Line Probe Assay – LPA


 

PROVE IT (Policy Relevant Outcomes from Validating Evidence on ImpacT)

Background

The World Health Organisation (WHO) has identified five priorities to accelerate progress towards achieving the 2015 United Nation’s Millennium Development Goals for tuberculosis (TB). The first of these is to “reach the missed cases”, the estimated 2.9 million TB cases that are not diagnosed or reported in national notification systems. Expanding diagnostic services, including access to rapid tests, has been identified as one of the strategies to achieve this.

Rapid, more sensitive molecular diagnostic tests have the technical capacity to address the challenges of smear, culture and conventional drug susceptibility tests. Two of these tests, the Hain-MDRTBPlus line probe assay (LPA) and Xpert®MTB/RIF (Xpert) have been approved by The World Health Organisation. The efficacy of both tests has been well established in laboratory and demonstration studies and policy recommendations have been based largely on these data; however, their effect in routine operational settings is not known.

 Aim

The PROVE IT evaluation assessed the impact of new molecular diagnostics on the diagnosis and treatment of tuberculosis in routine operational conditions. The evaluation compared a smear/culture/LPA-based to a newly introduced Xpert-based algorithm in which Xpert replaced smear microscopy for all presumptive TB cases who were thus simultaneously screened for TB and rifampicin resistance. The study was undertaken in primary health care (PHC) facilities in Cape Town.

Impact analysis was guided by the Impact Assessment Framework which aims to ensure a more comprehensive approach to the evaluation of new diagnostics. This consists of five layers: Effectiveness Analysis assesses the test impact on the numbers of cases diagnosed and started on treatment as well as the timeliness of results. Equity Analysis addresses patient important outcomes and analyses whether marginalised groups, who may be more effected, benefit from the new test. Health Systems Analysis assesses issues such as the human resource, laboratory infrastructure, procurement and quality assurance implications. Scale up Analysis assesses the economic costs and benefits of scaling up the new technology from both a provider and a patient perspective. Horizon Scanning assesses what other similar technologies are available or likely to become available and how these compare in their projected performance.

 Findings to Date

  • The proportion of TB cases identified in the newly introduced Xpert-based algorithm did not increase as anticipated, with a risk difference of 0.2% (95% CI -1.8% to 2.3%, p=0.818). Efforts to ensure that the smear negative component of the algorithm is followed may help to improve diagnostic yield.
  • MDR-TB patients were started treatment more rapidly in the Xpert-based algorithm with a decrease of 25 days (95% CI 17 to 32 days, p<0.001) in the median treatment commencement time. However the median treatment commencement time in the Xpert-based algorithm was 17 days (95% CI 13 to 22 days), despite a median laboratory turnaround time (to result available in the laboratory) of <1 day (95% CI <1 to 1 day). Health system and patient factors contributing to delay need to be addressed.
  • The introduction of the Xpert-based algorithm brought relief by decreasing the cost incurred by MDR-TB patients. Median patient costs from the onset of illness to the start of treatment were reduced from $68.1 to $38.3 (p=0.004). However the loss of employment and individual and household income persists. Patients require financial support to mitigate of MDR-TB.

Contribution to the Evidence Base

There is a paucity of published data on the broader impact of molecular TB diagnostic tests beyond efficacy. This study will contribute to findings on their impact within a routine operational setting. The findings could be used to assist the health department to optimise the way in which tests are currently used to help ensure that patients receive the anticipated benefits. Study findings could serve to inform policy decisions about the implementation of Xpert elsewhere and for the future adoption of new diagnostic tests in South Africa.

Principal Investigator: Dr. Pren Naidoo; pnaidooicon.co.za