Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow–Based Immunoassay: A Multicenter Study

Abstract Background Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. Histoplasma antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting. Methods Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from 3 medical centers in endemic areas of the US. They were blinded and tested for the MVista Histoplasma LFA. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable; pulmonary or disseminated; immunocompetent or immunosuppressed; and mild, moderate, or severe. Results Three hundred fifty-two subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%), and 46 had disseminated and 20 had pulmonary histoplasmosis. Four cases were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (κ = 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3%, respectively. LFA sensitivity was higher in proven cases (93.2%), patients with disseminated (91.3%), moderate (78.6%), and severe disease (80%), and those with galactomannan levels >1.8 ng/mL (97.8%). Specificity was 99.3% in proven cases, 99.3% in patients with moderate or severe disease, and 96.8% in those with galactomannan levels >1.8 ng/mL. Cross-reactivity was noted with other endemic mycoses. Conclusions The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource-limited countries, especially in patients with high disease burden, potentially reducing morbidity and mortality.

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Retrospective Clinical Evaluation of Four Lateral Flow Assays for the Detection of SARS-CoV-2 Antibodies

10.1101/2020.07.01.20129882 ◽

2020 ◽

Author(s):

Kathrine McAulay ◽

Andrew Bryan ◽

Alexander L. Greninger ◽

Francisca Grill ◽

Douglas Lake ◽

...

Keyword(s):

Symptom Onset ◽

Rapid Test ◽

The United States ◽

Cross Reactivity ◽

Lateral Flow ◽

Lateral Flow Assays ◽

Life Threatening ◽

History Of ◽

Coronavirus Infection ◽

Respiratory Coronavirus

AbstractCoronavirus disease 2019 (COVID-19) is a potentially life-threatening respiratory infection caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), for which numerous serologic assays are available. In a CLIA laboratory setting, we used a retrospective sample set (n = 457) to evaluate two lateral flow immunoassays (LFIAs; two iterations of Rapid Response™ COVID-19 Test Cassette, BTNX Inc.) and a subset of to evaluate SARS-COV-2 IgG/IgM Rapid Test, ACON Laboratories (n = 200); and Standard Q COVID-19 IgM/IgG Duo, SD BIOSENSOR (n = 155) for their capacity to detect of SARS-CoV-2 IgG. In a cohort of primarily hospitalized patients with RT-PCR confirmed COVID-19, the BTNX assays demonstrated 95% and 92% agreement with the Abbott SARS-CoV-2 IgG assay and sensitivity was highest at ≥ 14 days from symptom onset [BTNX kit 1, 95%; BTNX kit 2, 91%]. ACON and SD assays demonstrated 99% and 100% agreement with the Abbott assay at ≥ 14 days from symptom onset. Specificity was measured using 74 specimens collected prior to SARS-CoV-2 circulation in the United States and 31 “cross-reactivity challenge” specimens, including those from patients with a history of seasonal coronavirus infection and was 98% for BTNX kit 1 and ACON and 100% for BTNX kit 2 and SD. Taken with data from EUA assays, these results suggest that LFIAs may provide adequate results for rapid detection of SARS-CoV-2. Replicating these results in fingerstick blood in outpatient populations, would further support the possibility that LFIAs may be useful to increase access to serologic testing

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Recombinase-Aided Amplification Coupled with Lateral Flow Dipstick for Efficient and Accurate Detection of Porcine Parvovirus

Life ◽

10.3390/life11080762 ◽

2021 ◽

Vol 11 (8) ◽

pp. 762

Author(s):

Yihong He ◽

Wenxian Chen ◽

Jindai Fan ◽

Shuangqi Fan ◽

Hongxing Ding ◽

...

