Net survival in colon and rectal cancer by stage according to neoadjuvant treatment. A French population-based study.

AIM: Real-life estimations of survival by stage in colorectal cancer are scanty. We estimated population-based net survival by pathological stage and location, and for rectal cancer by patterns of evolution according to clinical and pathological stage with regard to neoadjuvant therapy. METHOD: Age-standardized net survival was estimated on 19,630 colorectal cancers diagnosed between 2009 and 2015. RESULTS: Five-year net survival was 64 % for colon and 62 % for rectal cancer. The highest absolute difference between colon and rectum was 12 % for stage II women aged 75 (91% vs. 79 %). Among patients with clinical stage III rectal cancer, 67 % no longer had pathological node involvement after neoadjuvant treatment. Survival was similar in clinical stage I, II or III and pathological stage III after neoadjuvant treatment and in pathological stage III without neoadjuvant treatment (between 67 % and 72 %). It ranged between 80 and 82 % in pathological stage II, without neoadjuvant treatment or with clinical stage I, II or III before neoadjuvant treatment. Survival ranged between 93 % and 95 % in pathological stage I, treated with surgery only or with clinical stage II or III before neoadjuvant treatment. CONCLUSION: Prognosis is associated with stage determined on surgical specimens rather than stage at the initial workup.

Ability of epidemiological studies to monitor HPV post-vaccination dynamics: a simulation study.

Genital human papillomavirus (HPV) infections are caused by a broad diversity of genotypes. As available vaccines target a subgroup of these genotypes, monitoring transmission dynamics of nonvaccine genotypes is essential. After reviewing the epidemiological literature on study designs aiming to monitor those dynamics, we evaluated their abilities to detect HPV-prevalence changes following vaccine introduction. We developed an agent-based model to simulate HPV transmission in a heterosexual population under various scenarios of vaccine coverage and genotypic interaction, and reproduced two study designs: post-vs.-prevaccine and vaccinated-vs.-unvaccinated comparisons. We calculated the total sample size required to detect statistically significant prevalence differences at the 5% significance level and 80% power. Although a decrease in vaccine-genotype prevalence was detectable as early as 1 year after vaccine introduction, simulations indicated that the indirect impact on nonvaccine-genotype prevalence (a decrease under synergistic interaction or an increase under competitive interaction) would only be measurable after >10 years whatever the vaccine coverage. Sample sizes required for nonvaccine genotypes were >5 times greater than for vaccine genotypes and tended to be smaller in the post-vs.-prevaccine than in the vaccinated-vs.-unvaccinated design. These results highlight that previously published epidemiological studies were not powerful enough to efficiently detect changes in nonvaccine-genotype prevalence.

Contact patterns and HPV-genotype interactions yield heterogeneous HPV-vaccine impacts depending on sexual behaviors: An individual-based model.

Human papillomaviruses are common sexually transmitted infections, caused by a large diversity of genotypes. In the context of vaccination against a subgroup of genotypes, better understanding the role of genotype interactions and human sexual behavior on genotype dynamics is essential. Herein, we present an individual-based model that integrates realistic heterosexual partnership behaviors and simulates interactions between vaccine and non-vaccine genotypes. Genotype interactions were considered, assuming a previous vaccine-genotype infection shortened (competition) or extended (synergy) the duration of a secondary non-vaccine-genotype infection. Sexual behavior determined papillomavirus acquisition and transmission: only 19.5% of active individuals at most 1 partner r during the year, but > 80% of those with ≥ 2 partners, were infected before vaccine introduction. The pre-vaccination situation was consistent with all genotype interaction scenarios. These genotype interactions, despite being undetectable during the pre-vaccination era, markedly impacted genotype prevalence after vaccination started, with a significant increase/decrease of non-vaccine genotypes prevalence for respectively competitive/synergistic interactions. These prevalence changes were more pronounced in individuals with ≤ 3 partners per year (up to 30% of prevalence modification assuming 65% vaccine coverage) but barely visible for individuals with > 3 partners per year (at most 0.30%). Results suggest the presence of genotype interaction, which is consistent with the pre-vaccine situation, may impact the dynamics of non-vaccine genotypes, particularly in less active individuals.

Virus epidemics, plant-controlled population bottlenecks and the durability of plant resistance.

Plant qualitative resistances to viruses are natural exhaustible resources that can be impaired by the emergence of resistance-breaking (RB) virus variants. Mathematical modelling can help determine optimal strategies for resistance durability by a rational deployment of resistance in agroecosystems. Here, we propose an innovative approach, built up from our previous empirical studies, based on plant cultivars combining qualitative resistance with quantitative resistance narrowing population bottlenecks exerted on viruses during host-to-host transmission and/or within-host infection. Narrow bottlenecks are expected to slow down virus adaptation to plant qualitative resistance. To study the effect of bottleneck size on yield, we developed a stochastic epidemic model with mixtures of susceptible and resistant plants, relying on continuous-time Markov chain processes. Overall, narrow bottlenecks are beneficial when the fitness cost of RB virus variants in susceptible plants is intermediate. In such cases, they could provide up to 95 additional percentage points of yield compared with deploying a qualitative resistance alone. As we have shown in previous works that virus population bottlenecks are at least partly heritable plant traits, our results suggest that breeding and deploying plant varieties exposing virus populations to narrowed bottlenecks will increase yield and delay the emergence of RB variants. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.

Transmission Routes of Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in a Neonatology Ward in Madagascar.

The diffusion of extended-spectrum beta-lactamase (E-ESBL)-producing Enterobacteriaceae is a major concern worldwide, especially in low-income countries, where they may lead to therapeutic failures. In hospitals, where colonization is the highest, E-ESBL transmission is poorly understood, limiting the possibility of establishing effective control measures. We assessed E-ESBL-acquisition routes in a neonatalogy ward in Madagascar. Individuals from a neonatology ward were longitudinally followed-up (August 2014-March 2015). Newborns' family members' and health-care workers (HCWs) were stool-sampled and tested for E-ESBL colonization weekly. Several hypothetical acquisition routes of newborns-e.g. direct contact with family members and HCWs and indirect contact with other newborns through environmental contamination, colonization pressure, or transient hand carriage-were examined and compared using mathematical modeling and Bayesian inference. In our results, high E-ESBL acquisition rates were found, reaching > 70% for newborns, > 55% for family members, and > 75% for HCWs. Modeling analyses indicated transmission sources for newborn colonization to be species dependent. Health-care workers' route were selected for Klebsiella pneumoniae and Escherichia coli, with respective estimated transmission strengths of 0.05 (0.008; 0.14) and 0.008 (0.001; 0.021) ind-1 day-1. Indirect transmissions associated with ward prevalence, e.g. through hand carriage or environment, were selected for Enterobacter cloacae, E. coli, and K. pneumoniae (range 0.27-0.41 ind-1 day-1). Importantly, family members were not identified as transmission source. To conclude, E-ESBL acquisition sources are strongly species dependent. Escherichia coli and E. cloacae involve more indirect contamination, whereas K. pneumoniae also spreads through contact with colonized HCWs. These findings should help improve control measures to reduce in-hospital transmission.