scholarly journals Flavivirus Cross-Reactivity to Dengue Nonstructural Protein 1 Antigen Detection Assays

Diagnostics ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 11
Author(s):  
Li Kiang Tan ◽  
Wing Yan Wong ◽  
Hui Ting Yang ◽  
Roland G. Huber ◽  
Peter J. Bond ◽  
...  
Keyword(s):  
False Positive ◽  
Yellow Fever Virus ◽  
Nonstructural Protein ◽  
Cross Reactivity ◽  
Clinical Samples ◽  
Viral Loads ◽  
Rapid Assays ◽  
Nonstructural Protein 1 ◽  
Ns1 Antigen ◽  
Positive Results

Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses of public health relevance. Both viruses circulate in the same endemic settings and acute infections generally manifest similar symptoms. This highlights the importance of accurate diagnosis for clinical management and outbreak control. One of the commonly used acute diagnostic markers for flaviviruses is nonstructural protein 1 (NS1). However, false positives due to antigenic cross-reactivity have been reported between DENV and ZIKV infections when using DENV NS1 antigen (NS1 Ag) detection assays in acute cases. Therefore, we investigated the lowest detectable virus titres and cross-reactivity of three commercial dengue NS1 Ag rapid assays and two ELISAs for different flaviviruses. Our results showed that substantially high viral titres of ZIKV, Kunjin virus (KUNV) and yellow fever virus (YFV) are required to give false-positive results when using DENV NS1 rapid detection assays. Commercial DENV NS1 ELISAs did not react with ZIKV and YFV. In comparison, tested assays detected DENV at a significantly low virus titre. Given the relatively low viral loads reported in clinical samples, our findings suggest that commercially available dengue NS1 Ag detection assays are less likely to generate false-positive results among clinical samples in areas where multiple flaviviruses cocirculate.

scholarly journals Repurposing Old Antibodies for New Diseases by Exploiting Cross Reactivity and Multicolored Nanoparticles

2020 ◽  
Author(s):  
Cristina Rodriguez-Quijada ◽  
Jose Gomez-Marquez ◽  
Kimberly Hamad-Schifferli
Keyword(s):  
Yellow Fever Virus ◽  
Nonstructural Protein ◽  
Polyclonal Antibodies ◽  
Cross Reactivity ◽  
Test Area ◽  
Denv Serotypes ◽  
Nonstructural Protein 1 ◽  
Gold Nps ◽  
Additional Image ◽  
Selective Sensor

ABSTRACTWe exploit the cross-reactivity of dengue (DENV) and zika (ZIKV) virus polyclonal antibodies for nonstructural protein 1 (NS1) to construct a selective sensor that can detect yellow fever virus (YFV) NS1 in a manner similar to chemical olfaction. DENV and ZIKV antibodies were screened for their ability to bind to DENV, ZIKV, and YFV NS1 by ELISA and in pairs in paper immunoassays. A strategic arrangement of antibodies immobilized on paper and conjugated to different colored gold NPs was used to distinguish the three biomarkers. Machine learning of test area RGB values showed that with two spots, readout accuracies of 100% and 87% were obtained for both pure NS1 and DENV/YFV mixtures, respectively. Additional image pre-processing allowed differentiation between all 4 DENV serotypes with 92% accuracy. The technique was extended to hack a commercial DENV test to detect YFV and ZIKV by augmentation with DENV and ZIKV polyclonal antibodies.TOC GRAPHIC

Serological Differences after Acute Zika Virus Infections between Children and Adults: Implication for Use of a Serological Test

2021 ◽  
Author(s):  
Jurai Wongsawat ◽  
Patama Suttha ◽  
Sumalee Chanama ◽  
Somkid Srisopa ◽  
Nichapa Yonchoho ◽  
...  
Keyword(s):  
Zika Virus ◽  
Nonstructural Protein ◽  
Serological Test ◽  
Cross Reactivity ◽  
Virus Infections ◽  
Positive Real ◽  
Nonstructural Protein 1 ◽  
Age Related ◽  
Polymerase Chain ◽  
Post Onset

