Effects of anthelmintics onHaemonchus contortus (Nematoda: Trichostrongylidae)

The review summarizes and evaluates recent information about the effects of anthelmintics onHaemonchus contortus. The topic is discussed under the headings effects of drugs on the absorptive surfaces, effects of drugs on metabolism, effects of drugs on the neuromuscular system, effects of drugs on developmental stages, anthelmintic efficacy, and resistant strains. Possible future lines of work are suggested in the conclusions.     

Effect of dexamethasone treatment on the immune response of Gulf Coast Native lambs to Haemonchus contortus infection

Neonatal and weaner Gulf Coast Native (Native) lambs were studied to determine whether an immunological basis underlies their natural resistance to Haemonchus contortus infection. Neonatal Native lambs (n = 8) and weaner Native lambs (n = 15) were randomly assigned to a treatment or a control group. Lambs in the treatment group received dexamethasone by intramuscular injection three times a week for 10 weeks (neonatal) and 15 weeks (weaners). All lambs were monitored for fecal egg count (FEC), blood packed cell volume (PCV), and white blood cell differential counts on a weekly basis for the duration of the studies. Neonatal lambs were kept on pasture with their dams and weaner lambs were dewormed at weaning and kept in pens where they received trickle infections. Serum antibody titers to H. contortus whole worm antigen (WWA) were determined using ELISA. Lymphocyte proliferation assays on peripheral blood mononuclear cells (PBMC) were done to assess lymphocyte function. All lambs were vaccinated with killed Brucella abortus strain 19 to assess the effect of dexamethasone treatment on antibody response. All lambs were necropsied at the end of each study to recover the contents of the gastrointestinal tract for nematode enumeration and identification. The results showed that mean FEC and mean PCV of the treatment group was significantly higher and lower, respectively, than in the control group in both neonatal and weaner lambs from weeks 6 and 5, respectively. At necropsy, total nematode count was significantly higher in treatment groups than in the control groups. Serum antibody titers to H. contortus WWA were significantly lower in treated groups than in control groups. Treatment groups showed a consistent depression in lymphocyte percentage being significantly lower from week 6 in both neonatal and weaner lambs. No differences were found in the response of PBMC to mitogen stimulation between the groups. Lambs in the control groups showed strong positive brucellosis card tests and the treatment groups did not. Dexamethasone treatment resulted in depression of the immune response and loss of natural resistance of Native lambs to H. contortus infection. The results of these studies suggest that some aspects of the immune response may underlie the natural resistance of Native sheep to H. contortus infection.     

Genetic variation of Haemonchus contortus (Trichostrongylidae) in sheep and goats from Malaysia and Yemen

The large stomach worm, Haemonchus contortus, commonly known as "the barber's pole worm", is a blood-sucking nematode found in the abomasa of sheep and goats. This work is the first documentation on the ND4 sequences of H. contortus from sheep and goats in Malaysia and Yemen and the results provide a preliminary insight on the genetic differences of H. contortus found in the two countries. In general, this study showed a high degree of diversity and low population structure of this species within the same country in comparison with higher genetic structuring at a wider geographical scale. The results also showed that the majority of genetic variance was within H. contortus populations. The Malaysian sheep and goat populations investigated appeared to share the same isolate of H. contortus while different isolates may be found in Yemen which must be taken into account in the design of an effective control strategy. Analysis of the internal transcribed spacer-2 (ITS-2) confirmed that all samples investigated in this study belonged to H. contortus. However presence of other Haemonchus species parasitizing these two hosts can only be confirmed by further detailed studies.     

