Bromoxanide, a new anthelmintic.
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Fenbendazole given orally to experimentally infected lambs at a dose rate of 5 mg per kg was found to be 100 per cent effective against three and 10-day larave and also against 20-day adults of H contortus, O circumcincta, N battus and T colubriformis. The same dose was also 100 per cent effective against 10-day, 17-day larvae and 27-day adult D filaria.
The efficacy of fenbendazole against the following gastrointestinal nematodes was tested in experimentally infected lambs: O circumcincta, H contortus, T colubriformis and N filicollis. As low a dose as 0.5 mg per kg reduced the egg output of a patent infection with H contortus and T colubriformis by 85 per cent to 100 per cent. A dose of 3.5 mg per kg has a 100 per cent effect on three or 10-day-old stages of H contortus and one of more than 99 per cent or 100 per cent T colubriformis. The same dose reduces seven-day-old stages of O circumcincta and N filicollis by more than 94 per cent or 100 per cent, while 10 mg per kg produces a 100 per cent elimination of seven-day-old stages of O circumcincta. In field trials and efficacy of more than 99 per cent was determined after oral dosage with 5.0 mg per kg against Ostertagia, Haemonchus, Trichostrongylus, Cooperia, Nematodirus and Chabertia. Fenbendazole has a wide therapeutic-toxic dose ratio. Discoloration of the wool does not occur. Fenbendazole can be administered as a drench or with the feed.
Sera from 53 sheep belonging to Castellano, Churro, Manchego, and Merino breeds were analyzed to test the diagnostic value of a 26-kD antigen from adult Haemonchus contortus at prepatency and early and late patency of experimental haemonchosis. Animals that received zero, 1, or 2 infections with the parasite were tested. In addition, sera from 20 experimentally infected and 10 noninfected Texel sheep were used to test the antigen. Sera from 37 infected animals at prepatency as well as at patency in primary and secondary infection were found positive with the 26-kD antigen. However, sera from 10 animals with the lowest worm burdens (second infection) did not recognize the antigen during early patency (day 28 postinfection). IgG1 was the only isotype implicated in antigen recognition because IgG2, IgA, and IgM, in the same sera, showed no reactivity with the peptide. Antigen specificity was confirmed because hyperimmune sera against infective larvae and adult stages of the most common gastrointestinal nematodes found in natural infections in sheep (Trichostrongylus colubriformis and Teladorsagia circumcincta) did not recognize this peptide. The antigen was recognized only by anti-adult H. contortus hyperimmune sera and appeared to be absent in the L3 parasite stage. In addition, the partial N-terminal amino acid sequence of the diagnostic peptide is reported.
A pen study was conducted to assess the effect of providing daily copper mineral supplement, or copper wire particle (COWP) capsules, on established or incoming mixed nematode infections in young sheep. For lambs with established (6 week old) infections, COWP resulted in 97% and 56% reduction of the adult and early L4 stages of H. contortus, respectively, compared with controls (p<0.001). Additionally there was a 74% reduction in Teladorsagia circumcincta infections in the COWP lambs compared with controls (p<0.01). However, no effect was observed when COWP were given at the commencement of a larval dosing period of 6 weeks. There was no significant effect of copper mineral supplement (given at the recommended rate to prevent Cu deficiency) on either established, or developing parasite infections. In addition, a field trial was conducted on a commercial farm to assess the effects of COWP in the management of recurrent H. contortus infections, but lack of parasites during the grazing season prevented an adequate assessment from being made. These results indicate that there is little, if any, benefit from a parasite control standpoint in recommending copper therapy, specifically to control parasites in Swedish sheep flocks.
