Predicting contagiousness to limit the spread of disease
Following exposure to a pathogen, people may become infected, and soon after they may begin to spread disease to others. Some people become infected and also become sick with symptoms (red). Some people become infected and do not exhibit symptoms, but still spread disease (yellow). Some people do not become infected (blue). Prometheus aims to develop tests to predict if people will spread disease, whether or not they show symptoms. (DARPA graphic)
IMagine the workplace during flu season. Some people get sick and display clear symptoms—a warning sign to coworkers to avoid contact and for that individual to stay home. Others are infected, but never or only belatedly exhibit the tell-tale signs of sickness, meaning they can infect coworkers without knowing it. If healthcare professionals had the ability to test in advance whether a person is likely to spread a disease following infection, they could recommend specific measures to treat the person or limit exposure and perhaps keep an outbreak from growing into an epidemic or pandemic.
DARPA’s new Prometheus program is setting out to develop that predictive capability. Prometheus seeks to discover a minimal set of molecular biomarkers that would indicate, less than 24 hours after exposure to a pathogen, whether an individual will become contagious. That window is narrow enough to allow for early treatment or the initiation of other mitigating steps before a person begins infecting others.
“Many infections are spread by people who haven’t yet displayed symptoms of their illness,” said Army Col. Matt Hepburn, the Prometheus program manager. “These people don’t know they are sick, so they often end up spreading the disease to close contacts. Our goal with Prometheus is to develop techniques that could alert people that they are likely to become contagious, so they can proactively take steps to keep the disease from spreading.”
Prometheus will focus on acute respiratory infections. As part of that effort, researchers on the program will set out to develop a fundamental understanding of the biological responses occurring in a recently infected person.
In particular, Prometheus will characterize the body’s molecular-level immune responses at multiple time points during the infection process. These “biomarkers”—measurable indicators of the severity or presence of some disease state—might help researchers predict the onset of contagiousness. Within hours after exposure to a pathogen, for example, a number of genes inside immune-system cells become active. Other biomarkers may be predictive of viral replication, well before there is a measurable increase in the amount of virus in the body. Among the many other biomarkers potentially useful for assessing infection status and likelihood of disease transmission are messenger RNA, certain genetic variations in the infected person’s DNA, and immune-system proteins.
Enabling a prognosis of individuals’ likelihood of spreading a disease would not only help mitigate an outbreak and speed treatment of affected individuals, but also would help researchers forecast the spread of the disease. Current models of outbreaks rely heavily on reported cases, which are generated after symptomatic patients visit a healthcare provider and receive a diagnosis. Patients who only exhibit mild symptoms may never seek medical care, yet may still be capable of spreading infection.
“Forecasts based on clinical diagnostics aren’t ideal because they’re based on incomplete and essentially historical information,” Hepburn said. “Identifying contagious or potentially contagious individuals early is a critical capability for outbreak mitigation – especially in relatively well-defined communities such as aboard a large ship or on a military base. If researchers can characterize the pre-symptomatic population, they stand a much better chance of building successful models of disease transmission and developing effective medical and public health interventions.”
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