Amy Pedersen

Simultaneous infection by multiple parasite species (viruses, bacteria, helminths, protozoa or fungi) is commonplace. Most reports show coinfected humans to have worse health than those with single infections. However, we have little understanding of how coinfecting parasites interact within human hosts. We used data from over 300 published studies to construct a network that offers the first broad indications of how groups of coinfecting parasites tend to interact. The network had three levels comprising parasites, the resources they consume, and the immune responses they elicit, connected by potential, observed, and experimentally proven links. Pairs of parasite species had most potential to interact indirectly through shared resources, rather than through immune responses or other parasites. Also, the network comprised 10 tightly knit groups, eight of which were associated with particular body parts, and seven of which were dominated by parasite-resource links. Coinfection in humans is therefore structured by physical location within the body, with bottom-up, resource-mediated processes most often influencing how, where, and which coinfecting parasites interact. The many indirect interactions show how treating an infection could affect other infections in coinfected patients, but the compartmentalised structure of the network will limit how far these indirect effects are likely to spread.

Many fundamental patterns of coinfection (multi-species infections) are undescribed, including the relative frequency of coinfection by various pathogens, differences between single-species infections and coinfection, and the burden of coinfection on human health. We aimed to address the paucity of general knowledge on coinfection by systematically collating and analysing data from recent publications to understand the types of coinfection and their effects.

From an electronic search to find all publications from 2009 on coinfection and its synonyms in humans we recorded data on i) coinfecting pathogens and their effect on ii) host health and iii) intensity of infection.

The most commonly reported coinfections differ from infections causing highest global mortality, with a notable lack of serious childhood infections in reported coinfections. We found that coinfection is generally reported to worsen human health (76% publications) and exacerbate infections (57% publications). Reported coinfections included all kinds of pathogens, but were most likely to contain bacteria.

These results suggest differences between coinfected patients and those with single infections, with coinfection having serious health effects. There is a pressing need to quantify the tendency towards negative effects and to evaluate any sampling biases in the coverage of coinfection research.

Coinfection by multiple parasites affects human health, parasite dynamics and the efficacy of infectious disease prevention and treatment. The capacity for different parasites (viruses, bacteria, fungi, protozoa, helminths) to interact is poorly understood. Interspecific interactions between coinfecting parasites could occur in many ways, either directly or indirectly with the host's immune system or bodily resources. We aimed to summarise connected resources, parasites and immune system components in coinfected humans using a network approach. The published literature contains thousands of records of coinfections in humans, associated immune responses, as well as parasite resource requirements. We used over 250 publications on human coinfection from 2009 to build an evidence-based parasite-immune system-resource network. We recorded the identity of coinfecting parasites, immune system components, host resources and the reported relationships between them. The network represents the potential for parasites to interact based on observation and theory found in recent coinfection literature. Results show the great taxonomic variety of coinfecting parasites, with particular involvement of viruses. Some parasites were reported in more coinfections, most notably HIV, suggesting that recent disease invasion and induced immunodeficiency may facilitate many parasite interactions. The network can also be used to generate numerous hypotheses for modelling work and suggestions for future observational and experimental research. The use of networks and other research tools to understand parasite interactions within coinfected hosts will help predict the potential for and consequences of disease invasions, as well as improve infectious disease interventions.

Many parasites circulate endemically within communities of multiple host species. To understand disease persistence within these communities, it is essential to know the contribution each host species makes to parasite transmission and maintenance. However, quantifying those contributions is challenging. We present a conceptual framework for classifying multihost sharing, based on key thresholds for parasite persistence. We then develop a generalized technique to quantify each species' contribution to parasite persistence, allowing natural systems to be located within the framework. We illustrate this approach using data on gastrointestinal parasites circulating within rodent communities and show that, although many parasites infect several host species, parasite persistence is often driven by just one host species. In some cases, however, parasites require multiple host species for maintenance. Our approach provides a quantitative method for differentiating these cases using minimal reliance on system-specific parameters, enabling informed decisions about parasite management within poorly understood multihost communities.

