Pathogenesis of simulated natural infections with Ostertagia ostertagi in calves

The possibility of a mucosal hypersensitivity reaction and its relationship to the pathogenesis of simulated natural infections with Ostertagia ostertagi were studied in calves. Four groups of 4 calves each were used. One group was used as noninfected control; a 2nd group was given increasing doses of infective larvae; a 3rd group was given increasing doses of larvae and these were removed by succeeding treatment with an anthelmintic; and a 4th group was given an initial dose of larvae which was then eliminated with an anthelmintic. All calves given larvae became sensitized, as shown by an intradermal skin test. The continuously infected calves had significantly (P less than 0.05) higher fecal egg counts, eosinophil counts, plasma pepsinogen values, and worm burdens and significantly (P less than 0.05) lower lymphocyte counts than did the other groups of calves. These animals also had the most extensive mucosal pathologic changes. The group given intermittent larval challenge exposures followed by an anthelmintic showed decreased lymphocyte values, but these were not significant. Plasma pepsinogen values of this group increased between every challenge exposure and treatment, a 3-day period. This indicated that a mucosal hypersensitivity reaction had occurred in these calves at these times, because they were shown to have been sensitized, and challenge-exposure infections were not present for sufficient time to have produced direct pathologic effects. It therefore seems that a part of the pathologic changes in O ostertagi infections may be the result of the continuous challenge exposure experienced by the animals through a constant intake of larvae from pasture and the intestinal reaction to this challenge exposure.     

Synergistic influence of Ostertagia ostertagi and Trichostrongylus axei on Ostertagia ostertagi larval inhibition and abomasal lesions in cattle

Parasite-free 4-month-old calves were inoculated with Ostertagia ostertagi and/or Trichostrongylus axei followed 6 weeks later by increasing doses of O ostertagi for 8 weeks. Clinical signs of parasitism, fecal egg counts, and plasma pepsinogen concentrations were monitored, and gross lesions and parasite burdens were determined postmortem. Clinical signs of parasitism were not observed and weight gains were not affected in experimentally infected calves. In calves infected with O ostertagi, mean plasma pepsinogen concentrations were greater than for control calves and were diagnostically significant 4 weeks after inoculation and during the last 4 weeks of serial inoculations with O ostertagi. In calves that were given O ostertagi and T axei, abomasal pH was significantly increased, and abomasal lesions were more pronounced than in control calves or in calves inoculated with only O ostertagi or T axei. Abomasal lymph nodes were enlarged in all parasitized calves; other lymph nodes in the calves inoculated with both O ostertagi and T axei were usually smaller than in calves inoculated with only O ostertagi or T axei. Numbers of O ostertagi-inhibited larvae were small in all inoculated calves, but the percentage inhibition was significantly greater in calves inoculated with both O ostertagi and T axei. The percentage inhibition was 3.53% for the O ostertagi-inoculated calves and 7.07% for calves inoculated with both O ostertagi and T axei. These percentages indicated a synergistic effect of concurrent abomasal parasitism, whereas a synergistic effect on T axei worm burden was not observed. The low percentage of larval inhibition indicated that factors other than host resistance are involved in naturally occurring pretype II ostertagiosis.     

Experimental infections with Cooperia oncophora in calves. A study with two different larval dose levels and dosing regimens.

The effect of different larval dose level and dosing regimens on the course of Cooperia oncophora infection in calves was studied. Four groups each of 4 calves were experimentally infected either with 50,000 or 200,000 C. oncophora larvae (L3) given either as single infections or as daily trickle infections. An additional group of calves remained as uninfected controls. The animals were necropsied on week 4 after infection. Mild to moderate clinical signs of parasitic gastroenteritis developed among calves given high doses of larvae, but liveweight gains were not significantly different from those of the uninfected controls. Serum pepsinogen levels of dosed animals were within normal ranges but rose slightly, and on day 14 p.i. they differed significantly from those of the controls. On that occasion, the levels of serum pepsinogen in the trickle infected groups significantly exhibited the levels of the single infected groups. Hypoalbuminaemia was not a feature on any occasion. The various groups did not differ significantly with regard to total worm counts and adult worm counts, but the groups receiving high larval dose harboured significantly more fourth stage larvae than the group receiving low doses of larvae, both in terms of absolute counts and in terms of percentages of total worm burdens. Within the same dose level, there was a tendency of a more even distribution of worms along the small intestine when the infections was given as a single infection compared with a trickle infection. The results indicate that C. oncophora larval dose and dosing regimens may influence the pathogenic effects and to some extent the distribution of the parasite in the small intestine.     

