PUBLIC HEALTH

PREVENTING THE NEXT PANDEMIC An international network for monitoring the fl ow of viruses from animals to humans might help scientists head off global epidemics By Nathan Wolfe

weat streamed down my back, thorny As the chimps feasted on the monkey’s raw KEY CONCEPTS shrubs cut my arms, and we were losing fl esh and entrails, I thought about how this them again. The wild chimpanzees my scene contained all the elements of a perfect ■ Most human infectious S colleagues and I had been following for nearly storm for allowing microorganisms to jump diseases originated in animals. fi ve hours had stopped their grunting, hooting from one species to the next, akin to space trav- and screeching. Usually these calls helped us elers leaping at warp speed from one galaxy to ■ Historically, epidemiolo- follow the animals through Uganda’s Kibale another. Any disease-causing agent present in gists have focused on Forest. For three large males to quiet abruptly that monkey now had the ideal conditions un- domestic animals as the surely meant trouble. Suddenly, as we ap- der which to enter a new type of host: the chimps source of these scourges. But wild animals, too, have proached a small clearing, we spotted them were handling and consuming fresh organs; transmitted many diseas- standing below a massive fi g tree and looking their hands were covered with blood, saliva and es to us, including HIV. up at a troop of red colobus monkeys eating and feces, all of which can carry pathogens; blood playing in the treetop. and other fl uids splattered into their eyes and ■ To address the threat

The monkeys carried on with their morning noses. Any sores or cuts on the hunters’ bodies ) posed by wild animals, researchers are studying meal, oblivious to the three apes below. After could provide a bug with direct entry into the the microbes of these appearing for a moment to confer with one an- bloodstream. Indeed, work conducted by my

creatures and the people other, the chimps split up. While the leader crept group and others has shown that hunting, by photoillustration who come into frequent toward the fi g tree, his compatriots made their animals such as chimpanzees as well as by hu- contact with them. way up two neighboring trees in silence. Then, mans, does provide a bridge allowing viruses to

■ Such monitoring may in an instant, the leader rushed up his tree jump from prey to predator. The pandemic form enable scientists to spot screaming. Leaves showered down as the mon- of HI V began in this way, by moving from mon- ( CHRISTIANSEN JEN emerging infectious keys frantically tried to evade their attacker. But keys into chimpanzees and, later, from chim- diseases early enough the chimp had calculated his bluster well: al- panzees into humans. Getty Images; to prevent them from though he failed to capture a monkey himself, Today HIV is so pervasive that it is hard to becoming pandemics. one of his partners grabbed a juvenile and made imagine the world without it. But a global pan- —The Editors his way down to the forest fl oor with the young demic was not inevitable. If scientists had been

monkey in tow, ready to share his catch. looking for signs of new kinds of infections in SCIENTIFIC OXFORD

76 SCIENTIFIC AMERICAN April 2009 DANGER: Wild animals can carry pathogens capable of jumping into humans— the fi rst step toward be- coming a major infectious killer—so a new plan for avoiding pandemics begins with them.

www.SciAm.com SCIENTIFIC AMERICAN 77 78 78 the local fauna, just as my friends in New Jersey Jersey New in myfriends as just fauna, local the hehunts world doneformillennia: have out the through- humans what hedoes so And here. rare are protein of animal forms monkey. those But villagers might very well prefer pork or beef to tissues. and system hunter’s circulatory in the baboon’s blood now have access to the agents way. the infectious along Any cuts open fl leg, his down drips and sweat own his with mingles prey his from blood the travels, to go before he reaches his village. As the hunter ed the animal for some miles and still has more transport- has He baboon. a50-pound back his on carrying path, aforest along barefoot walks he as shorts cotton simple only wears hunter The day. his about going hunter bushmeat typical a consider vulnerable, are populations African particularly high risk of infection. at be would people these that wesuspected and We pets. populations, human into as wereentering HIV them keep as of strains new well whether todetermine as were trying animals, wild er butch- and whohunt of country can of viruses in rural villagers in the Central Afri- astudy weinitiated when ago, 10 years began Our surveillance vision grew out of research we Viruses Stalking start. they before pandemics stop to needed warning early the provide may ping eavesdrop- such We activity. believe bugs’ the in orchanges microorganisms of new for signs ple who come into frequent contact with them peo- the and animals wild tomonitor plan new abold developed Irecently and my colleagues strains of infl some and virus encephalitis of Japanese case the in as tous, then and ones todomestic animals wild from bypassing orindirectly, HIV, did as animals, wild from directly come they whether diseases to become new allows travel, pandemic air and byroad extensively more quickly,connectedness of human populations, linked so inter- vast the today afew. And toname Ebola, infl including mals, ani- in originated present, and past diseases, infectious ofhuman half Morethan reservoir. animal an from emerged having in notalone is HIV spread. virus’s the mitigate and to intervene able been have well might epidemiologists that, fl af- ithad before itlong about known have could they 1970s, and 1960s the in back Africans icted millions of people. With a head start like If the hunter had his choice, he and his fellow fellow his heand choice, his had hunter the If Central these why wethought To understand

