Blood gastrin and pepsinogen responses to subclinical infection with Ostertagia ostertagi in adult dairy cattle

Blood gastrin and pepsinogen responses to a single infection with 100,000 Ostertagia ostertagi infective larvae in lactating dairy cows were investigated. None of the infected cows showed signs of clinical ostertagiasis, nor was there any difference in live weight gain, milk yield or faecal egg count between groups. Pepsinogen levels of the infected group were significantly elevated between days 3 and 24 after infection (peak 1041 mU tyrosine; day 14). In contrast, there was no significant difference in blood gastrin levels between infected and control animals suggesting that few adult worms had become established in the former group. These data are compared with the increases in both gastrin and pepsinogen levels recorded in susceptible calves exposed to the same level, pattern and strain of ostertagia infection in a previous experiment. It is suggested that gastrin assay may be of value in adult cattle for indicating when elevated pepsinogen levels are merely associated with a rise in larval intake and not with the establishment of large adult worm burdens.     

Forms of bovine pepsinogen in plasma from cattle with three different 'syndromes' of Ostertagia ostertagi infection

Calves infected orally with third stage larvae of Ostertagia ostertagi or infected with adult O ostertagi by direct transplantation into the abomasum had raised plasma pepsinogen activity, as did four-year-old dairy cattle challenged with O ostertagi third stage larvae on five occasions. Using fast protein liquid chromatography two forms of pepsinogen; pepsinogen 1 (PG1) and pepsinogen 2 (PG2) were identified in each of the parasitic infection regimes.     

Further studies on the response to transplanted adult Ostertagia ostertagi in calves

Calves infected by surgical transplantation of adult Ostertagia ostertagi had raised levels of plasma pepsinogen and those in which the largest number of worms established also had elevated plasma gastrin concentrations. Despite the elevated plasma pepsinogen values, the abomasal pH of the animals did not change significantly, and there was no significant difference in the percentage establishment of adult parasites in calves previously infected with O ostertagi third stage larvae and those which had been maintained parasite-naive before transplant.     

Gastrin and pepsinogen changes during an Ostertagia ostertagi challenge infection in calves

Daily changes in serum gastrin and pepsinogen concentration have been studied during two types of infection with Ostertagia ostertagi in calves. In a first experiment two calves were trickle infected (10 times 10,000 L3 Ostertagia) and two animals received a single infection of 100,000 L3 Ostertagia. Gastrin and pepsinogen changes are discussed in relation to adult wormburdens. The second experiment involved 8 calves and was designed to investigate pepsinogen and gastrin changes following a challenge infection in previously sensitized calves. The high dosed group was infected with 5,000 L3 O. ostertagi during 30 days, the low dosed group received 500 L3 O. ostertagi and group 3 served as uninfected control. At day 41 post infection all animals were treated with oxfendazole and on day 61 challenged with 100,000 L3 O. ostertagi. Only in the high dosed group a distinct pepsinogen and gastrin reaction was noticed. Both parameters dropped to almost preinfection levels after treatment. Two days post challenge a moderate rise (+/- 1,000 mU tyr) of the pepsinogen concentration was observed in the previously infected animals and gastrin showed a temporary slight increase in several animals 8 to 10 days post challenge. The effect of treatment and challenge infection is discussed in relation to gastrin and pepsinogen changes and immunity.     

Sequential histopathologic changes of type I, pre-type II and type II ostertagiasis in cattle

Yearling cattle in Louisiana were examined at monthly intervals for abomasal nematode burdens and histological lesions over a year. Tracer calves were grazed for 3 to 4 weeks and removed from pasture for 2 to 3 weeks, then slaughtered; a few animals were killed in extremis shortly after removal from pasture. Histological changes were correlated with worm burdens and characterized according to the type of Ostertagia ostertagi infection present. In cattle with acute Type I ostertagiasis, changes varied from eosinophil infiltration to glandular dilation and slight mucous cell hyperplasia with submucosal edema. During the summer months the cattle had worm burdens that were primarily early 4th stage larvae (EL4), with changes characterized by minimal glandular dilation and mucous cell metaplasia and moderate lymphoid cell proliferation and with intramucosal migration of EL4. In the autumn, the maturation of EL4 produced the Type II syndrome with severe glandular changes, prominent mucosal hyperplasia and marked lymphoid cell accumulation. With increased duration of the pre-Type II interval, there was greater development of the subepithelial lymphoid tissue and increased frequency of epithelial globule leukocytes. The lymphoproliferation which occurred during the prolonged pre-Type II interval appeared to be related to the increased severity and mortality seen with the Type II ostertagiasis syndrome.     

