Introduction
Methods
Study selection criteria and operational definitions
Study search strategy, study selection, and data extraction
Quality assessment of time delay estimates
Data synthesis and meta-analysis
Results
Search results
Description of included studies
Author | Year | Country | Study design | Setting | Level of healthcare system | HIV prevalence | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Boehme [30] | 2011 | Multipleb | Pre/post | Urban | Mixed | 0.19 | |||||||
Yoon [50] | 2012 | Uganda | Pre/post | Urban | Tertiary | 0.76 | |||||||
Kwak [51] | 2013 | South Korea | Observational | Urban | Tertiary | 0.27 | |||||||
Chaisson [52] | 2014 | USA | Hypothetical | Urban | Tertiary | NR | |||||||
Cohen [53] | 2014 | South Africa | Observational | Urban | Tertiary | 1.00 | |||||||
Cox [54] | 2014 | South Africa | Parallel Cl. RCT | Urban | Primary | 0.60 | |||||||
Durovni [32] | 2014 | Brazil | St.-we CI. RCT | Urban | Primary | 0.10 | |||||||
Mupfumi [34] | 2014 | Zimbabwe | Ind. RCT | Urban | Tertiary | 1.00 | |||||||
Sohn [55] | 2014 | Canada | Hypothetical | Urban | Tertiary | 0.02 | |||||||
Theron [37] | 2014 | Multiplea | Ind. RCT | Urban | Primary | 0.6 | |||||||
Calligaro [56] | 2015 | South Africa | Observational | Urban | Tertiary | 0.27 | |||||||
Muyoyeta [57] | 2015 | Zambia | Observational | Urban | Primary | 0.52 | |||||||
Page [35] | 2015 | Cambodia | Observational | NR | NR | NR | |||||||
Page [35] | 2015 | Kenya | Observational | NR | NR | NR | |||||||
Page [35] | 2015 | Swaziland | Observational | NR | NR | NR | |||||||
van den Handel [58] | 2015 | South Africa | Observational | Rural | Primary | 0.28 | |||||||
Hanrahan [59] | 2016 | Uganda | Observational | NR | NR | 0.69 | |||||||
Akanbi [60] | 2017 | Nigeria | Observational | Urban | Tertiary | 1.00 | |||||||
Calligaro [61] | 2017 | South Africa, Zimbabwe | Randomized, parallel group trial | Urban | Primary | 0.58 | |||||||
Mwansa-Kambafwile [62] | 2017 | South Africa | Observational | Urban | Primary | 0.73 | |||||||
Schmidt [63] | 2017 | South Africa | Observational | Rural | Primary | NR | |||||||
Shete [36] | 2017 | Uganda | Single arm interventional pilot | Rural | Primary | 0.53 | |||||||
de Castro [64] | 2018 | Brazil | Observational | Urban | Primary | 0.05 | |||||||
Khumsri [65] | 2018 | Thailand | RCT | Urban | Tertiary | NR | |||||||
Mugauri [66] | 2018 | Zimbabwe | Observational | Urban | Primary | NR | |||||||
Agizew [67] | 2019 | Bostwana | St.-we CI. RCT | NR | Primary | 1 | |||||||
Le [68] | 2019 | Vietnam | Observational | Rural | Tertiary | NR | |||||||
Nalugwa [69] | 2020 | Uganda | Observational | NR | Tertiary | 0.838 |
Author | Year | Diagnostic delay | Treatment initiation delay | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Index | Comparator | Term | Time period | Index | Comparator | Term | Time period | ||||||
n | Median (IQR) (days) | n | Median (IQR) (days) | n | Median (IQR) (days) | n | Median (IQR) (days) | ||||||
Boehme [30] | 2011 | 1429 | 1 day (0–2) | 3659 | Smear: 2 days (2–3) Culture: 58 days (42–62) | Time to detection | Collection of first sputum to receiving result by clinicians | 1907 | 5 daysd (2–8) | 4734 | 56 days (39–81) | Time to treatment initiation | First sputum collection to time to treatment initiation |
