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Background The GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated. Methods This study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specific IgG, IgM, IgA and IgE antibodies and IgG subclasses were detected by Enzyme-Linked Immunosorbent Assay. Results The results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies. Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to parasite immunity. Conclusions The data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine.

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Graphical abstract SummaryMaternal and/or fetal factors that influence Congenital Zika Syndrome (CZS) development remain elusive. Interferon lambda has been reported as an antiviral factor in Zika infections. Using functional analysis, we conducted a case-control study to demonstrate that maternal interferon lambda single nucleotide polymorphisms (SNPs) contribute to newborn protection. Mothers carrying CA/CC genotypes of rs8109886 SNP have 4.5 times reduced risk of having children with CZS. When we combined the genotypes CC from rs12979860 and CA/CC from rs8109886, 93% of the mothers delivered healthy newborns.Placenta coming from CZS cases displayed diminished level of IFNL2 along with higher tissue-specific type-I IFN genes, tagged by of IFIT5, indicating that lower IFNL levels upon ZIKV infection can lead to uncontrolled damage to overexpression of type-I IFN pathway.In summary, genetically regulated IFNL levels contribute to immune homeostasis and CZS prevention.

To identify the risk factors associated with all-cause mortality in patients with noncystic fibrosis bronchiectasis (NCFB). This prospective cohort study included 120 adult patients with NCFB, who were regularly treated at a specialized outpatient clinic of a university hospital between January 2017 and June 2020. All patients were diagnosed using high-resolution computed tomography. Demographic and clinical data, pulmonary function tests, and the Euro-quality-of-life 5-domain 3-level questionnaire were analyzed. The factors associated with death were determined using the Cox proportional hazards model. The all-cause mortality rate at 41 months was 10.8%. Adjusted multivariate analysis showed that the main contributing predictors for mortality were female sex, smoking, diabetes, chronic obstructive pulmonary disease, emergency visits, use of antibiotics due to exacerbation, secretion color change, exacerbation, predicted forced expiratory volume in 1 second, predicted forced vital capacity, lack of respiratory physiotherapy, absence of vaccination against pneumococci, and mobility domain. Multiple factors contribute to unfavorable outcomes in patients with NCFB, and early recognition of these factors may improve care management.

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; Pcorrected=0.032). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.

Background: Lifestyle Medicine (LM) aims to address six main behavioral domains: diet/nutrition, substance use (SU), physical activity (PA), social relationships, stress management, and sleep. Digital Health Interventions (DHIs) have been used to improve these domains. However, there is no consensus on how to measure lifestyle and its intermediate outcomes aside from measuring each behavior separately. We aimed to describe (1) the most frequent lifestyle domains addressed by DHIs, (2) the most frequent outcomes used to measure lifestyle changes, and (3) the most frequent DHI delivery methods.Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) Extension for Scoping Reviews. A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Web of Science for publications since 2010. We included systematic reviews and meta-analyses of clinical trials using DHI to promote health, behavioral, or lifestyle change.Results: Overall, 954 records were identified, and 72 systematic reviews were included. Of those, 35 conducted meta-analyses, 58 addressed diet/nutrition, and 60 focused on PA. Only one systematic review evaluated all six lifestyle domains simultaneously; 1 systematic review evaluated five lifestyle domains; 5 systematic reviews evaluated 4 lifestyle domains; 14 systematic reviews evaluated 3 lifestyle domains; and the remaining 52 systematic reviews evaluated only one or two domains. The most frequently evaluated domains were diet/nutrition and PA. The most frequent DHI delivery methods were smartphone apps and websites.Discussion: The concept of lifestyle is still unclear and fragmented, making it hard to evaluate the complex interconnections of unhealthy behaviors, and their impact on health. Clarifying this concept, refining its operationalization, and defining the reporting guidelines should be considered as the current research priorities. DHIs have the potential to improve lifestyle at primary, secondary, and tertiary levels of prevention—but most of them are targeting clinical populations. Although important advances have been made to evaluate DHIs, some of their characteristics, such as the rate at which they become obsolete, will require innovative research designs to evaluate long-term outcomes in health.

BackgroundTuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1β, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset.MethodsThe individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations.ResultsA higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-β rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed.ConclusionsOur results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection.