We obtained counts of pathogen species from an updated version of the previously published database (1
). As before, we defined a human pathogen as "a species infectious to and capable of causing disease in humans under natural transmission conditions." We included pathogens that have only been reported as causing a single case of human disease and those that only cause disease in immunocompromised persons. We also included instances of accidental laboratory infection but excluded infections resulting from deliberate exposure in the laboratory. We added recently recognized pathogens listed online by the Centers for Disease Control and Prevention, the World Health Organization (WHO), ProMED, and elsewhere (6–9
). We obtained taxonomic classifications online from the International Committee on Taxonomy of Viruses, the National Centre for Biotechnology Information, the CAB International Bioscience database of fungal names, and from standard texts (10–15
Pathogen species were categorized as emerging or reemerging based on previously published reviews of the literature (1,3
), again updated from online sources (6–8
). A species was regarded as emerging or reemerging if any recognized variant fell into this category (e.g., Escherichia coli
O157, H5N1 influenza A).
We considered the following pathogen groups: viruses (including prions), bacteria (including rickettsia), fungi (including microsporidia), protozoa, and helminths. We did not consider ectoparasites (ticks and lice). Each group was further divided into subgroups (families) to test whether biases existed in numbers of emerging and reemerging species at this level. The viruses were also divided according to genome type (e.g., negative single-stranded RNA viruses).
We examined 3 aspects of host range, both for all pathogens combined and separately for each of the viruses, bacteria, fungi, protozoa, and helminths. First, we distinguished pathogen species according to whether they were known to be zoonotic, using the WHO definition "diseases or infections which are naturally transmitted between vertebrate animals and humans" (16
). Note that this definition includes pathogens for which humans are the main host and other vertebrates are only occasional hosts, as well as the opposite, but excludes purely human pathogens that recently evolved from nonhuman pathogens, e.g., HIV. We then compared the fraction of emerging or reemerging species that were or were not zoonotic across the major pathogen groups and within each group by family.
Second, for all zoonotic species we identified the types of nonhuman vertebrate host they are known to infect, using the following broad categories: bats, carnivores, primates, rodents, ungulates, and other mammals and nonmammals (including birds, reptiles, amphibians, and fish). We excluded vertebrate intermediate hosts of parasites with complex life cycles. Host types were ranked by the number of zoonotic pathogen species associated with them, and rankings were compared by using Spearman rank correlation coefficient.
Third, we obtained a crude index of the breadth of host range by counting the number of the host types that each pathogen species is known to infect: 0 (i.e., not zoonotic), 1, 2, and 3 or more. We compared the fraction of emerging and reemerging species across these 4 classes.
For the emerging and reemerging pathogen species, we identified the main factors believed to drive their increased incidence, geographic range, or both, by conducting a systematic review of the emerging diseases literature. We allocated these drivers to 1 or more broad categories (). Note that although we chose categories that we considered to be useful and informative for our immediate purposes, and which were similar to those listed elsewhere (5
), this is inevitably a subjective procedure and alternative categorizations may be equally valid. We then ranked the drivers (by number of emerging and reemerging pathogen species associated with each) and compared the ranking of drivers for the major pathogen groups and for zoonotic versus nonzoonotic pathogens.
Main categories of drivers associated with emergence and reemergence of human pathogens
For the zoonotic species, we distinguished those known to be transmissible between humans, allowing that this might be through an indirect route (e.g., a vector or an intermediate host), from those for which humans can only acquire infection (directly or indirectly) from a nonhuman source. For the transmissible zoonotic species, we further distinguished those that are sufficiently transmissible to cause major epidemics in human populations from those that cause only relatively minor outbreaks. This classification was intended to distinguish between pathogens with R0>1 in humans from those with R0<1, where R0 is the basic reproduction number, i.e., the average number of secondary infections produced by a single primary infection introduced into a large population of previously unexposed hosts. Direct estimates of R0 are unavailable for most zoonotic pathogens.
Throughout the study, we quantified associations as the relative risk (RR) and tested for statistical significance using a standard χ2 test (with correction for small expected values). Although these statistical analyses are susceptible to bias introduced by related species (e.g., several species of hantavirus exist, most of which are zoonotic and many of which are regarded as emerging or reemerging), the analysis at the family level is an indication of the extent of any such bias.