Genetic parameters for resistance to gastrointestinal nematodes in sheep: a meta-analysis.

Gastrointestinal nematodes (GINs) are damaging parasites of global sheep populations. The key weapons in fighting GINs have been anthelmintic drugs, but the emergence of drug-resistant parasites has meant that alternative control methods are needed. One of these alternatives is to breed for enhanced host resistance to GINs, and decades of research have estimated the genetic contribution to different measures of resistance to GINs and their genetic correlations with other desirable performance traits. It is clear that parasite resistance is a heritable trait that can be selected for. Despite this consensus, estimates of both heritability of resistance and genetic correlations with other traits vary widely between studies, and the reasons for this variation have not been examined. This study provides a comprehensive and quantitative meta-analysis of genetic parameters for resistance to GINs in sheep, including measures of worm burden (faecal egg counts, FECs), anti-parasite immunity (GIN-specific antibodies), and parasite-induced pathology (FAMACHA© scores). Analysis of 591 heritability estimates from 121 studies revealed a global heritability estimate for resistance to GINs of 0.25 (95% confidence interval (CI) = 0.22-0.27) that was stable across breeds, ages, geographical location and analytical methods. Meanwhile, analysis of 559 genetic correlations from 54 studies revealed that resistance to GINs overall has a positive genetic correlation of +0.10 (95% CI = 0.02-0.19) with performance traits, and that this was consistent across breeds, ages, sexes and analytical methods. Importantly, the direction of the genetic correlation varied with the resistance trait measured: while FECs and FAMACHA© scores were favourably correlated with performance traits, adaptive immune markers were unfavourably correlated, suggesting that selection for enhanced immune responses to GINs could reduce animal performance. Overall, the results suggest that breeding for resistance to GINs should continue to form part of integrated management programs to reduce the impact of parasites on health and performance, but that selection for enhanced immune responses should be avoided.

The cost of host genetic resistance on body condition: Evidence from divergently selected sheep.

Trade-offs between host resistance to parasites and host growth or reproduction can occur due to allocation of limited available resources between competing demands. To predict potential trade-offs arising from genetic selection for host resistance, a better understanding of the associated nutritional costs is required. Here, we studied resistance costs by using sheep from lines divergently selected on their resistance to a common blood-feeding gastro-intestinal parasite (Haemonchus contortus). First, we assessed the effects of selection for high or low host resistance on condition traits (body weight, back fat, and muscle thickness) and infection traits (parasite fecal egg excretion and loss in blood haematocrit) at various life stages, in particular during the periparturient period when resource allocation to immunity may limit host resistance. Second, we analysed the condition-infection relationship to detect a possible trade-off, in particular during the periparturient period. We experimentally infected young females in four stages over their first 2 years of life, including twice around parturition (at 1 year and at 2 years of age). Linear mixed-model analyses revealed a large and consistent between-line difference in infection traits during growth and outside of the periparturient period, whereas this difference was strongly attenuated during the periparturient period. Despite their different responses to infection, lines had similar body condition traits. Using covariance decomposition, we then found that the phenotypic relationship between infection and condition was dominated by direct infection costs arising from parasite development within the host. Accounting for these within-individual effects, a cost of resistance on body weight was detected among ewes during their first reproduction. Although this cost and the reproductive constraint on resistance are unlikely to represent a major concern for animal breeding in nutrient-rich environments, this study provides important new insights regarding the nutritional costs of parasite resistance at different lifestages and how these may affect response to selection.

Long-term temporal trends in gastrointestinal parasite infection in wild Soay sheep.

Monitoring the prevalence and abundance of parasites over time is important for addressing their potential impact on host life histories, immunological profiles and their influence as a selective force. Only long-term ecological studies have the potential to shed light on both the temporal trends in infection prevalence and abundance and the drivers of such trends, because of their ability to dissect drivers that may be confounded over shorter time scales. Despite this, only a relatively small number of such studies exist. Here, we analysed changes in the prevalence and abundance of gastrointestinal parasites in the wild Soay sheep population of St. Kilda across 31 years. The host population density (PD) has increased across the study, and PD is known to increase parasite transmission, but we found that PD and year explained temporal variation in parasite prevalence and abundance independently. Prevalence of both strongyle nematodes and coccidian microparasites increased during the study, and this effect varied between lambs, yearlings and adults. Meanwhile, abundance of strongyles was more strongly linked to host PD than to temporal (yearly) dynamics, while abundance of coccidia showed a strong temporal trend without any influence of PD. Strikingly, coccidian abundance increased 3-fold across the course of the study in lambs, while increases in yearlings and adults were negligible. Our decades-long, intensive, individual-based study will enable the role of environmental change and selection pressures in driving these dynamics to be determined, potentially providing unparalleled insight into the drivers of temporal variation in parasite dynamics in the wild.

