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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 -
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 -
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 -
Preventive Veterinary Medicine Nov 2019BackgroundDetection and characterization of viral RNA pathogens from fieldwork are challenging due to the instability of the RNA molecule. FTA cards® have proved useful...
BackgroundDetection and characterization of viral RNA pathogens from fieldwork are challenging due to the instability of the RNA molecule. FTA cards® have proved useful for sample storage and latter identification of pathogens with importance for agricultural, animal and human health: however, for optimal handling, processing, and biosafety measures are not well-established. ObjectiveThis systematic review aims to summarize the reported effectiveness of FTA cards® for storage and transport of viral RNA, as well as the conditions for their handling and use in downstream processes. Finally, the biosafety measures required to protect researchers and clinical lab workers are considered. MethodsWe performed a systematic review following the PRISMA statement. We searched MEDLINE (PubMed), Scopus and Web of Science using the keywords "FTA cards" AND "RNA". Articles were screened by title and abstract, and after examination of inclusion and exclusion criteria, relevant information was extracted. The quality of the studies was assessed, and the evidence was qualitatively summarized. ResultsA total of 175 records were retrieved, and 11 additional documents were found by checking references of the eligible articles. A total of 47 articles were included. Samples from animals accounted for 38.3% of the publications, which identified viruses that cause disease in poultry, wild birds, suids, or bovids. Three different methods for RNA extraction were reported. Other factors that vary across reports include the size of RNA amplicon, storage temperature, and duration of storage. Only fourteen articles tested the inactivation of the virus on the FTA card®, and in one case, the virus remained infective. ConclusionFTA cards® could be a suitable option for RNA virus storage and transport for fieldwork in areas where proper conditions for RNA preservation are difficult to achieve. Three different protocols have been used for RNA detection from this matrix. Biospecimens in the form of dried blood spots should be considered potentially infectious unless specifically treated to inactivate viral pathogens.
Topics: Animal Diseases; Animals; RNA, Viral; Specimen Handling
PubMed: 31607414
DOI: 10.1016/j.prevetmed.2019.104772 -
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 -
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 -
The Cochrane Database of Systematic... Oct 2009Impaction grafting is a technique to restore bone loss both in the femur and the acetabulum during revision hip arthroplasty surgery. Initially impaction grafting was... (Review)
Review
BACKGROUND
Impaction grafting is a technique to restore bone loss both in the femur and the acetabulum during revision hip arthroplasty surgery. Initially impaction grafting was undertaken using fresh frozen femoral head allografts that were milled to create morselized bone pieces that could be impacted to create a neo-cancellous bone bed prior to cementation of the new implant. Results of medium and long term outcome studies have shown variable results using this technique. Currently both processed and non-processed allograft bone are used and the purpose of this review was to analyse the evidence for both.
OBJECTIVES
To determine the clinical effectiveness of processed (freeze dried or irradiated) bone in comparison to fresh frozen (unprocessed) bone.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1985 to 2008), EMBASE (1985 to 2008), CINAHL(1985 to 2008) and the National Research Register. Additional sources were also searched. Handsearching of relevant journals and conference abstracts was also undertaken. Searches were complete to 31 August 2008.
SELECTION CRITERIA
Randomised controlled trials that compared different types of bone for impaction grafting.
DATA COLLECTION AND ANALYSIS
Three hundred and sixty references were identified from the searches. Following detailed eligibility screening, three hundred and fifty nine references did not meet the eligibility criteria. Further details are required about one trial in order to determine it's eligibility.
MAIN RESULTS
No trials were identified that met the criteria for inclusion in the review.
AUTHORS' CONCLUSIONS
Good quality randomised controlled trials are required in this area so that a surgeon's choice of bone graft can be informed by evidence rather than personal preference.
Topics: Arthroplasty, Replacement, Hip; Bone Transplantation; Humans; Reoperation; Specimen Handling; Transplantation, Homologous
PubMed: 19821362
DOI: 10.1002/14651858.CD006351.pub2