Influence of sex on the resistance of sheep lambs to an experimental Haemonchus contortus infection

36 intact male and 69 female lambs of two breeds (n = 63 Merinoland; n = 42 Rh?n) aged 12 weeks were orally infected with 5000 infective-stage larvae, L3, of the nematode Haemonchus contortus. After 4 and 8 weeks faecal egg counts (FEC), haematocrit values and plasma testosterone levels were determined. All lambs were slaughtered at 20 weeks of age. The gastrointestinal tracts were examined for the presence of adult stages of H. contortus. Male lambs showed significantly higher log FEC (p < 0.001), higher mean establishment rates (p < 0.05), higher worm burdens (p < 0.01) and lower haematocrit values (p < 0.001) when compared with female lambs. Correlations between economically important traits (body weight, daily weight gain) and parasitological parameters were significantly higher in male animals. Testosterone level was 4 weeks after infection significantly positive correlated with worm burden. The results suggest that female lambs are more resistant against an experimental H. contortus infection when compared with male lambs. Testosterone seems to play an important role in resistance. This approach can be of importance if parasite resistance is incorporated into breeding programs and the estimated breeding values for rams are only based on male offspring information. Therefore male breeding values are probably not representative for the whole population.     

Evaluation of immune response to artificial infections of Haemonchus contortus in Gulf Coast Native compared with Suffolk lambs

Due to their critical functions in worm physiology, glutathione peroxidases in Haemonchus contortus are potential candidates for vaccine to control haemonchosis. However, information on the protection potential of these molecules is lacking. In this study, recombinant HC29 antigen was tested for protection against experimental H. contortus infections in goats. Fifteen animals were allocated into three trial groups. The animals of HC29 group was vaccinated with a recombinant HC29 DNA vaccine twice at day 0 and day 14, and then challenged with 5000 infective H. contortus L3 (third larval stage) on the 28th day. An unvaccinated positive control group was challenged with L3 at the same time. An unvaccinated negative control group was not challenged with L3. The results indicated HC29 DNA vaccine was transcribed at local injection sites and expressed in vivo post immunizations, respectively. Following L3 challenge, the mean eggs per gram feces and worm burdens of HC29 group were reduced by 36.1% and 35.6% respectively compared to the positive control group. After immunization with the DNA vaccine, significantly high levels of serum IgG, serum IgA, mucosal IgA and CD4(+) T lymphocytes were detected. These results suggest that recombinant H. contortus HC29 glutathione peroxidase DNA vaccine induced a partial immune response and has protective potentials against caprine haemonchosis.     

Differential immune response between fundic and pyloric abomasal regions upon experimental ovine infection with Haemonchus contortus

The effect of experimental haemonchosis on the number of tissue eosinophils, plasma cells and lymphocyte subpopulations was evaluated in the fundic abomasal region, the pyloric abomasal region and the abomasal lymph node of Blackbelly lambs, which are resistant to infection, and Columbia lambs, which are susceptible to infection. An increase in the number of tissue eosinophils and CD4+ and WC1(+)γδ T-cells was observed in the pyloric abomasal region of Blackbelly lambs and correlated with lower worm burden and greater resistance to infection. Increases in IgA+ plasma cells from the pyloric abomasal region were observed in both infected groups, but there was no difference between the groups. Therefore, increases in IgA+ plasma cells did not explain the resistance observed. Infection caused a significant increase in tissue eosinophils in the abomasal lymph node of Blackbelly lambs and a decrease in the number of CD4+ T-cells in lambs of both breeds. CD8+ T-cells and IgG+ and IgM+ plasma cells were not associated with either infection or resistance. In this work, clear differences were observed in the numbers of CD4+ and WC1(+)γδ T-cells, tissue eosinophils and IgA+ plasma cells between the abomasal regions studied. These differences indicate that the immunological response is not homogenous in all abomasal mucosa and that evaluating the response from a single abomasal region may not be representative of the cellular response across the abomasum.     

Cooperia pectinata (Nematoda: Trichostrongylidae) in New Zealand

Cooperia pectinata, a nematode parasite hitherto undetected in New Zealand, was recovered from the small intestine of a six-month-old red deer (Cervus elaphus) born on a deer farm in Taihape. The source of this infection is unknown but it seems likely that it originated from feral stock.     

Effects of dietary molybdenum on nematode and host during Haemonchus contortus infection in lambs.

