Winter's just begun and you're at the doctor's office. Nose stuffed up, throat sore, head loopy, wheezing as if you just ran a marathon. You know you have an acute respiratory infection (ARI). But is it viral or bacterial? Doesn't matter. You're going to get an antibiotic for it, or that's the case for 73% of us.
Most ARIs are not microbiologically confirmed in the clinic, and even if a viral cause is found, there's still the possibility of a bacterial coinfection, so out comes the prescription pad for some miracle pills, "just in case." Finding ways to reduce this type of clinical overuse of antibiotics (41% of all antibiotics prescribed are to treat ARIs) is critical if we're going to maintain the efficacies of our drugs.
This is the problem that Tsalik et al. sets up to address in the current issue of Science Translational Medicine. In their study, they utilize human gene expression changes to discriminate between and diagnose bacterial and viral ARIs. By analyzing blood samples from 273 patients who were healthy or diagnosed with either a viral or bacterial respiratory infection, they defined sets of gene expression changes that were characteristic for bacterial and viral infections. Using these markers, they could derive 87% specificity in diagnosing either infection (or coinfection) in the clinic, a 5-15% boost in accuracy over other diagnostic methods.
So what were the pathogen-specific host changes? For viruses, aside from the usual suspects (interferon genes, T cell signaling, RNA processing genes), there was a unique marker, the downregulation of KPNB1, which is a nuclear transport protein that is commonly co-opted by viruses to move around the cell. For bacterial infections, it was cell cycle genes and pathways involved in T, B and NK cell differentiation. But the most unique and predictive markers were a set of metabolic changes in fatty acid and amino acid metabolism and oxidative stress responses.
Of course, only more testing will prove whether these markers are the next step in ARI diagnosis. But don't be surprised if some time in the future, as you fidget miserably on the crinkly tissue paper, the doctor offers a blood draw instead of a prescription and sees you home empty-handed with a consolatory "Let's wait and see."