Dataset Information

Boosting can explain patterns of fluctuations of ratios of inapparent to symptomatic dengue virus infections.

ABSTRACT: Dengue is the most prevalent arboviral disease worldwide, and the four dengue virus (DENV) serotypes circulate endemically in many tropical and subtropical regions. Numerous studies have shown that the majority of DENV infections are inapparent, and that the ratio of inapparent to symptomatic infections (I/S) fluctuates substantially year-to-year. For example, in the ongoing Pediatric Dengue Cohort Study (PDCS) in Nicaragua, which was established in 2004, the I/S ratio has varied from 16.5:1 in 2006-2007 to 1.2:1 in 2009-2010. However, the mechanisms explaining these large fluctuations are not well understood. We hypothesized that in dengue-endemic areas, frequent boosting (i.e., exposures to DENV that do not lead to extensive viremia and result in a less than fourfold rise in antibody titers) of the immune response can be protective against symptomatic disease, and this can explain fluctuating I/S ratios. We formulate mechanistic epidemiologic models to examine the epidemiologic effects of protective homologous and heterologous boosting of the antibody response in preventing subsequent symptomatic DENV infection. We show that models that include frequent boosts that protect against symptomatic disease can recover the fluctuations in the I/S ratio that we observe, whereas a classic model without boosting cannot. Furthermore, we show that a boosting model can recover the inverse relationship between the number of symptomatic cases and the I/S ratio observed in the PDCS. These results highlight the importance of robust dengue control efforts, as intermediate dengue control may have the potential to decrease the protective effects of boosting.

SUBMITTER: Alexander LW

PROVIDER: S-EPMC8040803 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Dengue Fever to severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants of inapparent versus symptomatic DENV infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011 in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases were captured at the study health center, and paired healthy annual samples were examined on a yearly basis using serological methods to identify inapparent DENV infections. Overall, inapparent and symptomatic DENV infections were equally distributed by sex. The mean age of infection was 1.2 years higher for symptomatic DENV infections as compared to inapparent infections. Although inapparent versus symptomatic outcome did not differ by infection number (first, second or third/post-second DENV infections), substantial variation in the proportion of symptomatic DENV infections among all DENV infections was observed across study years. In participants with repeat DENV infections, the time interval between a first inapparent DENV infection and a second inapparent infection was significantly shorter than the interval between a first inapparent and a second symptomatic infection. This difference was not observed in subsequent infections. This result was confirmed using two different serological techniques that measure total anti-DENV antibodies and serotype-specific neutralizing antibodies, respectively. Taken together, these findings show that, in this study, age, study year and time interval between consecutive DENV infections influence inapparent versus symptomatic infection outcome, while sex and infection number had no significant effect. Moreover, these results suggest that the window of cross-protection induced by a first infection with DENV against a second symptomatic infection is approximately 2 years. These findings are important for modeling dengue epidemics and development of vaccines.

Project description:Dengue is a major international public health concern, and the number of outbreaks has escalated greatly. Human migration and international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake, and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but "inapparent" was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake.

Project description:BackgroundThe number of dengue fever (DF) cases and the number of dengue outbreaks have increased in recent years in Zhejiang Province, China. An unexpected dengue outbreak was reported in Hangzhou in 2017 and caused more than one thousand dengue cases. This study was undertaken to evaluate the effectiveness of the actual control measures, estimate the proportion of inapparent infections during this outbreak and simulate epidemic development based on different levels of control measures taking inapparent infections into consideration.MethodsThe epidemic data of dengue cases in Hangzhou, Zhejiang Province, in 2017 and the number of the people exposed to the outbreaks were obtained from the China Information Network System of Disease Prevention and Control. The epidemic without intervention measures was used to estimate the unknown parameters. A susceptible-exposed-infectious/inapparent-recovered (SEIAR) model was used to estimate the effectiveness of the control interventions. The inapparent infections were also evaluated at the same time.ResultsIn total, 1137 indigenous dengue cases were reported in Hangzhou in 2017. The number of indigenous dengue cases was estimated by the SEIAR model. This number was predicted to reach 6090 by the end of November 2, 2017, if no control measures were implemented. The total number of reported cases was reduced by 81.33% in contrast to the estimated incidence without intervention. The number of average daily inapparent cases was 10.18 times higher than the number of symptomatic cases. The earlier and more rigorously the vector control interventions were implemented, the more effective they were. The results showed that implementing vector control continuously for more than twenty days was more effective than every few days of implementation. Case isolation is not sufficient enough for epidemic control and only reduced the incidence by 38.10% in contrast to the estimated incidence without intervention, even if case isolation began seven days after the onset of the first case.ConclusionsThe practical control interventions in the outbreaks that occurred in Hangzhou City were highly effective. The proportion of inapparent infections was large, and it played an important role in transmitting the disease during this epidemic. Early, continuous and high efficacy vector control interventions are necessary to limit the development of a dengue epidemic. Timely diagnosis and case reporting are important in the intervention at an early stage of the epidemic.

Dataset Information

Boosting can explain patterns of fluctuations of ratios of inapparent to symptomatic dengue virus infections.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets