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Pathophysiology of nematodiasis in cattle.

Recent detailed studies of the physiologic changes occurring in cattle infected with some of the common gastrointestinal nematodes have shown that the weight loss and reduced carcass values resulting from these infections are a consequence of major alterations in host metabolism. Dramatic changes in protein metabolism were consistently found to involve decreased muscle synthesis and increased urinary nitrogen excretion. Because of the well-recognized loss of plasma proteins into the gut lumen and cellular damage at the mucosa occurring during nematode infections of the abomasum and duodenum, it has been assumed that protein was being lost in feces or not absorbed; however, this loss has proved not to be as significant as postabsorptive protein catabolism in these infections. Only when the colon and cecum are involved in protein-losing infections is the loss of protein into the feces significant. The mechanisms by which gastrointestinal nematode infections result in such altered host metabolic states are not known, but suggestions have been made that parasites directly or indirectly alter gut hormone levels. Gut hormone changes may also be responsible for diarrhea and anorexia. Another mechanism of altering metabolism has been proposed for chronic parasitisms that stimulate macrophages. Macrophages produce a peptide called cachectin, and cachectin is thought to mediate protein and lipid catabolism. This mechanism obviously could be contributing to weight loss and anorexia whenever nematodes cause sufficient macrophage activation, including during lungworm infections, which do not have enteric involvement.

Animals↗

Evaluation of Haemonchus contortus infections in sexually intact and ovariectomized ewes.

Three experiments were conducted to investigate experimentally the occurrence of periparturient nematode egg rise in ewes and the hormonal modulation of Haemonchus contortus infections. In the first experiment, fall-bred and winter-bred pregnant (n = 4 and 14, respectively) and nonpregnant (n = 5 and 29, respectively) ewes were treated with anthelmintic and were pastured together on fields that were contaminated with H contortus. Three weeks before lambing, all ewes were placed in concrete pens; fecal egg counts for the winter-bred group were obtained on alternate days. Pregnant and lactating ewes had significantly larger numbers (P less than 0.01) of H contortus eggs than did the nonpregnant controls 1 week before and after lambing. Lactating, fall-bred ewes had significantly (P less than 0.01) more adult worms in their abomasum through natural acquisition than the nonpregnant controls. In the second experiment, fall-bred and winter-bred, helminth-free, pregnant (n = 4 and 8, respectively) and nonpregnant (n = 3 and 15, respectively) ewes were inoculated on 5 alternate days, beginning 70 days after breeding with 20,000 infective H contortus larvae. The ewes were maintained on concrete pens throughout pregnancy. Fecal egg counts were significantly (P less than 0.05) greater in pregnant ewes, beginning 1 week before lambing until 1 week after lambing. Abomasums of lactating ewes from both lambing seasons yielded significantly (P less than 0.01) more adult worms at necropsy than nonpregnant ewes. In the third experiment, ewes were ovariectomized (n = 15) or sham-operated (n = 9); half of the control ewes were bred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Size of inoculum dose regulates in part worm burdens, fecundity, and lengths in ovine Haemonchus contortus infections.

Density-dependent factors frequently have been shown to regulate population parameters of free-living and parasitic helminths. To test the effects of various infection levels of Haemonchus contortus on fecundity and worm size, lambs were inoculated with 3,000, 10,000, and 30,000 infective larvae. Daily eggs per gram (epg) and daily total fecal production per lamb were monitored continuously. Worms were collected from abomasa on 6, 15, 22, and 30 days postinfection (PI). Female worms were smaller on each day in the high-dose group when compared to female worms from the low-dose group; males in the high-dose group were smaller from days 15 through 30 PI. The high- and medium-dose groups had higher mortality rates on day 30 PI, and fecundity (eggs/female/day) was 78% lower. Daily epg and daily total eggs/lamb/day were lower in the high-dose group. Fecundity and worm size were correlated with the log-transformed dose level but not with adult worm number. Early parasite and/or host responses apparently exert long-term negative effects on growth and reproduction relative to the size of the establishing population of H. contortus.

Abomasum↗

Hypergastrinaemia of sheep infected with Haemonchus contortus.

Radioimmunoassay of plasma gastrin has shown that a hypergastrinaemia occurs in yearling sheep, after infection with 10(6) infective third stage larvae of Haemonchus contortus. Plasma gastrin concentrations began to rise two to four days after infection, that is, at about the same time as, or slightly before, the abomasal pH was observed to increase.