Yoon [50] | 2012 | 190 | Same day (0–1) | 246 | 1 day (0–26) | Time to detection | Enrolment to first positive result | 190 | 6 daysd (1–61) | 246 | 7 days (3–53) | Time-to-TB treatment | Enrolment to treatment initiation |
Kwak [51] | 2013 | 681 | 6 days (3–7) | 681 | Smear: 12 days (7–19.25) Culture: 38.5 (35.75–50.25) | Time to confirmation of receipt of results | Request of diagnostic test to confirmation of results by duty physician | 43 | 7 days (4–9) | 86 | 21 days (7–33.5) | Time to anti-TB treatment | Request of diagnostic test to initiation of ATT |
Chaisson [52] | 2014 | 142 | 1 day (0–2) | 142 | 2 days (1–4) | Time to result | Order for admission to time to reporting results | NR | NR | NR | NR | NR | NR |
Cohen [53] | 2014 | 156 | 6.3 days (5.3–8.1) | 90 | 3.3 days (2.1–5.2) | Total diagnostic time | Sputum collection to clinician receipt of result | NR | NR | NR | NR | NR | NR |
Cox [54] | 2014 | NR | NR | NR | NR | NR | NR | 982 | 4 days (2–8) | 1003 | 8 days (2–27) | Time to TB treatment initiation | Enrolmentc to treatment initiation |
Durovni [32] | 2014 | 1385 | 7.3 days (3.4–9.0) | 831 | 7.5 days (4.9–10.0) | Time to positive result | Specimen processing to lab-confirmed TB notification | 1385 | 8.1 days (5.4–9.3) | 831 | 11.4 days (8.5–14.5) | Time to treatment initiation | NR |
Mupfumi [34] | 2014 | 214 | 2 days (1–13) | 210 | 6 days (1–25) | Time to diagnosis | Clinical presentation (baseline visit) to TB diagnosis | 214 | 5 days (3–13) | 210 | 8 days (3–23) | Time to treatment initiation | Clinical presentation (baseline visit) to treatment initiation |
Sohn [55] | 2014 | 11 | 1 day (0–4) | 11 | Smear: 1 day (1–2) Culture: 21.5 days (14–30) | Time to diagnosis | Time between first sample and the positive Xpert result | 11 | Hypothetically reduce by 12 days (4–23) in smear negative TB patient | 11 | 26 days (4–30) | Time to reporting | Time from first sample to treatment initiation |
Theron [37] | 2014 | NR | 81% diagnosed on same day | NR | 43% diagnosed on same day | NR | NR | 744 | Same day (0–3) | 758 | 1 day (0–4) | Time to treatment | Enrolmentc to treatment initiation |
Calligaro [56] | 2015 | 111 | 0.2 days (0.2–0.3) | 115 | 12.1 days (0.3–22.2) | Time to diagnosis | NA | 111 | 0.3 days (0.2–1.2) | 115 | 0.7 days (0.2–2.2) | Time to initiation of treatment | NR |
Muyoyeta [57] | 2015 | NR | NR | NR | NR | NR | NR | 553 | 2 days (1–5) | 212 | 3 days (2–6) | Time to TB treatment | Date to first presentation to diagnostic services to date pt. was commenced on TB treatment |
Page [35] | 2015 | NR | NR | NR | NR | NR | NR | 15 | 16 days (6–33) | 77 | 4 days (2–6) | Delay in treatment initiation | Collection of first specimen and treatment start |
Page [35] | 2015 | NR | NR | NR | NR | NR | NR | 17 | 4 days (2–7) | 3 | 1 day (1–35) | ||
Page [35] | 2015 | NR | NR | NR | NR | NR | 63 | 6.5 days (3–10) | 7 | 8 days (1–11) | |||
van den Handel [58] | 2015 | NR | NR | NR | NR | NR | NR | 75 | 1 day (0–2) | 68 | 11.5 days (6–24) | Time to treatment | First sputum sample collection to anti-TB treatment initiation |
Hanrahan [59] | 2016 | NR | NR | NR | NR | NR | NR | 48 | 0 days (0–0) | 39 | Empiric: 14 days (5–35) Culture: 144 days (28–180) | Time to treatment | Sputum collection to TB treatment |
Akanbi [60] | 2017 | NR | NR | NR | NR | NR | NR | 56 | 5 days (2–8) | 20 | 12 days (5–35) | Time to treatment | Baseline visit (specimen collection) to treatment initiation |