Experimental and natural infection of calves with Bunostomum phlebotomum

An experiment was conducted to determine the efficiency of a method of experimental infection of weaner beef calves with Bunostomum phlebotomum and to compare such infection with that established by natural infection. Six calves, maintained on a concrete-floored pen, were inoculated with B. phlebotomum L3 by placing the larval inocuulum, in small volume, in the outer chamber of the ear while the animal was restrained for 18 min. Inoculation doses of 20, 30, 40, 50, 60, and 80 thousand L3 were used. Six other calves were grazed on pasture known to be heavily contaminated with hookworm. All animals were killed 72 days after experimental infection and 93 days after initial exposure to pasture infection. The experimental and naturally-infected calves became patent at 55 and 66 days, respectively, after exposure to L3. Red blood cell counts and hemoglobin values were markedly depressed in both groups and lowest values coincided with onset of patency. There was difference in liveweight changes, but both groups lost weight during the prepatent period of infection and gained weight with the onset of patency. The largest number of hookworms was established at the 30000 L3 inoculation level; little or no establishment was observed at the 2 highest levels. Sizeable adult hookworm burdens were established in 4 out of 6 pastured calves. Intestinal pathology was generally more severe in experimentally-infected calves, consisting of a thickened mucosa and masses of punctate, hemorrhagic foci. Pastured calves also acquired large burdens of Ostertagia ostertagi, particularly inhibited early fourth-stage larvae. Moderate to severe abomasal pathology and elevated plasma pepsinogen were associated with ostertagiasis in the pastured calves. The experimental infection method is efficient in establishing high levels of B. phlebotomum infection in calves currently or previously infected with other gastrointestinal nematodes.     

Efficacy of ivermectin delivered from a sustained-release bolus against inhibited early fourth-stage larvae of Ostertagia ostertagi and other nematodes in cattle.

The anthelmintic efficacy of ivermectin (IVM) delivered from a sustained-release (SR) bolus was evaluated against natural infections with gastrointestinal tract nematodes in 12 crossbred beef heifers in spring. The 12 calves were randomly allotted to 2 groups of 6 calves each. Group-1 calves were treated with an SR bolus designed to deliver 8 mg of ivermectin/d. Group-2 calves were nontreated controls. Cattle groups were kept in separate concrete-floored pens (grass hay nutrition) and slaughter was performed at 35 days after treatment. Fecal egg counts for group-1 calves remained zero after treatment, except for detection of less than 1 egg/g of feces in 1 calf at the time of slaughter; counts in nontreated calves increased. Mean and range of Ostertagia ostertagi inhibited larvae in nontreated calves were 27,093 and 10,622 to 56,368, respectively. Efficacy of the IVM SR bolus was 100% against O ostertagi developing fourth-stage larvae (L4) and inhibited early L4, Haemonchus placei adults, Cooperia punctata and C spatulata adult males, Cooperia spp adult females, Cooperia spp L4, Trichostrongylus colubriformis adults, Bunostomum phlebotomum adults, and Oesophagostomum radiatum adults. Efficacy for O ostertagi and T axei adults was 99.9%. Numbers of nontreated calves infected with C pectinata adult males and Oes radiatum L4 were too low to evaluate efficacy. Calves treated with the IVM bolus gained 10.2 kg, whereas nontreated calves lost 1.8 kg. Abomasal lesions were clearly greater in nontreated calves on the basis of index comparisons of abomasal weight and total live weight and gross pathologic features.     

Immune modulation by Ostertagia ostertagi and the effects of diet

IgG1 antibody responses to Ostertagia ostertagi third stage larvae (L3) and the third party antigen, keyhole limpet haemocyanin (KLH), and faecal egg counts were determined in calves infected with a single dose of O. ostertagi and in uninfected, pair-fed calves. The infected and uninfected calves were given diets either high (H) or low (L) in protein and energy. The diets were within the normal range of husbandry practice in the UK. IgG1 antibody responses to L3 antigen were significantly greater from 6 weeks post-infection in infected calves given the L diet than in infected calves given the H diet (P less than 0.05). The effects of diet and infection on anti-KLH IgG1 responses were independent of each other. IgG1 responses to KLH were decreased by infection and by the L diet compared with the H diet.     