The addition of molybdenum (0.05 mmol kg-1 dry-matter) to the diet of lambs given a trickle infection of Haemonchus contortus larvae (500 third stage larvae d-1 over six weeks) reduced mean faecal egg counts (epg) from 3952 to 2312 +/- 402 by 32 days (P less than 0.02) and greatly reduced the mean number of worms recovered from the abomasum 14 days after infection ceased (907 compared with 4167: P less than 0.01). Infection reduced haemoglobin concentrations less in lambs given molybdenum although the difference was small relative to the reduction in worm burden. Lambs not given molybdenum had low intraepithelial mast cell counts in the abomasal mucosa and less abomasal hypertrophy than expected from abomasal parasitism. Molybdenum did not consistently reduce the copper status of the host or the parasite. Previous exposure to molybdenum greatly reduced protein but not proteinase activity in, or secreted by, adult worms cultured for eight hours. It is suggested that molybdenum either increased the inflammatory response which preceded worm rejection or that it indirectly enhanced that reaction by reducing the effectiveness of copper-dependent, anti-inflammatory enzymes in the gastrointestinal mucosa.     

Dose titration of sericea lespedeza leaf meal on Haemonchus contortus infection in lambs and kids

The objective of three experiments was to determine the impact of supplementing sericea lespedeza (Lespedeza cuneata; SL) in three concentrations in a loose or pelleted diet on gastrointestinal nematodes (GIN) in small ruminants. Experiments on lambs were conducted at the USDA, Agricultural Research Service in Booneville, AR (Exp. 1) and at Louisiana State University in Baton Rouge, LA (Exp. 2); an experiment on goat kids occurred at University of Maryland-Eastern Shore (Exp. 3). Exp. 1 used crossbred hair sheep lambs naturally infected with GIN that were randomly allocated to diets containing 0, 25, 50, and 75% SL diets (n=11 or 12/diet). Exp. 2 consisted of Haemonchus contortus-inoculated crossbred wool breed lambs that were blocked by gender and FEC and randomly assigned to 0, 25, 50, or 75% SL diet (n=8/diet). Fecal egg counts (FEC) and blood packed cell volume (PCV) were not influenced by SL supplementation in Exp. 1 and 2. Exp. 3 consisted of naturally GIN infected Boer crossbred goat kids in individual pens. Kids were blocked by FEC and randomly allotted to treatments of 0, 20, 40, or 60% SL with 9-13 goats/diet. The more SL fed, the greater the reduction in FEC (P<0.001). There was an increase in PCV in SL fed goats (P<0.001). Larval speciation at the end of the experiment indicated that feces from control animals produced 43% H. contortus larva while 20, 40 and 60% SL resulted in 39%, 35% and 31% H. contortus larvae, respectively. Feeding dried SL may be less effective in lambs than kids, though concurrent studies must be conducted to confirm this.     

Effect of nutritional status and fat reserves on the periparturient immune response to Haemonchus contortus infection in sheep

A study was made of the effect of body fat stored by ewes in early pregnancy on the subsequent immune response to gastrointestinal parasites around parturition. Pregnant ewes were given access to a lucerne pelleted diet either ad libitum (H) or at approximately 0.70 of their maintenance requirements (L) from the 42nd day of pregnancy in order to achieve a clearly differentiated level of body reserves by the 90th day of pregnancy. Then, all animals were put on the same plane of nutrition till 3 weeks after parturition. All ewes in both groups received 7,000 infective larvae of Haemonchus contortus per week for 7 weeks prior to lambing. The dietary treatments led to large differences between both groups of ewes in back-fat thickness that had a high correlation with mean plasma concentrations of leptin. In spite of the fact that animals were on the same plane of nutrition at infection time, host resistance, as measured by faecal egg counts, was significantly affected by the nutritional treatment established during early pregnancy. This effect produced noticeable differences in worm size and in worm burden at lambing. The response was accompanied by a marked increase in circulating eosinophils in better-fed ewes than in those maintained on a restricted diet in early pregnancy. Serum pepsinogen concentration, however, was inversely affected by the nutritional treatment till lambing, showing a maximum difference as early as 2 weeks after infection. The results support the view that higher levels of nutrition during early pregnancy enhance the expression of immunity against gastrointestinal parasites around parturition. Furthermore, the differences in the immune response appeared associated with serum leptin levels suggesting that leptin may be a key link between nutritional status and the protective immune reactivity against GI nematode infection.     

