Bovine immune responses to Fasciola hepatica during the early stages of infection

Fasciola hepatica (liver fluke), is a trematode parasite, particularly of ruminants, that is found throughout the world. Sheep show no resistance to the parasite, cattle may develop partial resistance and rats show complete resistance, which is immune-mediated, to challenge infections. In rats, resistance occurs early during infection, at the level of the gut and/or peritoneum. Little is known regarding the natural immune responses in cattle that occur during this period.This study was designed to investigate the effect that pre-exposure of cattle to 1-2 and 5-6 day old flukes had upon subsequent challenge infections, when compared to naive and chronically infected animals. Infection parameters, together with peripheral and local cellular and antibody responses to various F. hepatica protein preparations were investigated.A primary exposure to 5-6 day old flukes, terminated by triclabendazole treatment, was found to reduce the degree of liver damage and eosinophilia experienced after a challenge infection. Lower levels of the enzymes gammaglutamyl transferase and glutamate dehydrogenase were detected in sera, compared to those in naive animals (P < 0.05). Eosinophilia was also reduced (P < 0.01), as was egg output in the faeces during the early patent period (P < 0.05). Calves that were pre-exposed to 1-2 day old flukes showed no significant differences in the levels of these parameters, when compared to their naive counterparts.Sera taken prior to the secondary challenge from pre-exposed animals and those receiving an unterminated primary infection recognised a variety of proteins in Western blots of whole adult fluke somatic antigen (WFA) and excretory-secretory (ES) preparations. The IgGl antibody response to protein bands of 96-82, 76-68 and 60-52 kDa predominated. After secondary challenge the response of the chronically infected animals to these protein species was reduced and extremely strong recognition of bands in the region 30-28 kDa was observed. Pre-exposed animals maintained the response to the higher weight bands, showing a similar, but initially stronger recognition pattern, to that of naive challenged animals. The lower weight protein bands were not detected in these groups until much later.The IgGl/IgG2 isotype antibody response to purified cathepsin and haemcontaining high molecular weight fractions were also examined by ELISA. A ii monophasic, IgGl response was seen to the cathepsin fraction, which occurred late during the infection process and was not seen prior to secondary challenge in any of the four groups. A mixed IgGl/IgG2 antibody response to the haem fraction was seen within 14 days of primary infection. After secondary challenge, this response was boosted in the pre-exposed, but not the chronically infected, animals. No significant difference was noted in antibody titre to either protein fraction between pre-exposed or nai've animals.Peripheral blood mononuclear cells responded to stimulation with WFA and ES preparations, giving a strong proliferative response as early as 7 days post¬ infection. This suggests the presence of common antigens between adult and very early fluke stages. Proliferation was decreased after secondary challenge, particularly in the chronically infected group.In order to examine the local immune response in the 5-6 day pre-exposed group, mesenteric and hepatic lymph nodes were removed 10 days after secondary challenge. Substantial proliferation to WFA was seen with hepatic, but not mesenteric derived lymph node cells, suggesting that the gut response to this antigen preparation was not important. Pre-exposed animals showed a lower mean level of IFN-y and IL2 cytokines in supernatant fluid. Both groups produced similar levels of B cell stimulating factor. IgG antibody present in hepatic lymph node cell culture supernatant fluid from pre-exposed animals recognised proteins on WFA and ES Western blots of sizes 190-120, 96-82, 72-68 and 60-57.5 kDa. No such response was seen with supernatant fluid from naive challenged animals.These results suggest that pre-exposure to flukes of up to 5-6 days old provides a degree of protection against secondary challenge infections in cattle. Peripheral and local antibody is mainly directed against a series of proteins ranging from 96-57.5 kDa in size and to particular bands in metacercarial preparations. Although the main antibody response was IgGl dominated, the cellular response showed a mixed cytokine pattern, suggesting an unrestricted T helper cell response. Further investigation into the nature of immunoreactive bands identified, together with examination of IgE antibody responses, will aid understanding of the naturally occurring immune response during early infection

Issues in the Treatment of Depressed Children

Basic research into the cognitive, behavioral, familial, and physiological disturbances associated with depressive disorders during childhood is reviewed. hnplications for the development of a treatment program are discussed and a comprehensive treatment model is proposed. The proposed model includes intervention strategies for the child, parents, family, and school. The child component consists of intervention strategies for the affective, cognitive, behavioral, and physiological disturbances that are evident from the existing research. The parent training component is designed to address disturbances in parenting due to cognitive disturbances and skills deficits. The family therapy component emphasizes changing interaction patterns that communicate schema-consistent maladaptive interactions. A school consultation component is proposed in which school personnel support the skills training through prompting use of the skills and reinforcement of the use of the coping skills

E. coli O157 on Scottish cattle farms: evidence of local spread and persistence using repeat cross-sectional data

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections.&lt;p&gt;&lt;/p&gt; A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998 - 2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The presence of an E. coli O157 positive local farm (average distance: 5.96km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p &#60; 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p &#60; 0.001) from the same time frame.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources

Zoonotic causes of febrile illness in malaria endemic countries:a systematic review

Fever is one of the most common reasons for seeking health care globally and most human pathogens are zoonotic. We conducted a systematic review to describe the occurrence and distribution of zoonotic causes of human febrile illness reported in malaria endemic countries. We included data from 53 (48·2%) of 110 malaria endemic countries and 244 articles that described diagnosis of 30 zoonoses in febrile people. The majority (17) of zoonoses were bacterial, with nine viruses, three protozoa, and one helminth also identified. Leptospira species and non-typhoidal salmonella serovars were the most frequently reported pathogens. Despite evidence of profound data gaps, this Review reveals widespread distribution of multiple zoonoses that cause febrile illness. Greater understanding of the epidemiology of zoonoses in different settings is needed to improve awareness about these pathogens and the management of febrile illness

