The NLRP3 inflammasome is involved with the pathogenesis of Mayaro virus.

Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3-/-, Aim2-/-, Asc-/-and Casp1/11-/-mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1ß. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1ß and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans.

Evidence based on a meta-analysis of human cytomegalovirus infection in glioma.

Malignant gliomas are the most common types of incurable primary brain tumours. Therefore, to better clarify the aetiology and pathogenesis of the disease and analyse the risk factors involved, several researchers have highlighted a possible link to human cytomegalovirus (HCMV). Regarding this potential link, the numbers of studies and controversies concerning the relationship between HCMV infections and malignant gliomas have significantly increased. Therefore, we conducted a meta-analysis of observational studies to summarize and pool the available results on the association of HCMV in patients with glioma. Our meta-analysis was based on the PRISMA algorithm, using fixed/random models through STATA IC 13.1 software. Thus, 32 studies were included with a total of 2,190 participants/specimens (glioma, n = 1,871; non-glioma, n = 319). The overall estimate of combined HCMV frequency in patients with glioma was 63% (95% confidence interval [CI]: 56-70). There was an association between HCMV infection and glioma (adjusted OR = 3, 95% CI: 1.7-5.3). The pooled subgroup analysis of viral markers also showed a positive association between the pp65 protein (OR = 3.1, 95% CI: 1.8-5), and gB nucleic acids (OR = 3.1, 95% CI: 1.1-8). For the viral marker IE1-72 protein, the pooled frequency and association results were higher. However, there was no correlation of higher viral association according to the histological subtypes and low/high grade of gliomas. In conclusion, the available evidence suggests an association between HCMV and glioma. Consequently, precautions should be taken, as discussed in this report.

Safety, immunogenicity and efficacy of a recombinant tetravalent dengue vaccine: a meta-analysis of randomized trials.

The World Health Organization has stipulated a target: reduce the mortality rate caused by dengue disease by 50% until 2020. Most likely, this goal can be achieved by means of a dengue vaccine. Accordingly, the recombinant and tetravalent dengue vaccine (CYD-TDV), developed by the Sanofi Pasteur Group, is in an advanced stage of human testing. Although there are multiple randomized, placebo-controlled trials evaluating the CYD-TDV, individual results may have little power to identify differences between the populations studied. Thus, we conducted a meta-analysis to determine a more precise estimate of the overall parameters of safety, immunogenicity and efficacy of CYD-TDV. A data search was conducted in the PubMed, Medline, Cochrane Central Register of Controlled Trials and SciELO databases with defined selection criteria. We included for meta-analysis seven randomized and placebo-controlled studies that included 6678 patients randomized to receive the CYD-TDV (4586) or placebo (2092). Regarding vaccine safety, it was found that there was no significant difference between treated and placebo groups, as only approximately 5.5% of patients were withdrawn from the study. Regarding immunogenicity, the levels of neutralizing antibodies were measured by weighted mean differences (WMD), which were always higher in the vaccinated group (WMD/DENV1=59.7, 95% confidence interval [CI] 57-61; WMD/DENV2=99, 95% CI 95-102; WMD/DENV3=138, 95% CI 133-142; WMD/DENV4=123, 95% CI 119-126). The clinical efficacy of the vaccine was 59% (95% CI 15-80; RR=0.41, 95% CI 0.2-0.85, I(2)=30.9%). In conclusion, safety and a balanced immune response to the CYD-TDV were found. However, to fully establish the clinical effectiveness and robustness of immunogenicity, it is necessary to perform further studies to assess the long-term effects of the vaccine.