Predicting the effects of parasite co-infection across species boundaries

Abstract

It is normal for hosts to be co-infected by parasites. Interactions among co-infecting species can have profound consequences, including changing parasite transmission dynamics, altering disease severity and confounding attempts at parasite control. Despite the importance of co-infection, there is currently no way to predict how different parasite species may interact with one another, nor the consequences of those interactions. Here, we demonstrate a method that enables such prediction by identifying two nematode parasite groups based on taxonomy and characteristics of the parasitological niche. From an understanding of the interactions between the two defined groups in one host system (wild rabbits), we predict how two different nematode species, from the same defined groups, will interact in co-infections in a different host system (sheep), and then we test this experimentally. We show that, as predicted, in co-infections, the blood-feeding nematode Haemonchus contortus suppresses aspects of the sheep immune response, thereby facilitating the establishment and/or survival of the nematode Trichostrongylus colubriformis; and that the T. colubriformis-induced immune response negatively affects H. contortus This work is, to our knowledge, the first to use empirical data from one host system to successfully predict the specific outcome of a different co-infection in a second host species. The study therefore takes the first step in defining a practical framework for predicting interspecific parasite interactions in other animal systems.

Keywords: co-infection; helminths; immune response; immunomodulation; nematode; population dynamics.

Figure 1.

A schematic of the experimental protocol. Co-infection and mono-infection groups of animals were infected twice weekly for 10 weeks (shaded box) and the animals were then sampled (10 per infection group, and three for the control group) after 6, 10, 14 and 18 weeks post-initial infection.

Figure 2.

Effect of co-infection on within-host parasite dynamics. The predicted number of (a) T. colubriformis adult worms by time post-initial infection and infection group and (b) H. contortus hypobiosed larvae by infection group. Error bars are the 95% confidence intervals. In (a), the T. colubriformis mono-infection group is denoted by the closed grey squares, and the co-infection group by the crossed diamonds; the black arrow represents the last day of larval dosing and the grey arrow represents the first day by which the last larval dose may potentially have reached adulthood. Groups have been offset by one day to aid visualization.

Figure 3.

Immune responses during co-infection. (a) The predicted PC1 scores of jejunal immune response, with time post-initial infection and T. colubriformis infection group (i.e. mono- and co-infection). The T. colubriformis mono-infection group is denoted by the closed grey squares and the co-infection group is denoted by the crossed diamonds. (b) Predicted anti-H. contortus IgG1 titre concentration through time post-initial infection for the control (open black circles), H. contortus mono-infection (solid black circles) and co-infected (crossed diamonds) groups. In (a,b), groups have been offset by one day to aid visualization. Error bars are the 95% confidence intervals. The black arrow represents the last day of larval dosing and the grey arrow represents the first day by which the larvae from the last dose may have reached adulthood.

Figure 4.

Jejunal immune responses are shown as the bootstrapped number (per villus–crypt unit) of (a) eosinophils, (b) goblet cells, (c) globule leucocytes and (d) score of goblet cells with granules. Treatment groups have been offset by 1 day to aid visualization. Error bars are the 95% confidence intervals. The solid black line and dashed lines represent the bootstrapped mean for the control treatment group and its 95% confidence intervals, respectively. Grey squares represent T. colubriformis mono-infection, solid black circles H. contortus mono-infection and crossed diamonds co-infection.