THURSDAY, 10 DECEMBER 2020What causes some pathogens, disease-causing microorganisms, to become more harmful than others? How does our behaviour impact the way they evolve? Evolutionary biology helps us consider these questions
The Virulence-Transmission Trade-Off Model
Pathogens and their hosts have constantly been coevolving over millions of years, mainly resulting from interactions between the two species. This coevolution can be observed in a pathogen’s virulence, which is the relative ability of a microorganism to cause harm to a host organism. A common way of assessing this is by tracing mortality rates. Historically, organisms were thought to reduce their virulence over time, as the pathogen relies on the host for transmission. Thus, host mortality would reduce the amount of transmission time available to the pathogen. However, this pattern was not observed and so subsequent models of host-pathogen evolution have been proposed, with the coevolution of myxoma virus with the European rabbit being a prime example.
Myxomatosis is a lethal disease in rabbits caused by myxoma virus, resulting in blindness and swelling. Originating from South America, the myxoma virus was intentionally introduced to the Australian rabbit population in the 1950s in an attempt to control their numbers. As these rabbits had never been in contact with this virus before, they had not yet coevolved or developed any resistance. When the virus was first introduced, it led to a dramatic reduction of the population, killing more than 90% of the rabbits. However, over time the genetic resistance of the rabbits increased due to the strong selection pressure. Eight years later, the same strain had a mortality rate stabilising at around 30%.
So, why was an intermediate level of virulence favoured in the population? Myxoma virus is transmitted via airborne droplets or arthropods, such as fleas or mosquitos. Researchers found that highly virulent strains quickly produced large numbers of the virus on the skin, increasing the transmission rate to the pathogen’s vectors, an organism of a different species that transmits the disease, whereas strains with low virulence never obtained numbers as high. However, strains with intermediate virulence took longer but reached higher overall levels eventually. This meant that viruses with intermediate virulence levels were more effective at transmission as they had fairly high virus numbers on the skin, for a prolonged period compared to highly virulent ones.
This is the basic concept behind the ‘virulence-transmission trade-off theory’, which argues that intermediate virulence maximises pathogenicity as a result of a trade-off between virulence and transmission. While the replication rate of a pathogen increases with virulence, the duration of transmission is negatively impacted by it, due to host mortality. As a result, there will be an optimum level of virulence, where the overall transmission of the pathogen is maximised. This will be the most evolutionarily favourable level of virulence for a pathogen.
What causes the observed differences in virulence?
As a result of coevolution, population structure can influence host-pathogen interactions. A good example is host population density. High host population densities favour increased transmission rates, as more potential hosts can be encountered over a set period of time. This implies that optimal transmission occurs with higher virulence. This may be particularly important to us as a species as our population and population density increase.
What happens to virulence when the host and parasites have not coevolved? Pathogens crossing between species, so-called zoonotics, can lead to increased virulence. Because coevolution has not occurred, virulence is often far higher than optimal. This happened in the case of the myxoma virus spread, as it originated in South American rabbit species. Another good example is Ebola virus, which is so virulent that it is not transmitted very effectively. Similarly, cross-over between isolated populations can also impact virulence. A historical example from the 16th century is when European colonisation imported smallpox into North America and up to 90% of the population of the Americas died as a result of the non-native pathogen.
Implications of the model
The implications of current practices is most apparent in agriculture. Most farmed plants and animals are bred to reach maturity very quickly, after which they are harvested or killed. This decrease in lifespan significantly reduces the transmission time. Based on this theory, we would expect the optimal transmission rate and thus the virulence of the strain to increase. These more virulent strains could then in turn infect the wild populations, possibly causing collapse. This has been observed in some intensive aquaculture systems, but further research is still required to confirm this model.
Another interesting aspect is whether we can drive the certain pathogens to evolve to their less virulent forms. So far we have looked at viruses, however, it is important to consider virulence in other types of pathogens too, such as bacteria. Diphtheria is a disease caused by the diphtheria bacterium. It is a bacterium that produces a toxin, which inhibits protein synthesis and can eventually lead to severe systemic effects in the body, including heart failure and paralysis. The bacterium is found in two forms, the pathogenic form, which produces the toxin, and the benign, which causes minimal or no harm when infecting people. In an effort to eradicate the disease, people across several countries were vaccinated against the toxin produced. Due to these measures targeted against the pathogenic strain, it was nearly eradicated. As a result, the benign form became prevalent. Unfortunately, fewer people have been vaccinated in recent years, so the prevalence of the pathogenic strain has been increasing. However, the outcome of other diseases is not this clear cut, and it is often hard to predict the consequences of different management techniques.
Limitations of the model
Currently, the virulence-transmission trade-off model lacks empirical support, and in many cases, needs to be expanded or is not applicable. The hypothesis regarding the relationship between transmission and virulence does not always hold true. For example, pathogens can be loosely grouped based on their mode of transmission. Horizontal transmission happens between individuals of the same generation, for example through airborne droplets from sneezes, while vertical transmission occurs from one generation to the next, mostly through the placenta or from the birth canal during birth. As vertically transmitted pathogens rely on the reproduction of the host organism, the relationship between virulence and transmission is very different. As a consequence, the model cannot be applied in this context. Similarly, pathogens that spread by means of vectors or remain dormant for long periods of time are likely to have different virulence-transmission relationships. This means their transmission is not dependent on a living host and thus the cost of virulence varies from the model. This is one factor that contributes to the deadliness of anthrax, a bacterium that causes swelling and lesions amongst other things, as it can lie dormant as spores.
The link between virulence and transmission remains largely theoretical, and it is very hard to measure this relationship. While some scientists argue that it is less direct than posited, this model is currently one of the best for explaining the patterns of virulence. Like other models, there are limitations to it. It will likely require adaptation in order to consider different environments, routes of infection or different cell types affected. Hopefully, in the future our understanding of virulence will be such that we can control its evolution
Oakem Kyne is a second year undergraduate student invNatural Sciences at Fitzwilliam College. Artwork by Clara Munger