Paul W. Ewald

Transmission Modes and Evolution of the Parasitism‐Mutualism Continuuma

An analysis of fitness costs and benefits associated with pathogenicity suggests that modes of transmission are key determinants of evolution toward severely pathogenic, benign, or mutualistic symbioses. Specifically, this approach suggests that symbionts with mobile life history stages should evolve toward extremely severe parasitism, vector-borne symbionts should evolve toward severe parasitism in vertebrate hosts and benign parasitism in the vectors, waterborne symbionts should evolve toward severe parasitism, symbionts transmitted by predation should evolve toward severe parasitism in prey hosts and benign parasitism in predator hosts, and vertically transmitted symbionts should evolve toward benign parasitism and mutualism. Detailed reviews of the literature on human diseases support the hypothesized severity of vector-borne and waterborne transmission. Evaluation of the other associations is less detailed, but each association appears to be present. This framework draws attention to the need for detailed reviews of relationships between transmission modes and the nature of symbiotic interactions, and experimental manipulations of transmission.

Pathogen survival in the external environment and the evolution of virulence

Recent studies have provided evolutionary explanations for much of the variation in mortality among human infectious diseases. One gap in this knowledge concerns respiratory tract pathogens transmitted from person to person by direct contact or through environmental contamination. The sit‐and‐wait hypothesis predicts that virulence should be positively correlated with durability in the external environment because high durability reduces the dependence of transmission on host mobility. Reviewing the epidemiological and medical literature, we confirm this prediction for respiratory tract pathogens of humans. Our results clearly distinguish a high‐virulence high‐survival group of variola (smallpox) virus, Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordetella pertussis, Streptococcus pneumoniae, and influenza virus (where all pathogens have a mean percent mortality 0.01% and mean survival time >10 days) from a low‐virulence low‐survival group containing ten other pathogens. The correlation between virulence and durability explains three to four times of magnitude of difference in mean percent mortality and mean survival time, using both across‐species and phylogenetically controlled analyses. Our findings bear on several areas of active research and public health policy: (1) many pathogens used in the biological control of insects are potential sit‐and‐wait pathogens as they combine three attributes that are advantageous for pest control: high virulence, long durability after application, and host specificity; (2) emerging pathogens such as the‘hospital superbug’methicillin‐resistant Staphylococcus aureus (MRSA) and potential bioweapons pathogens such as smallpox virus and anthrax that are particularly dangerous can be discerned by quantifying their durability; (3) hospital settings and the AIDS pandemic may provide footholds for emerging sit‐and‐wait pathogens; and (4) studies on food‐borne and insect pathogens point to future research considering the potential evolutionary trade‐offs and genetic linkages between virulence and durability.

Evolution of virulence.

Human history cannot be understood well without understanding the causes and consequences of human disease. This fact has become amply apparent over the past few decades as the impacts of infectious diseases have been studied in the context of war, colonization, and competition [1–5] .I t is much less widely appreciated that the reverse is also true. Historical studies of infectious diseases may help guide modern health sciences to recognize options for controlling diseases of the present and future. Ecologic and evolutionary perspectives are enmeshed with the historical perspective of infectious diseases, because infectious agents spread and evolve over times scales that accord with historical events. They may influence historical events and may be influenced by such events. The influence of historical events on the evolution of pathogens largely has been neglected until the past quarter century. It has become clear that activities that were undertaken for one purpose can have unforeseen effects on the evolution of important characteristics of pathogens, such as virulence (which is defined broadly here to mean the degree of harm imposed on the host). An understanding of these evolutionary effects helps in understanding why some pathogens cause more harm than others, the environmental circumstances that permit this harm, and, most importantly for the future, the human activities that can ameliorate or prevent this harm.

Transmission modes and the evolution of virulence : With special reference to cholera, influenza, and AIDS.

Application of evolutionary principles to epidemiological problems indicates that cultural characteristics influence the evolution of parasite virulence by influencing the success of disease transmission from immobilized, infected hosts. This hypothesis is supported by positive correlations between virulence and transmission by biological vectors, water, and institutional attendants. The general evolutionary argument is then applied to the causes and consequences of increased virulence for three diseases: cholera, influenza and AIDS.

WATERBORNE TRANSMISSION AND THE EVOLUTION OF VIRULENCE AMONG GASTROINTESTINAL BACTERIA

Diarrhoeal diseases are primary contributors to millions of deaths annually. Yet, little is known about the evolutionary reasons for the differences in virulence among gastrointestinal pathogens. Applying the comparative, cost/benefit approach of evolutionary biology this paper proposes that waterborne transmission should favour evolution towards high virulence. This hypothesis is supported by a cross-specific test, which shows that waterborne transmission is strongly correlated with the virulence of bacterial gastrointestinal pathogens of humans. Alternative explanations of this correlation are not supported by available data. These findings bear on public health policy because they draw attention to a previously unrecognized long-range benefit gained from purification of water supplies; diarrhoeal pathogens may evolve to lower levels of virulence.

