Association of blood eosinophilia with the expression of resistance in Romney lambs to nematodes.

The dynamics of blood eosinophilia was studied in Romney lambs dosed twice weekly with 5000 infective larvae of Trichostrongylus colubriformis. A marked rise in blood eosinophil counts of the dosed lambs coincided with the start of the decline of faecal egg counts (FEC). Eosinophilia was also studied in grazing Romney lambs from a breeding programme, based on selection for high or low FEC. Comparison of the sire groups suggested that the magnitude of the eosinophil response was under genetic control. The significant negative correlations between blood eosinophil counts and FECs confirmed the association between eosinophilia and the expression of resistance in Romney lambs to nematodes. However, comparison of the mean blood eosinophil counts and FECs for both the ram and ewe lambs of the resistance sire groups suggested that the association of eosinophilia and resistance may be greater for some sire groups than others.     

Intergeneric relations between nematodes of the digestive tract in lambs: a multivariate approach.

The interactions between nematode genera of the ovine digestive tract have been examined through a multivariate analysis performed on data previously obtained in epidemiological surveys conducted in France and Morocco. Data referring both to the frequency of genera per sheep (analysis at the individual level) and to the number of worms per genus and per animal (analysis at the host population level) were examined. The results suggest that a highly stable equilibrium between genera occurred in individual hosts possibly regulated by the host response and the interactions between the worm populations. The regulative factors which act at the host population level tend to increase the stability of the system, to promote the expression of positive interactions between the genera and also to modulate the arrangement of intergeneric relations. The multivariate analysis thus provides a means for global analysis of the relations between nematode populations with potential applications to assess the efficacy of some control measures on the whole nematode community in the digestive tract.     

Use of lincomycin to control respiratory infections in lambs: Effects on health and production

The efficacy of lincomycin to control respiratory infections in lambs was assessed in two trials. In trial I, 72 lambs with active mycoplasmal pneumonia were allocated as follows: lambs in group T2 were treated with lincomycin (5 mg kg⁻¹ bodyweight, intramuscularly) twice 2 days apart, those in group T3 with lincomycin (5 mg kg⁻¹ bodyweight, intramuscularly) thrice with 2-day intervals, those in group O with oxytetracycline (20 mg kg⁻¹ bodyweight, intramuscularly) twice 4 days apart and those in group C were controls. In trial II, 48 25–30-day-old clinically healthy lambs were allocated as follows: lambs in group P2 received two injections of lincomycin (5 mg kg⁻¹ bodyweight, intramuscularly) when 30- and 60-day-old, lambs in group P1/30 received one injection of lincomycin (5 mg kg⁻¹ bodyweight, intramuscularly) when 30-day-old, lambs in group P1/60 received one injection of lincomycin (5 mg kg⁻¹ bodyweight, intramuscularly) when 60-day-old and lambs in group C were controls. In trial I, treatment with lincomycin was associated with improved clinical scores; clinical cure rate 42 days after treatment was 87%, 100%, 87% and 0% for group T2, T3, O and C, respectively (P < 0.001); treated lambs produced 18.5% (T2) or 26.5% (T3) heavier carcass than controls; no lung lesions were seen in group T3 lambs, whilst they were evident in 22% of group T2 or group O lambs and in 72% of control lambs; microorganisms were isolated from lung tissue samples of 5 group C and 1 group O lambs. In trial II, administration of lincomycin was associated with smaller clinical scores; prevalence rate of respiratory disorders at the end of the trial was 17%, 42%, 42% and 58% for group P2, P1/30, P1/60 and C, respectively (P < 0.01); treated lambs were >4.5% heavier than controls; lung lesions were recorded in 1 group P2, 2 group P1/30 and group P1/60 and 5 group C lambs; microorganisms were isolated from 1 group P2, 3 group P1/30, 2 group P1/60 and 5 group C lambs. It is concluded that administration of lincomycin is effective for the treatment and the prevention of mycoplasmal atypical pneumonia in lambs.     

Monitoring drug efficacy and early detection of drug resistance in human soil-transmitted nematodes: a pressing public health agenda for helminth control

Control of soil-transmitted helminth infection and elimination of lymphatic filariasis by periodic chemotherapy increase drug pressure for possible occurrence of resistance against single dose anthelminthics. In veterinary practice, frequent treatment of closed populations has led to a serious problem of anthelminthic drug resistance which is now largely irreversible. Reduced efficacy of single dose drugs against nematodes of humans should be taken as early warnings to tackle the issue in due time. Research and development of sensitive tools for monitoring and early detection of drug resistance is urgently needed to sustain the benefits of helminth control programs gained so far. A concerted action with international partners and the creation of a network of scientists to address this issue is the next pressing public health issue for helminth control.     

