Pyrazinamide (PZA) remains an essential TB drug will be a key component of new combination treatment regimens set to be assessed in several upcoming clinical trials of tuberculosis treatment. As such, developing the capability to perform reliable and rapid PZA drug susceptibility testing (DST) has become a high priority among multiple TB clinical research groups for use in developing eligibility criteria in clinical trials
This objective of this EDCTP
-funded study is to describe the epidemiology of PZA resistance in 9 African trial sites, contribute sequencing data and correlating phenotyping data to an international PZA resistance database and thus support the development of a new PZ resistance testing. The specific aims are as follows:
- To establish the prevalence of PZA resistance in treatment naïve patients and patients with MDR TB, which focus on sites where little data exist
- To describe and categorize mutations related to PZA resistance and their clinical and phenotypic presentation.
- To contribute to an international network (TB Diagnostic Forum), initiated by the NIH that involves major TB trials groups (TB Alliance/Gates, the ACTG/TBTC, PanACEA/EDCTP). Aim of the network is to establish essential knowledge and infrastructure to enable the full characterization of all study participants with regard to TB drug resistance. A second goal is to develop a rapid and easy to use molecular assays to test PZA resistance that could be further developed by a commercial provider.