Coinfection with malaria alters the dynamics and fitness of an intestinal nematode

Abstract

Infections with soil transmitted helminths (STHs) are highly prevalent in humans living in the intertropical region. While, in most cases, STHs can establish chronic infections, the dynamics of the infection can be altered when other parasites exploit the same host. These changes can have consequences in terms of the health of the host, the epidemiology of the disease (e.g., the duration of the infection and the inter-host transmission success) and the fitness of the parasite. Here, we investigated if the coinfection with Plasmodium yoelii alters the dynamics and the fitness of the murine nematode Heligmosomoides polygyrus. We found that, compared to single infected mice, coinfection produced an increase in the number of excreted eggs, while the biomass of adult worms in the intestine did not differ between single infected and coinfected mice. Moreover, the increase in egg excretion was also observed when Plasmodium infected hosts that had been harboring the nematode during the past four weeks (i.e., when the population size of adult worms can only decrease due to mortality). Therefore, the enhanced shedding of eggs reflects a plastic adjustment of worm fecundity to the environment provided by a coinfected host. This plastic response was modulated by the host Th2 immunity, as coinfection inhibited IL-4 and IL-13 gene expression, plasma levels of IL-5 and IL-13, and the expansion of GATA-3+ CD4+ T cells in the spleen. In agreement with this, experimentally inhibiting IL-13 with neutralizing antibodies reproduced the results observed in coinfected mice (an increase in egg excretion), while the administration of recombinant IL-13 reduced egg shedding. Interestingly, coinfection had a net positive effect on parasite fitness as shown by a longer persistence within the host and higher cumulative number of eggs excreted up to 99 days post-infection. Although the gene expression of Th2 cytokines was lower at day 99 p.i., coinfected mice still had a downregulated expression compared to single infected hosts. These results show that coinfection with Plasmodium has the potential to affect the epidemiology of STHs by increasing the number of eggs excreted over the whole infectious period and maintaining a larger environmental reservoir of transmissible stages. Author SummaryCoinfection between soil-transmitted helminths and malaria is common in several countries of the intertropical region, especially among the most vulnerable populations. Coinfection has the potential to worsen the symptoms caused by malaria, therefore it is important to understand what are the epidemiological and ecological factors that promote the occurrence of coinfection. Transmission of soil-transmitted helminths usually requires human contact with transmissible stages (parasitic eggs or larvae) in the environment; therefore, high egg excretion in the feces of infected people is a key factor contributing to maintain a reservoir of infective stages from which humans can get infected. In this study, we experimentally investigated whether coinfection with malaria alters the dynamics (egg excretion, infection persistence) of a murine intestinal nematode. We found that hosts infected with malaria and subsequently infected with the nematode, excreted more nematode eggs for a longer period, compared to single infected hosts. These changes were mediated by an impaired Th2 immune response in coinfected hosts. These results suggest that malaria coinfection produces positive feedback on key epidemiological traits of the nematode that can further enhance the risk of malaria/helminths cooccurrence.