Phylogenetics, Epidemiology and Temporal Patterns of Dengue Virus in Araraquara, São Paulo State.

Dengue virus (DENV) is a prominent arbovirus with global spread, causing approximately 390 million infections each year. In Brazil, yearly epidemics follow a well-documented pattern of serotype replacement every three to four years on average. Araraquara, located in the state of São Paulo, has faced significant impacts from DENV epidemics since the emergence of DENV-1 in 2010. The municipality then transitioned from low to moderate endemicity in less than 10 years. Yet, there remains an insufficient understanding of virus circulation dynamics, particularly concerning DENV-1, in the region, as well as the genetic characteristics of the virus. To address this, we sequenced 37 complete or partial DENV-1 genomes sampled from 2015 to 2022 in Araraquara. Then, using also Brazilian and worldwide DENV-1 sequences we reconstructed the evolutionary history of DENV-1 in Araraquara and estimated the time to the most recent common ancestor (tMRCA) for serotype 1, for genotype V and its main lineages. Within the last ten years, there have been at least three introductions of genotype V in Araraquara, distributed in two main lineages (L Ia and L Ib, and L II). The tMRCA for the first sampled lineage (2015/2016 epidemics) was approximately 15 years ago (in 2008). Crucially, our analysis challenges existing assumptions regarding the emergence time of the DENV-1 genotypes, suggesting that genotype V might have diverged more recently than previously described. The presence of the two lineages of genotype V in the municipality might have contributed to the extended persistence of DENV-1 in the region.

A cohort study to assess the incidence of dengue, Brazil, 2014-2018.

The present cohort study was set up with the aim of determining the incidence of dengue among children and adolescents, from 2 to 16 years of age, living in Araraquara, South-Eastern Brazil, a city classified as a mid-level endemicity location for dengue. Enrollment took place from September 2014 to March 2015. Baseline socio-demographic data were collected, and a blood sample from the participant was drawn, for dengue serology. Families were contacted weekly for fever surveillance. If the child developed fever, a nurse visited the household to collect a blood sample. PCR, NS1 and IgM were used for dengue diagnosis. Parents or legal guardians of participating children provided a written informed consent. 3,514 children and adolescents were enrolled in the cohort. Dengue baseline seroprevalence was 12.2% (95%CI: 11.1 - 13.3). The incidence density of symptomatic dengue was 8.94 per 100 person/years in the first year of follow-up, 0.58 in the second, and 0.19 in the fourth. No cases were confirmed in the third year. Incidence was associated with age, sex, baseline seroprevalence and with living in a house as opposed to an apartment. This study provides relevant information on the epidemiology of dengue in mid-level transmission settings that may be useful to policymakers in the evaluation of control strategies.

Comparison of clinical tools for dengue diagnosis in a pediatric population-based cohort.

BACKGROUND: We aimed to estimate and compare the ability of clinical tools for dengue diagnosis in a pediatric population. METHODS: We prospectively evaluated episodes of acute febrile syndrome identified during the follow-up of a population-based cohort of children and adolescents residing in a dengue endemic city. We estimated the area under the receiver operating characteristic curve (AU-ROC) for dengue diagnosis of three clinical tools: the summation of manifestations of the WHO case definition, a predefined clinical scale and a logistic regression model obtained in this study. RESULTS: We compared 219 dengue cases (confirmed by laboratory) and 286 patients with other febrile illnesses. In a multiple model, variables independently associated with dengue included the duration of fever, sleepiness and exanthema. Rhinorrhea, cough and minimal leukocyte count were inversely associated with dengue. This model reached an accuracy of 84.2% (for a cut-off of >0.5, sensitivity: 79.5%, specificity: 87.9%, positive predictive value: 83.7%, negative predictive value: 84.6%). The AU-ROC of this model (89.8%) was significantly higher than that obtained with either the predefined scale (82.1%) or the WHO definition manifestations (77%). CONCLUSION: We validated a predefined scale and identified a multiple model suitable for the clinical diagnosis of dengue in the pediatric population.

Cross reactivity of commercial anti-dengue immunoassays in patients with acute Zika virus infection.

Several countries have local transmission of multiple arboviruses, in particular, dengue and Zika viruses, which have recently spread through many American countries. Cross reactivity among Flaviviruses is high and present a challenge for accurate identification of the infecting agent. Thus, we evaluated the level of cross reactivity of anti-dengue IgM/G Enzyme-Linked Immunosorbent Assays (ELISA) from three manufacturers against 122 serum samples obtained at two time-points from 61 patients with non-dengue confirmed Zika virus infection. All anti-dengue ELISAs cross reacted with serum from patients with acute Zika infection at some level and a worrisome number of seroconversion for dengue IgG and IgM was observed. These findings may impact the interpretation of currently standard criteria for dengue diagnosis in endemic regions.