Performance of influenza rapid point‐of‐care tests in the detection of swine lineage A(H1N1) influenza viruses

Background In April 2009, an A(H1N1) influenza virus of swine lineage was detected in humans in the USA, and in just over a month has infected over 10 000 people in more than 40 countries. Objectives To determine the performance of the Binax Now, BD Directigen EZ, and the Quidel QuickVue influenza rapid point‐of‐care (POC) tests for the detection of the recently emerged swine lineage A(H1N1) virus. Methods Swine lineage A(H1N1) and human seasonal influenza strains were cultured and then diluted to specific infectivity titres. Viral dilutions were assayed by the rapid POC tests and by real‐time RT‐PCR. Results All three of the rapid POC tests successfully detected the swine lineage A(H1N1) viruses at levels between 10³ and 10⁵ TCID₅₀/ml (tissue culture infectious dose₅₀), with the BD Directigen test demonstrating marginally greater sensitivity than the other two tests. Viral infectivity and RNA load data for viruses at the detection limit of the rapid test kits, suggested that both the Quidel and the Binax tests were less sensitive for the detection of swine lineage A(H1N1) viruses than for human seasonal strains. In comparison the BD Directigen demonstrated similar sensitivity when detecting swine lineage A(H1N1) and human seasonal viruses. Conclusions The three rapid POC tests all detected the emergent swine lineage A(H1N1) virus when it was present at high virus concentrations. Early diagnosis of infection can assist in the rapid treatment. However the tests are significantly less sensitive than PCR assays and as such, negative results should be verified by a laboratory test.     

Cost‐effectiveness analysis of antiviral treatment in the management of seasonal influenza A: point‐of‐care rapid test versus clinical judgment

Background

A point‐of‐care rapid test (POCRT) may help early and targeted use of antiviral drugs for the management of influenza A infection.

Objective

(i) To determine whether antiviral treatment based on a POCRT for influenza A is cost‐effective and, (ii) to determine the thresholds of key test parameters (sensitivity, specificity and cost) at which a POCRT based‐strategy appears to be cost effective.

Methods

An hybrid « susceptible, infected, recovered (SIR) » compartmental transmission and Markov decision analytic model was used to simulate the cost‐effectiveness of antiviral treatment based on a POCRT for influenza A in the social perspective. Data input parameters used were retrieved from peer‐review published studies and government databases. The outcome considered was the incremental cost per life‐year saved for one seasonal influenza season.

Results

In the base‐case analysis, the antiviral treatment based on POCRT saves 2 lives/100 000 person‐years and costs $7600 less than the empirical antiviral treatment based on clinical judgment alone, which demonstrates that the POCRT‐based strategy is dominant. In one and two way‐sensitivity analyses, results were sensitive to the POCRT accuracy and cost, to the vaccination coverage as well as to the prevalence of influenza A. In probabilistic sensitivity analyses, the POCRT strategy is cost‐effective in 66% of cases, for a commonly accepted threshold of $50 000 per life‐year saved.

Conclusion

The influenza antiviral treatment based on POCRT could be cost‐effective in specific conditions of performance, price and disease prevalence.     

A simple and inexpensive point‐of‐care test for hepatitis B surface antigen detection: serological and molecular evaluation

Early identification of chronic hepatitis B is important for optimal disease management and prevention of transmission. Cost and lack of access to commercial hepatitis B surface antigen (HBsAg) immunoassays can compromise the effectiveness of HBV screening in resource‐limited settings and among marginalized populations. High‐quality point‐of‐care (POC) testing may improve HBV diagnosis in these situations. Currently available POC HBsAg assays are often limited in sensitivity. We evaluated the NanoSign^® HBs POC chromatographic immunoassay for its ability to detect HBsAg of different genotypes and with substitutions in the ‘a’ determinant. Thirty‐seven serum samples from patients with HBV infection, covering HBV genotypes A–G, were assessed for HBsAg titre with the Roche Elecsys HBsAg II quantification assay and with the POC assay. The POC assay reliably detected HBsAg at a concentration of at least 50 IU/mL for all genotypes, and at lower concentrations for some genotypes. Eight samples with substitutions in the HBV ‘a’ determinant were reliably detected after a 1/100 dilution. The POC strips were used to screen serum samples from 297 individuals at risk for HBV in local clinical settings (health fairs and outreach events) in parallel with commercial laboratory HBsAg testing (Quest Diagnostics EIA). POC testing was 73.7% sensitive and 97.8% specific for detection of HBsAg. Although the POC test demonstrated high sensitivity over a range of genotypes, false negatives were frequent in a clinical setting. Nevertheless, the POC assay offers advantages for testing in both developed and resource‐limited countries due to its low cost (0.50$) and immediately available results.     

