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Updated: Jul 18, 2025

Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Quantifying synergistic interactions: a meta-analysis of joint effects of chemical and parasitic stressors
Nina Cedergreen1, Kathrine Eggers Pedersen1, Brian Lund Fredensborg2
1Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871, Frederiksberg, Denmark.
Abstract:
The global biodiversity crisis emphasizes our need to understand how different stressors (climatic, chemical, parasitic, etc.) interact and affect biological communities. We provide a comprehensive meta-analysis investigating joint effects of chemical and parasitic stressors for 1064 chemical-parasitic combinations using the Multiplicative model on mortality of arthropods. We tested both features of the experimental setup (control mortality, stressor effect level) and the chemical mode of action, host and parasite phylogeny, and parasite-host interaction traits as explanatory factors for deviations from the reference model. Synergistic interactions, defined as higher mortality than predicted, were significantly more frequent than no interactions or antagony. Experimental setup significantly affected the results, with studies reporting high (> 10%) control mortality or using low stressor effects (< 20%) being more synergistic. Chemical mode of action played a significant role for synergy, but there was no effects of host and parasite phylogeny, or parasite-host interaction traits. The finding that experimental design played a greater role in finding synergy than biological factors, emphasize the need to standardize the design of mixed stressor studies across scientific disciplines. In addition, combinations testing more biological traits e.g. avoidance, coping, and repair processes are needed to test biology-based hypotheses for synergistic interactions.
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