Dynamics of Ostertagia spp. and Cooperia oncophora in field-grazed cattle from weaning to 2 years old in New Zealand, with particular reference to arrested development

Gastrointestinal nematode parasite burdens were monitored in a herd of field-grazed cattle from weaning to 2 years old to allow observations to be made on the dynamics of burdens of arrested Ostertagia spp. and Cooperia oncophora. Arrested Ostertagia spp. accumulated in the herd over their first autumn and winter to reach a peak in late winter/spring (August-October). From October until late January they declined at a rate comparable to that at which they had accumulated. Numbers continued to decline at a slower rate until the following autumn (May) when they began to increase again. Observations on the decline of worm burdens in a group of animals which had been moved from pasture to worm-free conditions in October indicated that intake of infective larvae over late spring/summer contributed little to the number of arrested Ostertagia spp. in the herd. No clinical Type II ostertagiosis was observed in the field-grazed animals over the time of decline of the arrested worm burden, nor was there an increase in the number of adult Ostertagia spp. present. However, two of the animals removed from pasture to worm-free conditions developed Type II ostertagiosis approximately a month after the move. Worm burdens of successive groups of "tracers" grazed with the herd every 2 months indicated that there was a small seasonal increase in the propensity of Ostertagia spp. for arrested development. However, estimated accumulation rates of arrested larvae calculated from tracer worm burdens, suggest that this seasonal increase in propensity was not adequate in itself to account for the accumulation rate observed in "resident" animals of the herd. No comparable accumulation of arrested C. oncophora took place in resident animals over the first autumn and winter of the trial despite the fact that tracer worm burdens over this period indicated a marked seasonal increase in the propensity for arrested development by this species.     

Diagnostic value of gastrin for clinical bovine ostertagiosis.

Gastrin values were evaluated in 130 parasite naive calves, in 61 first season grazing calves during six field trials and in 8 experimentally infected adult immune cows. The gastrin values were linked to pepsinogen levels and daily weight gain. Also the influence of an anthelmintic treatment on pepsinogen and gastrin values was assessed during a clinical outbreak of ostertagiosis in a group of first season grazing calves. Mean gastrin levels in parasite naive calves were 106 pg/ml. Results show that a group mean of 400 pg/ml gastrin in first season grazing calves indicates a reduced daily weight gain but with no obvious clinical signs. During clinical outbreaks mean gastrin levels frequently reached 1,000 pg/ml with a severe weight loss and a mean pepsinogen level of 5,000 mU tyr. The serum gastrin concentration was strongly reduced 4 days post treatment. No gastrin response was noted following an Ostertagia challenge in adult immune cows. The value of gastrin as a diagnostic aid for ostertagiosis is discussed in relation to pepsinogen, the adult worm burden, larval inhibition and the technique involved in assessing gastrin.     

Efficacy of doramectin against experimental infections by some nematode parasites in cattle in New Zealand

A study was undertaken to determine the efficacy of the novel avermectin, doramectin, against experimental larval and adult infections of three species of nematode parasite important to cattle production in New Zealand. Eighteen worm-free dairy bull beef calves were randomly allocated on live weight to three similar treatment groups. Each calf was given 30,000 Ostertagia ostertagi, 20,000 Cooperia spp. and 10,000 Trichostrongylus axei infective larvae as a single dose. One group was treated with doramectin 6 days after infection while the remaining groups received saline or doramectin 27 days after infection. Given as a single subcutaneous injection behind the ear, doramectin at 200 microg/kg removed 99.9-100% of adult and larval stages of O. ostertagi, Cooperia spp. and T. axei when compared to infections established in untreated controls (p<0.001). No adverse reactions were observed following treatment in the doramectin-treated animals. No injection site lesions were found by palpation following treatment or by injection site examination at necropsy.     

