Two Cases of False-Positive Dengue Non-Structural Protein 1 (NS1) Antigen in Patients with Hematological Malignancies and a Review of the Literature on the Use of NS1 for the Detection of Dengue Infection

Abstract: Early diagnosis of dengue fever and COVID-19 is made very easy due to technological advancements. The non-structural protein 1 antigen test strips are widely used in various regions; however, false-positive events have begun to be reported in the dengue-endemic areas with the COVID-19 pandemic, even though statistically non-structural protein 1 antigens are very specific to dengue infection. We reported a case of the false-positive non-structural protein 1 test in a patient with COVID-19 infection.

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Trend of Dengue Virus Infection with Seasonal Variation at HIMS, Varanasi, Uttar Pradesh, India

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/50602.15239 ◽

2021 ◽

Author(s):

Hari Om Trivedi ◽

Asim Kumar Singh ◽

Mukesh Kumar Singh

Keyword(s):

Platelet Count ◽

Seasonal Variation ◽

Dengue Virus ◽

Dengue Infection ◽

Uttar Pradesh ◽

Febrile Illness ◽

Cerebral Hypoperfusion ◽

Structural Protein ◽

Igg Antibody ◽

Ns1 Antigen

Introduction: Dengue is the most common mosquito borne arboviral infection in India, and it has become endemic in India with consistent episodes. Dengue is an acute febrile illness caused by Dengue Virus (DENV-1, DENV-2, DENV-3, DENV-4), an arthropod of family Flaviviridae, transmitted through the bite of female Aedes aegypti mosquitoes. Although, dengue is more prevalent in humans but also it may sometimes be seen in monkeys. The only animals to be affected when bitten by a mosquito, infected with dengue fever are monkeys other animals do not carry or spread dengue. Patient presents with hyperthermia, headache, severe joint and muscle pain, fatigue and skin rashes. Neurological manifestation in sever dengue results from multiorgan dysfunction due to cerebral edema, haemorrhage due to vascular leak, cerebral hypoperfusion, and electrolyte disturbances. Aim: To study serological markers with association of platelet count and trend of DENV infection with seasonal variation. Materials and Methods: The present retrospective study was conducted for a period of two years in Heritage Institute of Medical Sciences (HIMS), Varanasi, Uttar Pradesh, India, from January 2017 to December 2018. Blood samples were collected for 2140 suspected dengue patients. Out of the serologically positive cases, serological confirmation and platelet count was done for dengue infection. Data was presented as percentages. Results: Total 2140 suspected cases were admitted and out of them 199 (9.3%) were found to be seropositive for dengue infection. Non structural protein 1 (NS1) positive cases out of which total seropositive cases were reported to be 127 (63.81%) and 147 (73.86%) cases were positive for NS1 antigen either alone or along with antibody. Out of the total 199 positive cases thrombocytopenia was observed in 126 (63.31%) cases. Positive cases which were under 15 years of age were reported to be 92 (46.23%). Conclusion: The study concludes that NS1 antigen and IgM- IgG antibody consideration in the diagnosis of dengue infection builds the opportunity of early diagnosis so as to keep away the complications significantly.

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Hematological malignancies mimicking rheumatic syndromes: case series and review of the literature

Rheumatology International ◽

10.1007/s00296-018-4107-0 ◽

2018 ◽

Vol 38 (9) ◽

pp. 1743-1749 ◽

Cited By ~ 4

Author(s):

Gil Bornstein ◽

Nadav Furie ◽

Nimrod Perel ◽

Ilan Ben-Zvi ◽

Chagai Grossman

Keyword(s):

Hematological Malignancies ◽

Case Series ◽

Review Of The Literature

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FALSE-NEGATIVE DENGUE CASES IN RORAIMA, BRAZIL: AN APPROACH REGARDING THE HIGH NUMBER OF NEGATIVE RESULTS BY NS1 AG KITS

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652014000500014 ◽

2014 ◽

Vol 56 (5) ◽

pp. 447-450 ◽

Cited By ~ 7

Author(s):

Pablo O. A. Acosta ◽

Fabiana Granja ◽

Cátia A. Meneses ◽

Ismael A. S. Nascimento ◽

Débora D. Sousa ◽

...