Calligaro [61] | 2017 | NR | NR | NR | NR | NR | NR | 435 | 1 day (0.1–4) | 413 | 4 days (1–31) | Time-to-treatment initiation | Enrolment to initiated on treatment |
Mwansa-Kambafwile [62] | 2017 | NR | NR | NR | NR | NR | NR | 177 | 0 days (0–0) | 21 | 9 days (4–20) | Time to treatment initiation | NR to treatment initiation |
Schmidt [63] | 2017 | 851 | 0 days (0–1) | 738 | 2 days (1–22) | Time to laboratory diagnosis | Sputum sample collection to test result reported | 851 | 4 days (2–8) | NR | NR | Time to TB treatment initiation | Time from sputum sample collection to time when TB treatment was recorded as being initiated |
Shete [36] | 2017 | 1091 | 1 day (0–2) | 54 | 1 day (0–2) | Time-to-diagnosis | NR | 41 | 6 days (2–11) | 113 | 1 day (0–1) | Time-to-treatment | NR |
de Castro [64] | 2018 | 24 | 6 days (2–8) | 41 | 3 days (2–6) | Time from triage to NR | Triage to lab test result release | 24 | 14.5 days (8–28) | 41 | 8 days (6–12) | Time from triage to NR | Triage to treatment initiation |
Khumsri [65] | 2018 | 40 | 1.88e (SD 1.07) | 36 | 4.11e (SD 2.22) | Time to get correct diagnosis | Outpatient department visit to receive correct diagnosis | NR | NR | NR | NR | NR | NR |
Mugauri [66] | 2018 | NR | NR | NR | NR | NR | NR | 340 | 20.17 dayse (SD 10.3) | 318 | 22.44 dayse (SD 30.2) | Delay in treatment initiation from diagnosis | Diagnosis to treatment initiation |
Agizew [67] | 2019 | NR | NR | NR | NR | NR | NR | 159 | 6 days (2–17) | 42 | 22 days (3–51) | Time-to-treatment | Sputum collection to treatment initiation |
Le [68] | 2019 | 69 | 2 days (1–4) | NR | NR | NR | NR | 69 | 1 day (0–1) | 8 | 3 days (1–8) | Time to anti-TB treatment | Hospital admission to treatment initiation |
Nalugwa [69] | 2020 | NR | NR | NR | NR | NR | NR | 33 | 2 days (0–14) | NR | 0 days (0–1) | Time to treatment | NR to treatment initiation |
Author | Year | Country | Study design | Setting | Level of healthcare system | HIV prevalence | Type of culture | Type of LPA | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Boehme [30] | 2011 | Multiplea | Observational | Urban | Mixed | 0.19 | Both | Both | |||||
Chryssanthou [70] | 2011 | Sweden | Observational | Urban | Tertiary | NR | Liquid culture | Direct | |||||
Skenders [71] | 2011 | Latvia | Observational | NR | NR | NR | Liquid culture | Direct | |||||
Hanrahan [40] | 2012 | South Africa | Observational | NR | NR | 0.58 | Liquid culture | Both | |||||
Jacobson [72] | 2012 | South Africa | Observational | Rural | Tertiary | 0.30 | Liquid culture | Indirect | |||||
Lyu [73] | 2013 | South Korea | Observational | Urban | Tertiary | 0.01 | Liquid culture | Direct | |||||
Gauthier [74] | 2014 | Haiti | Observational | Urban | Tertiary | NR | Solid culture | Direct | |||||
Liquid culture | |||||||||||||
Kipiani [75] | 2014 | Georgia | Observational | Urban | Tertiary | 0.03 | Solid culture | Direct | |||||
Raizada [76] | 2014 | India | Observational | Urban | NR | NR | Solid culture | Direct | |||||
Singla [77] | 2014 | India | Observational | Urban | Tertiary | NR | Both | Direct | |||||
Bablishvili [78] | 2015 | Georgia | Observational | Urban | Tertiary | NR | Solid culture | Direct | |||||
Liquid culture | |||||||||||||
Cox [39] | 2015 | South Africa | Observational | Urban | Primary | 0.74 | Both | Direct | |||||
