Perspective Where Do Emerging Pathogens Come from? Understanding the origins of pathogens will help us to combat emerging infectious diseases Mark E. J. Woolhouse nfectious diseases continue to impose a caused a minor public health problem but still huge global public health burden, ac- had severe economic repercussions for affected counting for more than one-quarter of countries; and there is considerable concern I all deaths annually and a similar fraction about the possible emergence of a new subtype of morbidity. In addition to long-estab- of influenza A, with potentially devastating, lished infections such as malaria, tuberculosis, global consequences. and measles, we are also seeing the frequent The evolving nature of infectious disease emergence of new infectious diseases: HIV/ problems is a challenge to microbiologists on AIDS was unknown 25 years ago and is now one several different levels. There are practical chal- of the biggest killers; the virus responsible for lenges, such as developing diagnostics, treat- severe acquired respiratory syndrome (SARS) ments, and vaccines, and of designing effective surveillance and intervention strategies. Plus, there are intellectual challenges, in- cluding understanding the complex and Summary multifaceted causes of the emergence and • Emerging and re-emerging infectious diseases spread of new pathogens and the reemer- pose both practical and intellectual challenges, gence of those previously thought to be in including understanding their complex causes; decline. Neither the practical nor intellec- developing diagnostics, treatments, and vac- cines; and designing effective surveillance and tual challenges are likely to be met without intervention strategies. developing more effective working partner- • Of the catalogued pathogen species that infect ships among those in various disciplines, at humans, 538 are bacteria, 317 are fungi, 287 different institutions, and living in different are helminths, 208 are viruses, and 57 are pro- nations. tozoa; among those associated with emerging and re-emerging infectious disease, viruses are significantly over-represented, whereas hel- minths are under-represented. Pathogen Diversity • Species jumps by pathogens require both the opportunity and capacity to infect a new host A human pathogen can be defined as “a species; recent species jumps have usually in- microbial or parasite species that can infect volved RNA viruses, perhaps because their ge- and is capable of causing disease in humans netic lability allows them to adapt quickly to a under natural transmission conditions.” Mark Woolhouse is new host species. Professor of Infec- • Recently emerging or re-emerging pathogens Humans are affected by an impressive diver- tious Disease Epi- most often are RNA viruses having a taxonom- sity of pathogens. My colleagues Sonya ically broad host range, using a phylogenetically Gowtage-Sequeira, Ben Evans, and I re- demiology at the conserved cell receptor, being transmissible be- cently surveyed the recent literature, build- Centre for Infec- tween humans, and occurring in regions under- ing on earlier work by Louise Taylor and tious Diseases, Uni- going ecological, demographic or social change. Sophie Latham, and found 1,407 currently versity of Edin- recognized species of human pathogen. burgh, U.K. Volume 1, Number 11, 2006 / Microbe Y 511 FIGURE 1 category, with viruses significantly overrepresented and helminths under- represented. Within the scope of our survey, we found reports of 38 apparently novel human pathogen species associated with emerging diseases during the past 25 years (Fig. 1). Some species within this category likely were active before they were identified. For example, al- though HIV-1 was first reported in 1983, it is thought to have begun infect- ing humans several decades earlier. Two-thirds of these novel species are RNA viruses, a finding that may partly be due to ascertainment bias through improved viral diagnostics, especially PCR-based technologies. However, several inherent features of RNA virus biology may also help to explain why there are so many of them in this cate- gory. The accumulation of newly reported human pathogen species since 1980. The total of 38 Importance of Animal Reservoirs species includes only those associated with emerging infectious disease problems; newly recognized etiological agents of existing disease problems (e.g. Helicobacter Relatively few pathogen species—per- pylori, associated with peptic ulcers, or metapneumovirus, causing respiratory infections) are excluded. Also excluded are novel variants of known species, such as the O157:H7 haps no more than 100—do nothing serotype of E. coli and the H5N1 subtype of influenza A virus. The dates of emergence other than infect and cause