SCIENTIFIC AMERICAN uenza. In response to these threats, uenza, SARS, dengue and dengue SARS, uenza, owing into tries in Africa and Asia. Asia. and Africa in tries coun- 11 in projects health public and research active has currently Emerging Award, Explorer Wolfe National Geographic Society’s the and Award Pioneer Director’s the National Institutes of Health Arecipient 1998. in University infectious diseases from Harvard doctorate in and immunology casting Initiative. He earned a Fore- Viral Global the of director and University Stanford at gy Visiting Professor in Human Biolo- Nathan Wolfe [THE AUTHOR] likely emerged. they which from animals the and diseases 10 such lists right the at table The livestock. of those to crobes of wild creatures, in addition mi- the monitor to need the scores under- fact This animals. wild from come have to believed are humans of Many of the major infectious diseases Wild Animals Diseases from Infectious [CONTEXT] is Lorry I.Lorry

Lokey of ing hunted and butchered gorillas butchered and hunted ing hav- whoreported man a45-year-old example, hunter populations. In one particularly telling the entered had variants three all We that found bug. of the variant distinctive genetically own its harbors species primate of these each and gorillas, and mandrills monkeys, guenon ing includ- primates, tomost native is SFV belongs. rarely pursued by subsistence hunters bysubsistence pursued rarely es of virus- family same of the amember itis and Lancet, we fi which agent, One not previously humans. in seen viruses animal several revealed hunted the and per we gave them. of fi pieces byusing samples these obtain prey. to their We onthem from relied samples blood weneeded activities, hunting and health their about questions with them peppering and forstudy blood of their samples todrawing tion addi- in essential: was cooperation Their data. collecting webegin could trust their gaining after Only game. their toseize going we were that feared noteasy. was Many project on this more distantly. much tohumans related is which adeer, is than hunter tothe microorganisms other and ruses vi- its transfer to likely more is quarry primate his that and family of his that and survival own tral African hunter relies on this food for his Cen- the that are perhaps, differences, only The party. dinner venison annual fortheir ration prepa- in season, deer during farm do ontheir tracted gorilla SFV. gorilla tracted — Our analyses of the blood from the hunters hunters the from blood ofthe analyses Our Persuading the villagers to cooperate with us rst reported in a paper published in 2004 in 2004 in published apaper in reported rst the so-called retroviruses is known as simian foamy virus (SFV), (SFV), virus foamy simian as known is Yellow fever African primates African Chagas’ disease fever Yellow Asian macaques sleeping sickness African West Vivax malaria Rodents Old World primates sleeping sickness East African Chimpanzees Dengue fever Apes Plague Infl Hepatitis B AIDS IES SOURCE DISEASE uenza A Wild birds Wild A uenza mammals Many wild and domestic ruminants Wild and domestic ruminants Wild and domestic — to which HIV HIV to which

April 2009 — — had con- animals lter lter pa-

COURTESY OF TOM CLYNES (Wolfe) [STAGES TO WATCH] From Animal Microbe to Human Pathogen The process by which a pathogen of animals evolves into one exclusive to humans occurs in fi ve stages. Agents can become stuck in any of these stages. Those in early stages may be very deadly (Ebola, for example), but they claim few lives overall because they cannot spread freely among humans. The better able a virus is to propagate in humans, the more likely it is to become a pandemic.

DISEASE EXAMPLES: Reichenowi malaria Rabies Ebola Dengue HIV

Stage 1: Pathogen is present in animals but has not been detected in humans under natural conditions.

Stage 2: Animal pathogen has been trans- mitted to humans but not between humans.

Stage 3: Animal pathogen that can be trans- mitted between humans causes an outbreak of disease but only for a short period before dying out.

Stage 4: Pathogen exists in animals and undergoes a regular cycle of animal-to-human transmission but also sustains long outbreaks arising from human-to-human transmission.

