BackgroundDried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV.MethodsWe conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias.ResultsFor the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews.ConclusionHCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

BackgroundThe detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples.MethodsWe searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias.ResultsIn the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83–99) and 99% (95% CI: 53–100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) – one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95–99) and 98% (95% CI:95–99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity.ConclusionsThese findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Objectives To investigate whether Staphylococcus aureus bloodstream infection (SAB) patients at high risk for complications or relapse benefit from combination therapy with adjunctive rifampicin or fosfomycin. Methods In this post hoc analysis, SAB patients with native valve infective endocarditis, osteoarticular infections or implanted foreign devices were included. The co-primary endpoints were all-cause 90 day mortality and death or SAB-related late complications within 180 days. To overcome treatment selection bias and account for its time dependence, inverse probability of treatment weights were calculated and included in marginal structural Cox proportional hazard models (MSCMs). Results A total of 578 patients were included in the analysis, of which 313 (54%) received combination therapy with either rifampicin (n = 242) or fosfomycin (n = 58). In the multivariable MSCM, combination therapy was associated with a better outcome, that is, a lower rate of death or SAB-related late complications within 180 days (HR 0.65, 95% CI 0.46–0.92). This beneficial effect was primarily seen in patients with implanted foreign devices, in which combination therapy was associated with a lower rate of death or SAB-related late complications within 180 days (HR 0.53, 95% CI 0.35–0.79) and a lower 90 day mortality (HR 0.57, 95% CI 0.36–0.91). Upon agent-specific stratification, we found no significant differences in outcomes between combination therapy containing rifampicin and fosfomycin; however, the number of patients in most subgroups was not large enough to draw firm conclusions. Conclusions In patients with implanted foreign devices, combination therapy was associated with a better long-term outcome. Larger prospective studies are needed to validate these findings.