Prospective Longitudinal Study of Putative Agents Involved in Complex Gill Disorder in Atlantic salmon (Salmo salar).

Complex gill disorder (CGD) is an important condition in Atlantic salmon aquaculture, but the roles of the putative aetiological agents in the pathogenesis are uncertain. A longitudinal study was undertaken on two salmon farms in Scotland to determine the variations in loads of CGD-associated pathogens (Desmozoon lepeophtherii, Candidatus Branchiomonas cysticola, salmon gill pox virus (SGPV) and Neoparamoeba perurans) estimated by quantitative PCR. In freshwater, Ca. B. cysticola and SGPV were detected in both populations, but all four pathogens were detected on both farms during the marine stage. Candidatus B. cysticola and D. lepeophtherii were detected frequently, with SGPV detected sporadically. In the marine phase, increased N. perurans loads associated significantly (p < 0.05) with increases in semi-quantitative histological gill-score (HGS). Increased Ca. B. cysticola load associated significantly (p < 0.05) with increased HGS when only Farm B was analysed. Higher loads of D. lepeophtherii were associated significantly (p < 0.05) with increased HGS on Farm B despite the absence of D. lepeophtherii-type microvesicles. Variations in SGPV were not associated significantly (p > 0.05) with changes in HSG. This study also showed that water temperature (season) and certain management factors were associated with higher HGS. This increase in histological gill lesions will have a deleterious impact on fish health and welfare, and production performance.

Differences in the protection elicited by a recombinant Teladorsagia circumcincta vaccine in weaned lambs of two Canarian sheep breeds.

Gastrointestinal nematode (GIN) infections are a serious drawback on small ruminant production. Since anthelmintic resistance has extended, optimisation of alternative non-chemical control strategies has attracted interest. Recently, a prototype recombinant vaccine protected immunologically mature sheep from Texel-cross and Canaria Sheep breeds against Teladorsagia circumcincta. The level of protective immunity stimulated by the vaccine varied between individuals and with age. Previous studies suggest that Canaria Hair Breed (CHB) sheep is naturally resistant to GIN infection, with some evidence suggesting that this protection is present in young lambs. Here, we sought to enhance this resistance by immunising three-month-old CHB lambs with a T. circumcincta prototype recombinant vaccine. Following vaccination and a larval challenge period, levels of protection against T. circumcincta infection were compared in CHB lambs with Canaria Sheep (CS) lambs (a breed considered less resistant to GIN). Lambs from the resistant CHB breed appeared to respond more favourably to vaccination, shedding 63% fewer eggs over the sampling period than unvaccinated CHB lambs. No protection was evident in CS vaccinated lambs. At post-mortem, CHB vaccine recipients had a 68% reduction in mean total worm burden, and female worms were significantly shorter and contained fewer eggs in utero compared to unvaccinated CHB lambs. A higher anti-parasite IgG2 level was detected in immunised CHB lambs compared to unvaccinated control CHB animals, with data suggesting that IgA, globular leucocytes, CD45RA+, CD4+ and CD8+ T cells are implicated in this protective response. The development of effective immunity in vaccinated CHB lambs did not reduce lamb growth rate as immunised CHB lambs had a significantly higher average daily weight gain after challenge than their unvaccinated counterparts. Therefore, the protection of CHB lambs was enhanced by immunisation at weaning, suggesting a synergistic effect when combining vaccination with presumed genetic resistance.

Longitudinal dynamics of co-infecting gastrointestinal parasites in a wild sheep population.

