Abstract
Owing to the finding that Dengvaxia® (the only licensed dengue vaccine to date) increases the risk of severe illness among seronegative recipients, the World Health Organization has recommended screening individuals for their serostatus prior to vaccination. To decide whether and how to carry out screening, it is necessary to estimate the transmission intensity of dengue and to understand the performance of the screening method. In this study, we inferred the annual force of infection (FOI; a measurement of transmission intensity) of dengue virus in three locations in Vietnam: An Giang (FOI = 0.04 for the below 10 years age group and FOI = 0.20 for the above 10 years age group), Ho Chi Minh City (FOI = 0.12) and Quang Ngai (FOI = 0.05). In addition, we show that using a quantitative approach to immunoglobulin G (IgG) levels (measured by indirect enzyme-linked immunosorbent assays) can help to distinguish individuals with primary exposures (primary seropositive) from those with secondary exposures (secondary seropositive). We found that primary-seropositive individuals—the main targets of the vaccine—tend to have a lower IgG level, and, thus, they have a higher chance of being misclassified as seronegative than secondary-seropositive cases. However, screening performance can be improved by incorporating patient age and transmission intensity into the interpretation of IgG levels.
Highlights
Dengue is the most rapidly spreading mosquito-borne viral disease in humans [1]
The second aim of our analysis is to develop a statistical method to assess whether it is possible at a population level to use immunoglobulin G (IgG) levels to differentiate past primary dengue virus infection from secondary infection [41]
Multiple models of force of infection (FOI) and antibody acquisition were tested, with the majority of best-fitting models agreeing that Quang Ngai had a lower overall FOI than Ho Chi Minh City or An Giang and that the FOI in An Giang was likely to be age varying, while the FOIs in Ho Chi Minh City and Quang Ngai were generally constant
Summary
Dengue is the most rapidly spreading mosquito-borne viral disease in humans [1]. Globally, this acute systemic viral infection causes around 58.4 million symptomatic cases, leading to an estimate of 10 000–20 000 deaths annually [2,3,4]. While infection with one serotype results in long-term immunity against that serotype, it is thought to induce only short-lived crossprotection against the other serotypes [5,7,8] After this brief period of cross-protection, subneutralizing concentrations of pre-existing heterologous antibodies— generated as a result of the first exposure to dengue ( primary infection)—may favour viral uptake into cells and enhance viral replication, leading to more severe symptoms during a subsequent infection with a different serotype (secondary infection) [9,10,11]. Individuals are believed to be generally protected against all serotypes since postsecondary infections have rarely been observed as hospitalized cases [16,17,18]
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