Mechanisms underlying disease transmission between spatially separated animals

Transmission of infections between spatially separated hosts is a common problem, not only during major outbreaks of livestock diseases, but also in many other settings such as the transmission of infectious diseases between plants and crops or in healthcare settings. During the last major epidemics of livestock diseases in the Netherlands and abroad, disease transmission events occurred despite movement bans and other (bio-)security measures, implying that indirect transmission plays a major role. A better understanding of indirect transmission is necessary to put in place evidence based bio-security measures against neighbourhood (indirect) transmission. To gain more insight in the mechanisms underlying indirect transmission a series of experimental studies combined with mathematical modelling were conducted of which the results are presented in this thesis. First the effect of acidification of drinking water on the transmission parameters of direct and indirect transmission of Campylobacter jejuni (C. jejuni) between broilers was studied. It was shown that acidified drinking water has an effect on indirect transmission but not on direct transmission of C. jejuni between broilers. The sender and receiver sub-process of indirect transmission was then studied in more detail and it was shown that a significant negative interaction effect between acidification of the sender and receiver sub-processes exists, indicating that there is no additional effect of acidification of the drinking water on both sides of the transmission process compared to acidified drinking water only on one side. To study the transport of the pathogen in the environment in more detail, a series of indirect transmission experiments was carried out and a model framework was developed to study indirect transmission between spatially separated hosts. These studies showed that indirect transmission of C. jejuni between broilers is best described by a multistage environmental route from sending to receiving animal, suggesting that indirect transmission occurs through progressive (but slow) contamination of the environment surrounding the source. Indirect transmission experiments where repeated with both C. jejuni and Escherichia coli and the results showed that for C. jejuni it takes much longer for the first effective (viable) bacterium to cross the small distance of approximately 75 cm than it does for Escherichia coli. A new modelling approach to study indirect transmission was developed guided by these indirect transmission experiments. This model is capable of accurately describing the pathogen dispersal process by a diffusive transport mechanism which includes pathogen mortality. Lastly, a range of dose-response models were compared and tested how well these fitted to the data from a dose-response experiment. Here it was shown that for interpolation purposes two relatively simple models are best capable of describing the data from the dose-response experiment. For extrapolation purposes, however, it was shown that from the models that were studied a model that abides by the independent action hypothesis is best.</p

Acidification of drinking water inhibits indirect transmission, but not direct transmission of Campylobacter between broilers

In this study the effect of acidification of the drinking water of broiler chickens on both direct and indirect transmission of Campylobacter was evaluated. In the direct transmission experiment both susceptible and inoculated animals were housed together. In the indirect transmission experiment the susceptible animals were spatially separated from the inoculated animals and no direct animal to animal contact was possible. The transmission parameter ß was estimated for the groups supplied with acidified drinking water and for the control groups. The results showed that acidification of the drinking water had no effect on direct transmission (ß=3.7 day(-1) for both control and treatment). Indirect transmission however was influenced by acidification of the drinking water. A significant decrease in transmission was observed (

Small distances can keep bacteria at bay for days

Transmission of pathogens between spatially separated hosts, i.e., indirect transmission, is a commonly encountered phenomenon important for epidemic pathogen spread. The routes of indirect transmission often remain untraced, making it difficult to develop control strategies. Here we used a tailor-made design to study indirect transmission experimentally, using two different zoonotic bacteria in broilers. Previous experiments using a single bacterial species yielded a delay in the onset of transmission, which we hypothesized to result from the interplay between diffusive motion of infectious material and decay of infectivity in the environment. Indeed, a mathematical model of diffusive pathogen transfer predicts a delay in transmission that depends both on the distance between hosts and on the magnitude of the pathogen decay rate. Our experiments, carried out with two bacterial species with very different decay rates in the environment, confirm the difference in transmission delay predicted by the model. These results imply that for control of an infectious agent, the time between the distant exposure and the infection event is important. To illustrate how this can work we analyzed data observed on the spread of vancomycin-resistant Enterococcus in an intensive care unit. Indeed, a delayed vancomycin-resistant Enterococcus transmission component was identified in these data, and this component disappeared in a study period in which the environment was thoroughly cleaned. Therefore, we suggest that the impact of control strategies against indirect transmission can be assessed using our model by estimating the control measures’ effects on the diffusion coefficient and the pathogen decay rate

Genomic epidemiology of Escherichia coli: antimicrobial resistance through a One Health lens in sympatric humans, livestock and peri-domestic wildlife in Nairobi, Kenya

Background Livestock systems have been proposed as a reservoir for antimicrobial-resistant (AMR) bacteria and AMR genetic determinants that may infect or colonise humans, yet quantitative evidence regarding their epidemiological role remains lacking. Here, we used a combination of genomics, epidemiology and ecology to investigate patterns of AMR gene carriage in Escherichia coli, regarded as a sentinel organism. Methods We conducted a structured epidemiological survey of 99 households across Nairobi, Kenya, and whole genome sequenced E. coli isolates from 311 human, 606 livestock and 399 wildlife faecal samples. We used statistical models to investigate the prevalence of AMR carriage and characterise AMR gene diversity and structure of AMR genes in different host populations across the city. We also investigated household-level risk factors for the exchange of AMR genes between sympatric humans and livestock. Results We detected 56 unique acquired genes along with 13 point mutations present in variable proportions in human and animal isolates, known to confer resistance to nine antibiotic classes. We find that AMR gene community composition is not associated with host species, but AMR genes were frequently co-located, potentially enabling the acquisition and dispersal of multi-drug resistance in a single step. We find that whilst keeping livestock had no influence on human AMR gene carriage, the potential for AMR transmission across human-livestock interfaces is greatest when manure is poorly disposed of and in larger households. Conclusions Findings of widespread carriage of AMR bacteria in human and animal populations, including in long-distance wildlife species, in community settings highlight the value of evidence-based surveillance to address antimicrobial resistance on a global scale. Our genomic analysis provided an in-depth understanding of AMR determinants at the interfaces of One Health sectors that will inform AMR prevention and control