Hitchings, M. | bioRxiv Science

bioRxiv2018

Modeling Vaccine Trials in Epidemics with Mild and Asymptomatic Infection

Vaccine efficacy against susceptibility to infection (VES), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, as such infections may contribute to onward transmission and outcomes such as Congenital Zika Syndrome. However, estimating VES is resource-intensive. We aim to identify methods to accurately estimate VEs when limited information is available and resources are constrained. We model an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history follows a Susceptible, Exposed, Infectious and Symptomatic or Infectious and Asymptomatic, Recovered model. We then use seven approaches to estimate VES, and we also estimate vaccine efficacy against progression to symptoms (VEP). A corrected relative risk and an interval censored Cox model accurately estimate VES and only require serologic testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VES estimates across values of R0 and accurate estimates of VEP for higher values. Identifying resource-preserving methods for accurately estimating VES is important in designing trials for diseases with a high proportion of asymptomatic infection.

epidemiology↗

bioRxiv2018

Inter-population variation in the Atlantic salmon microbiome reflects environmental and genetic diversity

Microbial communities have a crucial influence on host phenotype, and are of broad interest to ecological and evolutionary research. Yet, the extent of variation that occurs in the microbiome within and between populations is unclear. We characterised the skin and gut microbiome of seven populations of juvenile Atlantic salmon (Salmo salar) inhabiting a diverse range of environments, including hatchery-reared and wild populations. We found shared skin OTUs across all populations and core gut microbiota for all wild fish, but the diversity and structure of both skin and gut microbial communities were distinct between populations. There was a marked difference between the gut microbiome of wild and captive fish. Hatchery-reared fish had lower intestinal microbial diversity, lacked core microbiota found in wild fish, and showed altered community structure and function. Captive fish skin and gut microbiomes were also less variable within populations, reflecting more uniform artificial rearing conditions. Surrounding water influenced the microbiome of the gut and, especially, the skin, but could not explain the degree of variation observed between populations. For both the gut and the skin, we found that there was greater difference in microbial community structure between more genetically distinct fish populations, and also that population genetic diversity was positively correlated with microbiome diversity. However, dietary differences are likely to be the major factor contributing to the large differences found in the gut microbiome between wild and captive fish. Our results highlight the scope of inter-population variation in the microbiome, and offer insights into the contributing deterministic factors.

ecology↗