Abomasum↗

Influence of dietary protein on the pathophysiology of haemonchosis in lambs given continuous infections.

Mixed-sex groups of three-month-old Finn Dorset and Dorset Horn lambs were given complete diets containing either high or low protein. A trickle infection with Haemonchus contortus of 200 larvae, given three times a week, began one month later for a 17 week period. Erythrokinetic, metabolic, digestibility and balance studies were conducted with the male lambs during weeks 12 to 14 of the infection. Clinical signs of haemonchosis became evident only in the low protein diet group. The infection was characterised by severe macrocytic anaemia, hypoproteinaemia, hypoalbuminaemia, reduced survival, high egg counts and a significantly greater worm burden. In the high protein diet group many lambs developed resistance to further infection in contrast to the low protein group in which no resistance developed. Live-weight gain was not affected by infection in the high protein diet group but decreased in the lambs given the low protein diet compared with uninfected controls. However, infection did not appear adversely to affect the digestive efficiency, nitrogen retention or iron absorption in either dietary group although loss of appetite occurred in the low protein group. Examination of a sample joint from the carcases showed infection was associated with a marked reduction in muscle mass in lambs given the low protein diet relative to the control animals.

Animals↗

Two field strains of Haemonchus contortus resistant to rafoxanide.

Two field strains of Haemonchus contortus, one from Pretoria on the Highveld and the other from White River in the Lowveld of the Transvaal, showed pronounced resistance to rafoxanide at a dosage rate of 7.5 mg/kg live mass per os. Both of these strains originated from kikuyu pastures under irrigation. Resistance in South Africa to rafoxanide and other anthelmintics, namely, closantel, ivermectin and the benzimidazoles is reviewed. It is concluded that apart from avoiding farming practices where integrated worm control is not possible, there is at present no solution to the problem of worm resistance in the country.

Animals↗

Anthelmintic efficacy of albendazole in cattle: comparison of critical and controlled tests.

Twelve calves were experimentally inoculated with 6 species of gastrointestinal nematodes and the liver fluke, Fasciola hepatica. Six calves were administered albendazole at 10 mg/kg of body weight, and the drug efficacy was determined by critical and controlled tests. Albendazole was only 74% effective against Haemonchus contortus (cambendazole-resistant strain), 99 to 100% effective against Ostertagia ostertagi, Trichostrongylus colubriformis, Cooperia oncophora, and Oesophagostomum radiatum, and 54% effective against the liver fluke. Except for H contortus, the critical test provided as accurate a measurement of drug activity against gastrointestinal nematodes as the controlled test provided.

Animals↗

Laboratory selection of Haemonchus contortus for resistance to ivermectin.

The eighth generation of adult Haemonchus contortus, selected by subjecting infected pairs of sheep to suboptimal ivermectin treatment once per generation from parent (P; BBH isolate) through F7 (IV-A; selected isolate), required an approximate 4-fold increase in the ivermectin dose to produce 95% efficacy compared with its contemporary parent isolate. In a dose titration experiment the dose-response curve of the drug pressure-derived isolate, IV-A, was significantly (0.02 less than P less than 0.05) less steep than was the response curve of the parent, BBH, isolate. Potency estimates based upon these nonparallel dose-response curves would not remain constant over a range of efficacy levels but would decrease rapidly at efficacies greater than 95%. Passage of a closed population of the F8 generation of IV-A sequentially through pairs of sheep for an additional 11 generations (F8A-F8K) without additional drug pressure being applied produced no reversion to sensitivity to ivermectin relative to the F7 generation, thus suggesting that the selected "resistance" was stable.

Analysis of Variance↗

Immune exclusion of Haemonchus contortus larvae in sheep: dose dependency, steroid sensitivity and persistence of the response.

Naive and immune sheep, treated with anthelmintic, challenged directly into the abomasum and killed 48 hours later were used to examine the steroid sensitivity, persistence and dose dependency of immune mechanisms which result in the failure of incoming Haemonchus contortus larvae to establish (immune exclusion). Immune exclusion was almost totally abolished by corticosteroid treatment, the mean percentage of larvae establishing in the mucosa of immune sheep was 1.4 per cent of the challenge infection whereas in those treated with dexamethasone it was 24.4 per cent and in naive sheep 27.3 per cent. Immune animals challenged after seven and 42 days without antigenic experience excluded more than 90 per cent of the challenge larvae from their mucosae, whereas those challenged after 84 days without antigenic experience were as susceptible as naive animals. Immune exclusion was dose dependent, animals challenged with 10(6) and 10(5) larvae excluded 93 per cent and 82.5 per cent of the challenge dose whereas those challenged with 10(4) larvae failed to exclude larvae.