Pathophysiology of the periparturient egg rise in sheep: the role of prolactin

The involvement of prolactin in the periparturient rise in the faecal nematode egg count in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to adult immune ewes from three weeks before parturition to three weeks afterwards. Ten ewes were injected twice daily with 2-bromo-alpha-ergocryptine (bromocriptine), an antagonist of prolactin secretion, for two weeks starting two days after lambing while 10 ewes remained untreated. Bromocriptine treatment was initiated approximately two weeks pre partum in three other ewes. Plasma pepsinogen concentrations rose significantly by one week after the start of O circumcincta larval challenge in all the ewes but faecal egg counts remained negative until approximately one week post partum. Plasma prolactin concentration was reduced to a very low level in all bromocriptine treated ewes but this did not alter the dynamics of the periparturient rise in faecal egg counts. Neither cell-mediated nor humoral immunity of the ewes, as assessed by their sensitivity to BCG inoculation and by antibody titre raised against horse red blood cells, respectively, were impaired during the rise in faecal egg count, nor were these parameters altered by manipulation of plasma prolactin concentration. Lamb growth rate was not retarded by low plasma prolactin concentration in the bromocriptine treated ewes. These results are not consistent with the generally held hypothesis that elevated plasma prolactin concentration is directly associated with the periparturient rise.     

The use of disophenol in studies of the pathogenicity of the arrested fourth-stage larvae of Haemonchus contortus in the sheep.

Disphenol was administered to sheep infected with Haemonchus contortus in order to prevent the development of populations of adult worms, and studies were made of the pathogenicity of the arrested fourth-stage larvae which remained. The treated sheep showed elevated plasma pepsinogen and abomasal pH, predominantly negative dry-matter balance, and evidence of greater fluid loss, including plasma, into the gastro-intestinal tract. It was concluded that arrested larvae may cause damage to the abomasal mucosa.     

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.     

Assessment of an oxfendazole pulsed release bolus for control of parasitic gastroenteritis in calves in a rotational grazing system

A group of 71 Friesian bullocks, aged six to nine months, vaccinated against lungworm, were randomly allocated on a liveweight basis to two groups of 40 and 31 animals. At turn-out each calf in the group of 40 calves was dosed orally with a pulsed release bolus designed to deliver five doses of oxfendazole at regular intervals during a period of up to 130 days, the first dose being released about 21 days after administration. The group treated with the bolus grazed 2.4 ha and the control group grazed 3.6 ha of permanent pasture for six weeks before having additional access to similar areas of silage aftermath. The control group was treated 99 days after turn-out and when they were housed with fenbendazole (7.5 mg/kg). Faecal worm egg counts, plasma pepsinogen activities, pasture larval counts and liveweights were recorded fortnightly. Significant reductions in worm egg counts and plasma pepsinogen activities were recorded in the calves dosed with the pulsed release bolus together with significant improvements in the liveweight of younger calves compared with control animals. Pasture larval counts were lower in the fields grazed by animals treated with the bolus.     

Infection with Ostertagia ostertagi in goats and calves

In order to determine the usefulness of the goat as a model host for Ostertagia ostertagi, a series of experiments was conducted in which young goats and calves were experimentally infected with L3 of calf-source and goat-source isolates. The goat-source isolate was derived from a continuous passage of the bovine parasite in goats. Patent infections resulted in 73 out of 86 inoculated goats (85%). The largest number of patent infections was observed when inoculation consisted of a single dose of goat-source larvae. Percent establishment of infection was generally low in goats inoculated with either larval source. Time taken to achieve patency in goats was frequently within the range normal for cattle infections, but was often extended (21-67 days). With the exception of the generally higher level of establishment of goat- or calf-source isolates in calves and the low frequency of the vulval flap in adult female worms established in goats, little difference was observed in percent establishment or worm population characteristics of the two isolates in goats as based on source of larval inoculum, inoculation course, and age of host at inoculation. Prolonged passage of infection in goats did not result in stabilized isolate more adapted to the goat or less adapted to calves. Fecal egg counts were generally minimal or negative in goats during the first 30 days of infection, but were often increased and not substantially lower than counts in calf infections after 60 or 90 days. Low level egg counts in goats were observed to persist for up to 17 months. During the spring of 2 years, goat kids grazed on a cattle pasture acquired O. ostertagi infections which included adult worms, but a larger number of early L4. The latter were presumed to be inhibited in development just as such inhibition occurs in cattle during spring.     