Point‐of‐care testing in haemostasis

Point‐of‐care testing (POCT) in haematology has seen a significant increase in both the spectrum of tests available and the number of tests performed annually. POCT is frequently undertaken with the belief that this will reduce the turnaround time for results and so improve patient care. The most obvious example of POCT in haemostasis is the out‐of‐hospital monitoring of the International Normalized Ratio in patients receiving a vitamin K antagonist, such as warfarin. Other areas include the use of the Activated Clotting Time to monitor anticoagulation for patients on cardio‐pulmonary bypass, platelet function testing to identify patients with apparent aspirin or clopidogrel resistance and thrombelastography to guide blood product replacement during cardiac and hepatic surgery. In contrast to laboratory testing, POCT is frequently undertaken by untrained or semi‐trained individuals and in many cases is not subject to the same strict quality control programmes that exist in the central laboratory. Although external quality assessment programmes do exist for some POCT assays these are still relatively few. The use of POCT in haematology, particularly in the field of haemostasis, is likely to expand and it is important that systems are in place to ensure that the generated results are accurate and precise.     

Validation of the international normalized ratio (INR) in a new point‐of‐care system designed for home monitoring of oral anticoagulation therapy

The new CoaguChek XS system is designed for use in patient self testing with a measuring range from 0.8 INR up to 8.0 INR, which has been calibrated against the mean INR of rTF/95 and ERM‐AD149. This study was performed to confirm the correct INR results received from two routinely manufactured lots of test strips when compared with the international reference preparations (IRP) rTF/95 and ERM‐AD149. At one study site capillary and noncitrated venous whole blood samples from 20 normal donors and 62 anticoagulated patients were applied to two test strip lots of the new system in duplicate. Additionally blood was collected in citrate tubes, processed to plasma, and PT results were obtained using rTF/95 and ERM‐AD149 by the manual tilt tube method. Method comparisons of the INR results of the CoaguChek XS system vs. the mean INR of the IRP demonstrated a mean relative bias of ?0.02% to ?0.4%, mean absolute relative deviations of 6.4–9.6%, and accuracy observing >95% of CoaguChek XS INR within limits of ±14% to ±21.5% to the mean INR of the IRP. The results of the study confirm the successful calibration of two lots of the new CoaguChek XS system, demonstrate the validity of the calibration concept and prove the accuracy of the new system in comparison with the IRP. Clinical decisions in oral anticoagulation therapy may be reliably made upon the INR results of the new system.     

Point‐of‐care testing of neonatal coagulation

The aim of this validation study was to compare prothrombin time (PT) and activated partial thromboplastin time (APTT) results from a point‐of‐care testing (POCT) device (Rapidpoint Coag) with those from standard laboratory tests. The subjects were newborn infants needing coagulation screen for any clinical indications within a regional neonatal intensive care unit. The level of agreement between POCT and laboratory measurements of PT and APTT was determined. For PT: the bias was from ?7.6 to 12.4 s and precision was 5.0 s. For the detection of prolonged PT at a level of 16 s, the sensitivity was 0.70, specificity was 0.57 and the positive predictive value (PPV) was 0.62. For APTT: the bias was from ?39.1 to 23.7 s, and precision was 15.7 s. For the detection of prolonged APTT at a level of 55 s, the sensitivity was 0.80, specificity was 0.95 and the PPV was 0.80. The POCT device tested has limited utility as a cot‐side device for screening for a prolongation of the APTT in the newborn but is not sensitive for screening for prolongation of the PT.     

The impact of the SARS-CoV-2 pandemic on global influenza surveillance: Insights from 18 National Influenza Centers based on a survey conducted between November 2021 and March 2022

Background

National Influenza Centers (NICs) have played a crucial role in the surveillance of SARS-CoV-2. The FluCov project, covering 22 countries, was initiated to monitor the impact of the SARS-CoV-2 pandemic on influenza activity.

Methods

This project consisted of an epidemiological bulletin and NIC survey. The survey, designed to assess the impact of the pandemic on the influenza surveillance system, was shared with 36 NICs located across 22 countries. NICs were invited to reply between November 2021 and March 2022.

