Table 2.
Characteristics of studies included in the systematic review on HCV antibody detection from DBS compared to venous blood sampling
| Author, Country | Study design | Study pop, Sample size | Storage conditions | DBS collection method | Serum and plasma antibody test | DBS antibody test | Suggested Cut-off | Specificity | Sensitivity | Correlation/Agreement | Effect of storage conditions |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Brandao Brazil 2013 |
Cross sectional | 386 persons, 40 anti-HCV pos, 346 blood donoers HCV non-reactive, | DBS samples air dried at room temperature for 4 h, stored at −20 °C. Temperature: −20 °C Time: Not specified |
capillary blood by finger prick 75 μl onto Whatman filter paper | MonolisaTM HCV AgAb ULTRA, Bio-Rad (Marnes-la-Coquette, France), and Murex HCV AgAb, Abbott (Kyalami, Republic of South Africa). | MonolisaTM HCV AgAb ULTRA, Bio-Rad (Marnes-la-Coquette, France), and Murex HCV AgAb, Abbott (Kyalami, Republic of South Africa). |
ROC cutoff: 0.287 nm for Monolisa assay ROC cut-off for Murex assay 0.238 nm Derived from the same sample |
99.7 (98.4–99.9) 95.9 (93.3–97.8) |
97.5 (86.8–99.9) 97.5 (86.8–99.9) |
PPV and NPV calculated Kappa = 0.99 (with ROC cut-off), |
stability up to 60 days of storage at room temperature, but less variation at −20 °C |
| Croom Australia 2006 | Cross sectional | 103 samples from high risk groups, negative samples from 94 indivdiuals tested at Haematology Lab | Air dried at room temperature, storage at −20 °C, plasma at −20 °C, time of storage 1 week −11 months Temperature: −20 °C Time: 1 week −11 months |
Venipuncture, 80 μl of each whole blood sample spotted onto Schleicher and Schuell cards (Grade 903) | Monolisa EIA, confirmation test: Murex anti HCV (version 4.0), EIA | Monolisa EIA, confirmation test: Murex anti HCV (version 4.0), EIA | NR | 100% (96–100) 108/108 |
100% (94–100) 75/75 |
NR | NR |
| Chevaliez France 2014 |
Unclear | 529 patients, 183 HCV seronegative, 346 seropositive | NR | NR | EIA HCV assay | EIA HCV assay | 0.2 | 98.9 (96.1–99.7) | 99.1 (97.4–99.7) | R = 0.56 | NR |
| Dokubo US 2014 |
Cross sectional within a prospective cohort study of those HCV positive being followed | 148 participants in a prospective study of HCV | DBS air-dried for 2 h, then sent to another insitute, then stored at −70 °C | Fingerstick on Whatman 903 cards 0.5 ml blood | Standard diagnostics HCV TMA (Norvatis®) ELISA v3.0(Ortho®). |
Standard diagnostics HCV TMA (Norvatis®) ELISA v3.0(Ortho®). |
100% (71/71) |
70% (54/77) |
Kappa 0.69 | NR | |
| Flores 2016 Brazil |
Cross sectional | Participants recruited from ambulatory and general hospital, known HCV/HIV serological status | DBS airdried 4 h, then frozen at -20C | Venipuncture, Whatman filter paper, 3–5 drops (~75 μl) | HCV Murex AB, Diasorin | HCV Murex AB, Diasorin | NR | 100% (99/99) |
94% (213/230) |
Spearman correlation r = 0.520 | NR |
| Gruner 2015 Germany |
Cross-sectional | Inpatients, 299 | Temperature: -20C, 4C or ambient temperature Time: Up to 14 days |
Venipuncture, 100 μl whole blood on paper card | Not specified | Not specified | Derived from different sample | NR | 99% 339/343 |
NR | NR |
