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Journal of Viral Hepatitis Apr 2015The entry of new all-oral direct acting antiviral therapy for hepatitis C provides an opportunity to scale up HCV care in low- and middle-income countries. In HIV, use... (Review)
Review
The entry of new all-oral direct acting antiviral therapy for hepatitis C provides an opportunity to scale up HCV care in low- and middle-income countries. In HIV, use of dried blood spots (DBS) has facilitated the diagnosis and management of HIV in resource-poor settings. DBS may be used in a similar way to facilitate diagnosis and management of HCV. Here, we present a systematic review of the literature of DBS for HCV RNA detection and genotyping. Using an a priori review protocol, three databases were searched for studies published up to August 2013 that reported the use of dried blood and serum spots in genotyping, detection and measurement of HCV RNA, as well as the rate of degradation of HCV RNA when stored in DBS at room temperature. Nine papers were eligible for inclusion; eight studied DBS and one dried serum. Two studies measured concordance between genotype and subtype determined by DBS and whole plasma and both found 100% concordance. Four studies measured endpoint detection limits of HCV RNA-positive samples by DBS and found positive predictive values of 100% down to 250, 334, 2500 and 24160 IU/mL. Two studies found deterioration of HCV RNA in DBS samples stored at room temperature, while two others failed to detect such deterioration. These results support the potential use of DBS for genotyping and HCV RNA detection. Studies of the use of DBS for HCV RNA viral load measurement and of the rate of degradation of HCV RNA when stored in DBS at ambient temperatures remain inconclusive.
Topics: Blood; Desiccation; Genotyping Techniques; Hepacivirus; Hepatitis C; Humans; RNA, Viral; Specimen Handling
PubMed: 25367722
DOI: 10.1111/jvh.12345 -
Journal of Acquired Immune Deficiency... Mar 2022Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood.
METHODS
Standard databases (PubMed and Medline), conferences, and gray literature were searched until January 2019. The quality of evidence was evaluated using the Standards for Reporting Studies of Diagnostic Accuracy and Quality Assessment of Diagnostic Accuracy Studies-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology, and to account for between-study variation.
RESULTS
We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots with that of plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared with that of plasma was 0.28 log10 copies/mL, whereas the difference in median viral load was 2.25 log10 copies/mL. More dried plasma spot values were undetectable compared with plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens were >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds.
DISCUSSION
Overall, dried plasma spot specimens performed relatively well compared with plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.
Topics: Dried Blood Spot Testing; HIV Infections; HIV-1; Humans; RNA, Viral; Sensitivity and Specificity; Treatment Failure; Viral Load
PubMed: 34732684
DOI: 10.1097/QAI.0000000000002855 -
PLoS Medicine Aug 2022Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate routine HIV viral load testing is essential for assessing the efficacy of antiretroviral treatment (ART) regimens and the emergence of drug resistance. While the use of plasma specimens is the standard for viral load testing, its use is restricted by the limited ambient temperature stability of viral load biomarkers in whole blood and plasma during storage and transportation and the limited cold chain available between many health care facilities in resource-limited settings. Alternative specimen types and technologies, such as dried blood spots, may address these issues and increase access to viral load testing; however, their technical performance is unclear. To address this, we conducted a meta-analysis comparing viral load results from paired dried blood spot and plasma specimens analyzed with commonly used viral load testing technologies.
METHODS AND FINDINGS
Standard databases, conferences, and gray literature were searched in 2013 and 2018. Nearly all studies identified (60) were conducted between 2007 and 2018. Data from 40 of the 60 studies were included in the meta-analysis, which accounted for a total of 10,871 paired dried blood spot:plasma data points. We used random effects models to determine the bias, accuracy, precision, and misclassification for each viral load technology and to account for between-study variation. Dried blood spot specimens produced consistently higher mean viral loads across all technologies when compared to plasma specimens. However, when used to identify treatment failure, each technology compared best to plasma at a threshold of 1,000 copies/ml, the present World Health Organization recommended treatment failure threshold. Some heterogeneity existed between technologies; however, 5 technologies had a sensitivity greater than 95%. Furthermore, 5 technologies had a specificity greater than 85% yet 2 technologies had a specificity less than 60% using a treatment failure threshold of 1,000 copies/ml. The study's main limitation was the direct applicability of findings as nearly all studies to date used dried blood spot samples prepared in laboratories using precision pipetting that resulted in consistent input volumes.
