Short summary

The urine tuberculosis lipoarabinomannan (LAM) strip-test (Determine®-TB Alere, USA) can potentially be used as a rule-in test for tuberculosis TB in patients with advanced HIV and facilitate early initiation of antituberculous treatment. In 2016, a Cochrane Review was published on the accuracy of lateral flow urine LAM (LF LAM) for diagnosis of tuberculosis. This project will update the systematic review.

Rationale

Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care test for tuberculosis (TB). Owing to suboptimal sensitivity, the urinary LAM assays are unsuitable as general screening tests for TB. However, unlike traditional diagnostic methods, they demonstrate improved sensitivity in HIV-TB co-infection which further increases with low CD4 counts. The urine lipoarabinomannan (LAM) lateral flow test (Determine®-TB Alere, USA 'LF LAM') potentially can be used as a rule-in test for TB in patients with advanced HIV-induced immunosuppression, and facilitate the early initiation of antituberculous treatment in them. In 2016, the original Cochrane Review on the diagnostic accuracy of LF LAM was published and served to support decisions regarding adoption of LF- LAM worldwide (WHO LF LAM policy guidance 2015). Since 2015, approximately 20 additional studies have been conducted. Recently, WHO has received numerous requests from MSF and others in the TB community who believe the evidence regarding LF-LAM should be reconsidered, in light of new diagnostic accuracy studies and two recent impact studies.

The aim of this project is to: 

• To assess the available data on the accuracy (sensitivity and specificity) of lateral flow urine lipoarabinomannan assay (LF-LAM) for diagnosis of active TB in HIV-infected adults and chiildren with signs of sympotms of TB, irrespecive of signs and symptoms of TB and in individuals with advanced HIV disease. 
• To assess the available data related to patient outcomes, i.e. impact of LF-LAM implementation on patient outcomes. Patient-important outcomes include mortality and time to treatment initiation.
• To conduct a review of the economic data on affordability, cost, and cost-effectiveness of LF-LAM implementation to assist in the diagnosis of TB diagnosis. 
• To outline issues to be addressed by WHO in subsequent policy recommendations.

The target audience is Policy makers, clinicians and other health care staff, HIV and TB programme managers, technical agencies, donors, and implementing partners supporting the use of  TB diagnostics in resource limited settings. 

The main review authors from the previous 2016 Cochrane Review have been invited to 

opt in as authors on this updated review. As of this writing, Maunank Shah, Nandini Dendukuri, Ian Schiller, and Karen Steingart have all opted in to be review authors on this updated review with Stephanie Bjerrum as a review author. 

Collaborating researchers and departments

Department of Infectious Diseases, Odense University Hospital

• Stephanie Bjerrum, MD, PHD

Department of Infectious Diseases, John Hopkins University.  

• Maunank Shah, Associate Professor of Medicine, MD, PHD

Department of Epidemiology, Biostatistics and Occupational Health, McGill International TB Centre. 

• Mikashmi Kohli, MD, PHD, Postdoctural Fellow

Cochrane Infectious Disease Group, Liverpool School of Tropical Medicine 

• Karen R Steingart, Honary Research Fellow

Publications associated with the project

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Shah M, Hanrahan C, Wang ZY, et al. Cochrane Database Syst Rev. 2016(5):CD011420.