The alpha defensin lateral flow test is effective in predicting eradication of periprosthetic joint infection after surgical debridement

The primary aim of this study was to assess the utility of the alpha defensin lateral flow (ADLF) test for predicting the eradication of PJI after surgical debridement. The secondary aim was to describe the reliability of ADLF test in diagnosis of PJI intra- operatively. A prospective observational study was conducted in three independent orthopaedic centres. Twenty-two patients undergoing revision surgery (debridement, antibiotics and implant retention (DAIR), single or two-stage revision) for PJI were recruited, 13 female and 9 male with an average age of 64 years. Samples were collected intra-operatively at the start of the first surgical procedure and then at the completion of debridement or prior to reimplantation depending on the operation performed. These samples were tested using ADLF and then sent for microbiological analysis. The ADLF result was then compared to the corresponding culture result in order to determine the diagnostic predictive accuracy. The reliability of ADLF test to predict eradication of infection after debridement of PJI was excellent for specificity and positive predictive value (PPV) of which both where 100%, but had a poor sensitivity (14.3%) and negative predictive value (NPV) (62.5%). The reliability of ADLF test to predict PJI was poor with only a 50% sensitivity and specificity. The ADLF test has a high specificity and PPV for diagnosing eradication of infection after debridement. In contrast the ADLF testing appears to have poor diagnostic accuracy for PJI when used on intra-operative samples, prior to surgical intervention. No benefits or funds were received in suppo

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Evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection

10.1101/19004473 ◽

2019 ◽

Author(s):

Alexander J. Trotter ◽

Rachael Dean ◽

Celia E. Whitehouse ◽

Jarle Mikalsen ◽

Claire Hill ◽

...

Keyword(s):

Synovial Fluid ◽

Sensitivity And Specificity ◽

Prosthetic Joint Infection ◽

Predictive Value ◽

Joint Infection ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Prosthetic Joint ◽

Flow Test ◽

Lateral Flow Test

AbstractBackgroundMicrobiological diagnosis of prosthetic joint infection (PJI) relies on culture techniques that are slow and insensitive. Rapid tests are urgently required to improve patient management. Calprotectin is a neutrophil biomarker of inflammation that has been demonstrated to be effective for the diagnosis of PJI. A calprotectin based lateral flow test has been developed for the rapid detection of PJI using synovial fluid samples.MethodsA convenience series of 69 synovial fluid samples from patients at the Norfolk and Norwich University Hospitals (NNUH) were collected intraoperatively from 52 hip and 17 knee revision operations. Calprotectin levels were measured using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone). For all samples, synovial fluid was pipetted onto the lateral flow device and the signal was read using a mobile phone app after 15 minutes incubation at room temperature.ResultsAccording to the Musculoskeletal Infection Society (MSIS) criteria, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test against the MSIS criteria was 75%. The test had a sensitivity and specificity of 75% and 76% respectively with a positive predictive value (PPV) of 62% and a negative predictive value (NPV) of 85%. Discordant results were then reviewed by the clinical team using available patient data to develop an alternative gold standard for defining presence/absence of infection (MSIS+). Compared to MSIS+, the test showed an overall accuracy of 83%, sensitivity and specificity of 95% and 78% respectively, a PPV of 62% and an NPV of 98%. Test accuracy for hip revisions was 77% and for knee revisions was 100%.ConclusionsThis study demonstrates that the calprotectin lateral flow assay is an effective diagnostic test for PJI. Our data suggests that the test is likely to generate false positive results in patients with metallosis and gross osteolysis.

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Preliminary evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection

Bone and Joint Research ◽

10.1302/2046-3758.95.bjr-2019-0213.r1 ◽

2020 ◽

Vol 9 (5) ◽

pp. 202-210 ◽

Cited By ~ 1

Author(s):

Alexander J. Trotter ◽

Rachael Dean ◽

Celia E. Whitehouse ◽

Jarle Mikalsen ◽

Claire Hill ◽

...

Keyword(s):

Synovial Fluid ◽

Prosthetic Joint Infection ◽

Test Performance ◽

Predictive Value ◽

Joint Infection ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Prosthetic Joint ◽

Flow Test ◽

Lateral Flow Test

Aims This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required. Cite this article: Bone Joint Res. 2020;9(5):202–210.