Keyword(s):

Detection Method ◽

Cross Reactivity ◽

Lateral Flow ◽

Porcine Parvovirus ◽

Swine Industry ◽

Resource Limited ◽

Efficient Detection ◽

Lateral Flow Dipstick ◽

Polymerase Chain ◽

Embryonic Death

Porcine parvovirus (PPV) infection is the primary cause of SMEDI (stillbirth; mummification; embryonic death; infertility) syndrome, which is a global burden for the swine industry. Thus, it is crucial to establish a rapid and efficient detection method against PPV infection. In the present work, we developed a recombinase-aided amplification (RAA) assay, coupled with a lateral flow dipstick (LFD), to achieve an amplification of PPV DNA at 37 °C within 15 min. The detection limits of PPV RAA-LFD assay were 102 copies/μL recombinant plasmid pMD19-T-VP1, 6.38 × 10−7 ng/μL PPV DNA, and 10−1 TCID50/mL virus, respectively. This method was highly specific for PPV detection with no cross-reactivity for other swine pathogens. In contrast to polymerase chain reaction (PCR), the PPV RAA-LFD assay is more sensitive and cost-saving. Hence, the established PPV RAA-LFD assay provided an alternative for PPV detection, especially in resource-limited regions.

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Test performance evaluation of SARS-CoV-2 serological assays

10.1101/2020.04.25.20074856 ◽

2020 ◽

Cited By ~ 52

Author(s):

Jeffrey D. Whitman ◽

Joseph Hiatt ◽

Cody T. Mowery ◽

Brian R. Shy ◽

Ruby Yu ◽

...

Keyword(s):

Test Performance ◽

Severe Disease ◽

Cross Reactivity ◽

Time Interval ◽

Rt Pcr ◽

Serum Samples ◽

Serological Tests ◽

Full Spectrum ◽

Assay Performance ◽

Lateral Flow Assays

ABSTRACTBackgroundSerological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data.MethodWe conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 130 plasma or serum samples from 80 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system.ResultsAmong specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.8-94.8%. No consistent cross-reactivity was observed.ConclusionOur evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

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Evaluation of Six Commercial Mid- to High-Volume Antibody and Six Point-of-Care Lateral Flow Assays for Detection of SARS-CoV-2 Antibodies

Journal of Clinical Microbiology ◽

10.1128/jcm.01361-20 ◽

2020 ◽

Vol 58 (10) ◽

Cited By ~ 12

Author(s):

Carmen L. Charlton ◽

Jamil N. Kanji ◽

Kam Johal ◽

Ashley Bailey ◽

Sabrina S. Plitt ◽

...

Keyword(s):

Symptom Onset ◽

Point Of Care ◽

Acute Infection ◽

High Volume ◽

Respiratory Viruses ◽

Cross Reactivity ◽

Lateral Flow ◽

Serological Tests ◽

Deep Blue ◽

Lateral Flow Assays

ABSTRACT Coronavirus disease (COVID) serological tests are essential to determine the overall seroprevalence of a population and to facilitate exposure estimates within that population. We performed a head-to-head assessment of enzyme immunoassays (EIAs) and point-of-care lateral flow assays (POCTs) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Demographics, symptoms, comorbidities, treatment, and mortality of patients whose sera were used were also reviewed. Six EIAs (Abbott, Affinity, Bio-Rad, DiaSorin, Euroimmun, and Roche) and six POCTs (BTNX, Biolidics, Deep Blue, Genrui, Getein BioTech, and Innovita) were evaluated for the detection of SARS-CoV-2 antibodies in known COVID-19-infected individuals. Sensitivity of EIAs ranged from 50 to 100%, with only four assays having overall sensitivities of >95% after 21 days after symptom onset. Notably, cross-reactivity with other respiratory viruses (parainfluenza virus [PIV-4] [n = 5], human metapneumovirus [hMPV] [n = 3], rhinovirus/enterovirus [n = 1], CoV-229E [n = 2], CoV-NL63 [n = 2], and CoV-OC43 [n = 2]) was observed; however, overall specificity of EIAs was good (92 to 100%; all but one assay had specificity above 95%). POCTs were 0 to 100% sensitive >21 days after onset, with specificity ranging from 96 to 100%. However, many POCTs had faint banding and were often difficult to interpret. Serology assays can detect SARS-CoV-2 antibodies as early as 10 days after symptom onset. Serology assays vary in their sensitivity based on the marker (IgA/IgM versus IgG versus total) and by manufacturer; however, overall only 4 EIAs and 4 POCTs had sensitivities of >95% >21 days after symptom onset. Cross-reactivity with other seasonal coronaviruses is of concern. Serology assays should not be used for the diagnosis of acute infection but rather in carefully designed serosurveys to facilitate understanding of seroprevalence in a population and to identify previous exposure to SARS-CoV-2.

