ABSTRACT
The aim of this study was to analyze the characteristics of Dengue virus (DENV)-infected children and the accuracy of dengue diagnosis based on clinical presentations. The inclusion criteria were children ≥1-year-old presenting febrile illness with 1-7 days of onset. Children (n = 110) aged 2-15 years were included in this study. DENV infection was confirmed with virological tests using serum, salvia, and/or urine samples. The attending pediatricians classified 56/110 (50.91%) of the children as suspected dengue cases. The DENV infection was confirmed by specific laboratory tests in 52/56 (92.9%) of the suspected dengue cases but also in 44/54 (81.5%) of the unsuspected dengue cases; total of 96/110 (87.27%) confirmed dengue cases. The clinical diagnosis gave an overall sensitivity of 54.2% (52/96) and a specificity of 71.4% (10/14). The positive predictive value of the clinical diagnosis was 92.8% and negative predictive value was 18.5%. After the third day of onset of symptoms, the DENV genome detection rate was similar in serum and saliva samples, suggesting that saliva samples represent an alternative to blood samples for early dengue diagnosis. Vaccination against Yellow fever virus did not influence the antibody response against DENV-1, DENV-2, and DENV-3, which circulated during the study period. Although the signs and symptoms were compatible with dengue, the attending pediatricians did not suspect the disease in several children. Therefore, the inclusion of virological tests for early diagnosis in the protocols for dengue surveillance would help in the implementation of prompt treatment of patients and epidemic containment strategies. J. Med. Virol. 88:1711-1719, 2016. © 2016 Wiley Periodicals, Inc.
Subject(s)
Dengue Virus/isolation & purification , Dengue/diagnosis , Dengue/epidemiology , Adolescent , Antibodies, Viral/blood , Brazil/epidemiology , Child , Child, Preschool , Dengue/immunology , Dengue/prevention & control , Dengue Virus/immunology , Enzyme-Linked Immunosorbent Assay , Epidemics , Female , Genome, Viral , Humans , Immunoglobulin M/blood , Infant , Male , Prevalence , RNA, Viral/blood , Saliva/virology , Sensitivity and Specificity , Urine/virology , Virus Shedding , Yellow fever virus/immunologyABSTRACT
The Flaviviridae family includes several virus pathogens associated with human diseases worldwide. Within this family, Dengue virus is the most serious threat to public health, especially in tropical and sub-tropical regions of the world. Currently, there are no vaccines or specific antiviral drugs against Dengue virus or against most of the viruses of this family. Therefore, the development of vaccines and the discovery of therapeutic compounds against the medically most important flaviviruses remain a global public health priority. We previously showed that phospholipase A2 isolated from the venom of Crotalus durissus terrificus was able to inhibit Dengue virus and Yellow fever virus infection in Vero cells. Here, we present evidence that phospholipase A2 has a direct effect on Dengue virus particles, inducing a partial exposure of genomic RNA, which strongly suggests inhibition via the cleavage of glycerophospholipids at the virus lipid bilayer envelope. This cleavage might induce a disruption of the lipid bilayer that causes a destabilization of the E proteins on the virus surface, resulting in inactivation. We show by computational analysis that phospholipase A2 might gain access to the Dengue virus lipid bilayer through the pores found on each of the twenty 3-fold vertices of the E protein shell on the virus surface. In addition, phospholipase A2 is able to inactivate other enveloped viruses, highlighting its potential as a natural product lead for developing broad-spectrum antiviral drugs.