The biocide activity of Bacillus thuringiensis (B. thuringiensis) IB-16 strain was evaluated against the blood-feeding nematode Haemonchus contortus (H. contortus) in vitro and in vivo assays. Twenty experimental jirds (Meriones unguiculatus) and 32 sheep were infected with H. contortus by oral route. Fourteen days post infection 10 jirds were treated with 0.2 mg per mL of IB-16 soluble toxin by intraperitoneal (i.p.) route and 8 sheep were treated with 0.5 mg of toxin per kg of body weight by intramuscular route 35 days after H. contortus infection. Same number of treated jirds and sheep were used as control. Fecal and blood samples were analyzed from experimental sheep to estimate the number of parasitic eggs, percentage of eosinophils, packed cell volume (PCV), and IgG title. All experimental jirds and 16 sheep (8 treated and 8 controls) were sacrificed at days 5, 7, and 30 after B. thuringiensis treatment. The percentage of nematode reduction was estimated from L(4) and H. contortus adults. The percentage of protection was 80.0 to jirds and 73.8 and 53.3 to sheep, sacrificed at days 7 and 30, respectively. Moreover, nonsignificant difference (P > or = 0.05) was detected from parasitic eggs, eosinophils, and PCV parameters. Significance level of IgG was observed only before H. contortus treatment with B. thuringiensis soluble toxin (P < or = 0.05) but nonsignificant difference was observed after treatment. These results showed that B. thuringiensis activity was similar to those observed by anthelmintic treatment and it could be used as an alternative biological method.
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The frequency distribution of female Haemonchus contortus bahiensis Grisi, 1974 in sheep from Venezuelan arid zones is 15.32% for the type with vulvar flap, 51.6% for the vulvar-knob and 33.07% for smooth type. A Shannon-Weaver diversity index corresponding to 1.44 bits was calculated for these forms with similarities in the general size, egg-size and in the number of the longitudinal cuticular ridges. An aggregated kind of distribution in the host population according to the K parameter of a negative binomial distribution was recorded for male and female worms. A complicated interaction was observed between the abundance, aggregation and prevalence of this ecotype and the importance of these findings is discussed with regard to host-parasite relationships.
The trichostrongylid nematode Haemonchus contortus released a hyaluronic acid-degrading enzyme during in vitro development from the third (L3) to fourth (L4) larval stage. The enzyme did not degrade chondroitin sulfate A. Enzyme activity was optimal between pH 4.0 and 6.0, and the enzyme was inhibited by high concentrations of NaCl; the divalent cations Cu2+, Zn2+, Ca2+, and Mn2+ were not inhibitory. The hyaluronidase had a molecular mass estimated at 57 kDa by sucrose density gradient centrifugation and at 111 kDa by substrate sodium dodecyl sulfate polyacrylamide gel electrophoresis (reducing and nonreducing conditions), suggesting the formation of a dimer during the electrophoretic separation conditions. The level of hyaluronidase released during in vitro development peaked between 24 and 48 hr in culture and then gradually decreased, with little or no activity present in the 168-hr culture fluid. The enzyme was not detected in culture fluid from 24-hr incubations of either the mid-L4 stage (obtained from sheep 7 days postinfection) or the adult stage (obtained from sheep 30-35 days postinfection). The temporal expression of the hyaluronidase suggested a role for this enzyme in the early stages of the L3-L4 developmental process.
The sensory neuronal ultrastructure of the amphids of the infective larva (L3) of Haemonchus contortus was analyzed, compared, and contrasted with that of the first-stage larva (L1). As in L1, each amphid of the L3 is innervated by 12 neurons. Thirteen ciliated dendritic processes of 10 neurons, 3 with double processes, lie in each amphidial channel. The dendritic process of each finger cell neuron ends in a large number of digitiform projections or "fingers," many more than in the L1. Processes of another pair of specialized neurons, probable homologs of wing cells in Caenorhabditis elegans, extend into the extreme anterior tip of the larva; they are much longer than those in L1. In L3, the neurons exit through the posterior wall of the amphidial chamber individually rather than in a bundle, as in L1. Cell constancy between L1 and L3 was confirmed, and the neurons were individually identified. Significant neuron-specific variations, presumably related to functional differences between the 2 stages were observed. In contrast, species-specific differences are surprisingly small. Haemonchus contortus is closely related to hookworms and has amphidial structure nearly identical to that in hookworms and similar to that in C. elegans, to which it is also closely related.