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Monoclonal Antibodies Application in Lateral Flow Immunochromatographic Assays for Drugs of Abuse Detection

Molecules ◽

10.3390/molecules26041058 ◽

2021 ◽

Vol 26 (4) ◽

pp. 1058

Author(s):

Zidane Qriouet ◽

Yahia Cherrah ◽

Hassan Sefrioui ◽

Zineb Qmichou

Keyword(s):

High Performance ◽

Drugs Of Abuse ◽

Limit Of Detection ◽

Lateral Flow ◽

Detection Sensitivity ◽

Gas Chromatography Mass Spectrometry ◽

Resource Limited ◽

Short Period ◽

Reaction Gas Chromatography ◽

Lateral Flow Assays

Lateral flow assays (lateral flow immunoassays and nucleic acid lateral flow assays) have experienced a great boom in a wide variety of early diagnostic and screening applications. As opposed to conventional examinations (High Performance Liquid Chromatography, Polymerase Chain Reaction, Gas chromatography-Mass Spectrometry, etc.), they obtain the results of a sample’s analysis within a short period. In resource-limited areas, these tests must be simple, reliable, and inexpensive. In this review, we outline the production process of antibodies against drugs of abuse (such as heroin, amphetamine, benzodiazepines, cannabis, etc.), used in lateral flow immunoassays as revelation or detection molecules, with a focus on the components, the principles, the formats, and the mechanisms of reaction of these assays. Further, we report the monoclonal antibody advantages over the polyclonal ones used against drugs of abuse. The perspective on aptamer use for lateral flow assay development was also discussed as a possible alternative to antibodies in view of improving the limit of detection, sensitivity, and specificity of lateral flow assays.

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Development of a reverse-transcription recombinase polymerase amplification assay with a lateral flow assay for rapid detection of avian orthoavulavirus 1

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638721990122 ◽

2021 ◽

Vol 33 (2) ◽

pp. 308-312

Author(s):

Jindai Fan ◽

Wenxian Chen ◽

Yuanyuan Zhang ◽

Zhixiang Liu ◽

Xiaoming Li ◽

...

Keyword(s):

Reverse Transcription ◽

Newcastle Disease ◽

Cross Reactivity ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Recombinase Polymerase Amplification ◽

Control Measures ◽

Economic Losses ◽

Resource Limited ◽

Simple Detection

Newcastle disease is an avian infectious disease caused by avian orthoavulavirus 1, also known as Newcastle disease virus (NDV). This disease has caused significant economic losses to the poultry industry worldwide. The rapid and simple detection of NDV infection is crucial to inform the appropriate control measures. We developed a reverse-transcription recombinase polymerase amplification (RT-RPA) assay combined with a lateral flow assay (LFA) for NDV detection. The RPA assay can be completed at 37°C within 20 min, and the RPA result can be visualized by the LFA within 5 min. The NDV RT-RPA-LFA detected NDV specifically with no cross-reactivity with other pathogens. The detection limit of NDV cDNA with our RT-RPA-LFA was 3.34 × 10−3 ng/μL. Consequently, the RT-RPA-LFA showed good potential for the detection of NDV infection in the field, especially in resource-limited settings.

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721. Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay; A Multicenter Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.918 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S459-S460

Author(s):

Wassim Abdallah ◽

Thein Myint ◽

Richard W LaRue ◽

Melissa Minderman ◽

Suphansa Gunn ◽

...