High prevalence and factors associated with the distribution of the integron intI1 and intI2 genes in Scottish cattle herds

Integrons are genetic elements that capture and express antimicrobial resistance genes within arrays, facilitating horizontal spread of multiple drug resistance in a range of bacterial species. The aim of this study was to estimate prevalence for class 1, 2, and 3 integrons in Scottish cattle and examine whether spatial, seasonal or herd management factors influenced integron herd status. We used fecal samples collected from 108 Scottish cattle herds in a national, cross-sectional survey between 2014 and 2015, and screened fecal DNA extracts by multiplex PCR for the integrase genes intI1, intI2, and intI3. Herd-level prevalence was estimated [95% confidence interval (CI)] for intI1 as 76.9% (67.8–84.0%) and intI2 as 82.4% (73.9–88.6%). We did not detect intI3 in any of the herd samples tested. A regional effect was observed for intI1, highest in the North East (OR 11.5, 95% CI: 1.0–130.9, P = 0.05) and South East (OR 8.7, 95% CI: 1.1–20.9, P = 0.04), lowest in the Highlands. A generalized linear mixed model was used to test for potential associations between herd status and cattle management, soil type and regional livestock density variables. Within the final multivariable model, factors associated with herd positivity for intI1 included spring season of the year (OR 6.3, 95% CI: 1.1–36.4, P = 0.04) and watering cattle from a natural spring source (OR 4.4, 95% CI: 1.3–14.8, P = 0.017), and cattle being housed at the time of sampling for intI2 (OR 75.0, 95% CI: 10.4–540.5, P &lt; 0.001). This study provides baseline estimates for integron prevalence in Scottish cattle and identifies factors that may be associated with carriage that warrant future investigation

Phylogenetic relationship and virulence composition of Escherichia coli O26:H11 cattle and human strain collections in Scotland; 2002-2020

O26 is the commonest non-O157 Shiga toxin (stx)-producing Escherichia coli serogroup reported in human infections worldwide. Ruminants, particularly cattle, are the primary reservoir source for human infection. In this study, we compared the whole genomes and virulence profiles of O26:H11 strains (n = 99) isolated from Scottish cattle with strains from human infections (n = 96) held by the Scottish Escherichia coli O157/STEC Reference Laboratory, isolated between 2002 and 2020. Bovine strains were from two national cross-sectional cattle surveys conducted between 2002–2004 and 2014–2015. A maximum likelihood phylogeny was constructed from a core-genome alignment with the O26:H11 strain 11368 reference genome. Genomes were screened against a panel of 2,710 virulence genes using the Virulence Finder Database. All stx-positive bovine O26:H11 strains belonged to the ST21 lineage and were grouped into three main clades. Bovine and human source strains were interspersed, and the stx subtype was relatively clade-specific. Highly pathogenic stx2a-only ST21 strains were identified in two herds sampled in the second cattle survey and in human clinical infections from 2010 onwards. The closest pairwise distance was 9 single-nucleotide polymorphisms (SNPs) between Scottish bovine and human strains and 69 SNPs between the two cattle surveys. Bovine O26:H11 was compared to public EnteroBase ST29 complex genomes and found to have the greatest commonality with O26:H11 strains from the rest of the UK, followed by France, Italy, and Belgium. Virulence profiles of stx-positive bovine and human strains were similar but more conserved for the stx2a subtype. O26:H11 stx-negative ST29 (n = 17) and ST396 strains (n = 5) were isolated from 19 cattle herds; all were eae-positive, and 10 of these herds yielded strains positive for ehxA, espK, and Z2098, gene markers suggestive of enterohaemorrhagic potential. There was a significant association (p &lt; 0.001) between nucleotide sequence percent identity and stx status for the bacteriophage insertion site genes yecE for stx2 and yehV for stx1. Acquired antimicrobial resistance genes were identified in silico in 12.1% of bovine and 17.7% of human O26:H11 strains, with sul2, tet, aph(3″), and aph(6″) being most common. This study describes the diversity among Scottish bovine O26:H11 strains and investigates their relationship to human STEC infections

Acquisition and epidemiology of antibiotic-resistant Escherichia coli in a cohort of newborn calves

Objectives: The acquisition of antibiotic-resistant commensal Escherichia coli was examined in a cohort of newborn calves. Methods: Faecal samples were collected weekly from calves over a 4 month period and screened for E. coli resistant to ampicillin, apramycin and nalidixic acid at concentrations of 16, 8 and 8 mg/L, respect-ively. E. coli viable counts were performed on samples from a subset of calves. Results: All calves acquired ampicillin- and nalidixic acid-resistant E. coli, while only 67 % acquired apramycin-resistant E. coli during the study. Sixty-seven per cent of samples were resistant to at least one of the three antibiotics. Prevalence of ampicillin and nalidixic acid resistance was high initially and declined significantly with age (P &lt; 0.001). No temporal or age-related pattern was observed in the prevalence of apramycin resistance. Housing the cohort had a significant effect on the prevalence of nalidixic acid resist

Prevalence and Epidemiology of Non-O157 Escherichia coli Serogroups O26, O103, O111, and O145 and Shiga Toxin Gene Carriage in Scottish Cattle, 2014-2015

International audienceCattle are reservoirs for Shiga toxin Escherichia coli (STEC), bacteria shed in animal feces. Humans are infected through consumption of contaminated food or water and by direct contact, causing serious disease and kidney failure in the most vulnerable

Possible Selves and Academic Outcomes: How and When Possible Selves Impel Action

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89942/1/oyserman__bybee___terry_2006.pd