Symptomatic Dengue in Children in 10 Asian and Latin American Countries

L’Azou, Maïna; Moureau, Annick; Sarti, Elsa; Nealon, Joshua; Zambrano, Betzana; Wartel, T. Anh; Villar, Luis; Capeding, María Rosario; Ochiai, R. Leon

doi:10.1056/nejmoa1503877

Cited by 125 publications

(109 citation statements)

References 32 publications

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“…Our results also show higher levels of dengue virus exposure than those reported in other dengue endemic countries such as Sri Lanka (Colombo, 2008, 52.0% in those <12 years of age, and median age of seroconversion of 4.7 years) [13, 35], and Vietnam (Binh Thuan, 2003, 65.7% in 7–13 year olds) [14]. This elevated dengue exposure risk was also observed during a 2011 dengue vaccine trial in 5 Asian countries, where baseline dengue seroprevalence was highest in Indonesian children [36]. …”

Section: Discussionmentioning

confidence: 93%

Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children

Prayitno

Taurel²,

Nealon³

et al. 2017

PLoS Negl Trop Dis

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BackgroundIndonesia reports the second highest dengue disease burden in the world; these data are from passive surveillance reports and are likely to be significant underestimates. Age-stratified seroprevalence data are relatively unbiased indicators of past exposure and allow understanding of transmission dynamics.Methodology/Principal FindingsTo better understand dengue infection history and associated risk factors in Indonesia, a representative population-based cross-sectional dengue seroprevalence study was conducted in 1–18-year-old urban children. From October to November 2014, 3,210 children were enrolled from 30 geographically dispersed clusters. Serum samples were tested for anti-dengue IgG antibodies by indirect ELISA. A questionnaire investigated associations between dengue serologic status and household socio-demographic and behavioural factors. Overall, 3,194 samples were tested, giving an adjusted national seroprevalence in this urban population of 69.4% [95% CI: 64.4–74.3] (33.8% [95% CI: 26.4–41.2] in the 1–4-year-olds, 65.4% [95% CI: 69.1–71.7] in the 5–9-year-olds, 83.1% [95% CI: 77.1–89.0] in the 10–14-year-olds, and 89.0% [95% CI: 83.9–94.1] in the 15–18-year–olds). The median age of seroconversion estimated through a linear model was 4.8 years. Using a catalytic model and considering a constant force of infection we estimated 13.1% of children experience a primary infection per year. Through a hierarchical logistic multivariate model, the subject’s age group (1–4 vs 5–9 OR = 4.25; 1–4 vs. 10–14 OR = 12.60; and 1–4 vs 15–18 OR = 21.87; p<0.0001) and the number of cases diagnosed in the household since the subject was born (p = 0.0004) remained associated with dengue serological status.Conclusions/SignificanceThis is the first dengue seroprevalence study in Indonesia that is targeting a representative sample of the urban paediatric population. This study revealed that more than 80% of children aged 10 years or over have experienced dengue infection at least once. Prospective incidence studies would likely reveal dengue burdens far in excess of reported incidence rates.

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Section: Discussionmentioning

confidence: 93%

Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children

Prayitno

Taurel²,

Nealon³

et al. 2017

PLoS Negl Trop Dis

Self Cite

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“…Transmission intensity was characterised by the average proportion of 9-y-olds who are seropositive prior to vaccine introduction (labelled SP9), and models were run for the following transmission scenarios: 10% (very low transmission intensity), 30% (low), 50% (moderate), 70% (high), and 90% (very high). For comparison, the baseline seropositivity rate in children 9 to 12 y old in the trial settings in Asia and Latin America was between 48% (Mexico) and 91% (Colombia) [30]. Other studies of dengue seroprevalence (i.e., the proportion of individuals who have experienced at least one infection with any dengue serotype) in endemic areas have found values of SP9 in the range of 40% to 81% [31–34].…”

Section: Methodsmentioning

confidence: 99%

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study

et al. 2016

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BackgroundLarge Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.Methods and FindingsThe models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials.All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%–25% (all simulations: –3%–34%) and in high-transmission settings (SP9 ≥ 70%) by 13%–25% (all simulations: 10%– 34%). These endemicity levels are representative of the participating sites in both Phase III trials. In contrast, in settings with low transmission intensity (SP9 ≤ 30%), the models predicted that vaccination could lead to a substantial increase in hospitalisation because of dengue. Modelling reduced vaccine coverage or the addition of catch-up campaigns showed that the impact of vaccination scaled approximately linearly with the number of people vaccinated. In assessing the optimal age of vaccination, we found that targeting older children could increase the net benefit of vaccination in settings with moderate transmission intensity (SP9 = 50%). Overall, vaccination was predicted to be potentially cost-effective in most endemic settings if priced competitively.The results are based on the assumption that the vaccine acts similarly to natural infection. This assumption is consistent with the available trial results but cannot be directly validated in the absence of additional data. Furthermore, uncertainties remain regarding the level of protection provided against disease versus infection and the rate at whi...

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“…This model could be fit to age-seroprevalence data with several different techniques; here we used a maximum likelihood based approach (see Supplement for details). We fit to both yearly [14] and aggregated [15] age cohorts of seropositive count and sample size. Because the model has three parameters, there must be three or more points to constrain the fit.…”

Section: Dengue Infection and Intervention Modelmentioning

confidence: 99%

“…We used data from CYD14 [15] and long term study of Iquitos, Peru [14] to develop two practical examples for Malaysia and Peru, and to more generally bound the region of relevant force of exposure (represented by seroprevalence in 9-year-olds) and disparity (combination of high risk fraction and the odds seropositivity in 9-year-olds).…”

Section: Fig 2 Vaccination and Testing Versus Statusmentioning

confidence: 99%

Serostatus Testing & Dengue Vaccine Cost-Benefit Thresholds

Pearson

Abbas

Clifford

et al. 2019

Preprint

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The World Health Organisation currently recommends pre-screening for past infection prior to administration of the only licensed dengue vaccine, CYD-TDV. Using a bounding analysis, we show that despite additional testing costs, this approach can improve the economic viability of CYD-TDV: effective testing reduces unnecessary vaccination costs while increasing the health benefit for vaccine recipients. When testing is cheap enough, those trends outweigh additional screening costs and make test-then-vaccinate strategies net-beneficial in many settings.We derived these results using a general approach for determining price thresholds for testing and vaccination, as well as indicating optimal start and end ages of routine test-then-vaccinate programs. This approach only requires age-specific seroprevalence and a cost estimate for second infections. We demonstrate this approach across settings commonly used to evaluate CYD-TDV economics, and highlight implications of our simple model for more detailed studies. We found trends showing test-then-vaccinate strategies are generally more beneficial starting at younger ages, and that in some settings multiple years of testing can be more beneficial than only testing once, despite increased investment in testing.

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Symptomatic Dengue in Children in 10 Asian and Latin American Countries

Cited by 125 publications

References 32 publications

Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children

Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study

Serostatus Testing & Dengue Vaccine Cost-Benefit Thresholds

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