TABLE 1.

cfDNA isolation methodology of studies^a on blood- and urine-based cfDNA detection of M. tuberculosis by nucleic acid amplification techniques in which the methodological steps are a priori considered suitable for cfDNA isolation and detection^b,c

Publication’s first author	Yr	Sample type	Centrifugation, urine supernate collection	Preservative/storage	DNA extraction method	Test type	Target(s)	Amplicon target size(s) (bp)
Ushio	2016	Plasma	NA	EDTA/NR	Qiagen DNeasy blood and tissue kit	Digital PCR	IS6110, gyrB	71
Click	2018	Plasma	NA	EDTA/NR	QiaAmp circulating nucleic acid kit	qPCR	IS6110	106
Cannas	2008	Urine	Yes	EDTA/NR	Manual/resin	Nested PCR	IS6110	67 and 129
Fortun	2014	Urine	NR	NR/NR	NR	TMA	16S rRNA	NR
Labugger	2017	Urine	Yes	EDTA/NR	Manual/resin	PCR	IS6110	38
Patel	2017	Urine	NR	EDTA/NR	Manual/resin	PCR	DR region	38

^aSee references 23, 24, 25, 32, 33, and 34.

^bTwo additional studies reported one case report (63, 64). Both studies describe the identification of urinary M. tuberculosis cfDNA in extrapulmonary TB cases; the first refers to a disseminated TB case while the second to a pediatric tubercular otitis media case. Sample preanalytical steps were performed as reported in the Ushio et al. study and Cannas et al. study, respectively (63, 64). Data from these studies were not included here given that only samples from an individual patient were available.

^cNR, not reported; NA, not applicable; TMA, transcription-mediated amplification; DR, direct repeat.