Exposure of dairy cows to nematode infections at the end of the grazing season in The Netherlands

In autumn 2000, a study was carried out on 25 dairy farms in the vicinity of Utrecht with the aim to estimate infectivity levels for nematode parasites in cows. On each farm, faecal samples were collected from 15 cows, blood samples from 5 of these and herbage samples from 2 cow pastures. Faecal examination demonstrated a variation between farms and within farms in faecal egg output with a mean number of 4 eggs/g faeces (EPG) and Ostertagia spp. and Cooperia oncophora being the dominant species. In 6 out of 21 farms examined, lungworm larvae were detected in at least 1 cow. Serum pepsinogen values and serology using ELISA's with crude adult Ostertagia, crude adult C. oncophora and a specific recombinant C. oncophora protein as antigens indicated low to moderate infection levels. Pasture infectivity levels varied between farms with again Ostertagia spp. and C. oncophora as the dominant larval types and correlated with the crude worm Ostertagia ELISA, the crude worm Cooperia ELISA and the pepsinogen values. Exposure levels were high enough to enable the possible occurrence of production losses on the majority of farms.     

Serum pepsinogen levels and Ostertagia ostertagi populations in clinically normal adult beef cattle

Serum pepsinogen levels and Ostertagia ostertagi populations in clinically normal grass-fed bullocks were investigated in three groups of 10 prime cattle aged between 2.5 and 2.75 years slaughtered in late summer (February), early autumn (March) and late autumn (May) respectively. Apart from occasional foci of mucosal hyperplasia abomasa were grossly normal. Serum pepsinogen levels ranged between 0.2 and 2.5 i.u./l with group means of 1.4, l.5 and 1.3 i.u./l. O. ostertagi counts ranged between 0 and 5,194 with group means of 734,630 and 701 worms. The composition of the worm populations varied with a higher proportion of adults recovered in February and very few worms from most cattle in March, suggesting the termination of a parasite generation. An increase in numbers of early fourth-stage larvae in May indicated exposure to a new generation. These changes were not reflected in the pepsinogen levels. The findings are discussed in relation to the adequacy of the pepsinogen assay as a diagnostic aid in field infections, animal age, and correlations between pepsinogen levels and parasite populations.     

Effects of Ostertagia ostertagi infection on secretion of metabolic hormones in calves.

Effects of Ostertagia ostertagi infection on secretion of insulin, pancreatic glucagon, cortisol, gastrin, and pepsinogen were studied in calves inoculated with 100,000 (group 1) or 10,000 (group 2) O ostertagi infective larvae weekly for 14 weeks. Plasma insulin concentrations in both inoculated groups were lower than those in a non-infected (group 3) control group. The differences between group 1 and group 3 were significant (P < 0.05) at 2 and 12 weeks after initial inoculation. Plasma pancreatic glucagon and cortisol concentrations of groups 1 and 2 did not differ significantly from those of the control group, although plasma pancreatic glucagon concentration was consistently lower in group-1 calves from 4 weeks to end of the study. Plasma pepsinogen and serum gastrin concentrations also increased significantly (P < 0.05) in both groups that received inoculations. We concluded that decreased plasma insulin concentrations are contributory to changes in postabsorptive protein metabolism, and that serum gastrin concentrations are more representative of the pathologic changes in the abomasum than are plasma pepsinogen concentrations.     

Effect of meclofenamic acid on the response of parasite-naive lambs and adult sheep to Ostertagia circumcincta

Meclofenamic acid was used to inhibit prostaglandin synthesis in lambs challenged with Ostertagia circumcincta. It lowered the number of parasites which established in treated animals but not significantly. In treated animals plasma pepsinogen values were elevated at the time of parasite emergence but had dropped below the values achieved in control lambs towards the end of the experiment when parasites were at the adult, lumenal dwelling stage. Meclofenamic acid administered to adult immune ewes during challenge with third stage O circumcincta larvae did not significantly affect the establishment of the parasites, nor did it affect the rise in pepsinogen concentration associated with the challenge.     

