721. 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 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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Development and Performance verification of colloidal gold labeled SARS-CoV-2 antigen detection method for routine popular screening of COVID-19 with clinical samples in Poland and China

10.1101/2021.11.22.21266719 ◽

2021 ◽

Author(s):

Chuanxiang Guo ◽

Li Yao ◽

Fengling Chen ◽

Chao Zhang ◽

Wei Chen

Keyword(s):

Predictive Value ◽

Colloidal Gold ◽

Detection Method ◽

Age Distribution ◽

Antigen Detection ◽

Lateral Flow ◽

Rapid Screening ◽

Clinical Samples ◽

Lateral Flow Strip ◽

And Performance

In this research, we have constructed and optimized the colloidal gold labeled lateral flow strip (LFS) for rapid detection of antigen of SARS-CoV-2 and rapid screening of COVID-19. Based on the constructed and optimized colloidal gold lateral flow strip, the parameters of the LFS have been well evaluated with the clinical samples in the professional labs. The screening performance have also been evaluated from the aspects including the CT values, age distribution and onset of symptoms. Finally, based on the detection results of 420 clinical samples, the LFS can achieve the screening of COVID-19 with the positive percentage agreement (PPA, sensitivity), negative percent agreement (NPA, specificity), the positive predictive value (PPV) and the negative predictive value (NPV) of 96.8%, 100%, 100% and 96.6%, respectively, indicating the powerful potential for practical screening applications in pandemic control. Of great significance, this developed SARS-CoV-2 antigen detection method has also been successfully utilized for screening of delta-variant of SARS-CoV-2.

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Evaluation of two new rapid diagnostic tests (RDTs) for the diagnosis of malaria

Bangladesh Journal of Medical Microbiology ◽

10.3329/bjmm.v5i2.16931 ◽

2013 ◽

Vol 5 (2) ◽

pp. 11-15 ◽

Cited By ~ 2

Author(s):

Fahmida Jahan ◽

Rubayet Elahi ◽

Md. Khaja Mohiuddin ◽

Md. Gulam Musawwir Khan ◽

Mohammad Shafiul Alam ◽

...

Keyword(s):

Predictive Value ◽

Gold Standard ◽

Diagnostic Tests ◽

Rapid Diagnostic Tests ◽

Accurate Diagnosis ◽

The Other ◽

Antibody Detection ◽

Resource Limited Settings ◽

Malaria Rdts ◽

Resource Limited

Rapid diagnostic tests (RDTs) address the need for accurate diagnosis of malaria, particularly in resource limited settings. In this study, two malaria RDTs were compared with gold standard microscopy: On Site Pf/Pv test detecting Plasmodium falciparum-specific histidine rich protein-2 (Pf HR P2) and P. vivax-specific parasitic lactate dehydrogenase (pLDH) antigens; and SD Bioline anti-Pf/Pv test detecting anti-HR P2 and anti-pL DH antibodies for the diagnosis of P. falciparum and P. vivax infections, respectively. For OnSite test, the overall sensitivity was found 96.2% , specificity 98.2% , positive predictive value (PPV ) 98.2% , negative predictive value (NPV ) 96.4% and agreement with microscopy was found to be 0.94. On the other hand SD Bioline test, the overall sensitivity was 75.4%, specificity 83.7%, PPV 84.3% , NPV 74.5% and agreement with microscopy was 0.59. These data revealed that the R DT based on antigen detection (Onsite test) was more reliable than that based on the antibody detection (SD Bioline test).DOI: http://dx.doi.org/10.3329/bjmm.v5i2.16931 Bangladesh J Med Microbiol 2011; 05 (02): 11-15

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Evaluation of Coccidioides Antigen Detection in Dogs with Coccidioidomycosis

Clinical and Vaccine Immunology ◽

10.1128/cvi.05631-11 ◽

2012 ◽

Vol 19 (3) ◽

pp. 343-345 ◽

Cited By ~ 12

Author(s):

Emily J. Kirsch ◽

Russell T. Greene ◽

Annalisa Prahl ◽

Stanley I. Rubin ◽

Jane E. Sykes ◽

...

Keyword(s):