Eliseevb [79] | 2016 | Russia | Observational | NR | NR | 0.06 | Solid culture | Direct | |||||
Liquid culture | |||||||||||||
Evans [80] | 2017 | South Africa | Observational | Urban | Tertiary | 0.89 | NR | NR | |||||
Iruedo [81] | 2017 | South Africa | Observational | Rural | Primary | 0.61 | NR | NR | |||||
Evans [82] | 2018 | South Africa | Observational | Urban | Primary | 0.26 | NR | NR | |||||
Lib,c [43] | 2019 | China | Observational | Urban | Tertiary | NR | Solid culture | Direct | |||||
Jeon [41] | 2020 | South Korea | Observational | Urban | Tertiary | NR | NR | NR | |||||
Ngabonziza [83] | 2020 | Rwanda | Observational | NR | Tertiary | 0.40 | NR | NR | |||||
Shi [42] | 2020 | China | Observational | Urban | Tertiary | NR | Solid culture | Direct |
Author | Year | Diagnostic delay | Treatment initiation delay | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Index | Comparator | Term | Time period | Index | Comparator | Term | Time period | ||||||
n | Median (IQR) (days) | n | Median (IQR) (days) | n | Median (IQR) (days) | n | Median (IQR) (days) | ||||||
Boehme [30] | 2011 | 244 | 63 (38–102) | 356 | 40 (27–53) | Time to detection | Specimen collection to receiving result by clinicians | NR | NR | NR | NR | NR | NR |
Chryssanthou [70] | 2011 | 127 | 21 (13–78) | 127 | 7 (1–16) | Lab processing time | Specimen arrival at lab to report of DST to clinician | NR | NR | NR | NR | NR | NR |
Skenders [71] | 2011 | NR | NR | NR | NR | NR | 47 | 40 (23–67) | 22 | 14 (7–22) | Admission to treatment start | Hospital admission to treatment start | |
Hanrahan [40] | 2012 | 1176 | 52 (41–77) | 1177 | 26 (11–52) | Test turnaround time | Date of sputum collection to DST results | 26 | 78 (52–93) | 52 | 62 (32–86) | Time to MDR-TB treatment | Date of sputum collection to MDR-TB treatment |
Jacobson [72] | 2012 | 89 | 55 (46–66) | 108 | 27 (20–34) | Lab processing time | Specimen arrival at lab to report of results | 89 | 80 (62–100) | 108 | 55 (37.5–78) | Time to MDR treatment initiation | Specimen collection to MDR treatment initiation |
Lyu [73] | 2013 | 428 | 83 (68–92) | 168 | 12.7 (8–17) | Turnaround time | Test request to reporting of results | NR | NR | NR | NR | NR | NR |
Gauthier [74] | 2014 | 221 | 54 (43–64) | 221 | 7.5 (6.5–8.5) | Turnaround time | NR to time to positivity | NR | NR | NR | NR | NR | NR |
221 | 19 (12–25) | 221 | 7.5 (6.5–8.5) | Turnaround time | NR to time to positivity | NR | NR | NR | NR | NR | NR | ||
Kipiani [75] | 2014 | NR | NR | NR | NR | NR | 72 | 83.9 (56–106) | 80 | 18.2 (11–24) | Time to MDR-TB treatment initiation | Sputum collection to start of SLD therapy | |
Raizada [76] | 2014 | 248 | 87 (42–208) | 248 | 11 (1–76) | Turnaround testing time | Specimen collection to DST result being available | NR | NR | NR | NR | NR | NR |
Singla [77] | 2014 | 121 | 107 (79–131) | 433 | 5 (3–6) | Diagnostic time in lab | Specimen arrival at lab to MDR-TB report | 51 | 157 (127–200) | 83 | 38 (30–79) | NR | Time from identification patients suspected for MDR-TB to MDR-TB treatment initiation |
Bablishvili [78] | 2015 | 155 | 33 (27–41) | 336 | 5 (3–7) | Time to MTB detection | Sample collection to recorded results | NR | NR | NR | NR | NR | NR |
227 | 9 (7–11) | 336 | 5 (3–7) | Time to MTB detection | Sample collection to recorded results | NR | NR | NR | NR | NR | NR | ||