Dynamics of infestation of cattle and pasture by gastrointestinal nematodes in an Atlantic temperate environment

The objective of the present study was to determine the dynamics of infestation of cattle and pasture by gastrointestinal nematodes in a mild humid environment in northwestern Spain. For this, infestation of pasture by free-living stages (L3), dynamics of faecal egg output, blood pepsinogen levels and worm burden in slaughtered animals were quantified. The results showed a high degree of annual variability, which was dependent on weather conditions. The seasons were clearly defined in the study area, with mild humid winters and relatively dry summers registered throughout the years of the study. Infestation of pasture by larvae varied from year to year, peaking during August in the first year, between August and December in the second year, and during October in the third year. The annual variation was mainly due to weather conditions, particularly the amount of rain in summer. The patterns of faecal egg output were similar in the first and third grazing seasons, with maximum levels observed in May/June; however, in the second year, the peak was reached in October. Blood pepsinogen levels increased from pasture turnout (March/April) until the end of the grazing season (November/December), reaching maximum values from August/September onwards. The nematode parasite species identified at necropsy were Ostertagia osteragi, O. lyrata, Cooperia oncophora, C. macmasteri, C. punctata and Trichuris ovis, with O. ostertagi and C. oncophora predominating. In faecal cultures, the following genera were also identified: Haemonchus, Trichostrongylus, Nematodirus, Bunostomum, Oesophagostomum and Strongyloides. There was a significant correlation (r=0.97, P<0.01) between worm burden (Ostertagia spp.) and pasture infestation (Ostertagia L3) 3 weeks prior to slaughter of the calves, and also between blood pepsinogen levels and pasture infestation by Ostertagia L3 (r=0.33, P<0.02). Correlations between worm burden and faecal egg output and between blood pepsinogen level and faecal egg output were not significant. The results obtained in the present study confirm that there is annual variability in the time-course of nematodosis in cattle, and demonstrate the importance of weather, particularly summer rainfall, in an Atlantic temperate environment.     

Serum pepsinogen levels and Ostertagia ostertagi populations in clinically normal adult beef cattle

Serum pepsinogen levels and Ostertagia ostertugi populations in clinically normal grass-fed bullocks were investigated in three groups of 10 prime cattle aged between 2.5 and 2.75 years slaughtered in late summer (February), early autumn (March) and late autumn (May) respectively. Apart from occasional foci of mucosal hyperplasia abomasa were grossly normal. Serum pepsinogen levels ranged between 0.2 and 2.5 i.u./l with group means of 1.4,l.S and 1.3 i.u./l. O. ostertagi counts ranged between 0 and5,194 with group means of 734,630 and 701 worms. The composition of the worm populations varied with a higher proportion of adults recovered in February and very few worms from most cattle in March, suggesting the termination of a parasite generation. An increase in numbers of early fourth-stage larvae in May indicated exposure to a new generation. These changes were not reflected in the pepsinogen levels.

The findings are discussed in relation to the adequacy of the pepsinogen assay as a diagnostic aid in field infections, animal age, and correlations between pepsinogen levels and parasite populations.     

The influence of a low cobalt intake on the neutrophil function and severity of Ostertagia infection in cattle

Two trials involving housed cattle examined the effect of Co depletion and supplementation on immune status as assessed by the neutrophil function test which measures the ability of isolated neutrophils to kill the yeast Candida albicans. A third trial investigated the extent to which Co status influenced the severity of Ostertagia ostertagi infection. In the first two trials liveweight gains were unaffected until some 40-60 weeks on the low dietary Co intake despite very low serum vitamin B12 values being recorded after 10 weeks. However, the immune status as measured by the neutrophil function test was reduced within 10 weeks of commencing the low Co diet. On administration of Ostertagia ostertagi larvae, Co-depleted cattle showed a greater weight loss than Co-supplemented cattle but showed no difference in the length of the prepatent period, worm egg production or serum gastrin and pepsinogen concentrations. After anthelmintic treatment both groups showed a similar response. It is postulated that the lowered immune response of Co-depleted cattle resulted in the greater severity of the Ostertagia ostertagi infection.     

