Infectious diseases remain a pressing problem in public health, resulting in over 13 million deaths each year globally.1 Among the most common causes of mortality are pneumonia, diarrheal disease, tuberculosis, HIV/AIDS, malaria, and measles.1 Many of these deaths, particularly from pneumonia and diarrheal disease, occur in small children.1 Changes in microorganisms contribute to the emergence of new infectious diseases, the re-emergence of infectious diseases once controlled, and the development of antimicrobial resistance.1 In order to identify diseases with high infection risk, it is important to consider transmission modes and the evolution of virulence.
The term ‘virulence’ refers to the harm caused by a pathogen infection, specifically in terms of morbidity and mortality.2 Virulence is a complex trait determined by a combination of pathogen, host, and environmental factors.2 The basic reproductive ratio R0 is defined as the expected number of secondary infectious arising from a single individual during their entire infectious period in a susceptible population and is fundamental to the study of infectious disease and virulence evolution.3 R0 serves as a threshold parameter that predicts the infection risk of a disease.3 Besides describing this threshold behavior, this metric provides other helpful information., such as how many people might need to be vaccinated in order to prevent an epidemic (1 – 1/R0).4
Modern evolutionary theory argues that the direction of virulence evolution can be anticipated if the key relationship between virulence and transmissibility is understood, also known as the ‘trade-off’ hypothesis.2 The transmission-virulence trade-off hypothesis is based on the idea that it is not possible for a pathogen to increase the duration of an infection without paying a cost.5,6 The shape of the trade-off curve depicting transmission rate vs. virulence can be used to predict disease outcome.6 If the curve is linear or convex, the pathogen evolves towards infinitely short infections with infinite transmission rates. If the curve is concave, as it typically is assumed to be, the virulence level is determined by the tangent of the curve that passes through the origin.6 The shape of the trade-off curve is affected by within-host processes, such as host death rate due to the infection or recovery rate.6 Some researchers hypothesize that ‘intermediate’ virulence grades are thought to be selectively advantageous.4
Infectious disease commonly displays intermediate virulence, maximizing pathogen fitness.6,7 In the case of HIV, the concept of intermediate virulence is key to understanding its pathogenesis.7 Using data collected from the Rakai District in Uganda, researchers were able to show that HIV follows the virulence-transmission trade-off.7 Higher virulence translates to a higher per-contact transmission rate, but also faster disease progression and death.7 An intermediate transmission rate maximizes opportunities for transmission, which is what is most seen in HIV infection.7
To spread, a pathogen must multiply within the host to ensure transmission, while also maintaining opportunities for transmission by avoiding host morbidity or death.5,7 In identifying diseases with high infection risk, the transmission-virulence trade-off curve may be a useful tool.6 Further research in this area is important for public health efforts to minimize the effect of future disease outbreaks.
References
- Cohen, M. (2000). Changing patterns of infectious disease. Nature, 406(6797), 762-767. doi:10.1038/35021206
- Geoghegan, J., & Holmes, E. (2018). The phylogenomics of evolving virus virulence. Nature Reviews Genetics, 19(12), 756-769. doi:10.1038/s41576-018-0055-5
- Heffernan, J., Smith, R., & Wahl, L. (2005). Perspectives on the basic reproductive ratio. Journal of The Royal Society Interface, 2(4), 281-293. doi:10.1098/rsif.2005.0042
- Mitchell, C., & Kribs, C. (2017). A Comparison of Methods for Calculating the Basic Reproductive Number for Periodic Epidemic Systems. Bulletin of Mathematical Biology, 79(8), 1846-1869. doi:10.1007/s11538-017-0309-y
- Ewald, P. (1980). Evolutionary biology and the treatment of signs and symptoms of infectious disease. Journal of Theoretical Biology, 86(1), 169-176. doi:10.1016/0022-5193(80)90073-9
- Alizon, S., Hurford, A., Mideo, N., & Van Baalen, M. (2008). Virulence evolution and the trade-off hypothesis: history, current state of affairs and the future. Journal of Evolutionary Biology, 22(2), 245-259. doi:10.1111/j.1420-9101.2008.01658.x
- Blanquart, F., Grabowski, M., Herbeck, J., Nalugoda, F., Serwadda, D., & Eller, M. et al. (2016). A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda. Elife, 5. doi:10.7554/elife.20492
