The Role of Heterogenous Real-world Data for Dengue Surveillance in Martinique: Observational Retrospective Study.

BACKGROUND: Traditionally, dengue prevention and control rely on vector control programs and reporting of symptomatic cases to a central health agency. However, case reporting is often delayed, and the true burden of dengue disease is often underestimated. Moreover, some countries do not have routine control measures for vector control. Therefore, researchers are constantly assessing novel data sources to improve traditional surveillance systems. These studies are mostly carried out in big territories and rarely in smaller endemic regions, such as Martinique and the Lesser Antilles. OBJECTIVE: The aim of this study was to determine whether heterogeneous real-world data sources could help reduce reporting delays and improve dengue monitoring in Martinique island, a small endemic region. METHODS: Heterogenous data sources (hospitalization data, entomological data, and Google Trends) and dengue surveillance reports for the last 14 years (January 2007 to February 2021) were analyzed to identify associations with dengue outbreaks and their time lags. RESULTS: The dengue hospitalization rate was the variable most strongly correlated with the increase in dengue positivity rate by real-time reverse transcription polymerase chain reaction (Pearson correlation coefficient=0.70) with a time lag of -3 weeks. Weekly entomological interventions were also correlated with the increase in dengue positivity rate by real-time reverse transcription polymerase chain reaction (Pearson correlation coefficient=0.59) with a time lag of -2 weeks. The most correlated query from Google Trends was the "Dengue" topic restricted to the Martinique region (Pearson correlation coefficient=0.637) with a time lag of -3 weeks. CONCLUSIONS: Real-word data are valuable data sources for dengue surveillance in smaller territories. Many of these sources precede the increase in dengue cases by several weeks, and therefore can help to improve the ability of traditional surveillance systems to provide an early response in dengue outbreaks. All these sources should be better integrated to improve the early response to dengue outbreaks and vector-borne diseases in smaller endemic territories.

Long-range chromatin interactions at the mouse Igf2/H19 locus reveal a novel paternally expressed long non-coding RNA.

Parental genomic imprinting at the Igf2/H19 locus is controlled by a methylation-sensitive CTCF insulator that prevents the access of downstream enhancers to the Igf2 gene on the maternal chromosome. However, on the paternal chromosome, it remains unclear whether long-range interactions with the enhancers are restricted to the Igf2 promoters or whether they encompass the entire gene body. Here, using the quantitative chromosome conformation capture assay, we show that, in the mouse liver, the endodermal enhancers have low contact frequencies with the Igf2 promoters but display, on the paternal chromosome, strong interactions with the intragenic differentially methylated regions 1 and 2. Interestingly, we found that enhancers also interact with a so-far poorly characterized intergenic region of the locus that produces a novel imprinted long non-coding transcript that we named the paternally expressed Igf2/H19 intergenic transcript (PIHit) RNA. PIHit is expressed exclusively from the paternal chromosome, contains a novel discrete differentially methylated region in a highly conserved sequence and, surprisingly, does not require an intact ICR/H19 gene region for its imprinting. Altogether, our data reveal a novel imprinted domain in the Igf2/H19 locus and lead us to propose a model for chromatin folding of this locus on the paternal chromosome.