Keyword(s):

Enzyme Immunoassay ◽

Predictive Value ◽

Severe Disease ◽

Antigen Detection ◽

Bachelor's Degree ◽

Lateral Flow ◽

Resource Limited Settings ◽

Disseminated Histoplasmosis ◽

Resource Limited ◽

Galactomannan Antigen

Abstract Background Accurate and timely methods for the diagnosis of histoplasmosis in endemic resource-limited settings are largely lacking. Histoplasma galactomannan antigen detection by enzyme immunoassay (EIA) is the most widely used method for the diagnosis of acute pulmonary and disseminated histoplasmosis in the United States (USA). EIA methods have constraints in resource-limited settings including cost, turnaround time, and the need for large reference laboratories, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFA) are practical methods that can be used in this setting for Histoplasma antigen detection. Methods Frozen urine specimens were submitted to MiraVista (MVista) for Histoplasma antigen EIA testing from three academic medical centers in highly endemic areas of the USA. They were also blinded and tested for the MVista Histoplasma LFA by skilled MVista technologists. Medical records were reviewed for clinical information. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable, pulmonary, or disseminated, immune competent or immune suppressed, and mild, moderate, or severe. Results 352 subjects were enrolled, including 66 cases of histoplasmosis (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (68%). 76% had disseminated histoplasmosis. 6% were mild, 66% moderate, and 28% severe. A high degree of concordance was found between LFA and EIA results (kappa 0.837, OR 372.7, LR 204, p< 0.001). Overall, the sensitivity and specificity of the LFA were 78.8% and 99.3% respectively (kappa 0.84, p< 0.001). The sensitivity was higher in proven cases (93.2%), in patient with disseminated (94.7%), moderate (80%) and severe disease (94%), and those with galactomannan levels ≥ 2 ng/mL (97.7%). Specificity was 99.3% in proven cases, 99.3% in patient with moderate and severe disease, and 96.4% in those with galactomannan levels ≥ 2 ng/mL. Table 1. Statistical characteristics of the LFA test for histoplasmosis in different categories. PPV: Positive Predictive Value. NPV: Negative Predictive Value. EIA: Enzyme Immunoassay. The LFA test for histoplasmosis is more accurate in patients with high burden of infection. Conclusion The MVista Histoplasma galactomannan LFA may meet the need for accurate rapid diagnosis of histoplasmosis in resource-limited settings, especially in patients with relatively high disease burden, potentially reducing morbidity and mortality. Disclosures Melissa Minderman, Bachelor's Degree, Molecular Biology, MiraVista Diagnostics (Employee) Suphansa Gunn, Bachelor's Degree, psychology, MiraVista Diagnostics (Employee) Lawrence J. Wheat, MD, MiraVista Diagnostics (Employee)

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Evaluation of Commercial Rapid Lateral Flow Tests, Alone or in Combination, for SARS-CoV-2 Antibody Testing

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.20-1390 ◽

2021 ◽

Author(s):

Peter U. Fischer ◽

Kerstin Fischer ◽

Kurt C. Curtis ◽

Yuefang Huang ◽

Nicole Fetcho ◽

...

Keyword(s):