| Kania Burkina-Faso 2013 | Cross sectional | 218 HIV screening participants, 5 anti-HCV pos, 213 anti-HCV neg | NR | Venipuncture, 5 spots whole blood (50 μl) on Whatman 903 | Monolisa HCV-Ab-Ag ULTRA assay (Bio-Rad), further assessment with Inno-Lia HCV Score assay (Innogenetics) | Monolisa HCV-Ab-Ag ULTRA assay (Bio-Rad), further assessment with Inno-Lia HCV Score assay (Innogenetics) | 0.439 | 100% (97,8–100%) | 100% (46,3–100%) | kappa: 1,00 (0,93–1,00) | NR |
| Larrat France 2012 |
Cross sectional | One hundred thirteen HCV-positive cases consecutively recruited 17 HIV/HCV co-infected patients (15%) |
DSB dried 24 h at room temperature | Finger prick blood on Whatman card | Monolisa® HCV-Ag-Ab-ULTRA, Bio-Rad) |
Oraquick HCV CEIA Biorad |
0.1 0.2 cEIA |
100 (95.8–100) 88/88 100 (95.8–100) 88/88 |
97.4(92.5–99.1) 110/113 98.2 (93.8–99.5) 111/113 |
ROC AUC OMT cEIA Biorad: 0.99 ROC AUC FSB cEIA Biorad: 0.918 |
At 3 days room temperature 3/3 HCV negative samples NR, ODs lower in HIV co-infected patients |
| Lee Malaysia 2011 | Cross sectional | 150 paired samples | Left to dry overnight at room temperature, then stored −20 °C | Venipuncture, 50 μl whole blood on filter paper | Abbott | Abbott | ROC cut off 0.10 RLU | 100% | 97.3% | ROC curve AUC: 0.99 R = 0.631 |
NR |
| Lukacs Germany 2005 | Unclear | 7 samples from known HCV patients | NR | NR | NR | Luminex | NR | NR | 100% 7/7 | NR | NR |
| McCarron UK 1999 |
Case control | NR | NR | NR | NR | NR | 0.99 1.99 |
87.5% 100% |
100% 97.2% |
NR | NR |
| Marques Brazil 2012 |
Cross sectional | 21 and 24 HCV reactive patients, 234 individual and 132 HCV negative |
serum stored at −20 °C | Venipuncture, 75 μl whole blood on Whatman paper | Two methods: HCV-Ab Radim, Pomezzia, Italy and ETI-AB-HCVK-4 DiaSorin, Vercelli, Italy | Two methods: HCV-Ab Radim, Pomezzia, Italy and ETI-AB-HCVK-4 DiaSorin, Vercelli, Italy | Radim: manu-facturer’s cut off ROC curve for DiaSorin EIA using the same sample population |
99.5% (98–99.9) 98.9% (96.80–99.55) |
97.5% (86.84–99.94) 88.9% (75.95–96.29) |
NR | 2–8 degrees C, 20–25 degrees C, and −20 degrees were evaluated, −20 resulted in lowest variation Methods of cut off determination: the receiver operating characteristic curve(AUROC) |
| Marques Brazil 2016 |
Recruited at Viral Hepatitis Lab | 99 (59 anti HCV/HCV RNA pos, 40 neg samples) | NR | Venipuncture, 3–5 drops on Whatman filter paper | HCV Ab Radim, Pomezia, Italy | HCV Ab Radim, Pomezia, Italy | 100% 40/40 |
94.9% 56/59 |
|||
| Mossner Denmark 2016 | Cohort | 404 Prospective patients from hepatitis clinic and blood donors | Temperature: Room temperature Time 1–5 days | Finger prick, 75 μ on Whatman filter paper | Architect HCV Ab, using the Architect system (Abbott Diagnostics, Delkenheim, Germany) |
Architect HCV Ab, using the Architect system (Abbott Diagnostics, Delkenheim, Germany) |
NR | 100% 288/288 |
97% 112/116 |
NR | Variation of 24 h to up to 7 d found no difference in stability of samples |
| Nandagopal India 2014 | Unclear | Murex | 60 samples | Venipuncture,50 μl of whole blood 903 Whatman card | NR | NR | NR | 100 (29/29) | 100 (31/31) | Pearson correlation coefficient 0.98 | NR |
| O Brien US 2001 |
Multicenter prospective trial (one-arm only) | 1286 subjects enrolled in multi-centre study, | Air dry for 30 min, sent in FedEx envelope | Self collected capillary blood with at home kit | NR | HCV Check, Home Access Corp. self use DBS home kit | NR Several inconclusive and indeterminate results not included in diagnostic accuracy calculations |
100% 686/686 |
99.5% 402/404 | NR | NR |
| Parker UK 1997 |
