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Biomedical subjects

P W Ewald

Publications and source records attributed to P W Ewald.

12 recordsLinked to original sources

Chlamydia pneumoniae and cardiovascular disease: an evolutionary perspective on infectious causation and antibiotic treatment.

Evolutionary considerations implicate infectious causation of atherosclerosis and help to resolve different risk factors as parts of an overall process of disease causation. An evolutionary approach also provides insight for the timing of research efforts to provide better control of pathogen evolution. In particular, evolutionary considerations emphasize the need to understand the transmissibility of Chlamydia pneumoniae from systemic infections in order to control the evolution of antibiotic resistance.

Anti-Bacterial Agents↗

The evolution of virulence and emerging diseases.

Insights into the evolution of virulence may aid efforts to control or even prevent emerging diseases. Specifically, dangerous pathogens can be distinguished from those that pose relatively little threat by identifying characteristics that favor intense exploitation of hosts by pathogens, hence causing high virulence. Studies to date have implicated several such characteristics, including transmission by vectors, attendants, water, and durable propagules. These insights may improve the return on investments in disease control by directing effort and resources to the most-dangerous emerging pathogens. The approach also should help us to identify those control measures that will guard against the future emergence of dangerous pathogens, even those that have not yet been identified.

Arthropod Vectors↗

Evolution of mutation rate and virulence among human retroviruses.

High mutation rates are generally considered to be detrimental to the fitness of multicellular organisms because mutations untune finely tuned biological machinery. However, high mutation rates may be favoured by a need to evade an immune system that has been strongly stimulated to recognize those variants that reproduced earlier during the infection. HIV infections conform to this situation because they are characterized by large numbers of viruses that are continually breaking latency and large numbers that are actively replicating throughout a long period of infection. To be transmitted, HIVs are thus generally exposed to an immune system that has been activated to destroy them in response to prior viral replication in the individual. Increases in sexual contact should contribute to this predicament by favouring evolution toward relatively high rates of replication early during infection. Because rapid replication and high mutation rate probably contribute to rapid progression of infections to AIDS, the interplay of sexual activity, replication rate, and mutation rate helps explain why HIV-1 has only recently caused a lethal pandemic, even though molecular data suggest that it may have been present in humans for more than a century. This interplay also offers an explanation for geographic differences in progression to cancer found among infections due to the other major group of human retroviruses, human T-cell lymphotropic viruses (HTLV). Finally, it suggests ways in which we can use natural selection as a tool to control the AIDS pandemic and prevent similar pandemics from arising in the future.

Biological Evolution↗

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.

Bacteria↗

Transmission modes and evolution of the parasitism-mutualism continuum.

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.

Animals↗

Evolutionary control of infectious disease: prospects for vectorborne and waterborne pathogens.

Evolutionary theory may contribute to practical solutions for control of disease by identifying interventions that may cause pathogens to evolve to reduced virulence. Theory predicts, for example, that pathogens transmitted by water or arthropod vectors should evolve to relatively high levels of virulence because such pathogens can gain the evolutionary benefits of relatively high levels of host exploitation while paying little price from host illness. The entrance of Vibrio cholerae into South America in 1991 has generated a natural experiment that allows testing of this idea by determining whether geographic and temporal variations in toxigenicity correspond to variation in the potential for waterborne transmission. Preliminary studies show such correspondences: toxigenicity is negatively associated with access to uncontaminated water in Brazil; and in Chile, where the potential for waterborne transmission is particularly low, toxigenicity of strains declined between 1991 and 1998. In theory vector-proofing of houses should be similarly associated with benignity of vectorborne pathogens, such as the agents of dengue, malaria, and Chagas' disease. These preliminary studies draw attention to the need for definitive prospective experiments to determine whether interventions such as provisioning of uncontaminated water and vector-proofing of houses cause evolutionary reductions in virulence.

Animals↗

Guarding against the most dangerous emerging pathogens.

Control of emerging infectious diseases will be difficult because of the large number of disease-causing organisms that are emerging or could emerge and the great diversity of geographic areas in which emergence can occur. The modern view of the evolution of pathogen virulence--specifically its focus on the tradeoff between costs and benefits to the pathogen from increased host exploitation--allows control programs to identify and focus on the most dangerous pathogens (those that can be established with high virulence in human populations).

Animals↗