SOURCE: “Origins of Major Human Infectious Diseases,” by Nathan D. Wolfe, Claire Panosian Dunavan and Stage 5: Pathogen has become exclusive to humans. Jared Diamond, in Nature, Vol. 447; May 17, 2007

In those same Central African populations spontaneously. But the fact that SFV and HTLV we also found a variety of retroviruses known TWO-WAY are in the same family as HIV, which did spawn as human T lymphotropic viruses (HTLVs), so STREET a global epidemic, means that epidemiologists named because of their propensity for infecting must keep a close eye on them . immune cells called T lymphocytes. Two of the My colleagues and I have outlined fi ve stages HTLVs, HTLV-1 and HTLV-2, were already in the transformation of a pathogen of animals well known to affect millions of people around into one that specializes on humans. In stage 1, the world and contribute to cancer and neuro- the agent lives only in animals. In stage 2, it can ) logical disease in some infected individuals. But be transmitted to a human only from an animal. HTLV-3 and HTLV-4, which we described in A stage 3 germ is transmitted primarily from an- illustration ( 2005 in the Proceedings of the National Acad- imals to humans, but it can also spread among emy of Sciences USA, were new to science. Giv- Pathogens do not jump only humans for a short time before dying out. Once en the high degree of genetic similarity between from animals into humans—they the agent reaches stage 4, it can sustain longer can also travel in the other direc- HTLV-3 and its simian counterpart, STLV-3, it outbreaks among humans. By the time it attains

); MELISSA THOMAS MELISSA ); tion. Some infectious diseases appears as if this virus was picked up through that people have transmitted, stage 5, it has become an exclusive pathogen of hunting STLV-3-infected monkeys. The origin and continue to transmit, to humans and no longer utilizes an animal host. herder in Italy in herder ( of HTLV-4 remains unclear, but perhaps we animals include: Pathogens in stage 4 or stage 5 have the poten- will fi nd its primate ancestor as we continue to tial to cause massive human die-offs. ■ Tuberculosis (cattle) explore these viruses in monkeys. We do not yet Getty Images know whether SFV or the new HTLVs cause ill- ■ Yellow fever Forecasting the Next Pandemic ness in people. Viruses do not necessarily make (South American monkeys) Had we been watching hunters 30 years ago, we their hosts sick, and viruses that do sicken peo- might have been able to catch HIV early, before ■ Measles (mountain gorillas) ple and even spread from person to person do it reached the pandemic state. But that moment ■ WILFRIED KRECICHWOST KRECICHWOST WILFRIED not always cause pandemics; often they retreat Poliomyelitis (chimpanzees) has passed. The question now is, How can we

www.SciAm.com SCIENTIFIC AMERICAN 79 [PREVENTION PROPOSAL] Building a Surveillance Network By monitoring microorganisms in wild animals and the people who are frequently exposed to them, scientists may be able spot an emerging infectious disease before it becomes widespread. To that end, the author recently organized the Global Viral Forecasting Initia- tive (GVFI), a network of 100 scientists and public health offi cials in six countries (red and orange dots) who are working to track potentially dangerous agents as they move from animals into human populations. The GVFI focuses on tropical regions (green) in particu- lar, because they are home to a wide variety of animal species and because humans there commonly come into contact with them through hunting and other activities. Eventually the GVFI hopes to expand the network to include more countries with high levels of biodi- COUNTRY: Cameroon versity, some of which are shown here (yellow dots). VIRUSES PREVIOUSLY SPAWNED: HIV SENTINEL POPULATION UNDER STUDY FOR NEW PATHOGENS: People who hunt and butcher wild animals

COUNTRY: Democratic VIRUSES PREVIOUSLY SPAWNED: Primary study site (human and animal testing) Tentative site for future study Marburg, monkeypox, Ebola Secondary study site (animal testing only) Tropical region SENTINEL POPULATION: People who hunt and butcher wild animals

prevent the next big killers? Once my colleagues works to document the full range of viruses, and I had determined that we could study bacteria and parasites that are crossing over remote populations effectively, we knew we from animals into humans. could extend our work more broadly to listen in Though still a fl edgling effort, the GVFI now ) on viral “chatter”—the pattern of transfer of has around 100 scientists following sentinel

animal viruses to humans. With global surveil- populations or animals in Cameroon, China, illustration (

lance, we realized, we might be able to sound the Democratic Republic of the Congo, , the alarm about an emerging infectious disease and Malaysia—all hotspots for TAKING ACTION before it boils over. emerging infectious diseases. Many of the sen-

Fortunately, through partnership with tinels are hunters, but we are also screening oth- THOMAS MELISSA ); If investigators fi nd signs that Google.org and the Skoll Foundation we were er populations at high risk of contracting dis- an emerging pathogen has spread able to launch the Global Viral Forecasting eases from wildlife, such as individuals who beyond humans who have direct Initiative (GVFI), a program in which epidemi- work in Asia’s “wet markets,” where live ani-

contact with animals into the );

ologists, public health workers and conserva- mals are sold for food. workers market DRC in

mainstream population, they ( will sound an alarm. Protecting tion biologists the world over collaborate to Finding a new microorganism in a hunter is

the blood supply will be one identify infectious agents at their point of origin only the fi rst step in tracking an emerging patho- Photo AP important step toward preventing and to monitor those organisms as they bubble gen, however. We must then determine whether Cameroon in hunter a pandemic. This measure will require rapid development and up from animals into humans and fl ow outward it causes disease, whether it is transmissible from deployment of a diagnostic test from there. Instead of focusing narrowly on just person to person, and whether it has penetrated KARL AMMANN ( AMMANN KARL for the germ. viruses or a particular disease du jour, the GVFI urban centers, where the high density of occu- ZUYDAM VAN SCHALF