The effect of ruminoreticulum bypass in yarded lambs on the efficacy of oxfendazole against resistant Trichostrongylus spp. helminths

An observational study was performed to investigate the effects of yarding and ruminoreticulum bypass on the efficacy of oxfendazole against resistant Trichostrongylus spp. helminths. Ruminoreticulum bypass was observed in 9-month old Perendale lambs using video-taped fluoroscopy and the efficacy of oxfendazole was estimated using the faecal egg count reduction test. Yarding and withholding feed for 24 h before drenching with oxfendazole significantly enhanced the faecal egg count reduction for resistant Trichostrongylus spp. parasites (p < 0.05), but ruminoreticulum bypass of the drench in the yarded animals had no negative effect on anthelmintic efficacy (p > 0.05). The effect of ruminoreticulum bypass on the efficacy of oxfendazole may depend on the resistant parasite species present. The positive effects of yarding sheep for 24 h before drenching, on the efficacy of oxfendazole against resistant Trichostrongylus spp., probably outweigh any negative effects of ruminoreticulum bypass. However further studies are required, with different resistant parasite genera present, before firm recommendations can be made.     

Entomopathogenic nematodes to control black vine weevil (Coleoptera: Curculionidae) on strawberry.

We investigated the potential of heterorhabditid nematodes to control larvae of the black vine weevil, Otiorhynchus sulcatus (F.), in 2 field experiments in commercial strawberry plantings. In both experiments, nematodes were applied directly onto the straw mulch, or onto the soil after temporary removal of the mulch. Heterorhabditis marelatus Lui & Berry (Rhabditida: Heterorhabditidae) reduced numbers of weevil larvae and the percentage of plants infested in both experiments, irrespective of straw removal. In the 1st field experiment, a sponge-packed H. marelatus formulation produced lower numbers of O. sulcatus larvae per strawberry plant (mean O. sulcatus larvae per plant = 0.7) and proportion of infested plants (42%) compared with a vermiculite formulation (mean O. sulcatus larvae per plant = 1.8, proportion infested plants 67%) and an untreated control (mean O. sulcatus larvae per plant = 1.9, proportion infested plants 75%). In the first 2 wk after application, more H. marelatus were found in soil samples collected from plots treated with sponge-packed nematodes, than from plots treated with vermiculite-formulated nematodes. In the 2nd field experiment, sponge-packed formulations of H. bacteriophora Poinar (Rhabditida: Heterorhabditidae) and H. marelatus were tested. H. marelatus caused a reduction in both numbers of weevil larvae (mean O. sulcatus larvae per plant = 0.1) and proportion of infested plants (9%) but H. bacteriophora did not (mean O. sulcatus larvae per plant = 0.45, proportion infested plants 34%). More H. bacteriophora were recovered from soil samples than H. marelatus during the first 7 d of this experiment. However, laboratory studies revealed no difference in the persistence of these 2 nematodes in sand.     

Testing the flexibility of fasting-induced hypometabolism in birds: effect of photoperiod and repeated food deprivations

We tested whether photoperiod and repeated fasts modulate the fasting-induced nocturnal hypometabolic response in Japanese quails and pigeons. Quails did not compensate a shorter dark phase by a deeper hypothermia, but instead showed diurnal hypothermia that seemed to be conditioned by the removal of food. Body mass loss measurements indicated that this response saved energy. Repeated fasts in constant photoperiod in quails and pigeons slightly augmented the hypometabolic response only in quails. During fasting intervals, body mass increased in pigeons, but decreased in quails. Apart from the diurnal hypothermia seen in quails, photoperiod and repeated fasts had little influence on fasting-induced hypometabolism.     

Hyperbaric-induced subfertility in mice: lack of effect of decompression

Male mice were exposed to 50 atmospheres absolute (ATA). He for 30 min, twice weekly for 5 wk and their fertility assessed by subsequently mating with untreated virgin females. The exposure schedule was designed to provide compression and decompression times the same as previous positive studies of hyperbaric-induced subfertility but with much shorter periods at maximum pressure (30 min vs. 24 h). We postulated that, if subfertility were associated with exposure to pressure per se rather than with compression or decompression, then the present experiments would fail to produce a decrease in male fertility. The data were compared with those of a control group placed in the hyperbaric chamber at 1 ATA. The pregnancy rate for exposed vs. control mice was 89 vs. 86%, and the mean live liter size was 6.2 vs. 5.6. There were no statistically significant differences between these and other indexes of male fertility, and the results support our hypothesis that the hyperbaric-induced subfertility in male mice is not associated with these decompression procedures.     