In the course of a revision of species of Haemonchus Cobb, 1898 (Nematoda), commonly referred to as large stomach worms and significant pathogens of ruminants, a new species was discovered in the grey rhebuck Pelea capreolus, and the bontebok Damaliscus pygarthus, in South Africa. The new species, Haemonchus horaki, was previously reported as a long-spicule form of H. contortus (Rudolphi, 1803) Ransom, 1911. The new species, compared with H. contortus, can be distinguished by significantly longer spicules (555-615 microm vs. 383-475 microm); a synlophe with fewer ridges (26 vs. 30 in the region of the posterior part of the esophagus) that extend more posteriorly (within 1 mm of the copulatory bursa in males and postvulvar in females, vs. 2/3 to 3/4 of prebursal and prevulvar lengths); and an asymmetrical dorsal lobe with a long dorsal ray divided for more than half of its length, forming 2 branches of unequal length (vs. a dorsal ray divided for less than half of its length and forming 2 equal branches in H. contortus).
Phylogenetic analysis of 25 morphological characters among the 12 species of Haemonchus resulted in 1 most parsimonious tree (60 steps; consistency index = 0.67, retention index = 0.80). Monophyly for Haemonchus was diagnosed by 3 unequivocal synapomorphies, including the asymmetric origin of the dorsal ray, relative size of the ventral rays, and the presence of a barb on each spicule tip. Species of Haemonchus have complex histories with respect to host and geographic associations: (1) origins in Africa with basal diversification in antelopes (H. krugeri, H. lawrencei, H. dinniki, H. horaki), (2) independent events of colonization for those species in Caprini and Bovinae (H. contortus, H. placei, H. bedfordi, H. similis), (3) colonization and development of core host associations within Camelidae (H. longistipes) and among Antilopinae, Tragelaphini, and Giraffidae (H. mitchelli, H. okapiae, H. vegliai), and (4) geographically widespread species that are represented only by those that have been translocated with domestic stock. The North American fauna is characterized by 3 introduced and exotic species, H. placei, H. contortus, H. similis, which emphasizes the importance of continued documentation of faunal diversity in the context of predictive foundations derived from phylogenetic studies. Satellite associations for species of Haemonchus, particularly among Cervidae and Camelidae in the Neotropics and Cervidae, Antilocapridae, and possibly wild Caprinae in the Nearctic, have been a consequence of introductions and exchange of parasites at historical interfaces for managed and natural ecosystems. Such distributions are emblematic of the overriding significance of anthropogenic factors as determinants of the global distributions for pathogenic parasites in domestic and wild ruminants.
This study was designed to evaluate breed differences in resistance to Haemonchus contortus in lambs. A total of 181 ewe lambs representing crossbred Dorsets (DO) and Dorpers (DP; out of 1/2-Dorset, 1/4-Rambouillet, 1/4-Finnsheep ewes) and straight-bred Katahdins (KT) were evaluated over 3 yr. An additional 144 DO, DP, KT, and Barbados Blackbelly x St. Croix (HH) wethers were evaluated over 2 yr. Lambs were weaned at 60 to 90 d of age. After deworming at about 4 mo of age, ewe lambs received approximately 10,000 infective larvae and were evaluated for parasite resistance in drylot, whereas wethers were evaluated on pasture under conditions of natural infection. Each sex was analyzed separately. Egg counts per gram of feces (FEC), log-transformed FEC (LFEC), packed cell volumes (%), and body weights (kg) measured at 3, 4, 5, and 6 wk after deworming and reinfection were analyzed. Breed influenced all traits (P < 0.05) except BW in ewe lambs and PCV in wethers. Year and week influenced (P < 0.05) all traits. At most times, DP had the highest FEC, DO had the lowest PCV, and KT and HH had lower FEC and higher PCV than either DO or DP. Clearly, Dorper sheep were not more resistant to parasites than DO, but they were able to cope with infection better by maintaining similar or higher (P < 0.05) PCV and similar BW. Katahdin and HH were more resistant, with lower FEC (P < 0.05) than DO or DP. Breed differences were more apparent when infection levels were higher; DO and DP were less affected when infection levels were low and when animals were on a better plane of nutrition. Caribbean hair sheep originated in hot, humid regions of West Africa. They and the derivative Katahdin breed seem relatively resistant to parasitism. The Dorper, in contrast, was developed in more arid regions and exhibited little parasite resistance.