Effect of copper oxide wire particles dosage and feed supplement level on Haemonchus contortus infection in lambs

The objective of the experiment was to determine the optimal dose of copper oxide wire particles (COWPs) to reduce infection of Haemonchus contortus in male lambs. Five to six-month-old hair breed lambs were housed on concrete and fed 450 (L; n = 25) or 675 g (H; n = 25) corn/soybean meal supplement and bermudagrass hay. In July, lambs were inoculated with 10,000 L(3) larvae (97% H. contortus; Day 0). Lambs were administered 0, 2, 4, or 6 g COWP on Day 28. Concentrations of copper in the liver were determined. There were no effects of supplement level on concentrations of copper in the liver and a linear relationship existed between COWP treatment and concentrations of copper in liver (P < 0.001). Least squares means of the 0, 2, 4, 6 g COWP treatments were 62.2, 135.7, 161.1, and 208.4 ppm (P < 0.001). Between Days 0 and 28, PCV declined and by Day 42, PCV of all COWP-treated lambs was markedly higher than control lambs and remained higher (COWP x day, P < 0.05). By Day 21, PCV was greater in the H compared with the L group of lambs (P < 0.001). Within 14 days of COWP treatment FEC declined from more than 8000 eggs/g (epg) to less than 250 epg in all COWP-treated lambs (COWP x day, P < 0.001). The numbers of H. contortus in the abomasum were greatly reduced in all COWP-treated groups of lambs and remaining nematodes were predominantly males. FEC were greater in L versus H supplemented lambs and values decreased to a greater extent in H lambs when treated with COWP (supplement x COWP; P < 0.02). The 2 g COWP was effective in alleviating H. contortus infection and reducing number of egg-laying nematodes in the abomasum with the lowest concentration of copper in the liver of the COWP treatment groups. PCV values were more favorable for lambs fed the higher level of supplement, especially when FEC were greater than 8000 epg.     

Preference for condensed tannins by sheep in response to challenge infection with Haemonchus contortus

Herbivores prefer feeds that supply required nutrients and avoid those with excess nutrients and plant secondary compounds (PSC). Nevertheless, PSC such as condensed tannins can provide beneficial medicinal effects to herbivores as they act against infective diseases such as parasitism. The objectives of this study were to determine: (1) if parasitized lambs increased preference for a tannin-rich feed after they experienced the beneficial antiparasitic effects of condensed tannins relative to parasitized lambs that did not experience such benefits, and (2) if preference for the tannin-rich feed in the former group decreased when parasite burdens subsided. Twenty two lambs were familiarized with beet pulp and beet pulp+8% quebracho tannins (beet pulp+tannins) and choices were given between the two feeds (initial preference tests). Subsequently, all animals were dosed with 10,000 L(3) stage larvae of Haemonchus contortus. Twenty-two days later, animals were exposed to beet pulp (Control group; n=11) or beet pulp+tannins (Treatment group; n=11) during 24 d. After exposure (during a parasitic infection) animals in both groups were given choices between the two feeds. Lastly, animals in both groups received an antiparasitic drench and were again given a choice between both feeds (after a parasitic infection). Lambs preferred beet pulp to beet pulp+tannins throughout the study (P<0.001) and no difference in preference for the tannin-rich feed was detected between groups during initial preference tests (P>0.05). However, during a parasitic infection, intake of and preference for the tannin-rich feed was higher for lambs that experienced the beneficial effects of condensed tannins while parasitized (Treatment) than for lambs that did not (Control) (P<0.05). When parasitic infections were terminated by chemotherapy, differences between groups disappeared (P>0.05). Preference by the Treatment group for the tannin-rich feed was lower after than during a parasite infection (P<0.05). In contrast, preference by the Control group did not change during these periods (P>0.05). Lambs in the Treatment group displayed lower FEC than lambs in the Control group (Group × Sampling Date; P<0.05). These results show lambs learned about the antiparasitic effects of condensed tannins and increased their preference for the tannin-rich feed, which subsided after chemotherapy, indicating preference was due to parasite infection. These findings suggest management that allows animals to select tannin-rich feeds can enable parasitized animals to self-medicate.     

Effect of Haemonchus contortus infection on the clearance of antipyrine, sulfobromophthalein, chloramphenicol, and sulfathiazole in lambs

A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP after treatment with thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that the lambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected.     

