Interactions in mixed-species infections

Fundamental aspects of disease ecology – from the geographic distributions of parasite species, to the spread and severity of infections – are shaped by interactions between parasites. 

Malaria parasites are highly diverse organisms, in which multiple-species infections are quite common. For example, in Papua New Guinea there are reports of people simultaneously infected with the four species of human malaria (P. falciparum, P. malariae, P. ovale and P. vivax). Many field samples of rodent malaria parasite contain multiple parasite species.

(credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

Interactions in the host

A BALB/c strain mouse (Mus musculus). (Credit: Steph Hillier) 

Much research into the nature and consequences of interactions between con-specifics co-infecting the same hosts has occurred, but little is known about how hetero-specifics interact. We have shown that infection with a resource generalist parasite species facilitates a resource specialist, and that this is driven by altered resource availability in mixed-species infections, not by cross-species immune responses. 

However, whilst facilitation accelerates replication of the specialist species, it results in substantially more severe disease (host mortality). These complex benefits and costs are thought to occur in mixed-species infections of the two human malaria parasite species that cause the vast majority of disease (Plasmodium falciparum and Plasmodium vivax). 

Interactions in the vector

An Anopheles stephensi mosquito taking a blood meal. (Credit: Sinclair Stammers)

Male and female sexual stages (gametocytes) must produce gametes and mate in the blood meal of a mosquito for transmission to occur. Gametogenesis and mating in co-infecting species are stimulated by the same cues so there is potential for hybridization, because gametes of multiple species will be searching for mates within the same restricted time and space window. 

Proteins essential to the fertility of each sex have been identified and are thought to be targets for transmission interventions. We have revealed that some of these molecules are also responsible for pre-zygotic species recognition between gametes and that targeting these ligands could promote hybridization between different species. Specifically, hybridisation occurs at very low levels in our mate crossing experiments but occurs just as often as mating between conspecifics in strains where the genes for these proteins are knocked out.

(credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

(credit: EviMalar, Jamie Hall, Edward Ross, Wellcome Trust)

What next?

We would like to know how the costs and benefits of facilitation play out to shape the geographic distributions and epidemiologies of parasite species, and how interactions over resources play out for other species.

If the virulence and transmission of human malaria species is linked, interventions that target one species could benefit another. We would also like to know how common hybridisation is in nature. This has implications for introgression (e.g., of drug-resistance genes) between species.