Cox [39] | 2015 | NR | NR | NR | NR | NR | NR | 95 | 76 (62–111) | 173 | 28 (16–40) | Time to treatment | Time from collection to treatment initiation |
Eliseevb [79] | 2016 | NR | NR | NR | NR | NR | NR | 38 | 90 (76.3–117.3) | 72 | 24 (19–51) | Time to MDR-TB treatment initiation | First visit to treatment |
NR | NR | NR | NR | NR | NR | 58 | 74 (55–99.8) | 72 | 24 (19–51) | Time to MDR-TB treatment initiation | First visit to treatment | ||
Evans [80] | 2017 | NR | NR | NR | NR | NR | NR | 256 | 81 (49–115) | 256 | 38 (23–54) | NR | Sputum collection to treatment initiation |
Iruedo [81] | 2017 | 143 | 45 (39–59) | 28 | 11.5 (8–21) | Time to diagnosis | Sputum collection to issue of report to clinic | 143 | 64 (50–103) | 28 | 29 (14.5–53) | Time to treatment | Sputum collection to treatment initiation |
Evans [82] | 2018 | NR | NR | NR | NR | NR | NR | 7 | 81 (28–97) | 129 | 38 (23–51) | Time to treatment initiation | Specimen collection to treatment initiation |
Lib,c [43] | 2019 | 155 | 53 (49–60) | 155 | 3 (2–4) | Turnaround time | Sample receipt to reporting date of results | NR | NR | NR | NR | NR | NR |
Jeon [41] | 2020 | NR | NR | NR | NR | NR | NR | 263 | 13 (5–25) | 202 | 5 (2–9.3) | Time to MDR treatment initiation | MDR-TB diagnosis to MDR-TB treatment initiation |
Ngabonziza [83] | 2020 | 313 | 87 (78–98) | 197 | 40 (25–55) | RR-TB diagnostic delay | Specimen collection to results being available | NR | NR | NR | NR | NR | NR |
Shi [42] | 2020 | 105 | 62 (53–69) | 113 | 16 (10–19) | NR | NR | 37 | 69 (59–77) | 42 | 19 (14–23) | NR | NR |
Quality assessment of time delay estimates
Impact of NAATs on delay
Subgroup | # of studies | Median reduction (95% CI) | I2 | p-value |
---|---|---|---|---|
Year | ||||
Pre-2015 | 8 | 1.21 (− 0.67 to 3.10) | 98.99% | 0.20 |
Post-2015 | 4 | 3.15 (− 2.72 to 9.01) | 98.56% | 0.29 |
Empiric treatment rate | ||||
High ≥ 50% | 5 | 1.58 (0.55–2.61) | 89.18% | 0.003 |
Low < 50% | 7 | 1.85 (− 1.91 to 5.6) | 99.31% | 0.34 |
HIV prevalence | ||||
High ≥ 50% | 5 | 1.12 (− 1.19 to 3.43) | 96.31% | 0.34 |
Low < 50% | 7 | 2.31 (− 1.09 to 5.71) | 99.62% | 0.18 |
Healthcare level | ||||
Primary | 4 | 0.83 (− 1.83 to 3.49) | 96.25% | 0.54 |
Tertiary | 7 | 2.54 (− 0.84 to 5.92) | 98.87% | 0.14 |
Study design | ||||
RCT | 3 | 4.56 (− 2.72 to 11.43) | 99.19% | 0.19 |
Observational | 6 | 1.17 (− 1.18 to 4.1) | 97.85% | 0.44 |
Overall | 12 | 1.78 (− 0.27 to 3.85) | 99.25% | 0.089 |
Subgroup | # of studies | Median reduction (95% CI) | I2 | p-value |
---|---|---|---|---|
Year | ||||
Pre-2015 | 6 | 5.04 (0.09–9.99) | 99.64% | 0.046 |
Post-2015 | 12 | 2.54 (0.45–4.62) | 98.86% | 0.017 |
Empiric treatment rate | ||||
High ≥ 50% | 12 | 2.64 (0.93–4.35) | 98.34% | 0.002 |
Low < 50% | 6 | 1.71 (− 4.24 to 7.66) | 98.81% | 0.56 |
HIV prevalence | ||||
High ≥ 50% | 12 | 1.09 (− 0.78 to 2.95) | 98.36% | 0.25 |
Low < 50% | 6 | 4.61 (− 0.79 to 10.00) | 99.50% | 0.09 |
Healthcare level | ||||
Primary | 8 | 1.27 (− 1.45 to 4.00) | 99.07% | 0.36 |
Tertiary | 4 | 5.27 (− 1.06 to 11.60) | 98.87% | 0.1 |
POCT program | ||||
POCT | 7 | 3.98 (1.13–6.81) | 99.23% | 0.0061 |
Lab | 11 | 0.79 (− 2.75 to 4.33) | 99.27% | 0.66 |
Study design | ||||
RCT | 5 | 2.85 (1.16–4.55) | 95.44% | 0.001 |
Observational | 13 | 1.67 (− 1.70 to 5.05) | 99.57% | 0.33 |
Overall | 21 | 2.55 (0.54–4.56) | 99.31% | 0.013 |