80 SCIENTIFIC AMERICAN April 2009 THE THREAT ority would be to determine the agent’s mode of FROM PETS transmission, which would inform tactics for blocking its spread. If an agent were sexually transmitted, for example, public health offi cials could launch awareness campaigns urging con- dom use, among other precautions. Governments can also take measures to keep new viruses from entering the blood banks in the fi rst place. In fact, following our discoveries concerning the relation between exposure to primates and these new viruses, the Canadian Wild animals and farm animals COUNTRY: China are not the only potential sources VIRUSES PREVIOUSLY SPAWNED: SARS, H5N1 government modifi ed its blood donation poli- SENTINEL POPULATION: “Wet market” workers cies to exclude donors who have had contact for the next major pandemic. Fido and Fluffy—and other pets, with nonhuman primates. too—could harbor pathogens In addition to our forecasting efforts, the devastating to humans. This new science of pandemic prevention includes possibility arises when pets come programs such as HealthMap and ProMED, into contact with germ-carrying which compile daily reports on outbreaks wild animals. The germs can jump into pets, which can then transmit around the world, and cutting-edge cyberwarn- these agents to their owners. ing systems such as those piloted by Google.org to use patterns in search engine data to success- fully forecast infl uenza. Likewise, national and international surveillance and response systems of local governments and the World Health Or- ganization will play an important role in stop- ping the next plague. For our part, we would ultimately like to ex- pand our surveillance network to more coun- ➥ MORE TO tries around the world, including such nations as EXPLORE Brazil and Indonesia, which have a tremendous diversity of animal species that could transmit Naturally Acquired Simian Retro- COUNTRY: Malaysia virus Infections in Central African VIRUSES PREVIOUSLY SPAWNED: Nipah pathogens to humans. Fuller development of the Hunters. Nathan D. Wolfe SENTINEL POPULATION: Wildlife hunters GVFI will be expensive: building out our net- et al. in Lancet, Vol. 363, No. 9413, work so that we have adequate staff and lab fa- pages 932–937; March 20, 2004. pants could fuel its spread. The appearance in an cilities for testing the sentinel populations every urban center, away from the original source, six months and testing the animals with which Emergence of Unique Primate T-Lymphotropic Viruses among would be a particularly worrisome sign of pan- these people are in contact will cost around $30 Central African Bushmeat Hunt- demic potential. million, and keeping it running will cost another ers. Nathan D. Wolfe et al. in Proceed-

); ); In the cases of HTLV-3 and HTLV-4, we are $10 million a year. But if it succeeds in averting ings of the National Academy of beginning to study high-risk populations in cit- even a single pandemic within the next 50 years, Sciences USA, Vol. 102, No. 22, ies near hotspots for emerging infectious dis- it will more than pay for itself. Even just mitigat- pages 7994–7999; May 31, 2005.

hunter in Malaysia in hunter ease, regularly testing them for these viruses. In- ing such an event would justify the cost.

( Bushmeat Hunting, Deforestation, dividuals with sickle cell disease who receive Humans work to forecast a variety of very and Prediction of Zoonotic Corbis routine blood transfusions for their condition complex natural threats. We rarely question the Disease Emergence. Nathan D. are one such population that could become in- logic behind trying to predict hurricanes, tsuna- Wolfe et al. in Emerging Infectious fected early on. If we fi nd people in these popu- mis, earthquakes and volcanoes. Yet we really Diseases, Vol. 11, pages 1822–1827; December 2005. lations who are infected, we would work to ini- have no reason to believe that predicting pan- ) dog ); KAZUYOSHI NOMACHI ( tiate worldwide monitoring of blood supplies, demics is inherently harder then predicting tsu- Origins of Major Human Infectious to protect blood recipients . To that end, we are namis. Given the enormous sums of money re- Diseases. Nathan D. Wolfe, Claire Panosian Dunavan and Jared wet market wet working with our long-term collaborator Bill quired to stop pandemics once they have already ( Getty Images Switzer and our colleagues at the U.S. Centers been established, it only makes sense to spend a Diamond in Nature, Vol. 447,

Reuters pages 279–283; May 17, 2007. for Disease Control and Prevention to develop portion of those public health dollars on stop- new diagnostic tests to check for the presence of ping them in the fi rst place. The ounce of preven- The Global Viral Forecasting Initiative ■ KIN CHEUNG CHEUNG KIN THOMAS BARWICK BARWICK THOMAS viruses in the blood supply. Another urgent pri- tion principle has never been more apt. Web site: www.gvfi .org

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