Within-year variation in infection is a ubiquitous feature of natural populations, but is determined by a complex interplay of environmental, parasitological and host factors. At the same time, co-infection is the norm in the wild. Longitudinal dynamics of co-infecting parasites may therefore be further complicated by covariation across multiple parasites. Here, we used fecal parasite egg and oocyst counts collected repeatedly from individually marked wild Soay sheep to investigate seasonal dynamics of six gastrointestinal parasite groups. Prevalence and abundance tended to be higher in spring and summer, and abundance was higher in lambs compared to adults. We found that within-year variation in highly prevalent strongyle nematode counts was dependent on adult reproductive status, where reproductive ewes had distinct dynamics compared to males and barren ewes. For similarly prevalent coccidia we found an overall peak in oocyst counts in spring but no differences among males, barren and pregnant ewes. Using multivariate mixed-effects models, we further show that apparent positive correlation between strongyle and coccidia counts was driven by short-term within-individual changes in both counts rather than long-term among-individual covariation. Overall, these results demonstrate that seasonality varies across demographic and parasite groups and highlight the value of investigating co-infection dynamics over time.

Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta.

Due to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

The influence of liver fluke infection on production in sheep and cattle: a meta-analysis.

Liver flukes (Fasciola spp.) are important parasites of ruminant livestock worldwide, causing profound damage to animal health and productivity. Many reviews have discussed the results of decades of research on the impact of fluke on livestock traits such as weight gain and milk production, but there have been no known attempts to collate previous research in a quantitative manner or to determine the factors that vary between studies that find substantial effects of fluke and others concluding that effects of fluke are negligible. Here, we use meta-analysis to provide quantitative "global" estimates of the impact of liver fluke on animal performance, and to identify elements of study design ("moderators") that influence variation between studies in their outcome. A literature search provided 233 comparisons of performance in fluke-infected and uninfected animals. We standardised these data as log response ratios and calculated effect size variances to weight studies by the accuracy of their estimates. We performed multi-level meta-analysis to estimate effects of fluke infection on daily weight gain, live weight, carcass weight, total weight gain and milk production. There were statistically-supported negative effects of fluke infection on daily weight gain, live weight and carcass weight (9%, 6% and 0.6% reductions, respectively), but not on total weight gain or milk production. A mixed-effects meta-analysis revealed that studies of younger animals found more severe effects of fluke on weight gain and that effects on live weight increased with time since infection. Limitations to the data that could be analysed, including a lack of statistical reporting in older papers and variation in the outcome variables measured, may have explained the relatively limited influence of modifiers that we detected. Our results provide, to our knowledge, the first quantitative estimate of the impact of liver fluke on performance across studies and highlight some elements of study design that can influence conclusions.

Maternally derived anti-helminth antibodies predict offspring survival in a wild mammal.

The transfer of antibodies from mother to offspring provides crucial protection against infection to offspring during early life in humans and domestic and laboratory animals. However, few studies have tested the consequences of variation in maternal antibody transfer for offspring fitness in the wild. Further, separating the immunoprotective effects of antibodies from their association with nutritional resources provided by mothers is difficult. Here, we measured plasma levels of total and parasite-specific antibodies in neonatal (less than 10 days old) wild Soay sheep over 25 years to quantify variation in maternal antibody transfer and test its association with offspring survival. Maternal antibody transfer was predicted by maternal age and previous antibody responses, and was consistent within mothers across years. Neonatal total IgG antibody levels were positively related to early growth, suggesting they reflected nutritional transfer. Neonatal parasite-specific IgG levels positively predicted first-year survival, independent of lamb weight, total IgG levels and subsequent lamb parasite-specific antibody levels. This relationship was partly mediated via an indirect negative association with parasite burden. We show that among-female variation in maternal antibody transfer can have long-term effects on offspring growth, parasite burden and fitness in the wild, and is likely to impact naturally occurring host-parasite dynamics.

Survival costs of reproduction are mediated by parasite infection in wild Soay sheep.

A trade-off between current and future fitness potentially explains variation in life-history strategies. A proposed mechanism behind this is parasite-mediated reproductive costs: individuals that allocate more resources to reproduction have fewer to allocate to defence against parasites, reducing future fitness. We examined how reproduction influenced faecal egg counts (FEC) of strongyle nematodes using data collected between 1989 and 2008 from a wild population of Soay sheep in the St. Kilda archipelago, Scotland (741 individuals). Increased reproduction was associated with increased FEC during the lambing season: females that gave birth, and particularly those that weaned a lamb, had higher FEC than females that failed to reproduce. Structural equation modelling revealed future reproductive costs: a positive effect of reproduction on spring FEC and a negative effect on summer body weight were negatively associated with overwinter survival. Overall, we provide evidence that parasite resistance and body weight are important mediators of survival costs of reproduction.