Epidemiology and control of bovine ostertagiasis in South America

Gastrointestinal parasitism has been recognized by practitioners as the most common disease in beef cattle, mainly in weaning calves and fattening steers. Among the different genera, Ostertagia ostertagi is the predominant parasite in the temperate climate, in which the major beef and dairy cattle area of South America is situated. Outbreaks of Type I ostertagiasis are usually seen after weaning time (autumn-winter) when larvae counts are high and food availability is low. The development of the disease is rapidly established and 15-30 kg are lost in 30-50 days. Epidemiological studies have demonstrated a fast evolution of parasite eggs to larvae (L3) in summer (1 week or less), evolution being 30-45 days during winter. Inhibition O. ostertagi occurs during spring (September-December) and development resumes in late summer and early autumn. The production effect is seen as a significant reduction in body weight gain and occasionally clinical Type II ostertagiasis appears. A similar epidemiological pattern of inhibition of Ostertagia sp. has been recorded in Uruguay and temperate areas in southern Brazil.     

Pathophysiologic effects of Ostertagia ostertagi in calves and their prevention by strategic anthelmintic treatments.

Pathophysiologic effects of Ostertagia ostertagi infection and their prevention by strategic anthelmintic treatments were studied in 3 groups each of 6 steer calves. Group-1 calves were noninfected controls. Group-2 calves were inoculated with 100,000 third-stage larvae on the 1st and 28th days of the experiment and grazed on pasture initially free of contamination. Group-3 calves were on a similar regimen as those in group 2, but were also treated with ivermectin 9 days after each larval inoculation. Group-2 calves had increased plasma pepsinogen and gastrin values and decreased weight gains, and total serum protein and albumin concentrations from the 2nd week of infection onward. They were anemic at 10 to 12 weeks and had lower carcass and meat quality at slaughter. Strategic anthelmintic treatments were effective in preventing these effects and calves in groups 1 and 3 had similar performances. On the basis of our findings, high pepsinogen values were related to worm burdens, whereas high gastrin concentrations were related to gastric lesions.     

Ostertagia ostertagi infection in the calf: effects of a trickle challenge on the hormonal control of digestive and metabolic function

Metabolic effects of a trickle challenge with the equivalent of 10,000 infective Ostertagia ostertagi larvae per day were investigated in 12 calves allocated to infected, pair-fed control or ad libitum-fed control groups. Changes in hormone levels reflecting abomasal, pituitary and pancreatic function were monitored using radioimmunoassay techniques previously validated for use in cattle. A range of metabolic profile parameters and blood metabolites was also measured. Feed intake of the infected calves began to decline as blood gastrin and pepsinogen levels reached a peak. The depression in appetite recorded in this group was responsible for significant increases in plasma urea and non-esterified fatty acid levels and associated with an increase in growth hormone/insulin ratio. No significant difference in glucagon levels was recorded between groups. A decline in blood albumin values was also shown in the infected group and associated with a drop in nitrogen digestibility. A significant depression in circulating calcium levels was related to either the hypoalbuminaemia or impaired mineral absorption in the intestine. A decrease in plasma cholesterol values in the infected group was associated with changes in digestive function.     

Pathophysiological and parasitological studies on Ostertagia ostertagi infections in calves

Friesian calves given a low level infection of the abomasal parasite Ostertagia ostertagi over a six week period displayed a mild diarrhoea with high faecal egg counts and elevated plasma pepsinogen values. At necropsy on day 23 abomasal lesions characteristic of ostertagiasis were widespread. At 42 and 84 days oedema and congestion were also prominent. Total worm burdens on days 23 and 42 were similar but a marked decrease had occurred by day 84. Feed digestibility and nitrogen economy were not markedly affected but radioisotopic measurements demonstrated an increase in albumin disappearance and catabolic rates, and plasma faecal clearance during the course of the infection. Prior administration of a morantel sustained release bolus to a group of similarly infected calves reduced the total worm burdens to less than 50 per cent of those recorded in the infected calves on days 23 and 42 and this fell to 3 per cent on day 84. Abomasal damage and the adverse pathophysiological changes associated with infection were prevented in this group.     