Keyword(s):

Health Care Providers ◽

Secondary Infection ◽

Dengue Infection ◽

False Negative ◽

Laboratory Data ◽

Detection Methods ◽

Lower Sensitivity ◽

Care Providers ◽

Qrt Pcr ◽

Ns1 Antigen

Serum samples from 150 NS1-negative (Platelia ELISA) patients presumptively diagnosed with dengue were analyzed by the TaqMan probed real-time reverse transcription PCR (TaqMan qRT-PCR) method. The qRT-PCR positive samples were tested for serotype by semi-nested RT-PCR and a qualitative immunochromatographic assay for IgG and IgM. Molecular detection methods showed 33 (22%) positive samples out of 150 NS1-antigen negative samples. Of these, 72% were collected up to day 2 after the onset of symptoms, when diagnostic sensitivity of NS1-antigen test assays is significantly enhanced. Most of the cases were not characterized as secondary infection. Twenty-eight samples were successfully serotyped, 75% of which for DENV-4, 14% for DENV-2, 7% for DENV-3 and 4% for DENV-1. These findings reaffirm the hyperendemic situation of the state of Roraima and suggest a lower sensitivity of the NS1 test, mainly when DENV-4 is the predominant serotype. Health care providers should therefore be aware of samples tested negative by NS1 antigen assays, especially when clinical symptoms and other laboratory data results show evidence of dengue infection.

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Comparison of Seven Commercial Antigen and Antibody Enzyme-Linked Immunosorbent Assays for Detection of Acute Dengue Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.05717-11 ◽

2012 ◽

Vol 19 (5) ◽

pp. 804-810 ◽

Cited By ~ 76

Author(s):

Stuart D. Blacksell ◽

Richard G. Jarman ◽

Robert V. Gibbons ◽

Ampai Tanganuchitcharnchai ◽

Mammen P. Mammen ◽

...

Keyword(s):

South Korea ◽

Dengue Virus ◽

Dengue Infection ◽

Virus Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

Capture Elisa ◽

Igm Antibody ◽

Antigen Elisa ◽

Ns1 Antigen ◽

Elisa Format

ABSTRACTSeven commercial assays were evaluated to determine their suitability for the diagnosis of acute dengue infection: (i) the Panbio dengue virus Pan-E NS1 early enzyme-linked immunosorbent assay (ELISA), second generation (Alere, Australia); (ii) the Panbio dengue virus IgM capture ELISA (Alere, Australia); (iii) the Panbio dengue virus IgG capture ELISA (Alere, Australia); (iv) the Standard Diagnostics dengue virus NS1 antigen ELISA (Standard Diagnostics, South Korea); (v) the Standard Diagnostics dengue virus IgM ELISA (Standard Diagnostics, South Korea); (vi) the Standard Diagnostics dengue virus IgG ELISA (Standard Diagnostics, South Korea); and (vii) the Platelia NS1 antigen ELISA (Bio-Rad, France). Samples from 239 Thai patients confirmed to be dengue virus positive and 98 Sri Lankan patients negative for dengue virus infection were tested. The sensitivities and specificities of the NS1 antigen ELISAs ranged from 45 to 57% and 93 to 100% and those of the IgM antibody ELISAs ranged from 85 to 89% and 88 to 100%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics ELISAs gave the best compromise between sensitivity and specificity (87 and 96%, respectively), as well as providing the best sensitivity for patients presenting at different times after fever onset. The Panbio IgG capture ELISA correctly classified 67% of secondary dengue infection cases. This study provides strong evidence of the value of combining dengue virus antigen- and antibody-based test results in the ELISA format for the diagnosis of acute dengue infection.