Early-life environment and differences in costs of reproduction in a preindustrial human population.

Reproduction is predicted to trade-off with long-term maternal survival, but the survival costs often vary between individuals, cohorts and populations, limiting our understanding of this trade-off, which is central to life-history theory. One potential factor generating variation in reproductive costs is variation in developmental conditions, but the role of early-life environment in modifying the reproduction-survival trade-off has rarely been investigated. We quantified the effect of early-life environment on the trade-off between female reproduction and survival in pre-industrial humans by analysing individual-based life-history data for >80 birth cohorts collected from Finnish church records, and between-year variation in local crop yields, annual spring temperature, and infant mortality as proxies of early-life environment. We predicted that women born during poor environmental conditions would show higher costs of reproduction in terms of survival compared to women born in better conditions. We found profound variation between the studied cohorts in the correlation between reproduction and longevity and in the early-life environment these cohorts were exposed to, but no evidence that differences in early-life environment or access to wealth affected the trade-off between reproduction and survival. Our results therefore do not support the hypothesis that differences in developmental conditions underlie the observed heterogeneity in reproduction-survival trade-off between individuals.

Sex differences in adult mortality rate mediated by early-life environmental conditions.

Variation in sex differences is affected by both genetic and environmental variation, with rapid change in sex differences being more likely due to environmental change. One case of rapid change in sex differences is human lifespan, which has become increasingly female-biased in recent centuries. Long-term consequences of variation in the early-life environment may, in part, explain such variation in sex differences, but whether the early-life environment mediates sex differences in life-history traits is poorly understood in animals. Combining longitudinal data on 60 cohorts of pre-industrial Finns with environmental data, we show that the early-life environment is associated with sex differences in adult mortality and expected lifespan. Specifically, low infant survival rates and high rye yields (an important food source) in early-life are associated with female-bias in adult lifespan. These results support the hypothesis that environmental change has the potential to affect sex differences in life-history traits in natural populations of long-lived mammals.

Evidence for Selection-by-Environment but Not Genotype-by-Environment Interactions for Fitness-Related Traits in a Wild Mammal Population.

How do environmental conditions influence selection and genetic variation in wild populations? There is widespread evidence for selection-by-environment interactions (S*E), but we reviewed studies of natural populations estimating the extent of genotype-by-environment interactions (G*E) in response to natural variation in environmental conditions and found that evidence for G*E appears to be rare within single populations in the wild. Studies estimating the simultaneous impact of environmental variation on both selection and genetic variation are especially scarce. Here, we used 24 years of data collected from a wild Soay sheep population to quantify how an important environmental variable, population density, impacts upon (1) selection through annual contribution to fitness and (2) expression of genetic variation, in six morphological and life history traits: body weight, hind leg length, parasite burden, horn length, horn growth, and testicular circumference. Our results supported the existence of S*E: selection was stronger in years of higher population density for all traits apart from horn growth, with directional selection being stronger under more adverse conditions. Quantitative genetic models revealed significant additive genetic variance for body weight, leg length, parasite burden, horn length, and testes size, but not for horn growth or our measure of annual fitness. However, random regression models found variation between individuals in their responses to the environment in only three traits, and did not support the presence of G*E for any trait. Our analyses of St Kilda Soay sheep data thus concurs with our cross-study review that, while natural environmental variation within a population can profoundly alter the strength of selection on phenotypic traits, there is less evidence for its effect on the expression of genetic variance in the wild.

Parasite-associated mortality in a long-lived mammal: Variation with host age, sex, and reproduction.

Parasites can cause severe host morbidity and threaten survival. As parasites are generally aggregated within certain host demographics, they are likely to affect a small proportion of the entire population, with specific hosts being at particular risk. However, little is known as to whether increased host mortality from parasitic causes is experienced by specific host demographics. Outside of theoretical studies, there is a paucity of literature concerning dynamics of parasite-associated host mortality. Empirical evidence mainly focuses on short-lived hosts or model systems, with data lacking from long-lived wild or semi-wild vertebrate populations. We investigated parasite-associated mortality utilizing a multigenerational database of mortality, health, and reproductive data for over 4,000 semi-captive timber elephants (Elephas maximus), with known causes of death for mortality events. We determined variation in mortality according to a number of host traits that are commonly associated with variation in parasitism within mammals: age, sex, and reproductive investment in females. We found that potentially parasite-associated mortality varied significantly across elephant ages, with individuals at extremes of lifespan (young and old) at highest risk. Mortality probability was significantly higher for males across all ages. Female reproducers experienced a lower probability of potentially parasite-associated mortality than females who did not reproduce at any investigated time frame. Our results demonstrate increased potentially parasite-associated mortality within particular demographic groups. These groups (males, juveniles, elderly adults) have been identified in other studies as susceptible to parasitism, stressing the need for further work investigating links between infection and mortality. Furthermore, we show variation between reproductive and non-reproductive females, with mothers being less at risk of potentially parasite mortality than nonreproducers.

