Stress Physiology in Free-ranging Female African Buffalo (Syncerus caffer) : Environmental Drivers, and Immunological and Infection Consequences

Fecal glucocorticoid metabolites (FGMs) are commonly used as indicators of an animal’s stress response in behavioral and eco-physiological studies. Stress in wild animals represents an immediate measure of the physiological response to changes in the environment, and, potentially, a prospective assessment of the animal’s health and well-being. In wild mammals, stress responses have been linked to changes in nutritional availability and predation, as well as anthropogenic disturbances including direct human contact and habitat loss. The recent global rise in infectious disease emergence in wildlife and humans, along with host stressors often implicated in adverse health consequences, raises the question whether stress has the potential to increase disease susceptibility, facilitate the spread of infections, and linking physiological effects of environmental change with disease dynamics. As such, a non-invasive measure of stress physiology may thus provide an integrative, mechanistically relevant measure of animal health at the interface of environmental drivers and immunological and infection consequences. Here I use a well-studied model system, African buffalo (Syncerus caffer), to investigate links between physiological stress (measured as FGMs) for studying disease processes and immune-mediated interactions between hosts in natural populations, and parasite/pathogen existence. For chapter 1, an adrenocorticotropic hormone (ACTH) experiment was performed on 12 buffalo to evaluate two commercially available FGM assays (radioimmunoassay and enzyme immunoassay) as a non-invasive tool for assessing stress in buffalo in field studies. For chapter 2 and 3, a longitudinal dataset of 200 buffalo (sampled every six months for four years) were used, to assess FGMs, and infections by viral and bacterial pathogens, gastrointestinal parasites, as well as a range of immune measures and physiological (hematological and biochemical) parameters. The ACTH-induced plasma cortisol peak was detectable in FGMs at 10 – 20 hours post-injection (chapter 1). Acute viral infections rather than chronic infections contributed to stress in buffalo, and consequently increased the risk of obtaining some chronic bacteria (chapter 2). While accounting for fixed animal effects and current exposures, results support the hypothesis that buffalo with elevated FGMs had elevated pro-inflammatory immune responses (chapter 3: increased IFNγ, Il-12 responses, bacterial competency, the proportion of neutrophils), but weak evidence suppressing responses to chronical subclinical infections, such as strongyles (chapter 3). Together, findings of chapter 1-3, suggest that measuring FGMs as a stress marker can be used as an indicative tool associated with animals’ environment, its physiological responses, some patterns of infectious diseases, and immunological consequences. Therefore, providing a widely used tool for scientists and wildlife managers interested in African buffalo management and conservation

Bovine tuberculosis disturbs parasite functional trait composition in African buffalo

Novel parasites can have wide-ranging impacts, not only on host populations, but also on the resident parasite community. Historically, impacts of novel parasites have been assessed by examining pairwise interactions between parasite species. However, parasite communities are complex networks of interacting species. Here we used multivariate taxonomic and trait-based approaches to determine how parasite community composition changed when African buffalo (Syncerus caffer) acquired an emerging disease, bovine tuberculosis (BTB). Both taxonomic and functional parasite richness increased significantly in animals that acquired BTB than in those that did not. Thus, the presence of BTB seems to catalyze extraordinary shifts in community composition. There were no differences in overall parasite taxonomic composition between infected and uninfected individuals, however. The trait-based analysis revealed an increase in direct-transmitted, quickly replicating parasites following BTB infection. This study demonstrates that trait-based approaches provide insight into parasite community dynamics in the context of emerging infections

Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host

Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as “infection resistance,” in which hosts delay or prevent infection, and “proliferation resistance,” in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2 = 0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection-resistant animals thus appear to follow a “fast” pace-of-life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health—such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population

Opposite outcomes of coinfection at individual and population scales

Coinfecting parasites and pathogens remain a leading challenge for global public health due to their consequences for individual-level infection risk and disease progression. However, a clear understanding of the population-level consequences of coinfection is lacking. Here, we constructed a model that includes three individual-level effects of coinfection: mortality, fecundity, and transmission. We used the model to investigate how these individual-level consequences of coinfection scale up to produce population-level infection patterns. To parameterize this model, we conducted a 4-y cohort study in African buffalo to estimate the individual-level effects of coinfection with two bacterial pathogens, bovine tuberculosis (bTB) and brucellosis, across a range of demographic and environmental contexts. At the individual level, our empirical results identified bTB as a risk factor for acquiring brucellosis, but we found no association between brucellosis and the risk of acquiring bTB. Both infections were associated with reductions in survival and neither infection was associated with reductions in fecundity. The model reproduced coinfection patterns in the data and predicted opposite impacts of coinfection at individual and population scales: Whereas bTB facilitated brucellosis infection at the individual level, our model predicted the presence of brucellosis to have a strong negative impact on bTB at the population level. In modeled populations where brucellosis was present, the endemic prevalence and basic reproduction number (R-0) of bTB were lower than in populations without brucellosis. Therefore, these results provide a data-driven example of competition between coinfecting pathogens that occurs when one pathogen facilitates secondary infections at the individual level