Information is limited regarding differential serological responses after acute Zika virus (ZIKV) infections and prevalence of cross-reactivity with anti-dengue virus (DENV) assays comparing children and adults. Early convalescent sera from a cohort of suspected mild DENV cases between December 2016 and September 2018 at Bamrasnaradura Infectious Diseases Institute in Thailand were tested for nonstructural protein 1 (NS1)–based anti-ZIKV IgM and IgG ELISAs (Euroimmun), and in-house anti-DENV IgM- and IgG-capture ELISAs. ZIKV cases were identified by positive real-time reverse transcriptase-polymerase chain reaction on urine. Sera from 26 (10 children and 16 adults) ZIKV and 237 (153 children and 74 adults) non-ZIKA cases collected at the median duration of 18 days (interquartile range [IQR] 18,19) post-onset of symptoms were tested. Comparing pediatric ZIKV to adult ZIKV cases, the mean anti-ZIKV IgM ratio was higher (2.12 versus 1.27 units, respectively; P = 0.07), whereas mean anti-ZIKV IgG ratio was lower (3.13 versus 4.24 units, respectively; P = 0.03). Sensitivity of anti-ZIKV IgM and specificity of anti-ZIKV IgG in pediatric ZIKV were higher than in adult ZIKV cases (80.0% versus 43.7% and 79.1% versus 43.2%, respectively). No cross-reactivity with anti-DENV IgM- and IgG-capture ELISA were reported in pediatric ZIKV cases in our study, whereas 25% and 12.5% were found in adult ZIKV cases, respectively. Age-related ZIKV serological differences have been observed. Positive NS1-based anti-ZIKV IgM and IgG ELISA at the early convalescent phase could be useful for ZIKV diagnosis in children, even in a dengue endemic setting.

scholarly journals Assessment of Campylobacter fetus subsp. venerealis molecular diagnosis using clinical samples of bulls

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Marta Filipa Silva ◽  
Ana Duarte ◽  
Gonçalo Pereira ◽  
Luísa Mateus ◽  
Luís Lopes-da-Costa ◽  
...  
Keyword(s):  
False Positive ◽  
Bacterial Species ◽  
Venereal Disease ◽  
High Rate ◽  
Clinical Samples ◽  
Campylobacter Fetus ◽  
Subspecies Level ◽  
Geographical Regions ◽  
Pcr Assays ◽  
Positive Results

Abstract Background Campylobacter fetus subsp. venerealis (Cfv) is the pathogen responsible for Bovine Genital Campylobacteriosis (BGC), a venereal disease of cattle associated with impaired reproductive performance. Although several PCR assays were developed to identify this pathogen, most of them are still poorly evaluated in clinical samples. This study evaluated real-time PCR assays for Cfv detection in preputial samples of bulls (n = 308). Results The detection at the subspecies level (Cfv) compared four assays: two targeting ISCfe1 and two targeting parA gene. The detection at the species level (C. fetus) considered an assay targeting the nahE gene and a commercial kit for C. fetus identification. At the subspecies level, assays directed either to different targets (parA and ISCfe1), or to the same target (ISCfe1 or parA), showed a high percentage of disagreeing results. All samples positive at the subspecies level (n = 169) were negative in C. fetus detection assays, which strongly suggests the horizontal gene transfer of ISCfe1 and parA to other bacterial species. This was confirmed by microbiological isolation of three Campylobacter portucalensis strains responsible for false positive results. Sequences with a high level of identity with ISCfe1 and parA gene of Cfv were identified in C. portucalensis genome. Conclusions Overall, this study reveals that PCR assays solely directed to a subspecies target originate a high rate of false positive results, due to the presence of parA and ISCfe1 homologous sequences in other bacterial species, namely of the genus Campylobacter. Although the specificity of these methods may be higher if applied to bulls from herds with clinical features of BGC or in other geographical regions, current PCR diagnosis should couple subspecies and species targets, and further research must be envisaged to identify Cfv specific molecular targets.

scholarly journals Investigation of Dengue Fever Outbreak in a Rural Area of Islamabad, Pakistan: A Case Control Study