Early-life disease exposure and associations with adult survival, cause of death, and reproductive success in preindustrial humans.

A leading hypothesis proposes that increased human life span since 1850 has resulted from decreased exposure to childhood infections, which has reduced chronic inflammation and later-life mortality rates, particularly from cardiovascular disease, stroke, and cancer. Early-life cohort mortality rate often predicts later-life survival in humans, but such associations could arise from factors other than disease exposure. Additionally, the impact of early-life disease exposure on reproduction remains unknown, and thus previous work ignores a major component of fitness through which selection acts upon life-history strategy. We collected data from seven 18th- and 19th-century Finnish populations experiencing naturally varying mortality and fertility levels. We quantified early-life disease exposure as the detrended child mortality rate from infectious diseases during an individual's first 5 y, controlling for important social factors. We found no support for an association between early-life disease exposure and all-cause mortality risk after age 15 or 50. We also found no link between early-life disease exposure and probability of death specifically from cardiovascular disease, stroke, or cancer. Independent of survival, there was no evidence to support associations between early-life disease exposure and any of several aspects of reproductive performance, including lifetime reproductive success and age at first birth, in either males or females. Our results do not support the prevailing assertion that exposure to infectious diseases in early life has long-lasting associations with later-life all-cause mortality risk or mortality putatively linked to chronic inflammation. Variation in adulthood conditions could therefore be the most likely source of recent increases in adult life span.

Elephants born in the high stress season have faster reproductive ageing.

Senescent declines in reproduction and survival are found across the tree of life, but little is known of the factors causing individual variation in reproductive ageing rates. One contributor may be variation in early developmental conditions, but only a few studies quantify the effects of early environment on reproductive ageing and none concern comparably long-lived species to humans. We determine the effects of 'stressful' birth conditions on lifetime reproduction in a large semi-captive population of Asian elephants (Elephas maximus). We categorise birth month into stressful vs. not-stressful periods based on longitudinal measures of glucocorticoid metabolites in reproductive-aged females, which peak during heavy workload and the start of the monsoon in June-August. Females born in these months exhibit faster reproductive senescence in adulthood and have significantly reduced lifetime reproductive success than their counterparts born at other times of year. Improving developmental conditions could therefore delay reproductive ageing in species as long-lived as humans.

A standardised faecal collection protocol for intestinal helminth egg counts in Asian elephants, Elephas maximus.

The quantitative assessment of parasite infection is necessary to measure, manage and reduce infection risk in both wild and captive animal populations. Traditional faecal flotation methods which aim to quantify parasite burden, such as the McMaster egg counting technique, are widely used in veterinary medicine, agricultural management and wildlife parasitology. Although many modifications to the McMaster method exist, few account for systematic variation in parasite egg output which may lead to inaccurate estimations of infection intensity through faecal egg counts (FEC). To adapt the McMaster method for use in sampling Asian elephants (Elephas maximus), we tested a number of possible sources of error regarding faecal sampling, focussing on helminth eggs and using a population of over 120 semi-captive elephants distributed across northern Myanmar. These included time of day of defecation, effects of storage in 10% formalin and 10% formol saline and variation in egg distribution between and within faecal boluses. We found no significant difference in the distribution of helminth eggs within faecal matter or for different defecation times, however, storage in formol saline and formalin significantly decreased egg recovery. This is the first study to analyse several collection and storage aspects of a widely-used traditional parasitology method for helminth parasites of E. maximus using known host individuals. We suggest that for the modified McMaster technique, a minimum of one fresh sample per elephant collected from any freshly produced bolus in the total faecal matter and at any point within a 7.5 h time period (7.30am-2.55 pm) will consistently represent parasite load. This study defines a protocol which may be used to test pre-analytic factors and effectively determine infection load in species which produce large quantities of vegetative faeces, such as non-ruminant megaherbivores.