Disentangling complex parasite interactions: Protection against cerebral malaria by one helminth species is jeopardized by co-infection with another.

Jessica L Abbate,Jessica L Abbate,Jessica L Abbate,Jessica L Abbate,Jessica L Abbate,Jessica L Abbate,Benjamin Roche,Mathieu Nacher,Mathieu Nacher,Jean-François Guégan,Jean-François Guégan,Jean-François Guégan,Jean-François Guégan,Vanessa O Ezenwa,Marc Choisy,Marc Choisy,Marc Choisy,Marc Choisy,Marc Choisy

doi:10.1371/journal.pntd.0006483

Abstract

Multi-species interactions can often have non-intuitive consequences. However, the study of parasite interactions has rarely gone beyond the effects of pairwise combinations of species, and the outcomes of multi-parasite interactions are poorly understood. We investigated the effects of co-infection by four gastrointestinal helminth species on the development of cerebral malaria among Plasmodium falciparum-infected patients. We characterized associations among the helminth parasite infra-community, and then tested for independent (direct) and co-infection dependent (indirect) effects of helminths on cerebral malaria risk. We found that infection by Ascaris lumbricoides and Trichuris trichiura were both associated with direct reductions in cerebral malaria risk. However, the benefit of T. trichiura infection was halved in the presence of hookworm, revealing a strong indirect effect. Our study suggests that the outcome of interactions between two parasite species can be significantly modified by a third, emphasizing the critical role that parasite community interactions play in shaping infection outcomes.

Highlights

Most hosts are co-infected by a range of pathogenic organisms (e.g., [1]), and interactions between co-infecting parasites can be important determinants of susceptibility to infection (e.g., [2]) as well as the severity of disease symptoms (e.g., [3])
Despite the fact that helminth species frequently co-occur together within an individual, no studies have investigated the role of within-host helminth community interactions on malaria severity
Half (49.6%) of all patients infected with helminths were infected with more than one helminth species, including 4 individuals who were co-infected with all four species (Table 2)

Summary

Introduction

Most hosts are co-infected by a range of pathogenic organisms (e.g., [1]), and interactions between co-infecting parasites can be important determinants of susceptibility to infection (e.g., [2]) as well as the severity of disease symptoms (e.g., [3]). Co-occurring parasites interact within a host via a number of mechanisms, including through active down-regulation of immune responses by some parasites, indirect competition through stimulation of host defenses, and direct competition for resources [4]. The resulting impacts of within-host parasite interactions on host health can be beneficial (e.g., cross-protection between influenza strains, [5]) or detrimental (e.g., stimulation of the immune system’s response against many helminth species reduces the capacity of vertebrate hosts to respond to some intracellular pathogens [6]). Remarkably few studies have looked beyond direct pairwise parasite-parasite interaction effects on disease (but see e.g., [19,20,21])

Methods

Results

Discussion

Conclusion