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Evaluation of Production Lots of a Rapid Point-of-Care Lateral Flow Serological Test Intended for Identification of IgM and IgG against the N-Terminal Part of the Spike Protein (S1) of SARS-CoV-2

Viruses ◽

10.3390/v13061043 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1043

Author(s):

Tove Hoffman ◽

Linda Kolstad ◽

Bengt Rönnberg ◽

Åke Lundkvist

Keyword(s):

Predictive Value ◽

Serological Test ◽

Point Of Care ◽

External Validation ◽

High Sensitivity ◽

Lateral Flow ◽

Spike Protein ◽

Individual Level ◽

Lateral Flow Test ◽

Production Errors

The potential of rapid point-of-care (POC) tests has been subject of doubt due to an eventual risk of production errors. The aim was therefore to evaluate the two separate production lots of a commercial POC lateral flow test, intended for the detection of IgM and IgG against the SARS-CoV-2 spike protein (S1). Control samples consisted of serum from individuals with confirmed SARS-CoV-2 infection and pre-COVID-19 negative sera gathered from a biobank. The presence of anti-S1 IgM/IgG in the sera was verified by an in-house Luminex-based serological assay (COVID-19 SIA). One hundred samples were verified as positive for anti-S1 IgG and 74 for anti-S1 IgM. Two hundred samples were verified as negative for anti-S1 IgM/IgG. For the two lots of the POC-test, the sensitivities were 93.2% and 87.8% for IgM and 93.0% and 100% for IgG. The specificities were 100% for IgM and 99.5% for IgG. The positive predictive value was 100% for IgM and 98.9% and 99.0% for IgG. The negative predictive value was 97.6% and 95.7% for IgM, and 96.6% and 100% for IgG. The evaluated POC-test is suitable to assess anti-SARS-CoV-2 S1 IgM and IgG, as a measure of previous virus exposure on an individual level. The external validation of separate lots of rapid POC-tests is encouraged to ensure high sensitivity before market introduction.

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Clinical Evaluation of a COVID-19 Antibody Lateral Flow Assay using Point of Care Samples

10.1101/2020.12.02.20242750 ◽

2020 ◽

Author(s):

Won Lee ◽

Steven Straube ◽

Ryan Sincic ◽

Jeanne A. Noble ◽

Juan Carlos Montoy ◽

...

Keyword(s):

Predictive Value ◽

Point Of Care ◽

Acute Infection ◽

High Specificity ◽

Lateral Flow ◽

Lateral Flow Immunoassay ◽

Onset Date ◽

Rt Pcr ◽

Serum Samples ◽

Antibody Positivity

ABSTRACTIntroductionThe ongoing SARS-CoV-2 pandemic has spurred the development of numerous point of care (PoC) immunoassays. Assessments of performance of available kits are necessary to determine their clinical utility. Previous studies have mostly performed these assessments in a laboratory setting, which raises concerns of translating findings for PoC use. The aim of this study was to assess the performance of a lateral flow immunoassay for the detection of SARS-CoV-2 antibodies using samples collected at PoC.MethodOne lateral flow immunoassay (Humasis® COVID-19 IgG/IgM) was tested. In total, 50 PCR RT-PCR positive and 52 RT-PCR negative samples were collected at PoC. Fifty serum specimens from Dec 2018 to Feb 2019 were used as controls for specificity. Serum samples collected between Dec 2019 to Feb 2020 were used as additional comparators. Clinical data including symptom onset date was collected from patient history and the medical record.ResultsThe overall sensitivity for the kit was 74% (95% CI: 59.7% -85.4%). The sensitivity for IgM and IgG detection >14 days after date of onset was 88% (95% CI: 68.8% -97.5%) and 84% (95% CI: 63.9% – 95.5%), with a negative predictive value (NPV) of 94% for IgM (95% CI: 83.5% - 98.8%) and 93% for IgG (95% CI: 81.8% - 97.9%). The overall specificity was 94% (95% CI: 83.5% - 98.8%). The Immunoglobulin specific specificity was 94% for IgM (95% CI: 83.5% - 98.8%) and 98% for IgG (95% CI: 89.4% - 100.0%), with a positive predictive value (PPV) of 88% for IgM (95% CI: 68.8% - 97.5%) and 95% for IgG (95% CI: 77.2% - 99.9%) respectively for samples collected from patients >14 days after date of onset. Specimen collected during early phase of COVID-19 pandemic (Dec 2019 to Feb 2020) showed 11.8% antibody positivity, and 11.3% of PCR-negative patients demonstrated antibody positivity.DiscussionHumasis® COVID-19 IgG/IgM LFA demonstrates greater than 90% PPV and NPV for samples collected 14 days after the onset of symptoms using samples collected at PoC. While not practical for the diagnosis of acute infection, the use of the lateral flow assays with high specificity may have utility for determining seroprevalence or seroconversion in longitudinal studies.

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