The incidence of dengue in Latin America has increased dramatically during the last decade. Understanding the pathogenic mechanisms in dengue is crucial for the identification of biomarkers for the triage of patients. We aimed to characterize the profile of cytokines (IFN-γ, TNF-α, IL-1β, IL-6, IL-18 and IL-10), chemokines (CXCL8/IL-8, CCL2/MCP-1 and CXCL10/IP-10) and coagulation mediators (Fibrinogen, D-dimer, Tissue factor-TF, Tissue factor pathway inhibitor-TFPI and Thrombomodulin) during the dengue-4 epidemic in Brazil. Laboratory-confirmed dengue cases had higher levels of TNF-α (p < 0.001), IL-6 (p = 0.005), IL-10 (p < 0.001), IL-18 (p = 0.001), CXCL8/IL-8 (p < 0.001), CCL2/MCP-1 (p < 0.001), CXCL10/IP-10 (p = 0.001), fibrinogen (p = 0.037), D-dimer (p = 0.01) and TFPI (p = 0.042) and lower levels of TF (p = 0.042) compared to healthy controls. A principal component analysis (PCA) distinguished between two profiles of mediators of inflammation and coagulation: protective (TNF-α, IL-1β and CXCL8/IL-8) and pathological (IL-6, TF and TFPI). Lastly, multivariate logistic regression analysis identified high aspartate aminotransferase-to-platelet ratio index (APRI) as independent risk factors associated with severity (adjusted OR: 1.33; 95% CI 1.03–1.71; p = 0.027), the area under the receiver operating characteristics curve (AUC) was 0.775 (95% CI 0.681–0.869) and an optimal cutoff value was 1.4 (sensitivity: 76%; specificity: 79%), so it could be a useful marker for the triage of patients attending primary care centers.

Currently, Brazil lives a triple arboviruses epidemic (DENV, ZIKV and CHIKV) making the differential diagnosis difficult for health professionals. Here, we aimed to investigate chikungunya cases and the possible occurrence of co-infections during the epidemic in Amapá (AP) that started in 2014 when the first autochthonous cases were reported and in Rio de Janeiro (RJ) in 2016. We further performed molecular characterization and genotyping of representative strains. In AP, 51.4% of the suspected cases were confirmed for CHIKV, 71.0% (76/107). Of those, 24 co-infections by CHIKV/DENV, two by CHIKV/DENV-1, and two by CHIKV/DENV-4 were observed. In RJ, 76.9% of the suspected cases were confirmed for CHIKV and co-infections by CHIKV/DENV (n = 8) and by CHIKV/ZIKV (n = 17) were observed. Overall, fever, arthralgia, myalgia, prostration, edema, exanthema, conjunctival hyperemia, lower back pain, dizziness, nausea, retroorbital pain, and anorexia were the predominating chikungunya clinical symptoms described. All strains analyzed from AP belonged to the Asian genotype and no amino acid changes were observed. In RJ, the East-Central-South-African genotype (ECSA) circulation was demonstrated and no E1-A226V mutation was observed. Despite this, an E1-V156A substitution was characterized in two samples and for the first time, the E1-K211T mutation was reported in all samples analyzed.

Keywords: Infectious endocarditis; HAIE; CAIE; Staphylococcus aureus; Enterococcus spp.; Streptococcus spp.

Chikungunya virus (CHIKV) infection causes intense cytokine/chemokine inflammatory responses and debilitating joint pain. Indoleamine2,3–dioxygenase 1 (IDO-1) is an enzyme that initiates the tryptophan degradation that is important in initial host innate immune defense against infectious pathogens. Besides that, IDO-1 activation acts as a regulatory mechanism to prevent overactive host immune responses. In this study, we evaluated IDO-1 activity and cytokine/chemokine patterns in CHIKV patients. Higher IDO-1 (Kyn/Trp ratio) activation was observed during the early acute phase of CHIKV infection and declined in the chronic phase. Importantly, increased concentrations of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Interferon γ (IFN-γ), C-C motif chemokine ligand 2/Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and C-X-C motif chemokine ligand 10/Interferon Protein-10 (CXCL10/IP-10) were found in the acute phase of infection, while C-C motif chemokine ligand 4/Macrophage Inflammatory Protein 1 β (CCL4/MIP-1β) was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis had significantly higher concentrations of CCL4/MIP-1β compared to patients without arthritis. Taken together, these data demonstrated increased IDO-1 activity, possibly exerting both antiviral effects and regulating exacerbated inflammatory responses. CCL4/MIP-1β may have an important role in the persistent inflammation and arthritic symptoms following chikungunya infection.

Background: Non-HACEK Gram-negative bacilli (NGNB) infective endocarditis (IE) has a growing frequency. We aimed to describe cases of NGNB IE and find associated risk factors. Methods: We conducted a prospective observational study of consecutive patients with definitive IE according to the modified Duke criteria in four institutions in Brazil. Results: Of 1154 adult patients enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 years, males predominated, accounting for 25/38 (65.8%). Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). Worsening heart failure occurred in 18/38 (47.4%). Higher prevalence of embolic events was found (55,3%), mostly to the central nervous system 7/38 (18.4%). Vegetations were most commonly on aortic valves 17/38 (44.7%). Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38 (34.2%). Overall mortality was 19/38 (50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), hemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors for mortality. Conclusions: The rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with central venous catheters, prosthetic valves, intracardiac devices and hemodialysis and had a high mortality rate.

Advances in knowledge of the pathophysiology of COVID-19 have been acquired; however, the host factors that could explain the mild and severe forms of the disease are not fully understood. Thus, we proposed to evaluate anti-SARS-CoV-2 antibodies and the inflammatory response of different groups of individuals, including healthcare workers (HCW), sick and dead COVID-19 patients and also recovered patients to contribute to this knowledge gap. Our objective is to relate the clinical evolution of these individuals with the level of detection and functionality of specific antibodies and with the production of inflammatory mediators. As main findings, IgA and IgG anti-SARS-CoV-2 were detected in asymptomatic HCW. IFN-γ and TNF-α levels were higher in symptomatic HCWs than patients with COVID-19 and those who died. Patients who died had higher levels of IL-6, IL-10, and CCL2/MCP-1. We found an imbalance between antiviral and pro-inflammatory mediators in the groups, in which IFN-γ and TNF-α seem to be more associated with protection and IL-6 and CCL2/MCP-1 with pathology. Our work is pioneering the Brazilian population and corroborates data from people from other countries.