Assessment of the therapeutic efficacy of various drugs against cryptosporidiosis in calves

The purpose of the research is studying the spread of cryptosporidiosis in calves and assessment of the extenseeffectiveness of antiprotozoal drugs.Materials and methods. The spread, seasonal and age-specific trends of cryptosporidiosis was studied on 395 spontaneously infected animals of five age groups. The first group was formed of calves up to 10 days of age, the second group of calves aged from 11 days to 2 months, the third group of calves from 2 to 4 months, the fourth group of calves from 4 to 6 months of age, and the fifth group of young animals from 6 months up to 1 year. To assess the efficacy of various drugs against cryptosporidiosis in calves, 5 groups of infected animals (4 experimental and 1 control), 10 animals each, were formed according to the principle of analogous pairs. The infection rate in cattle was determined by generally accepted coprological flotation methods, as well as by native smears with further staining according to Ziehl-Nielsen. We also considered clinical signs of cryptosporidiosis (diarrhea, dehydration).Results and discussion. We established the widespread occurrence of cryptosporidiosis in cattle on the farms of the Igrinsky, Uvinsky, Zavyalovsky Districts of the Udmurt Republic. The infection rate ranged from 20.25 to 80.0%. The largest percentage of infected calves was observed in the winter-spring period which was associated with the synchronization of the reproductive cycles of cows and a decrease in the resistance of the animal organism. Toltarox 5% and Galokur drugs in work environments showed 100% extense-effectiveness. It is not recommended to apply Amprolium 25% on these farms due to the low efficacy and the development of parasite resistance to this drug.

Toxoplasmosis: Current and Emerging Parasite Druggable Targets

Toxoplasmosis is a prevalent disease affecting a wide range of hosts including approximately one-third of the human population. It is caused by the sporozoan parasite Toxoplasma gondii (T. gondii), which instigates a range of symptoms, manifesting as acute and chronic forms and varying from ocular to deleterious congenital or neuro-toxoplasmosis. Toxoplasmosis may cause serious health problems in fetuses, newborns, and immunocompromised patients. Recently, associations between toxoplasmosis and various neuropathies and different types of cancer were documented. In the veterinary sector, toxoplasmosis results in recurring abortions, leading to significant economic losses. Treatment of toxoplasmosis remains intricate and encompasses general antiparasitic and antibacterial drugs. The efficacy of these drugs is hindered by intolerance, side effects, and emergence of parasite resistance. Furthermore, all currently used drugs in the clinic target acute toxoplasmosis, with no or little effect on the chronic form. In this review, we will provide a comprehensive overview on the currently used and emergent drugs and their respective parasitic targets to combat toxoplasmosis. We will also abridge the repurposing of certain drugs, their targets, and highlight future druggable targets to enhance the therapeutic efficacy against toxoplasmosis, hence lessening its burden and potentially alleviating the complications of its associated diseases.

Comparison between methods for measuring fecal egg count and estimating genetic parameters for gastrointestinal parasite resistance traits in sheep

Fecal egg count (FEC) is an indicative measurement for parasite infection in sheep. Different FEC methods may show inconsistent results. Not accounting for inconsistencies can be problematic when integrating measurements from different FEC methods for genetic evaluation. The objectives of this study were to evaluate the difference in means and variances between two fecal egg counting methods used in sheep, the Modified McMaster (LMMR) and the Triple Chamber McMaster (LTCM); to estimate variance components for the two FEC methods, treating them as two different traits; and to integrate FEC data from the two different methods and estimate genetic parameters for FEC and other gastrointestinal parasite resistance traits. Fecal samples were collected from a commercial Rideau-Arcott sheep farm in Ontario. Fecal egg counting was performed using both Modified McMaster and the Triple Chamber McMaster methods. Other parasite resistance trait records were collected from the same farm including eye score (FAMACHA ©), body condition score (BCS), and body weight (WT). The two FEC methods were highly genetically (0.94) and phenotypically (0.88) correlated. However, the mean and variance between the two FEC methods were significantly different (P < 0.0001). Therefore, re-scaling is required prior to integrating data from the different methods. For the multiple trait analysis, data from the two fecal egg counting methods were integrated (LFEC) by using records for the LMMR when available and replacing missing records with re-standardized LTCM records converted to the same mean and variance of LMMR. Heritability estimates were 0.12 ± 0.04, 0.07 ± 0.05 , 0.17 ± 0.06, and 0.24 ± 0.07 for LFEC egg count, FAMACHA ©, BCS, and WT, respectively. The estimated genetic correlations between fecal egg count and the other parasite resistance traits were low and not significant (P>0.05) for FAMACHA © (r= 0.24 ± 0.32) and WT (r= 0.22 ± 0.19), and essentially zero for BCS (r= -0.03 ± 0.25), suggesting little to no benefit of using such traits as indicators for LFEC.