Data from: Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host

Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life-history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as ‘infection resistance’, in which hosts delay or prevent infection, and ‘proliferation resistance’, in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2=0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection resistant animals thus appear to follow a ‘fast’ pace of life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health- such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population

Multi-strain compatibility polymorphism between a parasite and its snail host, a neglected vector of schistosomiasis in Africa

Interactions between Schistosoma mansoni and its snail host are understood primarily through experimental work with one South American vector species, Biomphalaria glabrata. However, 90% of schistosomiasis transmission occurs in Africa, where a diversity of Biomphalaria species may serve as vectors. With the long-term goal of determining the genetic and ecological determinants of infection in African snail hosts, we developed genetic models of Biomphalaria sudanica, a principal vector in the African Great Lakes. We determined laboratory infection dynamics of two S. mansoni lines in four B. sudanica lines. We measured the effects of the following variables on infection success and the number of cercariae produced (infection intensity): (i) the combination of parasite and snail line; (ii) the dose of parasites; and (iii) the size of snail at time of exposure. We found one snail line to be almost completely incompatible with both parasite lines, while other snail lines showed a polymorphism in compatibility: compatible with one parasite line while incompatible with another. Interestingly, these patterns were opposite in some of the snail lines. The parasite-snail combination had no significant effect on the number of cercariae produced in a successful infection. Miracidia dose had a strong effect on infection status, in that higher doses led to a greater proportion of infected snails, but had no effect on infection intensity. In one of the snail-schistosome combinations, snail size at the time of exposure affected both infection status and cercarial production in that the smallest size class of snails (1.5–2.9 mm) had the highest infection rates, and produced the greatest number of cercariae, suggesting that immunity increases with age and development. The strongest predictor of the infection intensity was the size of snail at the time of shedding: 1 ​mm of snail growth equated to a 19% increase in cercarial production. These results strongly suggest that infection status is determined in part by the interaction between snail and schistosome genetic lines, consistent with a gene-for-gene or matching allele model. This foundational work provides rationale for determining the genetic interactions between African snails and schistosomes, which may be applied to control strategies

The genome and transcriptome of the snail Biomphalaria sudanica s.l.: immune gene diversification and highly polymorphic genomic regions in an important African vector of Schistosoma mansoni

Abstract Background Control and elimination of schistosomiasis is an arduous task, with current strategies proving inadequate to break transmission. Exploration of genetic approaches to interrupt Schistosoma mansoni transmission, the causative agent for human intestinal schistosomiasis in sub-Saharan Africa and South America, has led to genomic research of the snail vector hosts of the genus Biomphalaria. Few complete genomic resources exist, with African Biomphalaria species being particularly underrepresented despite this being where the majority of S. mansoni infections occur. Here we generate and annotate the first genome assembly of Biomphalaria sudanica sensu lato, a species responsible for S. mansoni transmission in lake and marsh habitats of the African Rift Valley. Supported by whole-genome diversity data among five inbred lines, we describe orthologs of immune-relevant gene regions in the South American vector B. glabrata and present a bioinformatic pipeline to identify candidate novel pathogen recognition receptors (PRRs). Results De novo genome and transcriptome assembly of inbred B. sudanica originating from the shoreline of Lake Victoria (Kisumu, Kenya) resulted in a haploid genome size of ~ 944.2 Mb (6,728 fragments, N50 = 1.067 Mb), comprising 23,598 genes (BUSCO = 93.6% complete). The B. sudanica genome contains orthologues to all described immune genes/regions tied to protection against S. mansoni in B. glabrata, including the polymorphic transmembrane clusters (PTC1 and PTC2), RADres, and other loci. The B. sudanica PTC2 candidate immune genomic region contained many PRR-like genes across a much wider genomic region than has been shown in B. glabrata, as well as a large inversion between species. High levels of intra-species nucleotide diversity were seen in PTC2, as well as in regions linked to PTC1 and RADres orthologues. Immune related and putative PRR gene families were significantly over-represented in the sub-set of B. sudanica genes determined as hyperdiverse, including high extracellular diversity in transmembrane genes, which could be under pathogen-mediated balancing selection. However, no overall expansion in immunity related genes was seen in African compared to South American lineages. Conclusions The B. sudanica genome and analyses presented here will facilitate future research in vector immune defense mechanisms against pathogens. This genomic/transcriptomic resource provides necessary data for the future development of molecular snail vector control/surveillance tools, facilitating schistosome transmission interruption mechanisms in Africa