Clinical Implications of Quantitative Hepatitis B Virus DNA Measurements

The development of amplification techniques, home-made and commercial has revolutionised the ability to detect the hepatitis B virus both qualitatively and quantitatively. The objectives of this thesis were to describe the clinical implications of quantitative HBV DNA measurements. In chapter 2 we describe the predictive value of quantitative HBV DNA measurements in identifying non-responders to I

Pre-implementation guidelines for infectious disease point-of-care testing in medical institutions

Infectious disease point-of-care test (ID-POCT) devices are becoming widely available, and in this respect, international quality standards and guidelines are available for consultation once ID-POCT has been implemented into medical institutions. However, specific guidelines for consultation during the initial pre-implementation decision-making process are currently lacking. Further, there exist pre-implementation issues specific to ID-POCT. Here we present pre-implementation guidelines for consultation when considering the implementation of ID-POCT in medical institutions. </jats:p

Performance evaluation of a rapid molecular diagnostic, MultiCode based, sample-to-answer assay for the simultaneous detection of Influenza A, B and respiratory syncytial viruses

AbstractBackgroundClinical signs and symptoms of different airway pathogens are generally indistinguishable, making laboratory tests essential for clinical decisions regarding isolation and antiviral therapy. Immunochromatographic tests (ICT) and direct immunofluorescence assays (DFA) have lower sensitivities and specificities than molecular assays, but have the advantage of quick turnaround times and ease-of-use.ObjectiveTo evaluate the performance of a rapid molecular assay, ARIES FluA/B & RSV, using laboratory developed RT-PCR assays (LDA), ICT (BinaxNOW) and DFA.MethodsAnalytical and clinical performance were evaluated in a retrospective study arm (stored respiratory samples obtained between 2006–2015) and a prospective study arm (unselected fresh clinical samples obtained between December 2015 and March 2016 tested in parallel with LDAs).ResultsGenotype inclusivity and analytical specificity was 100%. However, ARIES was 0.5 log, 1–2logs and 2.5logs less sensitive for fluA, RSV and fluB respectively, compared to LDA. In total, 447 clinical samples were included, of which 15.4% tested positive for fluA, 9.2% for fluB and 26.0% for RSV, in both LDA and ARIES. ARIES clinical sensitivity compared to LDA was 98.6% (fluA), 93.3% (fluB) and 95.1% (RSV). Clinical specificity was 100% for all targets. ARIES detected 10.6% (4 fluA, 8 fluB, 11 RSV) and 26.9% (7 fluA, 3 fluB, 22 RSV) more samples compared to DFA and ICT, all confirmed by LDA.ConclusionAlthough analytically ARIES is less sensitive than LDA, the clinical performance of the assay in our tertiary care setting was comparable, and significantly better than that of the established rapid assays

From more testing to smart testing:data-guided SARS-CoV-2 testing choices, the Netherlands, May to September 2020

BACKGROUND: SARS-CoV-2 RT-PCR assays are more sensitive than rapid antigen detection assays (RDT) and can detect viral RNA even after an individual is no longer infectious. RDT can reduce the time to test and the results might better correlate with infectiousness. AIM: We assessed the ability of five RDT to identify infectious COVID-19 cases and systematically recorded the turnaround time of RT-PCR testing. METHODS: Sensitivity of RDT was determined using a serially diluted SARS-CoV-2 stock with known viral RNA concentration. The probability of detecting infectious virus at a given viral load was calculated using logistic regression of viral RNA concentration and matched culture results of 78 specimens from randomly selected non-hospitalised cases. The probability of each RDT to detect infectious cases was calculated as the sum of the projected probabilities for viral isolation success for every viral RNA load found at the time of diagnosis in 1,739 confirmed non-hospitalised COVID-19 cases. RESULTS: The distribution of quantification cycle values and estimated RNA loads for patients reporting to drive-through testing was skewed to high RNA loads. With the most sensitive RDT (Abbott and SD Biosensor), 97.30% (range: 88.65–99.77) of infectious individuals would be detected. This decreased to 92.73% (range: 60.30–99.77) for Coris BioConcept and GenBody, and 75.53% (range: 17.55–99.77) for RapiGEN. Only 32.9% of RT-PCR results were available on the same day as specimen collection. CONCLUSION: The most sensitive RDT detected infectious COVID-19 cases with high sensitivity and may considerably improve containment through more rapid isolation and contact tracing

Sustained response and HBsAg loss after nucleo(s)tide analogue discontinuation in chronic hepatitis B patients:the prospective SNAP study

Background &amp; Aim(s): Current guidelines suggest that nucleos(t)ide analogues (NA) can be discontinued before HBsAg loss in a selected group of chronic hepatitis B (CHB) patients. We aimed to study the safety and off-treatment response after NA cessation. Methods: This is a prospective, multicentre, cohort study in which eligible patients discontinued NA therapy. Adult patients, with a CHB mono-infection, HBeAg-negative, without a (history of) liver cirrhosis, who had achieved long-term viral suppression were eligible. Follow-up visits were planned at week 2-4-8-12-24-36-48-72-96. Re-treatment criteria included severe hepatitis (ALT &gt;10x ULN), signs of imminent liver failure (bilirubin &gt;1.5x ULN or INR &gt;1.5), or at the physician's own discretion. Results: In total, 33 patients were enrolled. Patients were predominantly Caucasian (45.5%) and had genotype A/B/C/D/unknown in 3/4/6/10/10 (9.1/12.1/18.2/30.3/30.3%). At week 48, 15 patients (45.5%) achieved a sustained response (HBV DNA &lt;2,000 IU/mL). At week 96, 13 patients (39.4%) achieved a sustained response, 4 (12.1%) achieved HBsAg loss, and 12 (36.4%) were re-treated. Severe hepatitis was the main reason for re-treatment (n=7, 21.2%). One patient with severe hepatitis developed jaundice, without signs of hepatic decompensation. Re-treatment was successful in all patients.Conclusion: NA therapy can be ceased in a highly selected group of CHB patients if close follow-up can be guaranteed. Treatment cessation may increase the chance of HBsAg loss in selected patients, which is counterbalanced by a significant risk of severe hepatitis.</p