The effect of colostrum period management on BW and immune system in lambs: from birth to weaning

The aim of this study was to investigate the BW and immune status of lambs reared under natural conditions or under artificial conditions fed two different colostrum amounts. In this study, 60 lambs were randomly divided into groups according to treatment. Twenty lambs remained with their dams (natural rearing (NR) group). Forty lambs were removed from their dams at birth. Lambs were bottle-fed with a pool of sheep colostrum, receiving either 4 g of IgG/kg of BW at birth (C4 group) or 8 g of IgG/kg of BW at birth (C8 group). The total colostrum amount was equally divided into three meals at 2, 14 and 24 h after birth. After this period, lambs were bottle-fed a commercial milk replacer. Blood plasma sample analysis and BW recordings were carried out before feeding at birth and then at 1, 2, 3, 4, 5 and 20 days after birth. Another blood sample analysis and BW recording was carried out when animals reached 10 kg of BW. During weaning (30 days), sampling was carried out every 5 days. Blood plasma was used to determine the concentrations of IgG and IgM and the complement system activity – total and alternative pathways. The NR group showed greater BW than the C4 and C8 groups during milk feeding period, whereas the C4 and C8 groups had greater BW than the NR group at the end of weaning period. The C8 and NR groups had greater plasma IgG and IgM concentrations than the C4 group during milk feeding period. In addition, C4 and C8 groups showed similar IgG concentrations and greater IgM concentrations than the NR group at the end of the weaning period. Complement system activity was greater in the NR group than in the C4 and C8 groups during the first 3 days after birth. In conclusion, lambs fed amounts of colostrum equivalent to 8 g of IgG/kg of BW showed similar immune variables compared to lambs reared under natural conditions, obtaining a greater BW at the end of the weaning period. Nevertheless, this study shows that not only the colostrum amount but also the management during the milk feeding and weaning period, such as stress produced by dam separation, milk quality and suckling frequency, can affect the final immune status of lambs.     

Functional role of P-glycoprotein in limiting peroral drug absorption: optimizing drug delivery

P-glycoprotein (P-gp) associated multi-drug resistance is one of the major challenges in the chemotherapy of various cancers. On the other hand, it is now widely recognized that P-gp influences drug transport across various biological membranes. To this end, there is an increasing trend to optimize pharmacokinetics and drug delivery right from the initial stages of drug discovery by exploring all the possible mechanisms involved in 'deliverability'. Recent advances in molecular biology techniques and biochemical characterization methodologies have helped in identification of various transporters involved in absorption or secretion of drugs. P-gp, an efflux pump expressed along the gastrointestinal tract, limits the permeability of many drugs and thus affects their peroral absorption and bioavailability. A fundamental insight and thorough understanding of P-gp and its functional role in limiting drug absorption is critical to improve predictability of dynamic absorption models and aid in selection of new candidates for development, and also widen the scope of peroral delivery for 'challenging' molecules.     

Cattle nematodes resistant to macrocyclic lactones: Comparative effects of P-glycoprotein modulation on the efficacy and disposition kinetics of ivermectin and moxidectin

The role of the drug efflux pump, known as P-glycoprotein, in the pharmacokinetic disposition (host) and resistance mechanisms (target parasites) of the macrocyclic lactone (ML) antiparasitic compounds has been demonstrated. To achieve a deeper comprehension on the relationship between their pharmacokinetic and pharmacodynamic behaviors, the aim of the current work was to assess the comparative effect of loperamide, a well-established P-glycoprotein modulator, on the ivermectin and moxidectin disposition kinetics and efficacy against resistant nematodes in cattle. Fifty (50) Aberdeen Angus male calves were divided into five (5) experimental groups. Group A remained as an untreated control. Animals in the other experimental Groups received ivermectin (Group B) and moxidectin (Group C) (200 μg/kg, subcutaneuosly) given alone or co-administered with loperamide (0.4 mg/kg, three times every 24 h) (Groups D and E). Blood samples were collected over 30 days post-treatment and drug plasma concentrations were measured by HPLC with fluorescence detection. Estimation of the anthelmintic efficacy for the different drug treatments was performed by the faecal egg count reduction test (FECRT). Nematode larvae were identified by pooled faecal cultures for each experimental group. Cooperia spp. and Ostertagia spp. were the largely predominant nematode larvae in pre-treatment cultures. A low nematodicidal efficacy (measured by the FECRT) was observed for both ivermectin (23%) and moxidectin (69%) in cattle, which agrees with a high degree of resistance to both molecules. Cooperia spp. was the most abundant nematode species recovered after the different drug treatments. The egg output reduction values increased from 23% to 50% (ivermectin) and from 69% to 87% (moxidectin) following their co-administration with loperamide. Enhanced systemic concentrations and an altered disposition of both ML in cattle, which correlates with a tendency to increased anthelmintic efficacy, were observed in the presence of loperamide. Overall, the in vivo modulation of P-glycoprotein activity modified the kinetic behavior and improved the efficacy of the ML against resistant nematodes in cattle. The work provides further evidence on the high degree of resistance to ML in cattle nematodes and, shows for the first time under field conditions, that modulation of P-glycoprotein may be a valid pharmacological approach to improve the activity and extend the lifespan of these antiparasitic molecules.     

