What's eating you
28 November 2014 by Emily Griffiths
These days we can get a prescription for many infections, but what happens when you have more than one at a time? Emily Griffiths explains how we can look at co-infection in a way that could help us devise more effective treatments.
Imagine going to the doctor with an infection and being sent home with a course of drugs. But your doctor doesn't know you actually have two infections. If you take the drugs for one, will the other one go away by itself? What if they make it worse?
It's common for humans to be infected by more than one parasite at the same time, especially among the poor. We are prey to more than 1,400 parasite species, including viruses, bacteria, helminths (worms), protozoa and fungi. Co-infection generally compounds ill-health, perhaps because ill people are more susceptible to infection, but also because it seems treatments for individual infections are less effective in co-infected people.
But why? Until we understand what effect the co-infecting parasites have - something about which we currently know very little - we can't know how to adapt or improve the treatments.
Parasites interact with each other, with the tissues of their host (we call these resources - literally the bits of us the parasites live off), and with the host's immune system. To make matters more complicated some interactions can be indirect, meaning they are mediated by one of those factors.
These interactions mean that treatments for one infection can affect or be affected by another parasite, but it's hard to predict how. It may be because of the way the drug affects the host's immune system; for example, the pathway to boosting immunity to one infection might make the patient more vulnerable to another. Or the relationship could rely on shared resources, either through facilitation - when infection by one parasite encourages co-infection of the same resource (which can happen with wound infections, or when you get the flu and then bacterial pneumonia); or through competition - for example when more than one virus is competing for the same type of cells, treating one could pave the way for the other to become more serious.
One way of trying to predict these effects is to see the various interactions between communities of parasites and their host as a network. Networks are frequently used to study free-living ecological communities in the form of food webs. For example, we could create a network to show all the feeding interactions in a freshwater stream using the gut contents of many individuals sampled at different times; this would allow us to predict how that fish community might respond to the invasion of a new species.
If we can apply similar principles to parasite co-infection within a host, we might be able to use the relationships between two co-infecting parasites to extrapolate possible relationships with other parasites.
Treatments for one infection can affect or be affected by another parasite, but it's hard to predict how.
We can think of infection as a food chain with parasites feeding off parts of the body, and the parasites being attacked by the immune system. If we apply that thinking to co-infection we effectively have a food web (or rather several, intertwined food webs) mapping out more than one parasite species, inhabiting various bits of the body, and triggering many immune responses.
To help understand this ecosystem and how it changes with treatment, we built a network for co-infected people using the results of more than 300 published studies. The network had three levels comprising parasites, the resources they consume and the immune responses they elicit, connected by potential, observed and experimentally proved links.
This is the first network of its kind assembled for any species; it begins to give us a broad indication of how groups of co-infecting parasites tend to interact.
Much co-infection research so far has studied immune-mediated interactions, but our results indicate that resources may have a bigger role in parasite interactions in humans than currently appreciated. We found that pairs of parasite species had twice the potential to interact indirectly through shared resources than through immune responses. We also saw that parasites in co-infected people tend to interact closely in shared parts of the body. This suggests we need to develop treatments that disrupt parasite growth in these areas.
Reported co-infection in humans is therefore structured by physical location within the body, with resource-mediated processes most often influencing how, where and which co-infecting parasites interact. The many indirect interactions in the network show how treating an infection could affect other infections in co-infected patients, though we can't yet see fully how far these indirect effects are likely to spread.
A next step is to find out how strong these feeding interactions are, and how they compare with immune attack. The more we understand the ecosystem within humans, the better chance we have of developing effective treatments for patients with multiple infections, perhaps through new treatments that go beyond anti-parasitic drugs.
Overall, we found that reported parasite interactions were most often indirect. So we need to understand how treating one parasite species indirectly affects co-infecting parasites - such indirect effects could be even more important than indicated by our analyses.
It may be a daunting process, because parasite communities in humans are complex, but the patterns of interactions revealed by our network are a step in the right direction. The more we understand the ecological interactions in parasite communities, the better able we will be to see the effects of treatment on the wider parasite community and on patient health.
Emily Griffiths was formerly a PhD student at the Department of Animal & Plant Sciences, University of Sheffield, and is currently at North Carolina State University.
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