Distinguishing Secondary Dengue Virus Infection From Zika Virus Infection With Previous Dengue by a Combination of 3 Simple Serological Tests (original) (raw)
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Comprehensive Evaluation of Differential Serodiagnosis between Zika and Dengue Viral Infections
Journal of Clinical Microbiology, 2018
Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to mitigate potential severe health outcomes.
Title: Rapid Antigen Tests for Dengue Virus Serotypes and Zika Virus in Patient Serum 2 3
The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed 62 to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections 63 during pregnancy correlate with severe defects, including microcephaly and neurological disorders. Because 64 ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross reactions 65 and false results in molecular, antigenic, and serologic diagnostics. We report here the characterization of 66 monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically 67 detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes and ZIKV 68 without cross reaction. To complement visual test analysis and remove user subjectivity in reading test results, 69 image processing and data analysis were used for data capture and test result quantification, generating 70 standardized objective data. Using a 30 l serum sample, the sensitivity and specificity values of the DENV 71 serotypes 1-4 tests and the pan DENV test (detects all four dengue serotypes) ranged from 0.76 to 1.00. 72 Similarly, sensitivity/specificity for the ZIKV rapid test was 0.81/0.86 using a 150 l serum input. Serum ZIKV 73 NS1 protein concentrations were approximately tenfold lower than corresponding DENV NS1 levels in infected 74 patients; moreover, ZIKV NS1 protein was not detected in PCR-positive patient urine samples. These new 75 approaches and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV 76 cases; moreover, the approach platform can be applied toward developing rapid antigen diagnostics for 77 emerging viruses.
The American Journal of Tropical Medicine and Hygiene
Zika virus (ZIKV) serological diagnostics are compromised in areas where dengue viruses (DENV) cocirculate because of their high levels of protein sequence homology. Here, we describe the characterization of a Zika blockade-of-binding ELISA (Zika BOB) and a Zika microneutralization assay (Zika MN) for the detection of ZIKV nonstructural protein 1 (NS1)-specific antibodies and ZIKV neutralizing antibodies, respectively. Zika BOB and Zika MN cutoffs were established as 10 and 100 endpoint titers, respectively, using samples collected pre-and post-virologically confirmed ZIKV infection from subjects living in DENV-endemic areas. Specificity of the assays was equally high, whereas sensitivity of Zika BOB was lower than that of Zika MN, especially in samples collected > 6 months post-infection. Immunosurveillance analysis, using combined results from both Zika BOB and Zika MN, carried out also in DENVendemic regions in Colombia, Honduras, Mexico, and Puerto Rico before (2013-2014) and after (2017-2018) ZIKV introduction in the Americas suggests unapparent ZIKV seroprevalence rates ranged from 25% to 80% over the specified period of time in the regions investigated.
Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum
Science Translational Medicine
The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-ml serum sample, the sensitivity and specificity values of the DENV1-4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-ml serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reactionpositive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.
Pakistan Journal of Medical Sciences
Objective: To detect ZIKV using reverse transcription-polymerase chain reaction (RT-PCR) among clinical samples tested negative for Dengue virus (DENV) by RT-PCR in Punjab, 2016. Methods: A descriptive cross-sectional study was carried out for duration of two months. Total of 506 samples were collected within seven days from onset of illness from all over hospitals of Punjab, Pakistan of which 350 were selected simply randomly to test for presence of ZIKV by using “Trioplex Real-Time RT-PCR Assay (Trioplex)”. Cohen’s kappa coefficient (κ) and 95% confidence interval (CI) were used to assess the degree of concordance between DENV positive results of non-structural protein 1 (NS1) and IgM solid-phase enzyme immunoassay (ELISA). Results: No samples were positive for any ZIKV, DENV or Chikungunya virus (CHIKV) by Trioplex. Among the 350 samples, 26 samples were positive concordant and the degree of concordance between NS1- and IgM-ELISA was 13% and κ coefficient was -0.71 (95% CI -0.79,...
Eurosurveillance, 2016
Serological diagnosis of Zika virus (ZIKV) infections is challenging due to high cross-reactivity between flaviviruses. We evaluated the diagnostic performance of a novel anti-ZIKV ELISA based on recombinant ZIKV non-structural protein 1 (NS1). Assay sensitivity was examined using sera from 27 patients with reverse transcription (RT)-PCR-confirmed and 85 with suspected ZIKV infection. Specificity was analysed using sera from 1,015 healthy individuals. Samples from 252 patients with dengue virus (n = 93), West Nile virus (n = 34), Japanese encephalitis virus (n = 25), chikungunya virus (n = 19) or Plasmodium spp. (n = 69) infections and from 12 yellow fever-vaccinated individuals were also examined. In confirmed ZIKV specimens collected ≥ 6 days after symptom onset, ELISA sensitivity was 58.8% (95% confidence interval (CI): 36.0–78.4) for IgM, 88.2% (95% CI: 64.4–98.0) for IgG, and 100% (95% CI: 78.4–100) for IgM/IgG, at 99.8% (95% CI: 99.2–100) specificity. Cross-reactivity with hig...
The American Journal of Tropical Medicine and Hygiene
Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DP...
Clinical and Laboratory Profile of Zika Virus Infection in Dengue Suspected Patients: A case series
Journal of Clinical Virology, 2016
Background: The Zika virus (ZIKV) is an emerging arthropod-borne virus related to the dengue virus (DENV), and shows a similar clinical profile as other arboviral diseases, such as dengue and chikungunya virus (CHIKV). Historically, ZIKV has been associated with sporadic cases of human infection, but is now responsible for outbreaks worldwide. In Brazil, cases have been reported since 2015, with some cases causing severe disease. Objective: To identify clinical symptoms of Zika in patients in Dengue suspected patients. Study design: Description of a series of cases, wherein we analyzed 100 clinical samples collected from patients who exhibited acute febrile disease for ≤5 days, from January to February 2016. Results: In this study, we report 13 cases of ZIKV infection in adults presenting dengue-like symptoms in a DENV endemic area. All patients presented with fever, with myalgia being the second most frequently observed symptom. Two patients had rashes, but none of them had conjunctivitis. Other less frequent manifestations included headache, arthralgia, diarrhea, and nausea. Conclusion: The co-circulation of ZIKV and DENV is a serious public health concern, since it represents both a clinical and diagnostic challenge in endemic areas, as well as in the field of travel medicine.