Results

We received 18 responses from NICs in 14 countries. Most NICs (76%) indicated that the number of samples tested for influenza decreased. Yet, many NICs (60%) were able to increase their laboratory testing capacity and the “robustness” (e.g., number of sentinel sites) (59%) of their surveillance systems. In addition, sample sources (e.g., hospital or outpatient setting) shifted. All NICs reported a higher burden of work following the onset of the pandemic, with some NICs hiring additional staff or partial outsourcing to other institutes or departments. Many NICs anticipate the future integration of SARS-CoV-2 surveillance into the existing respiratory surveillance system.

Discussion

The survey shows the profound impact of SARS-CoV-2 on national influenza surveillance in the first 27 months of the pandemic. Surveillance activities were temporarily disrupted, whilst priority was given to SARS-CoV-2. However, most NICs have shown rapid adaptive capacity underlining the importance of strong national influenza surveillance systems. These developments have the potential to benefit global respiratory surveillance in the years to come; however, questions about sustainability remain.     

Innovative technologies for point‐of‐care testing of viral hepatitis in low‐resource and decentralized settings

According to the Global Burden of Diseases, chronic viral hepatitis B and C are one of the most challenging global health conditions that rank among the first causes of morbidity and mortality worldwide. Low‐ and middle‐income countries are particularly affected by the health burden associated with HBV or HCV infection. One major gap in efficiently addressing the issue of viral hepatitis is universal screening. However, the costs and chronic lack of human resources for using traditional screening strategies based on serology and molecular biology preclude any scaling‐up. Point‐of‐care tests have been deemed a powerful potential solution to fill the current diagnostics gap in low‐resource and decentralized settings. Despite high interest resulting from their development in recent years, very few point‐of‐care devices have reached the market. Scaling down and automating all testing steps in 1 single device (eg, sample preparation, detection and readout) is indeed challenging. But innovations in multiple disciplines such as nanotechnologies, microfluidics, biosensors and synthetic biology have led to the creation of chip‐sized laboratory systems called “lab‐on‐a‐chip” devices. This review aims to explain how these innovations can overcome technological barriers that usually arise for each testing step while developing integrated point‐of‐care tests. Point‐of‐care test prototypes rarely meet the requirements for mass production, which also hinders their large‐scale production. In addition to logistical hurdles, legal and economic constraints specific to the commercialization of in vitro diagnostics, which have also participated in the low transfer of innovative point‐of‐care tests to the field, are discussed.     

Community‐based,point‐of‐care hepatitis C testing: perspectives and preferences of people who inject drugs

A barrier to hepatitis C treatment for people who inject drugs (PWID) is needing to attend multiple appointments for diagnosis. Point‐of‐care hepatitis C tests provide results within 20 to 105 minutes and can be offered opportunistically in nonclinical settings such as needle syringe programmes. In this nested qualitative study, we explored the acceptability of point‐of‐care testing for PWID. PWID attending participating needle syringe programmes were screened using the OraQuick HCV antibody mouth swab (result in 20 minutes); those with a reactive result then underwent venepuncture for a point‐of‐care RNA test: the Xpert HCV Viral Load (result in 105 minutes). Convenience sampling was used to select participants for a semi‐structured interview. A hybrid thematic analysis was performed, guided by Sekhon's “Theoretical Framework of Acceptability.” Nineteen participants were interviewed. Three core themes emerged: "people and place," "method of specimen collection," and "rapidity of result return." It was highly acceptable to be offered testing at the needle syringeprogrammes by nurses and community health workers, who were described as competent and nonjudgemental. Most participants reported that even if a finger‐stick point‐of‐care RNA test were an option in the future, they would prefer venepuncture, as the sample could be used for pre‐treatment workup and bundled testing. Waiting 20 minutes to receive the antibody test result was acceptable, whereas the 105 minutes required for the RNA result was unacceptable. Offering point‐of‐care hepatitis C testing at needle syringe programmes is acceptable to PWID, however tests that avoid venepuncture are not necessarily the most attractive to PWID.     

Costs of a clinical pathway with point‐of‐care testing during influenza epidemic in a Dutch hospital

Our study aim was to determine how a new clinical pathway, including PCR‐based influenza point‐of‐care test (POCT), influences the hospitalisation costs of patients suspected of influenza presenting at the emergency department of a Dutch hospital during two consecutive influenza epidemics (2016‐2017 and 2017‐2018). Compared to mean costs per patient of €3661 in 2016‐2017, the implementation of this new clinical pathway with influenza POCT in 2017 was associated with mean costs per influenza‐positive patient of €2495 in 2017‐2018 (P = .3). Our study suggests favourable economic results regarding a new clinical pathway with influenza POCT, reflecting a more efficient care of patients suspected of influenza presenting at the emergency department.