disease in of some key examples discussed in the text are highlighted. humans. Many of them are commensals that do not ordinarily cause disease; many others are distributed in the wider Of course, a species count provides only environment such as water or soil; and yet oth- a simple measure of pathogen diversity. Much ers also infect host species other than humans. medically important variation—in traits such as The latter category constitutes the zoonoses, virulence factors, immunogenicity, and drug re- which the World Health Organization (WHO) sistance—occurs within pathogen species as defines as “diseases or infections which are nat- well as between them. However, focusing on urally transmitted between vertebrate animals species proves revealing. Of the catalogued and humans.” Almost 60% of human pathogen pathogen species that infect humans, 538 are species are zoonotic. A small minority of these, bacteria, 317 are fungi, 287 are helminths, 208 the “anthroponoses,” are mainly passed from are viruses, and 57 are protozoa. Within this humans to animals rather than the other way taxonomic diversity, individual species manifest around: measles virus, for example, is essentially a wide variety of life cycles, transmission routes, a human virus that also can infect great apes. pathogenicities, and epidemiologies. But for hundreds of human pathogen species, an We are particularly interested in pathogens animal reservoir is an important feature of their associated with emerging and reemerging infec- biology. tious diseases. These are defined by the Centers The most striking feature of such animal res- for Disease Control and Prevention (CDC) as ervoirs is their diversity. We share our patho- “diseases of infectious origin whose incidence in gens with ungulates, carnivores, rodents, pri- humans has increased within the past two de- mates, sometimes other kinds of mammals such cades or threatens to increase in the near fu- as bats, and also nonmammals, especially birds. ture.” Of the species in our survey, 177 cause Many of the reservoirs are domestic animals, diseases that are regarded as falling into this but just as many are wildlife species. These pat- 512 Y Microbe / Volume 1, Number 11, 2006 terns apply to the whole range of pathogens from viruses to helminths. Examples of human pathogens emerging via species jump Stephen Morse at Columbia University Pathogen Original host Year reported suggested more than 10 years ago that emerging and reemerging pathogens were Ebola virus Bats(?) 1977 Escherichia coli O157:H7 Cattle 1982 disproportionately zoonotic, and subsequent Borrelia burgdorferi Rodents(?) 1982 research has confirmed his observation. HIV-1 Chimpanzees 1983 Emerging and reemerging zoonoses are not HIV-2 Primates 1986 associated with any particular animal reser- Hendra virus Bats 1994 voirs but they are associated with pathogens vCJD Cattle 1996 Australian bat lyssavirus Bats 1996 that can infect several different kinds of H5N1 influenza A virus Chickens 1997 hosts. Nipah virus Bats 1999 Several recently emerged human patho- SARS coronavirus Palm civets(?) 2003 gens illustrate these findings. Examples are the SARS coronavirus and the agent respon- sible for bovine spongiform encephalopathy jumps, are poorly understood. One key factor, (BSE), both of which are zoonotic and can infect at least for viral pathogens, appears to be their a wide variety of animals and recently appeared use of cell receptors that are phylogenetically in humans. Even some novel pathogens that are conserved across a range of host species. not now regarded as zoonotic, such as HIV-1, The ability to infect a host species is merely were acquired by humans from animals. the first step; invading the new host species also These are but a few recent examples of a depends on the ability to transmit between indi- process that has been going on for millennia. vidual hosts within a species. Many emerging Jared Diamond of the University of California, pathogens have no or very limited transmissibil- Los Angeles, is among those who note that ity between humans, including variant Creutz- many of the most serious infectious diseases of feldt Jakob disease (vCJD), lyssavirus, influenza humans, including measles, influenza, and A subtype H5N1, and Borrelia burgdorferi, smallpox, likely have animal origins. which causes Lyme disease. Other poorly trans- mitted pathogens cause self-limiting outbreaks, including Ebola virus and Escherichia coli Invading New Host Populations O157:H7. Meanwhile, some pathogens such as When a pathogen of one host species first in- the SARS coronavirus spread much more freely vades a new one, it is called a “species jump” among their newly acquired human hosts. (see table). Successful species jumps require both The quantitative framework