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.

Distinct Immune Phenotypes and Cytokine Profiles in Children with Differing Severity of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is usually mild and self-limited in children. However, a few Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections in children may progress to severe disease with respiratory distress or can result in a multisystem inflammatory syndrome (MIS-C) associated with COVID-19. The immune mechanisms for these differential clinical outcomes are largely unknown. METHODS: A prospective cohort study was performed to analyze the laboratory parameters, antibody response, immune phenotypes and cytokine profiles of 51 children with different clinical presentations of COVID-19. RESULTS: We found that the absolute lymphocyte counts gradually decreased with disease severity. Furthermore, SARS-CoV-2 IgG levels in the acute phase and convalescence were not significantly different in patients with different disease severity. A decrease in CD3 + , CD4 + and CD8 + T cells was observed as disease severity increased. Both CD4 + and CD8 + T cells were activated in children with COVID-19, but no difference in the percentage of HLADR + -expressing cells was detected across the severity groups. In contrast, MIS-C patients exhibited augmented exhausted effector memory CD8 + T cells. Interestingly, the cytokine profile in sera of moderate/severe and MIS-C patients revealed an increase in anti-inflammatory IL-1RA and a suppression of tumor necrosis factor-α, RANTES, eotaxin and PDGF-BB. MIS-C patients also exhibited augmented IL-1ß. CONCLUSIONS: We report distinct immune profiles dependent on severity in pediatric COVID-19 patients. Further investigation in a larger population will help unravel the immune mechanisms underlying pediatric COVID-19.

Genetic Susceptibility to Life-threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants.

BACKGROUND: Genetic background may be an important host determinant of respiratory syncytial virus (RSV) disease severity, but full characterization of susceptibility genes remains unclear. This study aimed to assess the presence of specific single-nucleotide polymorphisms (SNPs) in selected genes codifying for different components of the antiviral innate immune response, to determine their role for developing RSV life-threatening disease (LTD). METHODS: Prospective cohort study including previously healthy full-term infants hospitalized with a first RSV infection during 2017-2018. RSV detection, quantification and subgroup determination, and genotyping for SNPs in Toll-like receptor 4 (TLR4 rs4986790, rs4986791), Toll-like receptor 8 (TLR8 rs3761624), macrophage receptor with collagenous structure(MARCO rs1318645) and myxovirus resistance 1(MX1 rs469390) were performed by real-time polymerase chain reaction in nasopharyngeal aspirates obtained on admission. Patients with LTD were those admitted to the intensive care unit requiring ventilatory support. RESULTS: Seventy-five patients were studied, 15 (20%) developed LTD. Infants with concurrent SNPs in MX1 and TLR8, MARCO and TLR8 or MARCO, MX1 and TLR8 had an increased risk of developing LTD. Multivariable logistic regression analysis confirmed this significant association (odds ratio [OR] = 3.75, P = 0.046; OR = 3.92, P = 0.040; OR = 5.56, P = 0.010, respectively). No differences were seen in viral load of patients with LTD compared with those with better outcome (P = 0.737). In addition, no differences in viral load were seen in patients with the described high-risk SNPs compared with those without these polymorphisms. CONCLUSIONS: Life-threatening RSV infection in previously healthy infants was significantly associated with the presence of combined SNPs in MARCO, MX1 and TLR8.

Modeling the long-term persistence of hepatitis A antibody after a two-dose vaccination schedule in Argentinean children.

BACKGROUND: Long-term seroprotection data are essential for decision-making on the need and timing of vaccine boosters. Based on data from longitudinal serological studies, modeling can provide estimates on long-term antibody persistence and inform such decision-making. METHODS: We examined long-term anti-hepatitis A virus (anti-HAV) antibody persistence in Argentinean children ≤15 years after the initial study where they completed a 2-dose course of inactivated hepatitis A vaccine (Avaxim 80U Pediatric, Sanofi Pasteur, Lyon, France). Blood serum samples were taken at baseline, 2 weeks (post first dose), 6 months (pre-booster), 6.5 months (post-booster), 10 years and 14-15 years after first vaccine dose. We fitted 8 statistical model types, predominantly mixed effects models, to anti-HAV persistence data, to identify the most appropriate and best fitting models for our data set and to predict individuals' anti-HAV levels and seroprotection rates up to 30 years post vaccination. RESULTS: Fifty-four children (mean age at enrollment 30.4 months) were enrolled up to 15 years post first vaccine dose. There were 3 distinct periods of antibody concentration: rapid rise up to peak concentration post-booster, rapid decay from post-booster to 10 years, followed by slower decay. A 3-segmented linear mixed effects model was the most appropriate for the data set. Extrapolating based on the available 14-15-year follow-up, the analysis predicted that 88% of individuals anti-HAV seronegative prior to vaccination would remain seroprotected at 30 years post vaccination and lifelong seroprotection for vaccinees seropositive prior to vaccination. CONCLUSIONS: Currently available data demonstrate that Avaxim 80U Pediatric confers to most vaccinees a high level of seroprotection against hepatitis A infection for at least 20-30 years.

Case characteristics and use of oseltamivir in children and household contacts.

In May 2009, the onset of pandemic influenza A (H1N1) began in Buenos Aires schools and a containment program was implemented. We report the first 191 school-aged cases. Influenza (H1N1) was a mild disease in children. Oseltamivir was well tolerated and resulted in a significantly reduced duration of symptoms in this group. Oseltamivir was also effective at preventing secondary cases.