Enzyme Immunoassay ◽

Fungal Infections ◽

Rapid Diagnosis ◽

Antigen Detection ◽

Antibody Testing ◽

Content Type ◽

Healthy Dogs ◽

Galactomannan Antigen ◽

Antigen Antibody ◽

Urine And Serum

ABSTRACTAntigen detection has been reported to be a promising method for rapid diagnosis of coccidioidomycosis in humans.Coccidioidesantigen detection has not been previously reported in dogs with coccidioidomycosis and was evaluated in 60 cases diagnosed based on detection of anti-Coccidioidesantibodies at titers of 1:16 or more in serum. Controls included dogs with presumed histoplasmosis or blastomycosis, other fungal infections, or nonfungal diseases and healthy dogs. Urine and serum specimens were tested using an enzyme immunoassay forCoccidioidesgalactomannan antigen. Antibody testing was performed at commercial veterinary reference laboratories. Antigen was detected in urine or serum of 12 of 60 (20.0%), urine only in 2 of 57 (3.5%), and serum only in 11 of 58 (19.0%) dogs with coccidioidomycosis. Antigen was detected in the urine of 3 of 43 (7.0%) and serum of 1 of 37 (2.7%) dogs with histoplasmosis or blastomycosis but not in 13 dogs with other fungal infections (serum, 9; urine, 13), 41 dogs with nonfungal diseases (urine, 41; serum, 18), or healthy dogs (serum, 21; urine, 21). Detection of antigen was an insensitive method for diagnosis of coccidioidomycosis in dogs in which the diagnosis was based primarily upon detection of antibodies at titers of 1:16 or higher, and the highest sensitivity was in serum.

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Detection of Histoplasma capsulatum Antigen in Panamanian Patients with Disseminated Histoplasmosis and AIDS

Clinical and Vaccine Immunology ◽

10.1128/cvi.00358-07 ◽

2008 ◽

Vol 15 (4) ◽

pp. 681-683 ◽

Cited By ~ 18

Author(s):

Maria Eugenia Gutierrez ◽

Alfredo Canton ◽

Patricia Connolly ◽

Robert Zarnowski ◽

L. Joseph Wheat

Keyword(s):

United States ◽

Latin American ◽

Histoplasma Capsulatum ◽

Severe Disease ◽

Nuclear Gene ◽

The United States ◽

Antigen Detection ◽

Disseminated Histoplasmosis ◽

Antigen Assay ◽

Progressive Disseminated Histoplasmosis

ABSTRACT Histoplasmosis is a common endemic mycosis in the Americas, often causing severe disease in patients with AIDS. Antigen detection has become an important method for rapid diagnosis of histoplasmosis in the United States but not in Central or South America. Isolates from patients in the United States are predominantly found to be class 2 isolates when typed using the nuclear gene YPS3, while isolates from Latin America are predominantly typed as class 5 or class 6. Whether infection with these Latin American genotypes produces positive results in the Histoplasma antigen assay has not been reported. In this study, we have compared the sensitivity of antigen detection for AIDS patients from Panama who had progressive disseminated histoplasmosis to that for those in the United States. Antigenuria was detected in the MVista Histoplasma antigen enzyme immunoassay (EIA) in 95.2% of Panamanian cases versus 100% of U.S. cases. Antigenemia was detected in 94.7% of the Panamanian cases versus 92% of the U.S. cases. Two clinical isolates from Panama were typed using YPS3 and were found to be restriction fragment length polymorphism class 6. We conclude that the MVista Histoplasma antigen EIA is a sensitive method for diagnosis of histoplasmosis in Panama.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab454 ◽

2021 ◽

Vol 8 (9) ◽

Author(s):

Wassim Abdallah ◽

Thein Myint ◽

Richard LaRue ◽

Melissa Minderman ◽

Suphansa Gunn ◽

...

Keyword(s):

Severe Disease ◽

The United States ◽

Cross Reactivity ◽

Lateral Flow ◽

Medical Centers ◽

Resource Limited ◽

Pulmonary Histoplasmosis ◽

Lateral Flow Assays ◽

Poor Outcomes ◽

Endemic Mycoses

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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Total lymphocyte count as a tool for timing opportunistic infection prophylaxis in resource-limited settings: a study from India

The Journal of Infection in Developing Countries ◽

10.3855/jidc.1011 ◽

2010 ◽

Vol 4 (10) ◽

pp. 645-649 ◽

Cited By ~ 3

Author(s):

Sreenivasan Srirangaraj ◽

Dasegowda Venkatesha

Keyword(s):

Opportunistic Infection ◽

Predictive Value ◽

Lymphocyte Count ◽

Total Lymphocyte Count ◽

Active Tuberculosis ◽

Cd4 Count ◽

Resource Limited Settings ◽

Cd4 Counts ◽

Total Lymphocyte ◽

Resource Limited

Introduction: In resource-limited settings, due to the high cost of CD4 cell count testing, physicians must decide about opportunistic infection (OI) prophylaxis without a laboratory evaluation of HIV stage and level of immune suppression. This study aimed to evaluate the correlation of total lymphocyte count (TLC), an inexpensive laboratory parameter, to CD4 count, and to determine a range of TLC cut-offs for the initiation of OI prophylaxis that is appropriate for resource-limited settings. Methodology: Spearman correlation between CD4 count and TLC was assessed in patients attending the Anti-Retroviral Therapy (ART) centre at Mysore, India. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of various TLC cut-offs were computed for CD4 counts < 200 cells/mm3. Correlation and statistical indices were computed for all patients and for HIV patients with active tuberculosis. Results: Good correlation was noted between the 106 paired TLC and CD4 counts (r = 0.3497).TLC < 1200cells/mm3 had 88.14% sensitivity and 34.78% specificity for CD4 count < 200 cells/mm3. In those patients with active tuberculosis, TLC< 2000cells/mm3 had 95.24% sensitivity and 100% specificity for CD4 count < 200cells/ mm3. Conclusions: TLC could serve as a low-cost tool for determining when to initiate prophylaxis in resource-constrained settings.

