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December 11, 2003

Potential for pathogens to evolve missing from emerging-disease models

With outbreaks of new and frightening infectious diseases such as SARS and monkey pox jumping from the animal kingdom to humans, tracking their spread is vital to public health efforts to contain them. A novel mathematical model now gives public health leaders another tool to assess the risk of new infectious disease emergence that emphasizes the potentially perilous role of pathogen evolution.


The research by Carl Bergstrom, UW assistant professor of biology, Rustom Antia and Roland Regoes, Emory University biologists, and Jacob Koella, P and M Curie University in Paris, appears in the Dec. 11 issue of Nature in their letter “The Role of Evolution in the Emergence of Infectious Disease.”


Tracking the evolution of pathogens is not a new concept, but mutations are usually not taken into account in the models used to assess the emergence of infectious disease. What the researchers developed is a proposed framework to deal with these mutations that should be kept in mind when developing models for emerging infectious diseases such as monkey pox.


New pathogens are typically believed to emerge from animal populations when ecological changes increase the pathogens’ opportunities to enter the human population and generate subsequent human-to-human transmission.


Current mathematical models used for predicting the spread of emerging infectious diseases in humans operate from the standpoint that diseases stay contained if the basic reproductive number of disease transmissions remains less then one. This means that the average number of secondary infections from persons infected with a disease stays below one. While the disease may still spread to other individuals, the pathogen lines of infection eventually become extinct, preventing the disease from epidemically spreading across the population.


In work funded in part by the National Institutes of Health, the researchers found that factors, such as ecological changes, that increase the basic reproductive number of the potential pathogen (but remaining below one and not at a level sufficient to cause an epidemic) can still greatly increase the length of the random chains of disease transmission. These long transmission chains provide opportunity for the pathogen to adapt to human hosts, and subsequently for the disease to emerge and spread.


One example, Bergstrom says, is monkey pox, which is thought to be related to smallpox, a disease driven to extinction by vaccination. However, as immunity to smallpox wanes because people aren’t generally being vaccinated against the disease anymore, the protection provided against things such as monkey pox also wanes. That might be the ecological change that could markedly increase the probability of the evolution of monkey pox, allowing it to emerge into a successful human pathogen.


Bergstrom and Regoes were responsible for much of the mathematical modeling, which incorporates branching-process models. The model shows that transmission rates of a new pathogen can remain well below an epidemic level, but a disease can still potentially break out dramatically as new strains evolve and become better adapted for human transmission, Regoes says.