Case control design | 80 anti HCV positive samples, 52 negative 569 dB sample fields from South African neonates |
Air dry at room temperature before storage at 4 °C | NR, Dried blood field samples | In house IgG ELISA, immunoblot RIBA 3.0 | In house IgG ELISA, immunoblot RIBA 3.0 | T/N 5.0 T/N10.0 |
541/569 95.1% | 78/80 98% 69/80 86.2% |
NR | |
| Ross Germany 2013 |
Unclear | 339 samples | Dried overnight at room temperature | Venipuncture 100 μl of whole blood applied to Whatman 903 filter paper |
ARCHITECT system (Abbott Diagnostics, Delkenheim, Germany). |
ARCHITECT system (Abbott Diagnostics, Delkenheim, Germany). |
NR | 100% (97.7–100) 160/160 |
97.8% (96–100) 175/179 |
NR | NR |
| Soulier France 2017 |
Cross-sectional | 511 patients recruited, with known serostatus for HCV | Temperature:-80 Time: NR |
Venipuncture, 50 μl on Whatman filter paper | EIA; aHCV Vitros ECi; Diagnostics, Raritan, New Jersey). | EIA; aHCV Vitros ECi; Ortho-Clinical Diagnostics, Raritan, New Jersey). | NR | 312/315 98% |
183/186 99% |
NR | 25 dB samples stored at ambient temperatures (24 °C) for a mean duration (±SD) of 19 ± 1 months Sensitivity for genotype detection in DBS 84.5% |
| Sheperd UK 2013 |
Cross sectional | 19 recently infected 300 chronic carrier 82 resolved infection |
DBS stored at 4 °C until use | NR, 50 μl on 903 Whatman Protein Saver cards | ORTHO HCV 3.0 ELISA Test System with Enhanced SAVekit (Ortho Clinical Diagnostics) was used to detect anti-HCV in DBS | NR | Avidity cut-off AI < 30 | NR | NR | NR | NR |
| Tejada-Strop US 2015 |
Case control | 103 patients with known HCV result, 33 adult patients with chronic HepC with stored samples | -20 °C until 5 years later | NR, 75 μl of whole blood on 12 mm DBS | Two immunoassays, the VITROS anti-HCV IgG chemi-luminescence assay (CIA) and the HCV 3.0 enzyme immunoassay(EIA), both from Ortho Clinical Diagnostics (Rochester, NY), | Two immunoassays, the VITROS anti-HCV IgG chemi-luminescence assay (CIA) and the HCV 3.0 enzyme immunoassay(EIA), both from Ortho Clinical Diagnostics (Rochester, NY), | 3.26 CIA 1.5 EIA Derived in the same sample |
Not calculated | CIA 48/52 92% EIA 90% 47/52 For stored samples CIA: 100% (33/33) EIA: 32/33 97% |
100% (CIA and EIA) | NR |
| Tuaillon France 2010 |
Case control | 100 anti HCV pos serum samples and 100 anti HCV neg samples | 18 h dried at room temperature, stored at −20°c for 1–8 weeks | NR, 50 μl of whole blood on Whatman 12 mm paper discs | Ortho HCV 3.0 ELISA, immunoblot assay INNO-LIA HCV Score as confirmatory test | Ortho HCV 3.0 ELISA, immunoblot assay INNO-LIA HCV Score as confirmatory test | Threshold value 0.380 | 98% (97–100) | 99% 97–99) | NR | Stability of anti HCV and HCV RNA investigated by varying room temperature exposure 2–12 days until freezing, after 6 days at room temperature ODs > than cut off values |
| Waterboer Mongolia 2011 |
Cross sectional | 1022 sexually active women from cross sectional study (response rate 69%) | Room temperature up to 8 h, then −20 °C up to 1 month (serum + DBS) | Venipuncture, Whole blood applied to 5 spots on DBS filter paper cards (Whatman 903) | In house, the HCV (strain H77, subtype 1a) Core and NS3 proteins |
In house, the HCV (strain H77, subtype 1a) Core and NS3 proteins | Sera 1492 (Core) 371 (NS3) DBS 967 (Core) 310 (NS3) |
Not calculable from the data | Not calculable from the data | 98% Agreement (kappa 0.94) for Core 96.1% Agreement (kappa 0.90) for NS3 |
NR |