2021 ◽  
Author(s):  
Fawad Khalid Khan ◽  
Khurram Shahzad Akram ◽  
Ambreen Chaudhry ◽  
Mir Muhammad Hassan Bullo ◽  
zakir Hussain ◽  
...  
Keyword(s):  
Dengue Fever ◽  
Nonstructural Protein ◽  
Health Department ◽  
Control Measures ◽  
Outbreak Investigation ◽  
Blood Samples ◽  
Breeding Sites ◽  
Nonstructural Protein 1 ◽  
Breeding Grounds ◽  
Ns1 Antigen

Background: In the second week of October 2019, five suspected cases of dengue fever were reported from union council Sohan, Islamabad rural (population 45,747) to the health department, Islamabad Capital Territory (ICT).  Outbreak investigation was conducted with the objectives to identify risk factors and to recommend control measures. Methods: Outbreak investigation was conducted from 17 th October to 25 th November 2019. A case was defined as, “fever and two or more of the following signs/symptoms; headache, retro-orbital pain, joint/bone pain, myalgia and petechial rash with NS1 test (Nonstructural Protein 1) positive during 8 th October to 25 th November 2019 among residents of Sohan”. Age and sex-matched controls were recruited from the same neighborhood. All cases were positive for NS1 antigen. Blood samples from five suspected cases were collected and tested for laboratory confirmation. Results:   A total of 547 households were surveyed and 85 cases were identified. The mean age was 34.4 years + 16.05 (range 3-71 years). The attack rate was 0.19% whereas the most affected age group was the 45-54 years (AR 0.43%). Males were predominantly affected (n=48 56.5%). Among all cases, 32% (n=27)) had stagnant water inside or around their houses (aOR 2.65, CI 1.20-5.83, P= 0.005), 33% (n=28) were using mosquito repellent (aOR 0.35, CI 0.17-0.70, P <0.001), 31% (n=26) used indoor residual spray insecticide (aOR 0.48, CI 0.24-0.97, P =0.041), and 73% (n=62) used full protective clothing (aOR 0.17, CI 0.05-0.58, P <0.001). All five blood samples were tested positive for NS-1 antigen. Conclusion: The presence of accumulated rainwater in pools and empty receptacles around houses acted as breeding grounds for Aedes aegypti mosquitos and was the most probable cause of this outbreak. Following our recommendations, the health department-initiated mosquito breeding sites control activities through residual insecticide spray and advocacy on the use of protective measures against mosquito bites.

Mutation of critical residues reveals insights of yellow fever virus nonstructural protein 1 (NS1) stability and its formation

2019 ◽  
Vol 38 (17) ◽  
pp. 5277-5286 ◽  
Author(s):  
Gabriela de Lima Menezes ◽  
Ricardo Lemes Gonçalves ◽  
Raisa Melo Lima ◽  
Maristela Pereira ◽  
Marcos Lázaro Moreli ◽  
...  
Keyword(s):  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Nonstructural Protein ◽  
Fever Virus ◽  
Nonstructural Protein 1 ◽  
Critical Residues

scholarly journals Histoplasmosis-Associated Cross-Reactivity in the BioRad Platelia Aspergillus Enzyme Immunoassay

2007 ◽  
Vol 14 (5) ◽  
pp. 638-640 ◽  
Author(s):  
L. Joseph Wheat ◽  
Emily Hackett ◽  
Michelle Durkin ◽  
Patricia Connolly ◽  
Ruta Petraitiene ◽  
...  
Keyword(s):  
Enzyme Immunoassay ◽  
Experimental Infection ◽  
False Positive ◽  
Second Generation ◽  
Cross Reactivity ◽  
Positive Results

ABSTRACT We observed false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA) for specimens from patients with histoplasmosis and mice with experimental infection. Platelia Aspergillus EIA-positive specimens were negative in the second-generation Histoplasma antigen EIA. Care must be taken to exclude histoplasmosis for patients with positive Platelia Aspergillus EIA results.

