The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution.

Background Respiratory viral infections are a major cause of morbidity and mortality worldwide. However, their characterization is incomplete because prevalence estimates are based on syndromic surveillance data. Here, we address this shortcoming through the analysis of infection rates among individuals tested regularly for respiratory viral infections, irrespective of their symptoms. Methods We carried out longitudinal sampling and analysis among 214 individuals enrolled at multiple New York City locations from fall 2016 to spring 2018. We combined personal information with weekly nasal swab collection to investigate the prevalence of 18 respiratory viruses among different age groups and to assess risk factors associated with infection susceptibility. Results 17.5% of samples were positive for respiratory viruses. Some viruses circulated predominantly during winter, whereas others were found year round. Rhinovirus and coronavirus were most frequently detected. Children registered the highest positivity rates, and adults with daily contacts with children experienced significantly more infections than their counterparts without children. Conclusion Respiratory viral infections are widespread among the general population with the majority of individuals presenting multiple infections per year. The observations identify children as the principal source of respiratory infections. These findings motivate further active surveillance and analysis of differences in pathogenicity among respiratory viruses.

Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.

Respiratory viruses are common in human populations, causing significant levels of morbidity. Understanding the distribution of these viruses is critical for designing control methods. However, most data available are from medical records and thus predominantly represent symptomatic infections. Estimates for asymptomatic prevalence are sparse and span a broad range. In this study, we aimed to measure more precisely the proportion of infections that are asymptomatic in a general, ambulatory adult population. We recruited participants from a New York City tourist attraction and administered nasal swabs, testing them for adenovirus, coronavirus, human metapneumovirus, rhinovirus, influenza virus, respiratory syncytial virus, and parainfluenza virus. At recruitment, participants completed surveys on demographics and symptomology. Analysis of these data indicated that over 6% of participants tested positive for shedding of respiratory virus. While participants who tested positive were more likely to report symptoms than those who did not, over half of participants who tested positive were asymptomatic.

Evolution is a key aspect of the biology of many pathogens, driving processes ranging from immune escape to changes in virulence. Because evolution is inherently subject to feedbacks, and because pathogen evolution plays out at scales ranging from within-host to between-host and beyond, evolutionary questions provide special challenges to the modelling community. In this article, we provide an overview of five challenges in modelling the evolution of pathogens and their hosts, and point to areas for development, focussing in particular on the issue of linking theory and data.