Towards increased access to rapid diagnostics for resistance to pyrazinamide

Project Details


Multi-drug resistant tuberculosis (MDR-TB) is a global public health crisis. Promising new treatment regimens are threatened by high background prevalence of resistance not only to fluoroquinolones (FQs), but likely also pyrazinamide (PZA) which can lead to treatment failure, additional resistance, and ongoing transmission.
PZA will be maintained in most regimens in development as it has important sterilizing activity; however, there are few rapid and accurate assays to test for PZA resistance. Also, recently published WHO guidelines for the management of multidrug-resistant (MDR)-TB now urge resistance testing for PZA. Current diagnostic algorithms for resistance testing to PZA are sub-optimal.

Using smear positive and/or Xpert positive sputum samples from an ongoing clinical trial study (DIAMA) and DF projects (Bangladesh and Nigeria), we will evaluate the accuracy and feasibility of a novel low-tech line probe assay (line probe assay; LPA) to detect resistance to PZA in high burden settings. To improve the evidence base and adoption, we aim to integrate this LPA in routine practice. To maximize synergy with already widely implemented diagnostic devices and infrastructure we will evaluate the adaptation for use of the already widespread Twincubators (hybridization equipment for the Hain LifeSciences LPAs) for the Nipro PZA-LPA.

Taken together, our proposal aims to provide the evidence base that will allow the implementation of rapid genotypic PZA resistance testing for TB patients in greatest need.
Effective start/end date1/01/1931/12/19


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