Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13HLA-A, 24HLA-B, and 14HLA-Calleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g.B*27:05,B*57:01/02/03andB*58:01) and risk (e.g.B*35:02) alleles, as well as novel ones (e.g.A*03:01,B*15:39andB*39:02identified as protective, andA*68:03/05,B*15:30,B*35:12/14,B*39:01/06,B*39:05~C*07:02, andB*40:01~C*03:04identified as risk). Interestingly, both protective (e.g.B*39:02) and risk (e.g.B*39:01/05/06) subtypes were identified within the common and genetically diverseHLA-B*39allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman’s rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.
The poor prognosis of infections associated with multidrug-resistant Pseudomonas aeruginosa can be attributed to several conditions of the patient and virulence factors of the pathogen, such as the type III secretion system (T3SS), which presents the ability to inject four effectors into the host cell: ExoS, ExoT, ExoU and ExoY. The aim of this study was to analyze the distribution of exo genes through multiplex polymerase chain reaction in P. aeruginosa strains isolated from patients at a third-level pediatric hospital and their relationships with clinical variables, e.g., the origin of the sample, susceptibility profile and outcome, through a multinomial logistic regression model. A total of 336 bacterial strains were obtained from cystic fibrosis (CF; n = 55) and bloodstream infection (BSI; n = 281) samples, and eleven presence (+)/absence (−) exo virulotype patterns were identified. The virulotype V3 (exoU−/exoS+/exoT+/exoY+) was observed in 64.28%, followed by V1 (exoU+/exoS−/exoT+/exoY+) with 11.60%. Additionally, V2 (exoU+/exoS−/exoT+/exoY−) was present in 11.60%, and V7 (exoU−/exoS+/exoT+/exoY−) was present in 4.17%. The remaining virulotypes (8.33%) identified were clustered in the other virulotype (OV) group (V4, V5, V6, V8, V9, V10 and V11). The clinical records of 100 patients and their outcomes were reviewed. Fifteen patients died (CF = 4; BSI = 11). V2 and V1 were the virulotypes most related to pandrug resistance (PDR), whereas the V1 relative risk of death was determined to be almost four-fold greater than that of V3, followed by V2 and OV. In summary, the virulotypes V1, V2 and CF are related to death. This study highlights the association of T3SS virulotypes with the susceptibility profile, clinical origin and their potential for predicting a poor prognosis.
Mexico approved mandatory nutrient-based standards for foods sold in schools in 2011. The aim of this study was to analyse the association between compliance with nutrition standards for foods sold in schools and children’s school snacks. Data came from three surveys representative of Mexican elementary schools in 13 states and their students (2012, 2013 and 2015); n = 645 children from N = 99 different schools. Information on foods sold in schools and snacks consumed by children was collected through direct observation. Compliance with the standards was defined as the proportion of foods sold in school which met nutrition criteria established by the standards. Snacks were classified as healthy if they contained at least one fruit or vegetable and had no sugar-sweetened beverages. Robust logistic regression models for cross-sectional and repeated surveys aggregated at the school-level were fitted to quantify the association between school compliance with standards and healthy snacks. On average across waves 27% of foods sold complied with nutrition standards; 18% of children consumed a healthy snack. For snacks purchased in school, a 10% increase in school compliance with the standards was associated with a 32% increase in the odds of a healthy snack (OR = 1.32; 95%CI 1.09,1.61); no association was observed for snacks brought from home. The odds of a healthy snack increased over time in schools where compliance with the standards improved (OR = 3.89; 95%CI 1.47,10.31) but not in those where compliance remained constant or decreased. Only a small proportion of children are eating healthy snacks in school. School compliance with standards increases the likelihood of a healthy snack if it is bought at school. Our findings support better implementation of the standards and additional strategies to enhance the policy to achieve its aim of reducing childhood obesity.
26 September 2018 in Revista Peruana de Medicina Experimental Y Salud Pública
Background: Persistence of latent, replication-competent provirus in CD4+T cells of human immunodeficiency virus (HIV)-infected individuals on antiretroviral treatment (ART) is the main obstacle for virus eradication. Methylation of the proviral 5′ long terminal repeat (LTR) promoter region has been proposed as a possible mechanism contributing to HIV latency; however, conflicting observations exist regarding its relevance. We assessed 5′-LTR methylation profiles in total CD4+T cells from blood of 12 participants on short-term ART (30 months) followed up for 2 years, and a cross-sectional group of participants with long-term ART (6–15 years), using next generation sequencing. We then looked for associations between specific 5′-LTR methylation patterns and baseline and follow-up clinical characteristics.Results: 5′-LTR methylation was observed in all participants and behaved dynamically. The number of 5′-LTR variants found per sample ranged from 1 to 13, with median sequencing depth of 16270× (IQR 4107×-46760×). An overall significant 5′-LTR methylation increase was observed at month 42 compared to month 30 (median CpG Methylation Index: 74.7% vs. 0%,p= 0.025). This methylation increase was evident in a subset of participants (methylation increase group), while the rest maintained fairly high and constant methylation (constant methylation group). Persons in the methylation increase group were younger, had higher CD4+T cell gain, larger CD8% decrease, and larger CD4/CD8 ratio change after 48 months on ART (allp< 0.001). Using principal component analysis, the constant methylation and methylation increase groups showed low evidence of separation along time (factor 2:p= 0.04). Variance was largely explained (21%) by age, CD4+/CD8+T cell change, and CD4+T cell subpopulation proportions. Persons with long-term ART showed overall high methylation (median CpG Methylation Index: 78%; IQR 71–87%). No differences were observed in residual plasma viral load or proviral load comparing individuals on short-term (both at 30 or 42 months) and long-term ART.Conclusions: Our study shows evidence that HIV 5′-LTR methylation in total CD4+ T cells is dynamic along time and that it can follow different temporal patterns that are associated with a combination of baseline and follow-up clinical characteristics. These observations may account for differences observed between previous contrasting studies.