemic.

. Ironically,  the earliest major AIDS transmission method may have been mass vaccination to prevent influenza and other viral epidemics.  Invented in 1848,  hypodermic syringes,  as Quammen explains,  “until after World War I were hand-made of glass and metal by skilled craftsmen.  They were expensive, delicate,  and meant to be reused like any other precision medical instrument.

During the 1920s their manufacture became mechanized to the point where two million syringes were produced globally in 1930,  making them more available but not more expendableŠA famous French colonial doctor named Eugene Jamot,  working just east of the upper Sangha River during 1917-1919 treated 5,347 trypanosomiasis (“sleeping sickness”) cases using only six syringes.  This sort of production-line delivery of injectible medicines didn’t allow time for boiling a syringe and needle between uses.”

. Through 1937,  Jamot and colleagues delivered more than 3.9 million injections just against trypanosomiasis,  according to archival research by Canadian microbiologist Jacques Pepin.  “Once the reusable needles and syringes put the virus into enough people–say several hundred–it wouldn’t come to a dead end, wouldn’t burn out,  and sexual transmission could do the rest,”  Quammen assesses.

. Quammen,  unlike many others who have written about emerging diseases,  is a calm and methodical writer,  who spent about 15 years researching Spillover,  in work often overlapping the research behind his other books of distinctively different focus within the broader topics of biodiversity and evolution.  Quammen nonetheless concludes on a pensive and pessimistic note:  while we do not yet know what “The Next Big One” will be,  or when it will come,  human population growth and increased mobility practically guarantee that there will be more pandemics of relatively new and initially little understood diseases that kill tens of millions of people.

. Rosenberg concluded her 1994 letter to The New York Times by noting a “pressing need for surveillance to spot new disease outbreaks early, while there is still time to stop their spread. AIDS has shown the difficulties of trying to cope with a disease once it has become established,” she wrote.  “Yet,  astonishingly enough,  even now no country,  including the United States, and no international organization,  has a system for monitoring the emergence of new or unexpected diseases.  Alarmed at the potential for worldwide disaster,”  Rosenberg continued,  “prominent infectious disease experts from some 40 countries and every continent have come together to draft and seek international support for a global program to monitor emerging diseases.  The World Health Organization would like to implement this proposal,  but it cannot do much without resources and support from its member governments.”

. WHO,  nearly 18 years later,  still tends to respond to emerging diseases at least a day late and a dollar short,  despite the efforts of many dedicated WHO personnel.  Structurally,  as an arm of the United Nations,  WHO is too politicized and involved in too much else to monitor emerging disease effectively.

. But the ProMED listserv does.  Begun by a handful of epidemiologists who set up and moderated the postings on a rotating basis as volunteers in their limited free time,  ProMED today still works much as it did in 1994,  on a “stone soup” basis,  with a budget smaller than the cost of safely treating even one human Ebola, Hendra,  SARS,  or rabies case.  Now,  however, there are several dozen moderators.  Some of the cofounders, having retired from long and distinguished conventional careers in academia or government or hospital medicine,  now appear to give ProMED full-time attention,  along with other older experts who joined later and pitched in.

. Each ProMED moderator is an eminent authority on specific types of zoonoses.  Drawing upon their far-ranging expertise,  the moderators provide on-the-fly peer review of postings, offering thoughtful commentary about the evidence and what it may point toward.  Most importantly, however,  ProMED draws immediately from the cumulative knowledge of all 60,000 participants. Few if any other networks pool,  sift,  and rapidly distill a comparable volume of ideas and information pertaining to any sort of fast-developing problem.

. ProMED could be compared to a responsibly managed newsroom.  Indeed it is a newsroom, albeit with the reporters and editors scattered about the globe.  But ProMED also and perhaps more aptly could be compared to the triggering mechanism for the immune system of an organism, recognizing threats as rapidly as they appear and relaying information that enables public health agencies worldwide to respond.

. As Quammen points out in his final chapter,  “Whatever happens after that will depend on science,  politics,  social mores, public opinion,  public will,  and other forms of human behavior.  It will depend on how we citizens respond.”

. As a ProMED member almost since inception,  already citing ProMED postings in news coverage before Rosenberg wrote to The New York Times,  I recall that the official response to almost every emerging disease pandemic of the past 18 years has at least at first included doing almost the opposite of the moderators’ advice.

. I also recall that some of the moderators themselves,  especially in the early years,  at times offered “conventional wisdom” that they later recognized themselves as misguided,  after they learned much more from other members about the cultural,  animal behavioral,  and ecological dimensions of the issues they were confronting. Skepticism about the efficacy of “stamping out” evolved slowly.

. An understanding of the contributions of humane work to zoonotic disease control,  and even more,  of the potential of humane work and animal advocacy to advance zoonotic disease control,  has evolved more slowly still–not, however,  because of any evident resistance to the notion,  but because of a lack of participation by members of the humane community, who are nonetheless in the forefront of providing public information about many zoonotic disease vectors,  and lead the universe in providing anti-rabies vaccination.

. Much as emerging diseases seem to become more “intelligent” as they spread,  a phenomenon Quammen explains as the cumulative effect of chance mutations that benefit the pathogen, ProMED is making the “antibody” response to emerging disease swifter and smarter.

. AIDS was the last “big one” to erupt pre-ProMED.  Something else may yet come along–indeed,  may already be spreading–that will have a catastrophic effect comparable to AIDS,  confounding the ProMED network much as resistant bacteria thwart antibiotics,   but as of the moment,  post-ProMED,  even the most virulent epidemics have been contained while still afflicting relatively few humans,  and I suspect ProMED has also contributed mightily to lowering the animal death toll,  even though disease containment efforts continue to kill more domestic animals than any other human activity except slaughter for human consumption.