Symptom Onset ◽

Vaccination Campaign ◽

High Sensitivity ◽

The United States ◽

Lateral Flow ◽

Plasma Samples ◽

Antibody Testing ◽

The Status ◽

Lateral Flow Assays ◽

Lateral Flow Tests

Antibody tests can be tools for detecting current or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 [coronavirus disease 2019 (COVID-19)]) infections. Independent test evaluations are needed to document the performance with different sample sets. We evaluated six lateral flow assays (LFAs) and two laboratory-based tests (EUROIMMUN-SARS-CoV-2 ELISA and Abbott-Architect-SARS-CoV-2-IgG). We tested 210 plasma samples from 89 patients diagnosed with acute COVID-19. These samples were collected at different time points after the onset of symptoms. In addition, 80 convalescent plasma samples, and 168 pre-pandemic samples collected from adults in the United States and in Africa were tested. LFA performance varied widely, and some tests with high sensitivity had low specificity. LFA sensitivities were low (18.8–40.6%) for samples collected 0 to 3 days after symptom onset, and were greater (80.3–96.4%) for samples collected > 14 days after symptom onset. These results are similar to those obtained by ELISA (15.6% and 89.1%) and chemiluminescent microparticle assay (21.4% and 93.1%). The range of test specificity was between 82.7% and 97%. The combined use of two LFAs can increase specificity to more than 99% without a major loss of sensitivity. Because of suboptimal sensitivity with early COVID-19 samples and background reactivity with some pre-pandemic samples, none of the evaluated tests alone is reliable enough for definitive diagnosis of COVID-19 infection. However, antibody testing may be useful for assessing the status of the epidemic or vaccination campaign. Some of the LFAs had sensitivities and specificities that were comparable to those of more expensive laboratory tests, and these may be useful for seroprevalence surveys in resource-limited settings.

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Gold-Aptamer-Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

10.26434/chemrxiv.8312324.v1 ◽

2019 ◽

Author(s):

Veeren Chauhan ◽

Mohamed M Elsutohy ◽

C Patrick McClure ◽

Will Irving ◽

Neil Roddis ◽

...

Keyword(s):

Nucleic Acid ◽

In Silico ◽

Point Of Care ◽

Lateral Flow ◽

Nucleic Acid Sequence ◽

In Silico Screening ◽

Lateral Flow Assays ◽

Life Threatening ◽

Software And Hardware ◽

Nucleic Acid Sequences

Enteroviruses are a ubiquitous mammalian pathogen that can produce mild to life-threatening disease. Bearing this in mind, we have developed a rapid, accurate and economical point-of-care biosensor that can detect a nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and aptamers to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral RNA sequence (23 bases), which was identified through in silico screening. Aptamers were designed to demonstrate specific complementarity towards the target enteroviral RNA to produce aggregated gold-aptamer nanoconstructs. Conserved target enteroviral nucleic acid sequence (≥ 1x10-7 M, ≥1.4×10-14 g/mL), initiates gold-aptamer-nanoconstructs disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow-assays that utilise gold-aptamer-nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (< 60 s) and could be interpreted with a bespoke software and hardware electronic interface. We anticipate our methodology will translate in-silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave-the-way forward in the clinical evaluation of disease and complement existing strategies at overcoming antimicrobial resistance.

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Personalized stratification of back to work risk amidst COVID-19: A machine learning approach (Preprint)

10.2196/preprints.22030 ◽

2020 ◽

Author(s):

Carson Lam ◽

Jacob Calvert ◽

Gina Barnes ◽

Emily Pellegrini ◽

Anna Lynn-Palevsky ◽

...

Keyword(s):

Machine Learning ◽

High Risk ◽

Learning Algorithm ◽

Severe Disease ◽

High Specificity ◽

Population Level ◽

The United States ◽

Health Condition ◽

Available P ◽

Severe Illness

BACKGROUND In the wake of COVID-19, the United States has developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans that should continue to stay at home due to being at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness and who should therefore not return to work until vaccination or widespread serological testing is available. OBJECTIVE This study evaluated a machine learning algorithm for the prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records. METHODS The algorithm was trained to identify patients for whom a diagnosis of COVID-19 was likely to result in hospitalization, and compared against four U.S policy-based criteria: age over 65, having a serious underlying health condition, age over 65 or having a serious underlying health condition, and age over 65 and having a serious underlying health condition. RESULTS This algorithm identified 80% of patients at risk for hospitalization due to COVID-19, versus at most 62% that are identified by government guidelines. The algorithm also achieved a high specificity of 95%, outperforming government guidelines. CONCLUSIONS This algorithm may help to enable a broad reopening of the American economy while ensuring that patients at high risk for serious disease remain home until vaccination and testing become available.

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