This study describes responses to artificial infection with Haemonchus contortus in ewes and lambs of 50% Dorset, 25% Rambouillet, and 25% Finn-sheep ancestry and provides estimates of genetic parameters for measures of parasite resistance. One hundred ninety-eight ewes out of 64 sires, and 386 lambs out of 25 sires were evaluated in autumn and spring of 2 yr. Ewes were dewormed shortly after weaning their lambs and lambs were dewormed at about 120 d of age. One week after deworming, ewes and lambs were dosed with approximately 10,000 infective larvae of H. contortus. After infection, BW, fecal egg counts (FEC), and packed cell volume (PCV) were measured weekly for 7 wk in lambs kept in drylot and fortnightly for 11 wk in ewes on pasture. Summary traits were defined as initial PCV, mean BW across all times, and means for PCV (MPCV) and log-transformed FEC (MLFEC) at wk 3 to 7 after infection for lambs and wk 3 to 11 after infection for ewes. Ewes and lambs did not lose weight overall in any year or season, but there was no consistent effect of year or lambing season on mean LFEC or mean PCV during infection in either ewes or lambs. Yearling ewes were less resistant to infection than older ewes, with lower PCV (P < 0.05) and higher LFEC (P < 0.05). During infection, PCV was positively correlated with BW and negatively correlated with LFEC in both ewes and lambs. In lambs, heritabilities were 0.39 (P < 0.01) for PCV, 0.10 (P < 0.05) for LFEC across all measurement times, and 0.19 (P < 0.01) for three measures of LFEC taken at the peak of infection. Heritability estimates for ewes were 0.15 (P < 0.05) for PCV and 0.31 (P < 0.01) for LFEC. Repeatabilities for LFEC and PCV across measurement times were moderate in ewes and lambs. Correlations between dam and lamb records for MLFEC were generally low, suggesting different mechanisms of resistance in lambs and nonlactating ewes. Ewes with higher genetic merit for growth as lambs were less resistant to infection as adults, but genetic merit for fertility and prolificacy were not related to parasite resistance. Lambs with higher genetic merit for body weight were more resistant to infection. Selection for resistance to H. contortus is therefore possible and should not adversely affect growth of lambs and fertility of ewes in this production environment.
Gastrointestinal nematode parasitism is arguably the most serious constraint affecting sheep production worldwide. Economic losses are caused by decreased production, the costs of prophylaxis and treatment, and the death of the infected animals. The nematode of particular concern is Haemonchus contortus, which can cause severe blood loss resulting in anemia, anorexia, depression, loss of condition, and eventual death. The control of nematode parasites traditionally relies on anthelmintic treatment. The evolution of anthelmintic resistance in nematode populations threatens the success of drug treatment programs. Alternative strategies for control of nematode infections are being developed, and one approach is to take advantage of the host's natural or acquired immune responses, which can be used in selection programs to increase the level of resistance in the population. Vaccination can also be used to stimulate or boost the host's acquired immunity. The induction of protective resistance is dependent on the pattern of cytokine gene expression induced during infection by two defined CD4+ T-helper cell subsets, which have been designated as Th1 or Th2. Intracellular parasites most often invoke a Th1-type response, and helminth parasites a Th2-type response. Breeds of sheep resistant to infection have developed resistance over a much longer term of host-parasite relationship than genetically selected resistant lines. The immune components involved in these different responses and types of host-parasite relationships will be reviewed. The potential for using vaccines has been investigated, with variable results, for several decades. The few successes and potential new antigen candidates will also be reviewed.
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