Nitrogen and mineral balance of lambs artificially infected with Haemonchus contortus and fed tanniferous sainfoin (Onobrychis viciifolia)

Tanniferous temperate legumes are assumed to possess anthelmintic properties, but it is unclear whether this is the direct result of condensed tannins (CT) or is mediated indirectly via an improved metabolic protein supply. A metabolism experiment was conducted to differentiate between these factors by feeding the CT plant sainfoin (19.7% CP in DM) to lambs infected with the abomasal blood-sucking nematode Hemonchus contortus. A total of 18 infected lambs were fed sainfoin either untreated or treated with polyethylene glycol, a CT-inactivating agent, or a grass-clover mixture (13.2% CP in DM) over 3 wk (n = 6). Six uninfected lambs received the grass-clover mixture as a control. In addition to indicators of infection (fecal egg count, packed-cell volume, abomasal worm burden, and serum protein), nutrient digestibility, the balance of N and selected minerals, ruminal fluid characteristics, and plasma AA levels were determined mostly in the final experimental week. The specific effects of the sainfoin CT, the extra CP with sainfoin, and the infection were statistically evaluated by contrast analysis. The sainfoin CT exerted no beneficial effects on resilience to nematode infection and exerted only minor effects on ruminal ammonia or blood urea concentrations and the excretory pattern of N. Plasma alanine, aspartate, and proline concentrations tended to be greater (P < or = 0.09) because of the sainfoin CT, whereas the other AA remained unaffected. Intake of the mineral supplement was lower (P < 0.001) for lambs fed sainfoin compared with those fed sainfoin treated with polyethylene glycol. Feeding the high-protein sainfoin instead of the grass-clover mixture increased (P < 0.001) N retention and apparent OM digestibility, whereas digestibility of NDF and ADF were decreased (P < 0.001). Feeding sainfoin also decreased (P < or = 0.04) plasma alanine, glycine, isoleucine, and total nonessential AA compared with the grass-clover mixture. Although fecal egg count, worm burden, and packed cell volume were not affected by the greater CP supply associated with sainfoin feeding, serum albumin level was increased (P = 0.008). The lack of effects of sainfoin on resilience to nematode infection might have been the result of the unexpectedly low CT content (3.6% in DM) of the material used. It cannot be excluded that longer term feeding of this batch of sainfoin might have been effective.     

Is there a relationship between haemoglobin genotype and the innate resistance to experimental Haemonchus contortus infection in Merino lambs?

Responses to a single or repeated infection with 7000 infective larvae of Haemonchus contortus were studied in an experiment using a total of 106 3-month-old lambs with AA, AB or BB haemoglobin (Hb) genotypes. Results were assessed by faecal egg counts, adult worm counts, haematocrit values, haemoglobin concentrations, total serum protein and serum antibody IgG1 and IgA ELISA titres. None of these parameters showed a strong relationship to the Hb type. The prevalence of low responder (greater than 500 worms) and of high responder (less than 50 worms) animals in groups AA, AB and BB Hb types was 3.8 and 34.6, 20.6 and 35.2, 28.1 and 43.7%, respectively, suggesting that the responsiveness to nematode infection is under the control of gene(s) not closely linked with those determining the Hb genotype. Worm counts of a primary infection are more subject to variation than those of a secondary infection. There is a strong relationship between adult worm counts and faecal egg counts taken close to the time of slaughter. In living animals low and high responder discrimination can be based on individual faecal egg counts around 50 days after a secondary infection. Haematocrit values proved to be of little value in the low and high responder selection. In this regard neither Hb concentration nor total serum protein values are of practical significance. In 3-month-old lambs primary infection induced partial immunity which could prevent the establishment of a part of the secondary infection, irrespective of the presence or absence of the primary worm population. The development of immunity was not associated with an increase of serum IgG1 and IgA antibody levels. Specific antibody production was not influenced by Hb types. Mean antibody levels of low responder lambs showed no difference from those of high responders. Thus, serum IgG1 and IgA levels are of no predictive value in identifying lambs which are genetically resistant to Haemonchus infection.