Data for this review were identified in PubMed searches and relevant journal articles and excluded those studies not published in English. Emerging or reemerging pathogens must be considered on multiple levels. First, pathogens not previously known have been identified. For example, alteration in the processing of cattle feed in the United Kingdom resulted in extended host range and emergence of bovine spongiform encephalopathy in cattle (
6). Similarly, mixing of multiple species under stressful conditions can promote a species jump such as that witnessed with SARS-CoV (
7). New opportunities can be created by climatic changes such as global warming and ecologic alterations facilitated through changed land use and movements of infected hosts, susceptible animals, or disease vectors.
In 1987, 1997–1998, and 2006–2007, outbreaks of infection with Rift Valley fever virus in Africa were associated with changes in river flow and flooding resulting from damming of rivers or heavy rainfall. Many zoonotic pathogens fall into the category of generalist agents exhibiting extensive host diversity, e.g., Coxiella burnetii, the etiologic agent of Q fever. This bacterium can successfully infect hosts ranging from domestic animals to wildlife, reptiles, fish, birds, and ticks.
Others agents have restricted specific transmission dynamics because of limited host ranges. These agents include simian immunodeficiency viruses 1 and 2, which are found in chimpanzees and sooty mangabees, and Rift Valley virus, which is transmitted by Aedes spp. and Culex spp. mosquitoes and found in sheep and goats. For many zoonotic agents, the potential to cause infection in accidental hosts, such as humans, exists, but often this represents a dead-end host. Pathogens such as Anaplasma spp., Erhlichia spp., Rickettsia spp., Bartonella spp., West Nile virus, and rabies virus can be included in this group.
From an epidemiologic point of view, “A reservoir should be defined as one or more epidemiologically connected populations or environments in which a pathogen can be permanently maintained and from which infection is transmitted to the defined target species” (
8). Conversely, some zoonoses in specific conditions show remarkable ability for human-to-human transmission beyond the confines of natural sylvatic cycles. This ability was seen during a recent outbreak of plague among diamond miners in the Congo. This outbreak was initiated by an infection of a miner, which became pneumonic and resulted in 136 secondary cases of pneumonic plague and 57 deaths (
9). Transmission of plague is complex and dynamic, with combinations of stochastic and adaptive mechanisms. As seen in this example, rapid transmission often occurs, but this is accompanied by slower, localized transmission among enzootic reservoir species, which often use vector-borne expansion among low-density hosts (
10). Other zoonoses, given correct circumstances, can result in human-to-human transmission. These zoonoses include those that cause Ebola fever, influenza A, plague, tularemia, and SARS (
11).
New or emerging virulence traits can evolve and result in large-scale transmission and concomitant alteration of pathogenicity. This new pathogenicity may include increased invasiveness, enhanced spread, toxin production, or antimicrobial drug resistance.
Y.
pestis has shown a resurgence in regions such as Madagascar, with isolates showing a marked increase in resistance to antimicrobial agents (
12). Similarly, a recently evolved outer surface protein A serotype of a Lyme borreliosis spirochete (
Borrelia garinii serotype 4), has shown particularly aggressive tendencies and is often associated with hyperinvasive infection (
13). Concern has also been noted about increasingly frequent isolation of
Corynebacterium ulcerans carrying the diphtheria toxigenic phage.
Mutation is the ultimate source of genetic variation, on which natural selection, genetic drift, gene flow, and recombination act to shape the genetic structure of populations. This factor is especially notable in viruses, which have relatively small genomes and short generation times, particularly among viruses with more error-prone RNA genomic replication (
14). However, most mutations are deleterious and under pressure of innate and adaptive host immunity, viruses probably always experience selection for mutation rates >0. The upper limit on mutation rates will be determined by factors such as natural selection, genomic architecture, and the ability to avoid loss of viability or genetic information, albeit, that a loss of genetic information and increased specialization is observed in co-evolution with a host (
15).
According to evolutionary theory, higher mutation rates should be favored in a changing environment, such as altered host immune defenses. However, in experimental settings, artificially increased mutation rates are often associated with lower virus titers. In addition, a complex relationship exists between underlying mutational dynamics and the ability to generate antigenic variation, which in turn has serious implications for the epidemiologic potential of the virus.
Evolutionary changes are not always a prerequisite for viral emergence in a new host. Some viruses (e.g., poxviruses), have a wide host range and show a relatively low mutation rate. However, in other viruses such as Venezuelan equine encephalitis virus, evolutionary change is essential for efficient infection and transmission to new hosts (
16). Because most viruses replicate poorly when transferred to new hosts, greater variation is more likely to assist viral adaptation to its new host.
All too frequently, the diagnosis of zoonotic disease is delayed through lack of clinical suspicion or failure to obtain adequate clinical histories. Some zoonotic infections are unusual (e.g., scabies infection after handling of pet guinea pigs). Other infections may have a less obvious animal link. Mowing lawns is believed to be a risk factor for acquiring tularemia (caused by
Francisella tularensis) in disease-endemic areas where lagomorph reservoirs may be killed by mowers or hedge trimmers (
17).
For some infections, zoonotic transmission occurs indirectly through food. Human brucellosis is not usually acquired through animal contact but is transmitted more often by consumption of infected animal products such as unpasteurized dairy products (
18).
Salmonella spp. have repeatedly caused outbreaks of salmonellosis after persons have eaten uncooked eggs (
19). Hepatitis E virus has been transmitted through consumption of uncooked deer meat (
20).
Exposure routes may be airborne, as demonstrated for several outbreaks of Q fever (
21). An ongoing airborne Q fever outbreak in the Netherlands related to goat farming has raised awareness of this previously neglected zoonosis (
22). How humans were exposed to these animals would not have been apparent; the exposures were identified by epidemiologic mapping of the distribution of cases. These examples underscore the necessity of gathering comprehensive patient data to effectively diagnose zoonoses.
See letter "
Reemerging,
