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Performance Evaluation of a Dengue IgG Rapid Diagnostic Test Designed to Determine Dengue Serostatus as Part of Prevaccination Screening.

ABSTRACT: The World Health Organization has recommended prevaccination screening for prior dengue infection as the preferred approach prior to vaccination with the dengue vaccine CYD-TDV. These screening tests need to be highly specific and sensitive, and deliverable at the point-of-care. We evaluate here the sensitivity and specificity of the newly developed OnSite Dengue IgG rapid diagnostic test (RDT). A retrospective double-blind study of the sensitivity and specificity of the OnSite Dengue IgG RDT was performed using a sample panel consisting of archived serum specimens collected during CYD-TDV clinical trials in Latin American and Asia, with the reference serostatus for each sample determined by an algorithm using measured dengue PRNT₉₀, PRNT₅₀, and NS1 IgG ELISA. An additional panel of dengue seronegative samples positive for other flaviviruses and infections was used to assess cross-reactivity. Samples were included from 579 participants; 346 in the specificity panel and 233 in the sensitivity panel. The OnSite dengue IgG RDT exhibited a specificity of 98.0% (95% CI = 95.9 to 99.2) and sensitivity of 95.3% (95% CI = 91.7 to 97.6). The sensitivity for samples exhibiting a multitypic immune profile (PRNT₉₀-positive to >1 dengue serotype) was 98.8% while for monotypic immune samples (PRNT₉₀-positive to a single dengue serotype) it was 88.1%. The OnSite dengue IgG RDT showed minimal to no cross-reactivity to related flaviviruses. These findings support the use of the OnSite dengue IgG RDT to determine dengue serostatus in CYD-TDV prevaccination screening. IMPORTANCE Dengue remains a significant public health issue, with over 5.2 million cases reported to the World Health Organization (WHO) in 2019. The tetravalent dengue vaccine (CYD-TDV) is currently licensed for use in those aged ≥9 years; however, vaccinees with no previous exposure to dengue experience an increased risk of hospitalized and severe dengue upon subsequent heterotypic infection. Consequently, WHO recommends screening for prior dengue infection before vaccination. Screening tests for previous infection need to be highly specific and sensitive, and deliverable at the point-of-care. High sensitivity ensures that the largest number of individuals with previous infection can be identified and vaccinated, while high specificity prevents the inadvertent vaccination of those without previous infection. This study of the OnSite Dengue IgG Rapid Test, which was explicitly developed to meet this need, found that it had both high specificity (98.0% [95% CI = 95.9 to 99.2]) and sensitivity (95.3% [95% CI = 91.7 to 97.6]).

SUBMITTER: Liberal V

PROVIDER: S-EPMC9241662 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDetection of dengue virus antibodies is important for understanding future dengue virus risk and for prevaccination screening. We aimed to evaluate the performance of a dengue IgG indirect ELISA in determining dengue seroprevalence in a cohort of children in the Philippines, using a focus reduction neutralisation test (FRNT) as the reference test.MethodsIn this prospective population-based cohort study, we enrolled healthy children residing in Bogo or Balamban, Cebu, Philippines, who were to be aged 9-14 years at the time of a mass dengue vaccination campaign. Sera were collected from participants and batch tested by indirect IgG ELISA and FRNT. The primary endpoint was dengue seroprevalence in the cohort, detected by ELISA, and validated by that detected by reference FRNT. This study is registered with ClinicalTrials.gov, NCT03465254.FindingsWe collected 2996 serum samples between May 2, and June 2, 2017, and we tested each sample with IgG ELISA. Using 1961 samples (65·5%) that were tested with FRNT, and 1035 samples (34·5%) with imputed results, we found that 320 (10·7%) of 2996 children were dengue naive and 2676 (89·3%) were seropositive for previous dengue virus infection. Based on the 1961 non-imputed FRNT results classified as dengue seronegative or seropositive, the ELISA (with a 0·9 index value cutoff) showed 95·2% sensitivity, 93·4% specificity, 6·6% false positivity, and 4·8% false negativity. However, sensitivity of the ELISA was poor (77·1%) among children with immunity to just one dengue virus serotype. Of the 11 sera that were false positive with ELISA, seven samples (63·6%) were seropositive for Zika virus or Japanese encephalitis virus with FRNT.InterpretationMost children (89·3%) assessed in our study and eligible to participate in the mass dengue vaccination campaign were seropositive for previous dengue virus infection. Compared with FRNT, ELISA had high sensitivity and specificity (>90%), but the false-negative and false-positive rates makes the test suboptimal for prevaccination screening. Individuals who are falsely identified as seropositive by dengue IgG ELISA and then vaccinated might be at risk of developing severe disease during a subsequent exposure to wild-type dengue virus. Those with a monotypic profile would benefit the most from vaccination, but the sensitivity of the IgG ELISA was much lower in this group than in those with a multitypic profile.FundingPhilippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency through the International Vaccine Institute, and University of North Carolina, Chapel Hill, NC, USA.