Pathogenicity of O. circumcincta, O. ostertagi and H. contortus in weanling stag fawns (Cervus elaphus)

Groups of four stag fawns, weighing 51 +/- 0.8 kg, were-infected with 30,000 larvae of one of three nematode parasites: O.circumcincta, O.ostertagia, or H.contortus. A further four remained as control. Individual feed intake, body-weight, faecal egg count and plasma pepsinogen concentration were measured during seven weeks after infection. Only infection with H.contortus caused significant elevation of pepsinogen concentration to 380ml/ L and consistent depression of feed intake (15%). Worm egg counts were below 300 e.p.g. in deer infected with all worm species. It is concluded that while resistance to development of parasites common to other species appears to be high further investigation of the susceptibility of deer to H. contortus infection would be justifiable.     

Appetite, digestive efficiency, feed utilization and carcass evaluation of housed calves naturally infected with gastrointestinal nematodes

The progress of two groups of 10 calves, which had previously been exposed to trichostrongyle infections by grazing infected pastures, was monitored from housing in October to slaughter the following April. Each of the animals of one group had received a morantel sustained release bolus, the other control group remained untreated. The high faecal egg counts and serum pepsinogen concentrations, together with the clinical signs of ostertagiosis observed in the controls in October, persisted during the first month of housing but improved thereafter. From late November onwards, no difference in feed intake and digestive efficiency was observed between the groups. The control calves exhibited a significantly greater feed conversion efficiency over the period February-April, (7.5 vs. 12.3 kg feed kg-1 liveweight gain, P less than 0.001). This reduced the liveweight advantage of the MSRB group over the controls at housing to 25 kg.     

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.     

Efficacy of the morantel sustained release trilaminate bolus against gastrointestinal nematodes and its influence on immunity in calves.

An experiment was conducted in calves to investigate the efficacy of a morantel sustained release trilaminate bolus (MSRT) to control gastrointestinal parasitism and to assess the development of immunity during the use of MSRT. Two groups (M and U) of four calves each were infected three times a week with a mixed Ostertagia ostertagi and Cooperia oncophora infection for 12 weeks. Calves of Group M received an MSRT at the start of the experiment. Twenty weeks after the start of the experiment, all animals, including a previously uninfected control group (C), received a challenge with 100,000 Ostertagia and 100,000 Cooperia. After a further 4 weeks all calves were necropsied for worm counts. During the trial calves were weighed and faecal egg counts, larval differentiation and pepsinogen concentrations were determined. The results demonstrated the high level of efficacy of the MSRT in reducing the faecal egg output and preventing parasitic gastroenteritis under conditions of a continuous high rate of infection. Efficacy of treatment was higher for Cooperia than for Ostertagia. Post-mortem worm counts suggested a partially impaired immunity build-up in Group M, at least for Cooperia.     

Adverse immune reactions and the pathogenesis of Ostertagia ostertagi infections in calves

The possible development of type-1 hypersensitivity reactions in the abomasal mucosa caused by soluble L3 products of Ostertagia ostertagi was studied in 4-month-old calves sensitized by repeated exposure to L3 over a 50-day period followed by anthelmintic treatment. Four groups each of 4 calves were used. Group 1 served as nonsensitized controls and group 2 as sensitized controls, group 3 was challenge exposed at 2-week intervals beginning at week 10 with a soluble L3 product (OAG), and group 4 was challenge exposed at 2-week intervals with an oral dose of L3, followed by anthelmintic treatment 3 days later. All calves infected with L3 became sensitized, as indicated by a positive reaction to an intradermal skin test. However, a passive cutaneous anaphylaxis was only partly effective in indicating the presence of homocytotropic antibody in the infected calves. Sensitized calves had significantly (P less than 0.05) higher eosinophil counts and plasma pepsinogen values for the entire 14 weeks than uninfected controls. Globule leukocyte and mast cell counts from the abomasal mucosa were also significantly (P less than 0.05) higher. Studies for possible immunomodulation revealed that lymphocyte counts decreased between every 2-week challenge-exposure period for groups-3 and -4 calves. A transient depression of blood lymphocyte (BL) responses to phytohemagglutinin (PHA), a T-cell mitogen, was observed over the first 8 weeks in the infected calves. Increases in BL responses to OAG were also observed. Differences were not observed in BL responses to pokeweed mitogen, a T- and B-cell mitogen. Blood lymphocyte responses to PHA in group-3 calves were low following the initial challenge exposure with OAG.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

Response to transplanted adult Ostertagia ostertagi in calves

Plasma pepsinogen levels became elevated in groups of recipient calves immediately after transplant with adult Ostertagia ostertagi. These rises occurred in both previously parasite-naive calves and in calves which had experienced prior infection terminated with an anthelmintic either seven or 21 days before transplant. From the results it appears that adult O ostertagi play a significant role in the elevated plasma pepsinogen levels associated with bovine ostertagiasis.