Genotype by environment interaction in the assessment of tolerance of partially resistant potato clones to potato cyst nematodes

Genotype by environment interactions in a number of field trials in different years are examined in relation to tolerance of potato cyst nematodes and the subsequent yield losses. A biplot technique is used to display the interaction effects graphically and facilitate identification of any patterns in the data. The results are assessed and discussed in relation to breeding strategies and the variation found between different nematode populations.     

Genome-wide identification and comprehensive analysis of Excretory/Secretory proteins in nematodes provide potential drug targets for parasite control

Nematodes are responsible for causing severe diseases in plants, humans and other animals. Infection is associated with the release of Excretory/Secretory (ES) proteins into host cytoplasm and interference with the host immune system which make them attractive targets for therapeutic use. The identification of ES proteins through bioinformatics approaches is cost- and time-effective and could be used for screening of potential targets for parasitic diseases for further experimental studies. Here, we identified and functionally annotated 93,949 ES proteins, in the genome of 73 nematodes using integration of various bioinformatics tools. 30.6% of ES proteins were found to be supported at RNA level. The predicted ES proteins, annotated by Gene Ontology terms, domains, metabolic pathways, proteases and enzyme class analysis were enriched in molecular functions of proteases, protease inhibitors, c-type lectin and hydrolases which are strongly associated with typical functions of ES proteins. We identified a total of 452 ES proteins from human and plant parasitic nematodes, homologues to DrugBank-approved targets and C. elegans RNA interference phenotype genes which could represent potential targets for parasite control and provide valuable resource for further experimental studies to understand host-pathogen interactions.     

替加环素与多粘菌素B对泛耐药鲍曼不动杆菌体外研究

目的为治愈耐舒普深的泛耐药鲍曼不动杆菌（PDR-Ab）提供新药。方法替加环素采用二倍琼脂稀释法,多粘菌素B用E-test条法测分离目标菌株100株的最低抑菌浓度（M IC）,并用WHONET 5.4软件分析数据。结果多粘菌素B对耐舒普深的泛耐药鲍曼不动杆菌株的M IC值分布情况为：1.5 mg/L为2株,1.0 mg/L为9株,0.75 mg/L为9株,0.5 mg/L为38株,0.38 mg/L为34株,0.25 mg/L为8株,均为敏感;替加环素对耐舒普深的泛耐药鲍曼不动杆菌株的M IC值分布情况为：≥32 mg/L为0株、16 mg/L为2株、8 mg/L为3株、4 mg/L为4株、2 mg/L为6株、1 mg/L为9株、0.5 mg/L为30株、0.25 mg/L为33株、0.125 mg/L为9株、0.06 mg/L为2株、0.03 mg/L为2株,敏感率为95.0%,中敏率为3.0%,耐药率为2.0%。结论替加环素或多粘菌素B是目前对耐舒普深的泛耐药鲍曼不动杆菌最有效药物之一。     

Ecology in the service of biological control: the case of entomopathogenic nematodes

 Biological control manipulations of natural enemies to reduce pest populations represent large-scale ecological experiments that have both benefited from and contributed to various areas of modern ecology. Unfortunately, economic expediency and the need for rapid implementation often require that biological control programs be based more on trial and error than on sound ecological theory and testing. This approach has led to some remarkable successes but it has also produced dismal failures. This point is particularly well illustrated in the historical development and use of entomopathogenic nematodes for the biological control of insect pests. Intense effort has focused on developing these natural enemies as alternatives to chemical insecticides, in part because laboratory assays indicated that these nematodes possess a broad host range. This illusory attribute launched hundreds of field releases, many of which failed due to ecological barriers to infection that are not apparent from laboratory exposures, where conditions are optimal and host-parasite contact assured. For example, the entomopathogenic nematode Steinernema carpocapsae is a poor choice to control scarab larvae because this nematode uses an ambusher foraging strategy near the soil surface whereas the equally sedentary scarab remains within the soil profile, shows a weak host recognition response to scarabs, has difficulty overcoming the scarab immune response, and has low reproduction in this host. Conversely, two other nematodes, Heterorhabditis bacteriophora and S. glaseri, are highly adapted to parasitize scarabs: they use a cruising foraging strategy, respond strongly to scarabs, easily overcome the immune response, and reproduce well in these hosts. Increased understanding of the ecology of entomopathogenic nematodes has enabled better matches between parasites and hosts, and more accurate predictions of field performance. These results underline the importance of a strong partnership between basic and applied ecology in the area of biological control. Received: 15 July 1996 / Accepted: 5 November 1996