In a recent article, we described a conceptual and analytical model to identify the key host species for parasite transmission in multi-host communities and used data from 11 gastro-intestinal parasites infecting up to five small mammal host species as an illustrative example of how the framework could be applied. A limitation of these empirical data was uncertainty in the identification of parasite species using egg/oocyst morphology, which could overestimate parasite sharing between host species. Here, we show that the key results of the original analysis, namely that (1) parasites naturally infect multiple host species, but typically rely on a small subset of infected host species for long-term maintenance, (2) that different mechanisms underlie how particular host species dominate transmission and (3) that these different mechanisms influence the predicted efficiency of disease control measures, are robust to analysis of a smaller subset of host-parasite combinations that we have greatest confidence in identifying. We further comment briefly on the need for accurate parasite identification, ideally using molecular techniques to quantify cross-species transmission and differentiate covert host specificity from true host generalism.

Recent studies have provided an unprecedented view of the microbial communities colonizing captive mice; yet the host and environmental factors that shape the rodent gut microbiota in their natural habitat remain largely unexplored. Here, we present results from a 2-year 16 S ribosomal RNA gene sequencing-based survey of wild wood mice (Apodemus sylvaticus) in two nearby woodlands. Similar to other mammals, wild mice were colonized by 10 bacterial phyla and dominated by the Firmicutes, Bacteroidetes and Proteobacteria. Within the Firmicutes, the Lactobacillus genus was most abundant. Putative bacterial pathogens were widespread and often abundant members of the wild mouse gut microbiota. Among a suite of extrinsic (environmental) and intrinsic (host-related) factors examined, seasonal changes dominated in driving qualitative and quantitative differences in the gut microbiota. In both years examined, we observed a strong seasonal shift in gut microbial community structure, potentiall...

Hosts are typically coinfected by multiple parasite species, resulting in potentially overwhelming levels of complexity. We argue that an individual host can be considered to be an ecosystem in that it is an environment containing a diversity of entities (e.g., parasitic organisms, commensal symbionts, host immune components) that interact with each other, potentially competing for space, energy, and resources, ultimately influencing the condition of the host. Tools and concepts from ecosystem ecology can be applied to better understand the dynamics and responses of within-individual host-parasite ecosystems. Examples from both wildlife and human systems demonstrate how this framework is useful in breaking down complex interactions into components that can be monitored, measured, and managed to inform the design of better disease-management strategies.

It has become increasingly clear that parasites can have significant impacts on the dynamics of wildlife populations. Recently, researchers have shifted from using observational approaches to infer the impact of parasites on the health and fitness of individuals to using antiparasite drug treatments to test directly the consequences of infection. However, it is not clear the extent to which these experiments work in wildlife systems, or whether the results of these individual-level treatment experiments can predict the population-level consequences of parasitism. Here, we assess the results of treatment experiments, laying out the benefits and limitations of this approach, and discuss how they can be used to improve our understanding of the role of parasites in wildlife populations.

Controlling parasites that infect multiple host species often requires targeting single species that dominate transmission. Yet, it is rarely recognised that such 'key hosts' can arise through disparate mechanisms, potentially requiring different approaches for control. We identify three distinct, but not mutually exclusive, processes that underlie host species heterogeneity: infection prevalence, population abundance and infectiousness. We construct a theoretical framework to isolate the role of each process from ecological data and to explore the outcome of different control approaches. Applying this framework to data on 11 gastrointestinal parasites in small mammal communities across the eastern United States reveals variation not only in the magnitude of transmission asymmetries among host species but also in the processes driving heterogeneity. These differences influence the efficiency by which different control strategies reduce transmission. Identifying and tailoring interventions to a specific type of key host may therefore enable more effective management of multihost parasites.