Which Lynch syndrome screening programs could be implemented in the "real world"? A systematic review of economic evaluations

Purpose: Lynch syndrome (LS) screening can significantly reduce cancer morbidity and mortality in mutation carriers. Our aim was to identify cost-effective LS screening programs that can be implemented in the "real world."Methods: We performed a systematic review of full economic evaluations of genetic screening for LS in different target populations; health outcomes were estimated in life-years gained or quality-adjusted life-years.Results: Overall, 20 studies were included in the systematic review. Based on the study populations, we identified six categories of LS screening program: colorectal cancer (CRC)-based, endometrial cancer-based, general population-based, LS family registry-based, cascade testing-based, and genetics clinic-based screening programs. We performed an in-depth analysis of CRC-based LS programs, classifying them into three additional subcategories: universal, age-targeted, and selective. In five studies, universal programs based on immunohistochemistry, either alone or in combination with the BRAF test, were cost-effective compared with no screening, while in two studies age-targeted programs with a cutoff of 70 years were cost-effective when compared with age-targeted programs with lower age thresholds. Conclusion: Universal or <70 years-age-targeted CRC-based LS screening programs are cost-effective and should be implemented in the "real world

Emergence of a New Epidemic Neisseria meningitidis Serogroup A Clone in the African Meningitis Belt: High-Resolution Picture of Genomic Changes That Mediate Immune Evasion

In the African "meningitis belt," outbreaks of meningococcal meningitis occur in cycles, representing a model for the role of host-pathogen interactions in epidemic processes. The periodicity of the epidemics is not well understood, nor is it currently possible to predict them. In our longitudinal colonization and disease surveys, we have observed waves of clonal replacement with the same serogroup, suggesting that immunity to noncapsular antigens plays a significant role in natural herd immunity. Here, through comparative genomic analysis of 100 meningococcal isolates, we provide a high-resolution view of the evolutionary changes that occurred during clonal replacement of a hypervirulent meningococcal clone (ST-7) by a descendant clone (ST-2859). We show that the majority of genetic changes are due to homologous recombination of laterally acquired DNA, with more than 20% of these events involving acquisition of DNA from other species. Signals of adaptation to evade herd immunity were indicated by genomic hot spots of recombination. Most striking is the high frequency of changes involving the pgl locus, which determines the glycosylation patterns of major protein antigens. High-frequency changes were also observed for genes involved in the regulation of pilus expression and the synthesis of Maf3 adhesins, highlighting the importance of these surface features in host-pathogen interaction and immune evasion. Importance: While established meningococcal capsule polysaccharide vaccines are protective through the induction of anticapsular antibodies, findings of our longitudinal studies in the African meningitis belt have indicated that immunity to noncapsular antigens plays a significant role in natural herd immunity. Our results show that meningococci evade herd immunity through the rapid homologous replacement of just a few key genomic loci that affect noncapsular cell surface components. Identification of recombination hot spots thus represents an eminent approach to gain insight into targets of protective natural immune responses. Moreover, our results highlight the role of the dynamics of the protein glycosylation repertoire in immune evasion by Neisseria meningitidis. These results have major implications for the design of next-generation protein-based subunit vaccines

Vaccination coverage and factors associated with adherence to the vaccination schedule in young children of a rural area in Burkina Faso

Background: Vaccination is an important tool for reducing infectious disease morbidity and mortality. In the past, less than 80% of children 12–23 months of age were fully immunized in Burkina Faso. Objectives: To describe coverage and assess factors associated with adherence to the vaccination schedule in rural area Burkina Faso. Methods: The study population was extracted from the Nouna Health and Demographic surveillance system cohort. Data from four rounds of interviews conducted between November 2012 and June 2014 were considered. This study included 4016 children aged 12–23 months. We assessed the effects of several background factors, including sex, factors reflecting access to health care (residence, place of birth), and maternal factors (age, education, marital status), on being fully immunized defined as having received Bacillus Calmette–Guérin (BCG), three doses of diphtheria–tetanus–pertussis and oral polio vaccine, and measles vaccine by 12 months of age. The associations were studied using binomial regression to derive prevalence ratios (PRs) in univariate and multivariate regression models. Results: The full vaccination coverage increased significantly over time (72% in 2012, 79% in 2013, and 81% in 2014, p = 0.003), and the coverage was significantly lower in urban than in rural areas (PR 0.84; 0.80–0.89). Vaccination coverage was neither influenced by sex nor influenced by place of birth or by maternal factors. Conclusion: The study documented a further improvement in full vaccination coverage in Burkina Faso in recent years and better vaccination coverage in rural than in urban areas. The organization of healthcare systems with systematic outreach activities in the rural areas may explain the difference between rural and urban areas