scholarly journals Antibody-based assay discriminates Zika virus infection from other flaviviruses

2017 ◽  
Vol 114 (31) ◽  
pp. 8384-8389 ◽  
Author(s):  
Angel Balmaseda ◽  
Karin Stettler ◽  
Raquel Medialdea-Carrera ◽  
Damaris Collado ◽  
Xia Jin ◽  
...  
Keyword(s):  
Zika Virus ◽  
Nonstructural Protein ◽  
Serological Test ◽  
Low Cost ◽  
Human Monoclonal Antibody ◽  
Cross Reactivity ◽  
Control Group ◽  
Rt Pcr ◽  
Mild Disease ◽  
Nonstructural Protein 1

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test. We previously generated a ZIKV nonstructural protein 1 (NS1)-specific human monoclonal antibody, which we used to develop an NS1-based competition ELISA. Well-characterized samples from RT-PCR-confirmed patients with Zika and individuals exposed to other flavivirus infections or vaccination were used in a comprehensive analysis to determine the sensitivity and specificity of the NS1 blockade-of-binding (BOB) assay, which was established in laboratories in five countries (Nicaragua, Brazil, Italy, United Kingdom, and Switzerland). Of 158 sera/plasma from RT-PCR-confirmed ZIKV infections, 145 (91.8%) yielded greater than 50% inhibition. Of 171 patients with primary or secondary DENV infections, 152 (88.9%) scored negative. When the control group was extended to patients infected by other flaviviruses, other viruses, or healthy donors (n= 540), the specificity was 95.9%. We also analyzed longitudinal samples from DENV-immune and DENV-naive ZIKV infections and found inhibition was achieved within 10 d postonset of illness and maintained over time. Thus, the Zika NS1 BOB assay is sensitive, specific, robust, simple, low-cost, and accessible, and can detect recent and past ZIKV infections for surveillance, seroprevalence studies, and intervention trials.

scholarly journals Immunologic testing for SARS-CoV-2 infection from the antigen perspective

2020 ◽  
pp. JCM.02160-20
Author(s):  
Dandan Li ◽  
Jinming Li
Keyword(s):  
Cross Reactivity ◽  
Diagnostic Methods ◽  
Clinical Samples ◽  
Serological Testing ◽  
S Protein ◽  
N Protein ◽  
Viral Loads ◽  
Improved Performance ◽  
Human Coronaviruses ◽  
Novel Coronavirus

Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally as a severe pandemic. SARS-CoV-2 infection stimulates antigen-specific antibody responses. Multiple serologic tests have been developed for SARS-CoV-2. However, which antigens are most suitable for serological testing remains poorly understood. Specifically, which antigens have the highest sensitivity and specificity for serological testing and which have the least cross-reactivity with other coronaviruses are currently unknown. Previous studies have shown that the S1 domain of the spike (S) protein has very low cross-reactivity between epidemic coronaviruses and common human coronaviruses, whereas the S2 domain of the S protein, and the nucleocapsid protein (N protein) show low-level cross-reactivity. Therefore, S1 is considered more specific than the native homotrimer of the S protein, and the receptor-binding domain as an antigen to test patient antibodies is more sensitive than the native N protein. In addition, an increasing number of studies have used multi-antigen protein arrays to screen serum from convalescent patients with COVID-19. Antigen combinations demonstrated improved performance as compared to each individual antigen. For rapid antigen detection, the sensitivity of the test is higher in the first week of onset of the disease with high viral loads. Highly sensitive and specific immunological diagnostic methods for antibodies or those that directly detect viral antigens in clinical samples would be beneficial for the rapid and accurate diagnosis of SARS-CoV-2 infection.

scholarly journals Cross-reactivity of SARS-CoV-2 with HIV chemiluminescent assay leading to false-positive results

2020 ◽  
pp. jclinpath-2020-206942
Author(s):  
Shaun S Tan ◽  
Ka Lip Chew ◽  
Sharon Saw ◽  
Roland Jureen ◽  
Sunil Sethi
Keyword(s):  
False Positive ◽  
Cross Reactivity ◽  
Positive Results
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