Infectious Causation of Disease: An Evolutionary Perspective

Over the past two centuries, diseases have been separated into three categories: infectious diseases, genetic diseases, and diseases caused by too much or too little of some noninfectious environmental constituent. At the end of the 19th century, the most rapid development was in the first of these categories; within three decades after the first cause-effect linkage of a bacterium to a disease, most of the bacterial causes of common acute infectious diseases had been identified. This rapid progress can be attributed in large part to Koch’s postulates, a rigorous systematic approach to identification of microbes as causes of disease. Koch’s postulates were useful because they could generate conclusive evidence of infectious causation, particularly when (1) the causative organisms could be isolated and experimentally transmitted, and (2) symptoms occurred soon after the onset of infection in a high proportion of infected individuals. While guiding researchers down one path, however, the postulates directed them away from alternative paths: researchers attempting to document infectious causation were guided away from diseases that had little chance of fulfilling the postulates, even though they might have been infectious. During the first half of the 20th century, when the study of infectious agents was shifting from bacteria to viruses, Mendel’s genetics was being integrated into the study of disease. Some diseases could not be ascribed to infectious causes using Koch’s postulates but could be shown to have

Food availability, intrusion pressure and territory size: an experimental study of Anna's hummingbirds (Calypte anna)

Theoretical considerations implicate food availability and intrusion pressure as important determinants of territory size, but empirical studies have led to contradictory conclusions about cause-and-effect relationships among these three variables. To investigate this problem, we provided patches of electronically controlled artificial flowers, which were defended by male Calypte anna. Food availability was experimentally manipulated, and intrusion rate and territory size were calculated from behavioral observations of the territory owner. Changes in both food availability and intrusion rate were found to be significantly correlated with changes in territory size under certain conditions. Intrusion rate, which was influenced by food availability, was negatively associated with territory size so long as food availability was high. This association persisted even after possible effects of food availability were controlled statistically. Food availability was negatively correlated with territory size only when intrusion rates were high and after owners had been defending territories for 3 days. As food availability and intrusion rate increased, owners increasingly restricted their defense to the patch itself; partial regressions revealed a significant association for intrusion rate but not food availability. When intrusion rate was low and food availability varied from low to high levels, no relationship was observed between food availability and territory size, apparently because of opposing influences of food abundance on territory size.

Mobility of Impatiens capensis flowers: effect on pollen deposition and hummingbird foraging

Flexible pedicels are characteristic of birdpollinated plants, yet have received little attention in studies of hummingbird-flower interactions. A major implication of flexible pedicels is that flowers may move during pollination. We examined whether such motion affected interactions between ruby-throated hummingbirds (Archilochus colubris) and jewelweed (Impatiens capensis) by increasing pollen deposition and by altering the effectiveness of nectar removal. For I. capensis, flower mobility enhanced pollen deposition: birds had significantly longer contact with anthers and more pollen deposited on their bills and crowns when foraging at mobile flowers than at flowers that had been experimentally immobilized. In contrast, flower mobility imposed a cost on hummingbirds by significantly increasing their handling times and reducing their extraction rates relative to their interactions with immobile flowers. Field observations indicated that the motion observed during hummingbird visits did not occur when bees (Bombus spp., Apis mellifera) visited I. capensis flowers, which suggests that the mobility of I. capensis flowers is an adaptation for hummingbird pollination.

Territory quality and territorial behavior in two sympatric species of hummingbirds

SummaryChanges in territorial behavior of blackchinned hummingbirds (Archilochus alexandri) in response to experimental changes in territory quality were investigated using artificial feeders and simultaneous, pair-wise observations of owners. Some of the responses of A. alexandri were similar to those documented by a previous study of the Annas hummingbird (Calypte anna): A. alexandri defending rich territories spent more time on their territories, encountered a greater percentage of intruders, and chased more intruders than did A. alexandri defending poor territories. In contrast to C. anna, A. alexandri supplemented chases with energetically inexpensive threat vocalizations more extensively when territory quality was increased. This difference may be related to A. alexandris more tenuous control of rich territories. When both species were observed on very poor territories, A. alexandri chased a greater percentage of intruders, consumed a greater proportion of available food, and obtained a greater net energy gain from their territories. When observed simultaneously on territories with ad lib food, both species defended highly exclusive territories but A. alexandri suffered higher intrusion pressure and spent more time and energy in defense. These interspecific differences in territorial behavior may facilitate sympatric coexistence of the two species through aggressive partitioning of flower patches according to productivity: the greater payoff received by C. anna on rich territories and A. alexandri on poor territories should favor a corresponding monopolization of rich areas by C. anna and poor areas by A. alexandri.

An evolutionary perspective on parasitism as a cause of cancer.

For the past half-century, the dominant paradigm of oncogenesis has been mutational changes that disregulate cellular control of proliferation. Parasitic causes of cancer were first incorporated into this paradigm by suggesting mechanisms through which parasitism might increase mutational damage, such as generation of mutagenic compounds during immunological activity. The growing recognition of the molecular mechanisms of pathogen-induced oncogenesis and the difficulty of generating oncogenic mutations without first having large populations of dysregulated cells, however, suggests that pathogens, particularly viruses, are major initiators of oncogenesis for many if not most cancers, and that the traditional mutation-driven process becomes the dominant process after this initiation. Molecular phylogenies of individual cancers should facilitate testing of this idea and the identification of causal pathogens.