Epidemiological and clinical features of the 2016-2018 Zika virus outbreak in northern Argentina.

BACKGROUND: During the American epidemic, Zika virus (ZIKV) expanded rapidly through dengue virus (DENV)-endemic regions. We analyzed the presentation of ZIKV infection in patients from the City of Orán, Argentina, and compared some of its features with dengue presentation in the same region. METHODS: A retrospective study was conducted at San Vicente de Paul Hospital during 2016-2018. Clinical and demographic characteristics, pre-existing immunity to DENV, viral load and type I interferon (IFN) responses were studied in 63 patients with ZIKV infection. RESULTS: Clinical manifestations of ZIKV infection were generally mild compared with dengue, although rash (p<0.001) and itching (p<0.001) were significantly more prevalent in ZIKV patients. ZIKV patients aged <15 y manifested relatively mild disease compared with older ZIKV patients, showing a decreased prevalence of headache (p=0.008), retro-orbital pain (p=0.001) and arthralgia (p=0.001). Increased Zika incidence was observed in female patients (60.3%). Serum viral load was low to undetectable in ZIKV patients and was not associated with serum anti-DENV IgG titers. Interferon-α and IFN-ß serum levels did not correlate with serum viral load in ZIKV patients. CONCLUSIONS: Clinical presentation of ZIKV and DENV infections is largely overlapping, presenting a challenge for diagnosis and risk assessment for uniquely at-risk populations.

Age-associated differences in clinical manifestations and laboratory parameters during a dengue virus type 4 outbreak in Argentina.

Infection by any of the four dengue virus (DENV) serotypes produces a wide spectrum of clinical illness in humans. Differences in clinical manifestation and severity have been associated with secondary heterologous infection, patient age, and virus serotype. In this context, this retrospective study sought to analyze the presentation of dengue in patients during the 2014 DENV-4 outbreak affecting the City of Orán, Salta Province, Argentina. Demographic data, clinical manifestations, and laboratory abnormalities of laboratory-confirmed dengue patients were compared between age groups and between patients with and without warning signs. Of 301 patients with laboratory-confirmed dengue, 37.9% presented dengue with warning signs. Although nearly half of all patients had secondary DENV infections, no severe dengue cases, or deaths were reported. Furthermore, no association was found between incidence of warning signs and pre-existing immunity to DENV. Pediatric patients were least likely to present warning signs and showed significantly decreased risk of fever, retro-orbital pain, arthalgia, diarrhea and thrombocytopenia, and higher risk of rash compared to older patients. Female patients of all ages were also at higher risk of developing several symptoms. The characterization of DENV-4 infection in humans, a DENV serotype recently reported in Argentina, revealed differences in clinical manifestations, laboratory parameters and the presence/absence of warning signs based on age group. Further investigation of these age-related differences should contribute to better assessment of dengue disease in at risk populations.

T helper type 2 bias and type 17 suppression in primary dengue virus infection in infants and young children.

BACKGROUND: The immune response to dengue virus (DENV) primary infection in infants and young children is not well characterized. In Northern Argentina, >90% of the population was DENV-naïve before the 2009 outbreak, allowing evaluation of age-dependent primary responses to infection. METHODS: We conducted a comparative study of the immune response to DENV in 27 infected infants, young children and their mothers. Lymphocyte T helper (Th) 1, Th2, Th17 and inflammatory responses were assayed in blood during the 2009 DENV-1 epidemic. RESULTS: The immune response to DENV-1 was significantly biased to Th2 in infected infants and young children, compared to infants with other febrile illnesses (for IL-4 p < 0.001) and to their infected mothers (for IL-4 p < 0.01). In addition, IL-17 suppression was observed in the memory response to DENV-1 in infected infants (p < 0.01 vs placebo). CONCLUSION: Age-related differences in the primary response to DENV, characterized by an immature Th2 polarization and Th17 suppression in infants, should be studied further in order to expand our understanding of the mechanism of dengue pathogenesis.