CONCLUSIONS
This analysis provides evidence to support the implementation and scale-up of dried blood spot specimens for viral load testing using the same 1,000 copies/ml treatment failure threshold as used with plasma specimens. This may support improved access to viral load testing in resource-limited settings lacking the required infrastructure and cold chain storage for testing with plasma specimens.
Topics: Dried Blood Spot Testing; HIV Infections; HIV-1; Humans; RNA, Viral; Sensitivity and Specificity; Viral Load
PubMed: 35994520
DOI: 10.1371/journal.pmed.1004076 -
Antiviral Therapy 2009Dried spots on filter paper made of whole blood (dried blood spots; DBS), plasma (dried plasma spots; DPS) or serum (dried serum spots) hold promise as an affordable and... (Review)
Review
BACKGROUND
Dried spots on filter paper made of whole blood (dried blood spots; DBS), plasma (dried plasma spots; DPS) or serum (dried serum spots) hold promise as an affordable and practical alternative specimen source to liquid plasma for HIV type-1 (HIV-1) viral load determination and drug resistance genotyping in the context of the rapidly expanding access to antiretroviral therapy (ART) for HIV-1-infected individuals in low- and middle-income countries. This report reviews the current evidence for their utility.
METHODS
We systematically searched the English language literature published before 2009 on Medline, the websites of the World Health Organization and US Centers for Disease Control and Prevention, abstracts presented at relevant international conferences and references from relevant articles.
RESULTS
Data indicate that HIV-1 viral load determination and resistance genotyping from DBS and DPS is feasible, yielding comparable test performances, even after storage. Limitations include reduced analytical sensitivity resulting from small analyte volumes (approximately 3.5 log(10) copies/ml at 50 microl sample volume), nucleic acid degradation under extreme environmental conditions, impaired efficiency of nucleic acid extraction, potential interference of archived proviral DNA in genotypes obtained from DBS and the excision of spots from the filters in high-volume testing.
CONCLUSIONS
This technology offers the advantages of a stable specimen matrix, ease of sample collection and shipment. The current sensitivity in drug resistance testing is appropriate for public health surveillance among pretreatment populations. However, consistently improved analytical sensitivity is needed for their routine application in the therapeutic monitoring of individuals receiving ART, particularly at the onset of treatment failure.
Topics: Anti-HIV Agents; Blood Specimen Collection; Drug Resistance, Viral; HIV Infections; HIV-1; Humans; Plasma; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Viral Load
PubMed: 19704164
DOI: No ID Found -
PloS One 2014Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote... (Review)
Review
BACKGROUND
Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID.
METHODS AND FINDINGS
Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies.
CONCLUSIONS
Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation.
TRIAL REGISTRATION
PROSPERO Registration #: CRD42013003621.
Topics: Dried Blood Spot Testing; Early Diagnosis; HIV Infections; HIV-1; Humans; Infant; Reproducibility of Results; Sensitivity and Specificity; Viral Load
PubMed: 24603442
DOI: 10.1371/journal.pone.0086461 -
Public Health Dec 2017Dried blood spots (DBS) specimens can be used for hepatitis C virus (HCV) infection screening in cases where serum specimens are difficult to obtain. However,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Dried blood spots (DBS) specimens can be used for hepatitis C virus (HCV) infection screening in cases where serum specimens are difficult to obtain. However, uncertainties surround the sensitivity and specificity of DBS for HCV antibodies (anti-HCV) serology testing. We aimed to evaluate the accuracy of DBS use to screen for HCV infection.
STUDY DESIGN
We carried out a systematic review and meta-analysis.
METHODS
Medline and EMBASE databases were searched for articles published between 1989 and November 2016. We included studies comparing DBS to plasma/serum specimens to detect anti-HCV in adults. Two authors extracted data and assessed the quality of the studies using an adapted standards for reporting diagnostic accuracy studies (STARD) and independently checked the data for accuracy. Meta-analysis was computed with the bivariate and the hierarchical summary receiver-operating characteristic models.
