Serological inference of past primary and secondary dengue infection: implications for vaccination

Lam, Ha Minh; Phuong, Huynh Thi; Vy, Nguyen Ha Thao; Thanh, Nguyen Thi Le; Dung, Pham Ngoc; Muon, Thai Thi Ngoc; Châu, Nguyễn Văn Vĩnh; Rodríguez-Barraquer, Isabel; Cummings, Derek A. T.; Wills, Bridget; Boni, Maciej F.; Rabaa, Maia A.; Clapham, Hannah E.

doi:10.1098/rsif.2019.0207

Cited by 15 publications

(20 citation statements)

References 48 publications

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“…Furthermore, we were able to longitudinally follow the changes in the DENV infection status, based on IgG, among seronegative subjects at baseline. Also, we recognize that seropositive individuals, especially primary infections, often have a lower IgG level and could have been misclassified as seronegative [ 40 ]. Therefore, some of false negative subjects in Table 2 could be cases of primary infections, and this could have led to underestimated seropositivity, measured by IgG ELISA.…”

Section: Discussionmentioning

confidence: 99%

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015

et al. 2022

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Background To determine the seroprevalence and transmission dynamics of dengue virus (DENV), age-stratified longitudinal serological surveys were conducted in Bangphae district, Ratchaburi province, Thailand, for 3 years between April 2012 and April 2015. Methodology The surveys enrolled 2012 healthy children and adults between 1 and 55 years-of-age, and a longitudinal serosurvey of six repeated bleeds of the same cohort of individuals was conducted every 8 months for the first 2 years (M0, M8, M16) and every half a year (M24, M30, M36) for the rest of the study period. All samples were tested using in-house indirect sandwich dengue IgG ELISA to determine DENV antibody titer, and 640 paired samples which showed rising of DENV IgG titers in paired serum were further tested using in-house neutralization assay, Plaque Reduction Neutralization Test (PRNT50). Principal findings When compared against the gold standard based on the results of PRNT50, sensitivity and specificity of indirect ELISA were found to be both about 85%. The overall DENV IgG positivity determined by ELISA was 74.3% in 2012 and increased to 79.4% by the final sample collection in 2015. In our study sample, more than 98% of subjects older than 25 years were found to be seropositive. Among 518 IgG negative subjects at enrollment, the seroconversion rates were measured in paired bleeds; the rates (between successive visits, approximately 6 months) ranged between 4.8% (between M16 and M24) and 14.7% (between M0 and M8). The dominant serotype of primary DENV infection cases based on seroconversion was identified from the PRNT results and it was DENV-2. Conclusions Our study documented high levels of seroprevalence and rate of transmission. Given the importance of the serostatus and disease burden in consideration for dengue vaccine introduction, our data could be used in decision-making on implementation of various dengue control and preventive measures.

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Section: Discussionmentioning

confidence: 99%

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015

et al. 2022

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“…Serum samples used for this analysis come from a serum bank established in 2009 in southern Vietnam and maintained for the purposes of measuring exposure and seroincidence to a range of pathogens 36–42 . Every two months or every four months (depending on the site), 200 residual serum samples are collected from the haematology or biochemistry departments of ten major public hospitals: the Hospital for Tropical Diseases in Ho Chi Minh City, Hue Central Hospital in the city of Hue, Khanh Hoa General Hospital in Nha Trang, Dak Lak Provincial Hospital in Buon Ma Thuot city, Soc Trang General Hospital, Dong Thap General Hospital, Kien Giang General Hospital, Binh Dinh General Hospital, Quang Ngai General Hospital, An Giang General Hospital (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

“…Data. Serum samples used for this analysis come from a serum bank established in 2009 in southern Vietnam and maintained for the purposes of measuring exposure and seroincidence to a range of pathogens [36][37][38][39][40][41][42] Samples were tested for IgG antibodies to the HA1 region of the influenza virus haemagglutinin protein for eleven different human influenza A viruses by a protein microarray 40,43,44 , five strains of the H1 subtype and six strains of the H3 subtype (Table 1). Samples from individuals younger than six months of age were excluded from the analysis to avoid assigning maternal antibody profiles to infants.…”