Adrenal Cortex Hormones↗

Changes in the response of Haemonchus contortus eggs to the ovicidal activity of thiabendazole during the course of infection.

Hatching rates and susceptibility to thiabendazole were studied on Haemonchus contortus eggs collected after either a single, a challenge or a trickle infection of sheep with a non-resistant strain. Considerable changes were observed both in hatching rates and LC50 values for thiabendazole during the course of infection. Peaks in LC50 suggested that a susceptible strain can produce eggs at least tolerant and perhaps slightly resistant at some days pi even without any previous contact with anthelmintic. The peak obtained after a single infection was more transient than in the other cases thus suggesting that the immune response of the host may facilitate the selection of tolerant or resistant sub-populations of worms or of eggs. The inheritance of this feature was not clearly demonstrated. Nevertheless, the LC50 of a selected sub-population collected from an immune lamb and given to another lamb was higher and more constant than that of the original strain.

Animals↗

Changes in LC50 in an in vitro egg development assay during the patent period of Haemonchus contortus in sheep.

Using an in vitro egg development assay with thiabendazole as anthelmintic the LC50 of eggs produced by two sheep infected with either a susceptible or a resistant strain of Haemonchus contortus was followed during the patent period from 22 days to 77 days after infection. In both sheep the LC50 followed the same pattern. At the start of the patent period the average values for the susceptible and the resistant strain were, respectively, 0.05 and 0.21 micrograms ml-1 thiabendazole, after 40 to 60 days 0.09 and 0.35 micrograms ml-1, while after 77 days 0.07 and 0.24 micrograms ml-1 were recorded.

Animals↗

Prevalence of benzimidazole resistance of nematodes in sheep in The Netherlands.

A survey was carried out in The Netherlands to determine the prevalence of benzimidazole resistance in sheep nematodes. It was shown that 47 per cent of the 59 investigated flocks harboured trichostrongylid populations with resistance to benzimidazoles, as demonstrated by an LD50 value of 0.12 micrograms ml-1 thiabendazole or higher in an in vitro egg hatch assay. On these farms Haemonchus contortus was found to be the dominant species. In two flocks resistant Ostertagia and, or, Trichostrongylus species populations were found. Farms with resistance were revisited to determine the anthelmintic efficacy in vivo by means of treatment and egg count. In only four of the 19 flocks which showed resistance in vitro was an efficacy of less than 95 per cent in vivo achieved. This means that there is a discrepancy between the in vivo and in vitro results. Resistance was found more frequently on pure sheep farms than on mixed farms. It is suggested that mixed farms offer more refuge for susceptible H contortus populations.

Animals↗

Protection of lambs with a purified metabolite of exsheathed third-stage Haemonchus contortus larvae.

Helminth-free lambs (approx 4 months old) were inoculated SC with a purified metabolite of exsheathed third-stage Haemonchus contortus larvae. The metabolite was obtained from in vitro cultivation and was identified as XL3FA1. After 3 periodic XL3FA1 inoculations, lambs were challenge exposed with H contortus. Multiple vaccinations with XL3FA1 did not inhibit the development of worm populations in the lambs; however, worm egg production seemed to be inhibited.

Animals↗

Efficacy of levamisole and netobimin against Haemonchus contortus in lambs in Louisiana.

Efficacy of levamisole was evaluated in a suspected levamisole-resistant population of Haemonchus contortus in the Louisiana State University sheep flock. The efficacy of netobimin also was evaluated against this population of Haemonchus. In trial 1, 5 lambs naturally infected with H contortus were given 8 mg of levamisole/kg of body weight as a drench, and 5 lambs were not treated (controls). Nematode recovery after slaughter indicated 0% efficacy against H contortus. In trial 2, 30 nematode-free lambs were each given 8,300 F1 generation infective larvae of H contortus, which were derived from parent H contortus that survived 2 levamisole treatments in lambs being maintained in a nematode-free environment. Ten lambs were treated with 8 mg of levamisole/kg as a drench, 10 were treated with 20 mg of netobimin/kg as a drench, and 10 were not treated (control). Nematode recovery after slaughter revealed 62.3% and 99.8% efficacy for levamisole and netobimin, respectively, against H contortus.

Animals↗