Role of the bovine immune system and genome in resistance to gastrointestinal nematodes

Gastrointestinal nematode infections of cattle remain a constraint on the efficient raising of cattle on pasture throughout the world. Most of the common genera of parasites found in cattle stimulate an effective level of protective immunity in most animals within the herd after the animals have been on pasture for several months. In contrast, cattle remain susceptible to infection by Ostertagia for many months, and immunity that actually reduces the development of newly acquired larvae is usually not evident until the animals are more than 2 years old. This prolonged susceptibility to reinfection is a major reason that this parasite remains the most economically important GI nematode in temperate regions of the world. Although, animals remain susceptible to reinfection for a prolonged period of time, there are a number of manifestations of the immune response that result in an enhanced level of herd immunity. These include a delay in the development time of the parasites, an increase in the number of larvae that undergo an inhibition in development, morphological changes in the worms, stunting of newly acquired worms, and most importantly a reduction in the number of eggs produced by the female worms. The overall result of these manifestations of immunity is a reduction in parasite transmission within the cattle herd. The immune mechanisms responsible for these different types of functional immunity remain to be defined. In general, GI nematode infections in mammals elicit very strong Th2-like responses characterized by high levels of Interleukin 4 (IL4), high levels of IgG1 and IgE antibodies, and large numbers of mast cells. In cattle, the most extensively studied GI nematode, in regards to host immune responses, is Ostertagia ostertagi. In Ostertagia infections, antigens are presented to the host in the draining lymph nodes very soon after infection, and within the first 3-4 days of infection these cells have left the nodes, entered the peripheral circulation, and have homed to tissues immediately surrounding the parasite where they become established. The immune response seen in the abomasum is in many ways are similar to that seen other mammalian hosts, with high levels of expression of IL4 in the draining lymph nodes and in lymphocytes isolated from the mucosa. But unlike a number of other systems, lymphocyte populations taken from Ostertagia infected cattle seem to be up-regulated for a number of other cytokines, most notably Interferon (IFN, implying that in Ostertagia infections, the immune response elicit is not simply a stereotypic Th2 response. In addition, effector cell populations in the tissues surrounding the parasites, are not typical, inferring the Ostertagia has evolved means to suppress or evade protective immune mechanisms. Studies have also demonstrated that the number of nematode eggs/gram (EPG) in feces of pastured cattle is strongly influenced by host genetics and that the heritability of this trait is approximately 0.30. In addition, EPG values are not "normally" distributed and a small percentage of a herd is responsible for the majority of parasite transmission. This suggests that genetic management of a small percentage of the herd can considerably reduce overall parasite transmission. A selective breeding program has been initiated to identify the host genes controlling resistance/susceptibility to the parasites. The best indicator of the number of Cooperia infecting a host is the EPG value, while Ostertagia is best measured by serum pepsinogen levels, weight gain, and measures of anemia. Other phenotypic measures are either not significantly associated with parasite numbers or are very weakly correlated. In addition, calves can be separated into three types: (1) Type I which never demonstrates high EPG values, (2) Type II which shows rises in EPG values through the first 2 months on pasture which then fall and remain at levels associated with Type I calves, and (3) Type III calves which maintain high EPG levels. The approximate percentage of these calves is 25:50:25 respectively. Because these cattle are segregating for traits involved in resistance and susceptibility to GI nematodes, this resource population is being used to effectively detect the genomic locations of these Economic Trait Loci (ETL). For relational analysis between phenotype and genome location, over 80,000 genotypes have been generated by PCR amplification, and marker genotypes have been scored to produce inheritance data. The marker allele inheritance data is currently being statistically analyzed to detect patterns of co-segregation between allele haplotype and EPG phenotypes. Statistical power of this genome-wide scan has been strengthened by including genotypic data from the historic pedigree. In our herd, paternal half-sib families range from 5-13 progeny/sire, and extensive marker genotypes are available from ancestors of the population most of which are paternally descended from a single founding sire. Once ETL have been identified the next will be to refine ETL map resolution in attempt to discover the genes underlying disease phenotypes. Accurate identification of genes controlling resistance will offer the producer several alternatives for disease control. For a non-organic producer, the small percentage of susceptible animals can be targeted for drug administration. This approach would reduce both the cost of anthelmintics used and the odds for selection of drug resistant mutants, because the selective agent (drug) would not be applied over the entire parasite population. A second treatment option would be based on correcting a heritable immunologic condition. In this case, susceptible animals could be the targets for immunotherapy involving vaccines of immunomodulation. A final option would be genetic selection to remove susceptible animals from the herd. Producers with a high degree of risk for parasite-induced production losses, such as organic producers of producers in geographic areas with environmental conditions favorable to high rates of transmission would benefit the most from this strategy. In contrast, producers at low risk could take a more conservative approach and select against susceptibility when other factors were equal.