Whole genome sequencing of Mycobacterium tuberculosis for detection of recent transmission and tracing outbreaks: A systematic review.

Contact tracing complemented with genotyping is considered an important means of understanding person-to-person transmission of tuberculosis (TB). It still remains unclear whether Whole Genome Sequencing (WGS) of Mycobacterium tuberculosis can rule in transmission and how it performs in different human populations, risk groups and across TB lineages. This systematic review aimed to determine the sensitivity and specificity of WGS for detection of recent transmission using conventional epidemiology as the gold standard and investigate if WGS identifies previously undetected transmission events. Systematic review was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses group. A compound search strategy was developed to identify all relevant studies published between 01/01/2005 and 30/11/2014 using three online databases. Publications satisfying specific criteria have been identified and data extracted. A total of 12 publications were included. We established that WGS has a higher discriminatory power compared to conventional genotyping and detects transmission events missed by epidemiological investigations. A cut-off value of <6 SNPs between isolates may predict recent transmission. None of the studies performed a head-to-head comparison between WGS and conventional genotyping using unselected prospectively collected isolates. Minimum reporting criteria for WGS studies have been proposed and quality control parameters considered. Crown