Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission

Medina, Freddy A.; Vila, Frances; Premkumar, Lakshmanane; Lorenzi, Olga; Paz–Bailey, Gabriela; Alvarado, Luisa I.; Rivera‐Amill, Vanessa; Silva, Aravinda M. de; Waterman, Steve; Muñoz‐Jordán, Jorge L.

doi:10.4269/ajtmh.20-1651

Cited by 8 publications

(12 citation statements)

References 31 publications

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“…22,43 The IgM-NS1 ZIKV/DENV ratio improved the discrimination of recent ZIKV infection from DENV infection, possibly because it reduces the effect of cross-reactivity, as previously suggested. 19,32 This may be useful in cocirculation areas, especially in the differentiation of double-positive IgM cases for ZIKV and DENV, although the usefulness of NS1-based IgM assays is still controversial in endemic areas. Previous exposure to orthoflaviviruses affects the detection of IgM-NS1 antibodies, especially for ZIKV infection, possibly because the presence of cross-reactive IgG antibodies displaces the initial IgM response against the infecting orthoflavivirus.…”

Section: Discussionmentioning

confidence: 99%

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NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas

Castro-Trujillo,

Segura,

Bolívar-Marín

et al. 2023

Pediatric Infectious Disease Journal

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Background: Infections by dengue virus (DENV) and Zika virus (ZIKV) have some similar symptoms and a cross-reactive immune response, although with different risk populations and outcomes. Here, we evaluated the virological characteristics and the nonstructural protein 1 (NS1)-specific antibody responses to DENV and ZIKV in children suspected of dengue in different epidemiological moments in Colombia. Methods: Viral RNA, circulating NS1 and IgM/IgG specific for DENV and ZIKV were performed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) in 301 children suspected of dengue enrolled in a hospital setting during the ZIKV epidemic and a primary healthcare setting during a DENV epidemic. For the detection of DENV and ZIKV-specific IgM, an NS1-based ELISA was validated using characterized pediatric samples. Clinical and laboratory parameters were also evaluated. Results: DENV RNA or NS1 antigen was detected in the plasma of 62% of children, and in none, the ZIKV RNA was found. NS1-based ELISA for DENV and ZIKV IgM showed a sensitivity/specificity of 90/84% and 73/98%, respectively. Of 114 children without detectable viremia or antigenemia, 30.7%, 17.5%, 22% and 30% were IgM-DENV+, IgM-ZIKV+, IgM-DENV+ZIKV+ and IgM-DENV-ZIKV-, respectively. The ZIKV/DENV IgM-NS1 ratio allows the identification of the infecting ortho flavivirus in 88% of the children with IgM-DENV+ZIKV+, confirming a high predominance of DENV infections in the 2 pediatric settings. Conclusion: Overall, 88% of the children with clinical suspicion of dengue had an identifiable ortho flaviviral infection, with 80% caused by DENV, 7% by ZIKV and 0.7% classified as recent infections or coinfection, demonstrating active viral cocirculation in the pediatric population of southern Colombia. The IgM-NS1 detection improved the identification of ortho flaviviral infections in children without viremia or antigenemia, suggesting it is a helpful complementary tool for medical personnel in tropical regions with high viral cocirculation and different clinical scenes.

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Section: Discussionmentioning

confidence: 99%

“…The IgM-ZIKV/IgM-DENV ratio was evaluated by dividing the absolute optical density (OD) at 450 nm found for the IgM response of NS1 ZIKV by the OD 450 nm of the IgM for NS1 DENV in each patient. 32…”

Section: Validation Of Thementioning

confidence: 99%

NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas

Castro-Trujillo,

Segura,

Bolívar-Marín

et al. 2023

Pediatric Infectious Disease Journal

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“…Early convalescent specimens were retrospectively obtained from the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS), as described previously (12, 13). Samples to evaluate test performance for previous dengue infections were retrospectively obtained from the Communities Organized to Prevent Arboviruses (COPA) project in Puerto Rico that conducts annual serosurveys among participants 1-50 years of age.…”

Section: Methodsmentioning

confidence: 99%

“…Early convalescent specimens were retrospectively obtained from the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS), as described previously (12,13).…”

Section: Participant Enrollment and Ethics Statementmentioning

confidence: 99%

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Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination

Medina,

Vila,

Adams

et al. 2024

Preprint

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The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for 7 tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the 5 best performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9-16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the 4 best performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards.Of seven tests, five showed ≥75% sensitivity detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to Zika virus. For the detection of previous DENV infections the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation.

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Dengue: A review of laboratory diagnostics in the vaccine age

Frazer,

Norton

2024

Journal of Medical Microbiology

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Background. Dengue is an important arboviral infection of considerable public health significance. It occurs in a wide global belt within a variety of tropical regions. The timely laboratory diagnosis of Dengue infection is critical to inform both clinical management and an appropriate public health response. Vaccination against Dengue virus is being introduced in some areas. Discussion. Appropriate diagnostic strategies will vary between laboratories depending on the available resources and skills. Diagnostic methods available include viral culture, the serological detection of Dengue-specific antibodies in using enzyme immunoassays (EIAs), microsphere immunoassays, haemagglutination inhibition or in lateral flow point of care tests. The results of antibody tests may be influenced by prior vaccination and exposure to other flaviviruses. The detection of non-structural protein 1 in serum (NS1) has improved the early diagnosis of Dengue and is available in point-of-care assays in addition to EIAs. Direct detection of viral RNA from blood by PCR is more sensitive than NS1 antigen detection but requires molecular skills and resources. An increasing variety of isothermal nucleic acid detection methods are in development. Timing of specimen collection and choice of test is critical to optimize diagnostic accuracy. Metagenomics and the direct detection by sequencing of viral RNA from blood offers the ability to rapidly type isolates for epidemiologic purposes. Conclusion. The impact of vaccination on immune response must be recognized as it will impact test interpretation and diagnostic algorithms.

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Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission

Cited by 8 publications

References 31 publications

NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas

NS1-Specific Antibody Response Facilitates the Identification of Children With Dengue and Zika in Hyperendemic Areas

Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination

Dengue: A review of laboratory diagnostics in the vaccine age

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