RESULTS
Twelve studies (3307 specimens) were analyzed, where 11 of them evaluated the anti-HCV using enzyme immunoassays (EIAs), and the remaining one used rapid diagnostic tests. The studies were mostly case-controls (83.3%) and from developed countries (66.7%). The overall pooled sensitivity (95% confidence interval; CI) and specificity (95% CI) of DBS to detect anti-HCV was 98.1% (96.1-99.1%) and 99.7% (98.9-99.9%), respectively. In studies using EIAs, the pooled sensitivity and specificity were 97.3% (94.3-98.8%) and 99.6% (98.5-99.9%), respectively. Considering only studies using EIAs, sensitivity analysis excluding one study carried out in people who inject drugs showed the pooled sensitivity of 97.8% (96.2-98.8%) and specificity of 99.5% (98.5-99.9%).
CONCLUSIONS
In testing for anti-HCV by means of EIAs, the efficacy of DBS is found to be similar or slightly lower than that of serum specimens. However, the risk of finding negative and positive results that are both false when using DBS remains present. Therefore, further work including optimal storage and processing methodologies are recommended. This is to help establish consensus guidelines for use of DBS specimens for anti-HCV screening.
Topics: Case-Control Studies; Dried Blood Spot Testing; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Sensitivity and Specificity
PubMed: 29035801
DOI: 10.1016/j.puhe.2017.08.008 -
Diabetic Medicine : a Journal of the... Apr 2023In the UK people with diabetes who do not attend annual review appointments often have higher haemoglobin A (HbA ) levels. We aim to determine the acceptability of... (Review)
Review
AIM
In the UK people with diabetes who do not attend annual review appointments often have higher haemoglobin A (HbA ) levels. We aim to determine the acceptability of self-collected posted capillary blood samples, and if they produce accurate and reliable HbA results.
METHODS
We include adult studies comparing capillary blood to venous blood for measuring HbA . We exclude methods not suitable for postage. Electronic databases of MEDLINE, Embase, CINAHL, Web of Science, Google Scholar and OpenGrey were searched from inception to September 2021, as well as relevant conference abstracts. Two reviewers performed study selection, data extraction and risk of bias assessment independently. Narrative synthesis was performed.
RESULTS
Our search retrieved 3747 records. Following de-duplication and screening 30 articles were included. The mean difference (MD) and limits of agreement (LoA) between capillary and venous HbA were smaller and narrower respectively when micro/capillary tubes (micro/cap) were used for capillary blood storage compared to dried blood spots (capDBS) (micro/cap MD range -0.4 to 1.4 mmol/mol vs. capDBS MD range -4.3 to 7.2 mmol/mol, micro/cap LoA width 2.4 to 6 mmol/mol vs. capDBS LoA width 11.7 to 16.8 mmol/mol). After using self-collection kits, 83%-96% of participants reported satisfaction, 87%-99% found it easy and 69%-94% reported they would use it again.
CONCLUSION
Microtubes/capillary tubes look promising as a method of self-collecting and posting capillary blood samples for the measurement of HbA based on the accuracy and reliability findings presented. DBS samples demonstrated comparatively poorer accuracy. Data on acceptability were limited and further research is needed.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Reproducibility of Results; Glycated Hemoglobin; Blood Specimen Collection
PubMed: 36562666
DOI: 10.1111/dme.15033 -
Expert Review of Vaccines Feb 2022Venous serum and plasma are optimal specimens for serological testing but may be logistically infeasible. Dried blood spots (DBS) are a feasible alternative, provided...
INTRODUCTION
Venous serum and plasma are optimal specimens for serological testing but may be logistically infeasible. Dried blood spots (DBS) are a feasible alternative, provided results are adequately sensitive and specific. We aimed to assess the diagnostic accuracy of DBS to measure IgG and IgM antibodies for vaccine-preventable diseases and compare test validity of DBS with venous blood.