A paradox of parasite resistance: Disease-driven trophic cascades increase the cost of resistance, selecting for lower resistance with parasites than without them

Most evolutionary theory predicts that, during epidemics, hosts will evolve higher resistance to parasites that kill them. Here, we provide an alternative to that typical expectation, with an explanation centered on resource feedbacks. When resistance is costly, hosts evolve decreasing resistance without parasites, as expected. But with parasites, hosts can evolve lower resistance than they would in the absence of parasites. This outcome arises in an eco-evolutionary model when four conditions are met: first, resistance has a fecundity cost (here, via decreased foraging/exposure rate); second, resources increase during epidemics via trophic cascades; third, increased resources magnify the benefit of maintaining a fast foraging rate, thereby magnifying the cost of evolving a slower foraging/exposure rate (i.e., resistance); fourth, that amplification of the cost outweighs the benefit of resistance. When these conditions are met, hosts evolve lower resistance than without parasites. This phenomenon was previously observed in a mesocosm experiment with fungal parasites, zooplankton hosts, and algal resources. Re-analyzing this experiment produced evidence for our model's mechanism. Thus, both model and experiment indicate that, via resource feedbacks, parasites can counterintuitively select against resistance.

Sickle Cell Anemia and Babesia Infection

Babesia is an intraerythrocytic, obligate Apicomplexan parasite that has, in the last century, been implicated in human infections via zoonosis and is now widespread, especially in parts of the USA and Europe. It is naturally transmitted by the bite of a tick, but transfused blood from infected donors has also proven to be a major source of transmission. When infected, most humans are clinically asymptomatic, but the parasite can prove to be lethal when it infects immunocompromised individuals. Hemolysis and anemia are two common symptoms that accompany many infectious diseases, and this is particularly true of parasitic diseases that target red cells. Clinically, this becomes an acute problem for subjects who are prone to hemolysis and depend on frequent transfusions, like patients with sickle cell anemia or thalassemia. Little is known about Babesia’s pathogenesis in these hemoglobinopathies, and most parallels are drawn from its evolutionarily related Plasmodium parasite which shares the same environmental niche, the RBCs, in the human host. In vitro as well as in vivo Babesia-infected mouse sickle cell disease (SCD) models support the inhibition of intra-erythrocytic parasite proliferation, but mechanisms driving the protection of such hemoglobinopathies against infection are not fully studied. This review provides an overview of our current knowledge of Babesia infection and hemoglobinopathies, focusing on possible mechanisms behind this parasite resistance and the clinical repercussions faced by Babesia-infected human hosts harboring mutations in their globin gene.

PSVIII-10 Genome-wide CNV analysis unravels a deletion associated with parasite resistance in Florida native sheep

Florida Native sheep is an indigenous breed from Florida and expresses superior parasite resistance. Previous candidate and genome wide association studies with Florida Native sheep have identified single nucleotide polymorphisms with additive and non-additive effects associated with parasite resistance. However, the role of other potential DNA variants, such as copy number variants (CNVs), controlling this complex trait have not been evaluated. The objective of the present study was to investigate the importance of CNVs on resistance to natural Haemonchus contortus infections in Florida Native sheep. A total of 200 sheep were evaluated in the present study. Phenotypic records included fecal egg count (FEC, eggs/gram), FAMACHA score, and packed cell volume (PCV, %). Sheep were genotyped using the GGP Ovine 50K SNP chip. The copy number analysis was used to identify CNVs using the univariate method. A total of 170 animals with CNVs and phenotypic data were used for the association testing. Association tests were carried out using single linear regression and Principal Component Analysis (PCA) correction to identify CNVs associated with FEC, FAMACHA, and PCV. To confirm our results, a second association testing using the correlation-trend test with PCA correction was performed. Significant CNVs were detected when their adjusted p-value was < 0.05 after FDR correction. A deletion CNV in chromosome 21 was associated with FEC. This DNA variant was located in intron 2 of RAB3IL gene and overlapped a QTL associated with changes in eosinophil number. Our study demonstrated for the first time that CNVs could be potentially involved with parasite resistance in this heritage sheep breed.