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Tick-Borne Encephalitis Virus Vaccines Contain Non-Structural Protein 1 Antigen and May Elicit NS1-Specific Antibody Responses in Vaccinated Individuals

Vaccines ◽

10.3390/vaccines8010081 ◽

2020 ◽

Vol 8 (1) ◽

pp. 81 ◽

Cited By ~ 5

Author(s):

Jiri Salat ◽

Kamil Mikulasek ◽

Osmany Larralde ◽

Petra Pokorna Formanova ◽

Ales Chrdle ◽

...

Keyword(s):

Viral Envelope ◽

Structural Protein ◽

Specific Antibodies ◽

Virus Challenge ◽

Ms Analysis ◽

Tick Borne Encephalitis ◽

Ns1 Antigen ◽

The Mean ◽

Tick Borne Encephalitis Virus ◽

Viral Surface

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, namely FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific Western blot analysis also detected anti-NS1 antibodies in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

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NS-1 antigen positive Dengue Infection and molecular characterization of Dengue Viruses in a private Medical College Hospitalin Dhaka, Bangladesh

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v17i4.38334 ◽

2018 ◽

Vol 17 (4) ◽

pp. 669-673

Author(s):

Mahmuda Siddiqua ◽

Ahmed Nawsher Alam ◽

AKM Muraduzzaman ◽

Tahmina Shirin

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Dengue Infection ◽

Medical Science ◽

Cost Effective ◽

Rt Pcr ◽

Dengue Virus Infection ◽

Medical College ◽

Virus Serotype ◽

Ns1 Antigen

Introduction: Detection of dengue virus infection as soon as possible is critical for management of dengue virus infected patients. Immuno-chromatographic (ICT) tests are easy, cost effective method for dengue virus antigen detection.The sensitivity and specificity of ICT should compare with a gold standard test like RT-PCR. Aim of this study was to compare two test methods (ICT and RT-PCR), observe dengue serotype and seasonal impact on dengue infection.Methodology & result: The patients of Ibn Sina Medical College Hospital from October 2015 to October 2017 were tested for dengue NS1 antigen by ICT method. Out of 3201 sample tested 32.39% were found positive and 89 of which were re-tested for RT-PCR for comparison. Eighty eight of 89 NS1 positive cases showed positive by RT-PCR method giving an accuracy of 98.87%. Among the RT-PCR positive cases 45 were further analyzed for serotype. DEN-1, DEN-2 or both DEN- 1 and DEN-2 were found in 21, 23 and 1cases respectively. No cases of DEN-3 or DEN-4 were detected.Conclusion: This study showed that easily available and cost effective dengue NS1 antigen detection method (ICT) is as effective as molecular test (RT-PCR). DEN-1 and DEN-2 serotype were prevalent during last few years in Bangladesh. Continuous monitoring of dengue virus serotype is important for prevention and control of sudden epidemic by other serotype. Alert to be more during post monsoon when the peak of dengue virus infection was observed.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.669-673

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Incidence and Pattern of Clinical Dengue Cases among Travelers and NonTravelers in a District of Bangladesh

Bangladesh Journal of Infectious Diseases ◽

10.3329/bjid.v7i1.48669 ◽

2020 ◽

Vol 7 (1) ◽

pp. 3-7

Author(s):

Syed Abdul Kader ◽

Sonia Afrin Rob

Keyword(s):

