Influence of previous exposure to Zika Virus on acute Dengue infection: epidemiological, clinical, immunological, and virological aspects

Abstract

Arboviruses are important diseases of collective and individual impact all over the world. Especially in recent years, the expansion of dengue and Zika in intertropical areas stands out. Dengue is a viral infectious disease, considered the most important arbovirus in the world in terms of morbidity and mortality. Historically, more severe cases of the disease, with increased risk of hospitalizations and deaths are observed after a dengue infection by a heterologist serotype at first, resulting in a cytokine storm capable of promoting exuberant plasma extravasation. Recent studies, after the emergence of Zika as an arbovirus of public health impact, have suggested the hypothesis that the previous immunity triggered by an infection by another flavivirus could promote such a physio pathogenic mechanism with exacerbation of immune response and, consequently, more severe evolution to dengue. On the other hand, some studies suggest a protective effect of the previous presence of anti-Zika antibodies for secondary dengue infections. Considering the current epidemiological context of arboviruses in the country and especially in São José do Rio Preto, São Paulo, this study aims to evaluate the influence of antibodies produced against a previous Zika infection in the clinical evolution of dengue, during the last epidemic in the city, which occurred in 2019. To this end, it will evaluate whether the presence of anti-Zika IgG antibodies resulting from a previous infection is a risk predictor for severe forms of dengue (dengue with warning signs and severe dengue) and hospitalization for the disease. Initially, suspected symptomatic cases of dengue with up to 7 days of symptoms will be investigated through RT-PCR or NS1 antigen detection for dengue. Those who are positive and have sufficient clinical data to be classified according to the 3 clinical presentations of dengue will be eligible for study and will be evaluated for a history of dengue or Zika infection by detection of anti-dengue and anti-Zika IgG antibodies, respectively. Three groups will be selected for final analysis: naive/control (non-reactive anti-dengue IgG/non-reactive anti-Zika IgG), with a history of Zika only (non-reagent anti-dengue IgG/Anti-Zika Reagent IgG) and with a history of dengue only (anti-dengue IgG reagent/anti-Zika IgG non-reagent). Subsequently, the quantification of viral particles of dengue virus and the expression profile of cytokines in both groups will also be evaluated. Finally, the presence of anti-Zika IgG antibodies will be evaluated for being a predictor for more severe forms of dengue and hospitalization through appropriate statistical tests, as well as whether there is a difference in viral load and cytokine expression between groups. (AU)