PSVIII-8 Genetic parameters for parasite resistance in an endangered and heritage sheep breed from Florida

The Florida Native Sheep is one of the oldest sheep breeds in the United States. This heritage breed from Florida, naturally adapted to humid and hot climate conditions, is one of the most parasite resistant breeds from the Southern US. However, only approximately 1,000 individuals remain alive in the world. Therefore, conservation efforts and breeding programs are critical for survival of this breed. The objective of this research was to estimate genetic parameters for parasite resistance and body condition score in Florida Native sheep. The pedigree file contained 695 animals born between 2018 and 2020 and included 279 individuals with genotypes (38,429 SNP after quality control). The dataset contained 365 animals with phenotypic records at 38 days post-infection (natural Haemonchus contortus infection) for fecal egg count (FEC), blood packed count volume (PCV), FAMACHA score (FAM), and body condition score (BCS). Genetic parameters were estimated using a multi-trait model with a Bayesian implementation in the GIBBS3F90 program. Heritabilities were 0.38 0.07, 0.47 0.05, 0.27 0.04, and 0.52 0.07 for FEC, PCV, FAM, and BCS. Genetic correlations among parasite resistance traits were high and favorable: -0.82 0.06 (FEC-PCV), 0.83 0.07 (FEC-FAM), and -0.94 0.03 (PCV-FAM). Genetic correlations among parasite resistance traits and BCS were -0.42 0.11 (FEC-BCS), 0.75 0.09 (PCV-BCS), and -0.82 0.05 (FAM-BCS). Genetic progress for parasite resistance is possible in Florida Native sheep. The FAMACHA score is a phenotypic parameter easy to record in sheep; therefore, genetic selection for this trait can be effective to improve the remaining traits.

Colony fitness increases in the honey bee at queen mating frequencies higher than genetic diversity asymptote

Across the eusocial Hymenoptera, a queen’s mating frequency is positively associated with her workers’ genetic diversity and colony’s fitness. Over 90% of a colony’s diversity potential is achieved by its mother’s tenth effective mating (me); however, many females mate at levels of me > 10, a zone we here call hyperpolyandry. We compared honey bee colony fitness at mating levels near and above this genetic diversity asymptote. We were interested in how hyperpolyandry affects colony phenotypes arising from both common tasks (brood care) and rare specialized tasks (parasite resistance). We used an unselected wild line of bees and a Varroa Sensitive Hygiene (VSH) line selected to resist the parasite Varroa destructor. Virgin queens were instrumentally inseminated to replicate the following queen/colony conditions: (1) VSH semen/low polyandry (observed mating number = mo = 9), (2) VSH semen/high polyandry (mo = 54), (3) wild type semen/low polyandry, or (4) wild semen/high polyandry. There was a positive effect of polyandry on brood survival, an outcome of common tasks, with highest values at mo = 54. There was an interaction between polyandry and genetics such that differences between genetic lines expressed only at mo = 54, with fewer mites in VSH colonies. These results are consistent with two hypotheses for the evolution of mating levels in excess of the genetic diversity asymptote: hyperpolyandry improves colony fitness by (1) optimizing genotype compositions for common tasks and (2) by capturing rare specialist allele combinations, resisting cliff-edge ecological catastrophes. Significance statement Polyandry is a female’s practice of mating with several males, storing their sperm, and using it to produce one or more clutches of genetically diverse offspring. In the social Hymenoptera, polyandry increases the genetic diversity and task efficiency of workers, leading to improved colony fitness. Over 90% of the increase in a colony’s diversity potential is achieved by its mother’s tenth mating; however, many females practice hyperpolyandry, a term we reserve here for mating levels above this genetic diversity asymptote. We show that a token of colony fitness arising from common tasks, brood survival, improves universally as one moves from sub- to hyperpolyandrous mating levels. However, a colony phenotype arising from a rare parasite resistance task is only expressed in the presence of the controlling alleles and under conditions of hyperpolyandry. These results suggest adaptive mechanisms by which hyperpolyandry could evolve.