Project description:Importance:Recent studies have reported a higher relapse rate following an initial inflammatory demyelinating disorder in pediatric patients with persistent seropositivity of antibodies targeting myelin oligodendrocyte glycoprotein (MOG-IgG1). To date, the clinical implications of longitudinal MOG-IgG1 seropositivity using live cell assays with IgG1 secondary antibodies in adults after acute disseminated encephalomyelitis (ADEM) are unknown. Objective:To determine whether MOG-IgG1 serostatus (transient vs persistent) and titer change over time provide clinical utility in predicting the likelihood of relapse after ADEM. Design, Setting, and Participants:This cohort study identified patients with an initial diagnosis of ADEM evaluated at a single referral center between January 1, 1990, and October 1, 2017. Fifty-one patients were included, including 31 children and 20 adults. Longitudinal serologic testing was performed detecting autoantibodies targeting aquaporin 4 (AQP4-IgG) and MOG-IgG1 with clinically validated fluorescence-activated cell sorting assays. Patients were divided into 3 cohorts: persistent seropositivity, transient seropositivity, and seronegativity. Main Outcomes and Measures:Clinical demographic characteristics, longitudinal AQP4-IgG and MOG-IgG1 serostatus, titers, relapses, use of immunotherapy, and Expanded Disability Status Scale score at follow-up. Results:Of 51 patients presenting with an initial diagnosis of ADEM, 20 (39%) were adult, 24 (47%) were female, and ages ranged from 12 months to 57 years. Seventeen patients fulfilled criteria for persistent seropositivity; of those, 8 of 9 children (89%) and 7 of 8 adults (88%) had at least 1 relapse after median (range) follow-up periods of 75 (15-236) months and 39 (9-161) months, respectively. Eight patients (16%), including 4 adults, fulfilled criteria for transient seropositivity; of those, no children and 1 of 4 adults (25%) relapsed after median (range) follow-up periods of 32 (24-114) months and 16 (13-27) months, respectively. Of 24 patients with AQP4-IgG and MOG-IgG seronegativity, 6 of 17 children (35%) and 2 of 7 adults (29%) had at least 1 relapse after median (range) follow-up periods of 36 (3-203) months and 34 (15-217) months, respectively. There were only 2 patients, including 1 adult, with AQP4-IgG seropositivity, and both relapsed. The hazard ratio for relapses in those with persistent MOG-IgG1 positivity compared with AQP4-IgG and MOG-IgG1 seronegativity was 3.1 (95% CI, 1.1-8.9; P?=?.04) in children and 5.5 (95% CI, 1.4-22.5; P?=?.02) in adults. Immunotherapy was used in 5 of 9 children (56%) and 6 of 8 adults (75%) with persistent seropositivity and in 3 of 17 children (18%) and 1 of 7 adults (14%) with AQP4-IgG and MOG-IgG seronegativity. Conclusions and Relevance:Relapse occurred in 15 of 17 patients (88%) with persistent MOG-IgG1 seropositivity after ADEM; only 1 patient with transient seropositivity experienced relapse. Our data extend the clinical utility of MOG-IgG1 serological testing to adult patients and highlights that longitudinal serologic evaluation of MOG-IgG1 could help predict disease course and consideration of immunotherapy.

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Performance Evaluation of a Dengue IgG Rapid Diagnostic Test Designed to Determine Dengue Serostatus as Part of Prevaccination Screening.

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