Section: Methodsmentioning

confidence: 99%

Age-seroprevalence curves for the multi-strain structure of influenza A virus

Vinh

Nhat

Bruin

et al. 2021

Preprint

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The relationship between age and seroprevalence provides the simplest and least expensive approach to computing the annual attack rate of an infectious disease. However, many pathogens circulate as multiple serologically distinct strains, with no single assay able to determine seropositivity or seronegativity to an entire clade or family of co-circulating pathogens. An approach is needed to describe population exposure to an antigenically variable group of pathogens without focusing on any particular strain or serotype in the group. In this study, we focus on the two-subtype multi-strain taxonomy of human influenza A virus. We describe a data set of 24,402 general-population serum samples collected in central and southern Vietnam between 2009 to 2015, and assayed for influenza HA1 antibodies to eleven different strains of human influenza A (both H3 and H1 subtypes). We find that a principal components decomposition of the data results in the first principal component PC1 being an appropriate surrogate for seroprevalence (or composite antibody titer) which can be further decomposed for H1 and H3 contribution to the serological profile. Using this approach, we are able to provide the first ELISA-based standardized measurements of serology to reconstruct population exposure history, which correlates well with known influenza epidemiology. Annual attack rates in Vietnam are estimated at 25.6% (95% CI: 24.1% – 27.1%) for H3 and 16.0% (95% CI: 14.7% – 17.3%) for H1, with some variation in location-specific attack rates. The remaining principal components act as descriptors of influenza history and sort the population by birth year. The novel contributions of this analysis are (1) the introduction of dimensionality reduction on human antibody profiles to construct an age-seroprevalence relationship for an antigenically variable pathogen, (2) an analysis of >24,000 individuals, using >260,000 serological data points in total, allowing us to construct age-seroprevalence relationships with the precision of modern big data studies, and (3) a description of long-term attack rates in a non-vaccinated setting showing the natural history of influenza A virus in a densely-populated tropical country.

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“…We propose two main factors account for this difference. Age patterns of reporting post-primary infections might be influenced by spatio-temporal imbalances in immune status reporting, observed in this study and previously in Vietnam [ 32 ] and Taiwan [ 33 ]. In high transmission settings, where a higher proportion of the post-primary reporting population include tertiary/quaternary infections, the mean age would be higher than an equally high transmission setting where most of the post-primary infections were secondary infections.…”

Section: Discussionmentioning

confidence: 50%

Estimating the annual dengue force of infection from the age of reporting primary infections across urban centres in endemic countries

Biggs

Sherratt

et al. 2021

BMC Med

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Background Stratifying dengue risk within endemic countries is crucial for allocating limited control interventions. Current methods of monitoring dengue transmission intensity rely on potentially inaccurate incidence estimates. We investigated whether incidence or alternate metrics obtained from standard, or laboratory, surveillance operations represent accurate surrogate indicators of the burden of dengue and can be used to monitor the force of infection (FOI) across urban centres. Methods Among those who reported and resided in 13 cities across the Philippines, we collected epidemiological data from all dengue case reports between 2014 and 2017 (N 80,043) and additional laboratory data from a cross-section of sampled case reports (N 11,906) between 2014 and 2018. At the city level, we estimated the aggregated annual FOI from age-accumulated IgG among the non-dengue reporting population using catalytic modelling. We compared city-aggregated FOI estimates to aggregated incidence and the mean age of clinically and laboratory diagnosed dengue cases using Pearson’s Correlation coefficient and generated predicted FOI estimates using regression modelling. Results We observed spatial heterogeneity in the dengue average annual FOI across sampled cities, ranging from 0.054 [0.036–0.081] to 0.249 [0.223–0.279]. Compared to FOI estimates, the mean age of primary dengue infections had the strongest association (ρ −0.848, p value<0.001) followed by the mean age of those reporting with warning signs (ρ −0.642, p value 0.018). Using regression modelling, we estimated the predicted annual dengue FOI across urban centres from the age of those reporting with primary infections and revealed prominent spatio-temporal heterogeneity in transmission intensity. Conclusions We show the mean age of those reporting with their first dengue infection or those reporting with warning signs of dengue represent superior indicators of the dengue FOI compared to crude incidence across urban centres. Our work provides a framework for national dengue surveillance to routinely monitor transmission and target control interventions to populations most in need.

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Serological inference of past primary and secondary dengue infection: implications for vaccination

Cited by 15 publications

References 48 publications

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015

Dengue virus seroprevalence study in Bangphae district, Ratchaburi, Thailand: A cohort study in 2012-2015

Age-seroprevalence curves for the multi-strain structure of influenza A virus

Estimating the annual dengue force of infection from the age of reporting primary infections across urban centres in endemic countries

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