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Evaluation of the diagnostic accuracy of lateral flow devices as a tool to diagnose rabies in post-mortem animals

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008844 ◽

2020 ◽

Vol 14 (11) ◽

pp. e0008844

Author(s):

Kazunori Kimitsuki ◽

Nobuo Saito ◽

Kentaro Yamada ◽

Chun-Ho Park ◽

Satoshi Inoue ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Fluorescent Antibody ◽

Negative Control ◽

Lateral Flow ◽

Resource Limited Settings ◽

Diagnostic Laboratory ◽

Diagnostic Efficacy ◽

Resource Limited ◽

Efficient Detection ◽

Flow Devices

Implementation of lateral flow devices (LFDs) for rabies antigen detection is expected to improve surveillance through the efficient detection of rabid animals in resource-limited settings; however, the use of LFDs for diagnosis remains controversial because some commercially available kits show low sensitivity. Therefore, we compared the diagnostic efficacy of three LFDs (ADTEC, Bionote, and Elabscience kits) paralleled with the direct fluorescent antibody test (dFAT) using fresh samples and investigated the diagnostic accuracies. To do so, we evaluated rabies-suspected samples submitted to the Regional Animal Disease Diagnostic Laboratory III, Philippines. Furthermore, we conducted real-time RT-PCR and sequencing to measure the accuracy of field laboratory diagnosis. The total number of animals submitted during this study period was 184 cases, including negative control samples. Of these, 53.9% (84 cases) were positive in the dFAT. Dogs were the most common rabies-suspected animal (n = 135). The sensitivities of the ADTEC and Bionote kits were 0.88 (74 cases) and 0.95 (80 cases), respectively. The specificity of both kits was 1.00 (100 cases). Furthermore, the sensitivity and specificity of the ADTEC kit after directly homogenizing the samples in assay buffer without dilution in phosphate-buffered saline (ADTEC kit DM) were 0.94 (79 cases) and 1.00 (100 cases), respectively. By contrast, there were no positive results using the Elabscience kit among all dFAT-positive samples. The sensitivity and specificity of LFDs make these tests highly feasible if properly used. Therefore, LFD tests can be used to strengthen the surveillance of rabies-infected animals in endemic and resource-limited settings.

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A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

10.1101/2021.04.12.21255368 ◽

2021 ◽

Author(s):

Thomas S. Fulford ◽

Huy Van ◽

Nicholas A. Gherardin ◽

Shuning Zheng ◽

Marcin Ciula ◽

...

Keyword(s):

Point Of Care ◽

Venous Blood ◽

Lateral Flow ◽

Virus Infectivity ◽

Resource Limited Settings ◽

Neutralising Antibodies ◽

Active Immunisation ◽

Resource Limited ◽

Laboratory Facilities ◽

Strong Correlate

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Accordingly, the COVID-19 NAb-testTM test described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.

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MPT64 antigen detection test improves diagnosis of pediatric extrapulmonary tuberculosis in Mbeya, Tanzania

Scientific Reports ◽

10.1038/s41598-021-97010-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Erlend Grønningen ◽

Marywinnie Nanyaro ◽

Lisbet Sviland ◽

Esther Ngadaya ◽

William Muller ◽

...

Keyword(s):

Test Performance ◽

Predictive Value ◽

Extrapulmonary Tuberculosis ◽

Final Diagnosis ◽

Antigen Detection ◽

Diagnostic Challenge ◽

Routine Diagnostics ◽

Resource Limited ◽

Resource Setting ◽

Sensitivity Specificity

AbstractPediatric extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. A new immunochemistry based MPT64 antigen detection test has shown improved sensitivity compared to current laboratory tests. The aim of this study was to implement and validate the test performance in a resource limited African setting. Presumptive pediatric (0–18 y) EPTB patients were prospectively enrolled at Mbeya Zonal Referral Hospital, and followed to the end of treatment or until a final diagnosis was reached. Specimens from suspected sites of infection were subject to routine diagnostics, GeneXpert MTB/RIF assay and the MPT64 test. The performance of the tests was assessed using mycobacterial culture as well as a composite reference standard. 30 patients were categorized as TB cases, 31 as non-TB cases and 2 were uncategorized. In the TB group, the three most common infections were adenitis (30%), peritonitis (30%) and meningitis (20%). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 92%, 88%, 87%, 92% and 90%, respectively. Mortality was equally high among TB/non-TB cases (23% vs 21%), and malnutrition was the main comorbidity among TB cases. The MPT64 test was implementable in the routine diagnostics in a low-resource setting and improved the diagnosis of pediatric EPTB.

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