AREAS COVERED
In October 2020, we searched seven databases for peer-reviewed studies assessing the diagnostic accuracy of DBS specimens compared with serum in detecting antibodies to VPDs in humans. We extracted data and assessed risk of bias in all included studies. We calculated sensitivity and specificity with 95% confidence intervals for each index-reference test comparison. We narratively synthesized the identified evidence on diagnostic accuracy and blood collection and processing methods for DBS. Studies on measles and rubella IgG and IgM were the most frequently identified and reported generally high sensitivity and specificity.
EXPERT OPINION
Lack of standardization in collection, storage, and testing methods limited systematic comparison across studies. Our findings indicate a need for additional validation studies on the diagnostic accuracy of DBS to expand their use in serological surveillance. We recommend practical considerations to improve standardized reporting for DBS validation studies.
Topics: Dried Blood Spot Testing; Humans; Measles; Rubella; Sensitivity and Specificity; Vaccine-Preventable Diseases
PubMed: 34852211
DOI: 10.1080/14760584.2022.2013821 -
Therapeutic Drug Monitoring Aug 2023Volumetric absorptive microsampling (VAMS) is an emerging technique that may support multisample collection to enhance therapeutic drug monitoring in solid organ...
BACKGROUND
Volumetric absorptive microsampling (VAMS) is an emerging technique that may support multisample collection to enhance therapeutic drug monitoring in solid organ transplantation. This review aimed to assess whether tacrolimus and mycophenolic acid can be reliably assayed using VAMS and to identify knowledge gaps by providing granularity to existing analytical methods and clinical applications.
METHODS
A systematic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Embase, and Scopus databases were accessed for records from January 2014 to April 2022 to identify scientific reports on the clinical validation of VAMS for monitoring tacrolimus and mycophenolic acid concentrations. Data on the study population, sample sources, analytical methods, and comparison results were compiled.
RESULTS
Data from 12 studies were collected, including 9 studies pertaining to tacrolimus and 3 studies on the concurrent analysis of tacrolimus and mycophenolic acid. An additional 14 studies that provided information relevant to the secondary objectives (analytical validation and clinical application) were also included. The results of the clinical validation studies generally met the method agreement requirements described by regulatory agencies, but in many cases, it was essential to apply correction factors.
CONCLUSIONSS
Current evidence suggests that the existing analytical methods that use VAMS require additional optimization steps for the analysis of tacrolimus and mycophenolic acid. The recommendations put forth in this review can help guide future studies in achieving the goal of improving the care of transplant recipients by simplifying multisample collection for the dose optimization of these drugs.
Topics: Humans; Tacrolimus; Mycophenolic Acid; Drug Monitoring; Tandem Mass Spectrometry; Organ Transplantation; Blood Specimen Collection; Dried Blood Spot Testing
PubMed: 36728554
DOI: 10.1097/FTD.0000000000001066 -
PLOS Global Public Health 2024Testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) using dried blood spot (DBS) specimens has been an integral part of bio-behavioural...
Testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) using dried blood spot (DBS) specimens has been an integral part of bio-behavioural surveillance in Canada for almost two decades, though less is known regarding the use of DBS in surveillance of other sexually transmitted and blood-borne infections (STBBI). A systematic review was conducted using a peer-reviewed search strategy to assess the current evidence regarding the validity of STBBI testing using DBS specimens. Eligibility criteria included studies reporting use of DBS specimens for STBBI testing with either commercially available or "in-house" tests in populations 15 years of age or older. Studies reporting a measure of validity such as sensitivity, specificity, positive and negative predictive values were eligible for inclusion. Quality of studies and risk of bias were assessed using the QUADAS-2 tool. A total of 7,132 records were identified. Of these, 174 met the criteria for inclusion. Among the studies that reported validity measures, a substantial proportion demonstrated high sensitivity (≥90%) in 62.5% of cases (N = 334/534 sensitivity measurements), and high specificity (≥90%) was observed in 84.9% of instances (N = 383/451 specificity measurements). However, the quality of the studies varied greatly. Our findings support the validity of the use of DBS specimens in STBBI testing where sufficient evidence was available, but validity is highly dependent on thorough method development and validation.
PubMed: 38875246
DOI: 10.1371/journal.pgph.0003320