An Effective PZA Resistance Assay to Reduce Drug Side Effects and Improve Treatment Adherence

There are a few reasons why the treatment of tuberculosis (TB) can fail. One of them is the lack of adherence to the DOTS strategy (directly observed treatment, short-course, recommended by the World Health Organization). The absence of fast recovery and adverse effects are commonly associated to treatment drop-out. As a result, Multi-Drug Resistant TB is emerging. Pyrazinamide (PZA), the only drug effective against latent TB, produces serious hepatic side effects. It is important to determine PZA susceptibility in the early stages of treatment to provide a safe regimen and to improve adherence. Unfortunately, PZA-susceptibility assays are not adequate and lack reproducibility. These innovators propose to design an effective, fast and reproducible test to determine PZA resistance. Based on our previous studies, the rate at which pyrazinoic acid (POA) is extruded from the bacteria is an accurate biomarker of PZA resistance. The ultimate goal is an automatic machine for measuring PZA resistance. This project is funded under a collaborative agreement between CONCYTEC (Peru’s National Council for Science, Technology and Technological Innovation) and Grand Challenges Canada (funded by the Government of Canada) to support Stars in Global Health innovators based in Peru.