Laboratory cross-contamination of Mycobacterium tuberculosis: a systematic review and meta-analysis

Background: Microbiological cultures are the mainstay of the diagnosis of tuberculosis (TB). False positive TB results lead to significant unnecessary therapeutic and economic burden and are frequently caused by laboratory cross-contamination. The aim of this meta-analysis was to quantify the prevalence of laboratory cross-contamination.
Methods: Through a systematic review of five electronic databases, we identified studies reporting rates of laboratory cross-contamination, confirmed by molecular techniques in TB cultures. We evaluated the quality of the identified studies using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and conducted a meta-analysis using standard methodology recommended by the Cochrane Collaboration.
Results: Based on 31 eligible studies evaluating 29,839 TB cultures, we found that 2% (95% confidence intervals [CI]: 1-2%) of all positive TB cultures represent false positive results secondary to laboratory cross-contamination. More importantly, we evaluated the rate of laboratory cross-contamination in cases where a single positive TB culture was available in addition to at least one negative TB culture, and we found a rate of 15% (95%CI: 6-33%). Moreover, 9.2% (91/990) of all patients with a preliminary diagnosis of TB had false-positive results and received unnecessary and potentially harmful treatments.
Conclusions: Our results highlight a remarkably high prevalence of false positive TB results as a result of laboratory cross-contamination, especially in single-positive TB cultures, leading to the administration of unnecessary, harmful treatments. The need for the adoption of strict technical standards for mycobacterial cultures cannot be overstated.