Endemic Area ◽

Dengue Infection ◽

Laboratory Data ◽

Data Entry ◽

Cross Sectional Study ◽

P Value ◽

College Hospital ◽

Cross Sectional ◽

Test Kit ◽

Ns1 Antigen

Background: Expansion of Dengue fever caused by a mosquito borne arbovirus to new countries and, from urban to rural settings constitutes an important health problem in the world including Bangladesh. Objective: This study was conducted to evaluate spread of clinical Dengue to previously non-endemic Barisal district and get an idea of how recent this spread is by comparing proportions of non-travelers and travelers to an endemic area among the admitted patients. Methodology: The incidence of dengue infection in Barisal division with and without travel history to known endemic area was investigated in the current cross sectional study from a conveniently selected sample of patients admitted to the medicine department of Sher-e-Bangla medical College Hospital form Barisal district from July 15, through August, to September 15, 2019. Clinical and laboratory data were collected by attending doctors and checked by investigators. The primary diagnostic tool was NS1 antigen detected by SD Bioline Dengue NS1 Ag Test Kit. Data entry and analysis was done by SPSS version 24.0 software. Result: A total number of sample size was 212 admitted patents of whom 138(65.1%) were male, 74 (34.9 %) were female,116 (54.7%) of patients traveled to a known endemic zone, 96 (45.3%) did not; 206 (97.2%) were NS1 positive, 4 (1.9%) were IgM positive, 2 (0.9%) were IgM positive and IgG positive; Of travelling 116 patients, 92(79.3%) were male, 24(20.7%) were female, of travelling 96 patients 46(47.9%) were male, 50(52.1%) were female. p-value was <0.001. Conclusion: The study concluded that Dengue is becoming endemic in previously non-endemic zones like greater Barisal, though travelers still holds the major share of disease burden. Male preponderance in traveling to endemic zone was statistically significant. Bangladesh Journal of Infectious Diseases 2020;7(1):3-7

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Evaluation of Six Commercial Point-of-Care Tests for Diagnosis of Acute Dengue Infections: the Need for Combining NS1 Antigen and IgM/IgG Antibody Detection To Achieve Acceptable Levels of Accuracy

Clinical and Vaccine Immunology ◽

10.1128/cvi.05285-11 ◽

2011 ◽

Vol 18 (12) ◽

pp. 2095-2101 ◽

Cited By ~ 102

Author(s):

Stuart D. Blacksell ◽

Richard G. Jarman ◽

Mark S. Bailey ◽

Ampai Tanganuchitcharnchai ◽

Kemajittra Jenjaroen ◽

...

Keyword(s):

Dengue Fever ◽

Sensitivity And Specificity ◽

Dengue Infection ◽

Antibody Test ◽

Antibody Detection ◽

Sample Collection ◽

Igg Antibody ◽

Igm Antibody ◽

Ns1 Antigen ◽

Antibody Tests

ABSTRACTSix assays were evaluated in this study to determine their suitability for the diagnosis of acute dengue infection using samples from 259 Sri Lankan patients with acute fevers (99 confirmed dengue cases and 160 patients with other confirmed acute febrile illnesses): (i) the Merlin dengue fever IgG & IgM combo device (Merlin), (ii) the Standard Diagnostics Dengue Duo nonstructural 1 (NS1) antigen and IgG/IgM combo device (Standard Diagnostics, South Korea), (iii) the Biosynex Immunoquick dengue fever IgG and IgM (Biosynex, France) assay, (iv) the Bio-Rad NS1 antigen strip (Bio-Rad, France), (v) the Panbio Dengue Duo IgG/IgM Cassette (Inverness, Australia), and (vi) the Panbio dengue NS1 antigen strip (Inverness, Australia). The median number of days of fever prior to admission sample collection was 5 days (interquartile range, 3 to 7 days). Sensitivity and specificity of the NS1 antigen tests ranged from 49 to 59% and from 93 to 99%, respectively, and sensitivity and sensitivity of the IgM antibody test ranged from 71 to 80% and from 46 to 90%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics Dengue Duo test gave the best compromise of sensitivity and specificity (93% and 89%, respectively) and provided the best sensitivity in patients presenting at different times after fever onset. The Merlin IgM/IgG antibody tests correctly classified 64% and 86% of the primary and secondary dengue infection cases, respectively, and the Standard Diagnostics IgM/IgG antibody tests correctly classified 71% and 83% of the primary and secondary dengue infection cases, respectively. This study provides strong evidence of the value of combining dengue antigen- and antibody-based test results in the rapid diagnostic test (RDT) format for the acute diagnosis of dengue.

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