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Management practices and use of anthelmintics on dairy cattle farms in The Netherlands: results of a questionnaire survey.

In December 1996, a questionnaire about farm management and parasite control measures in calves was sent to 956 randomly chosen dairy cattle farmers in The Netherlands. Another 150 farmers in the vicinity of Deventer who had vaccinated their calves in 1995 against lungworm were approached with the same questions. Our object was to investigate the consequences on worm control of the withdrawal of the lungworm vaccine from the market for reasons of possible BSE contamination of the vaccine. OF the returned questionnaires, 411 (43%) of the 'at random' group and 89 (59.3%) of the 'Deventer' group were valid. The most important data with regard to the farms of the 'at random' group (41) were: mean area 31.6 ha, mean number of calves 23, heifers 23 and milking cows 53. Sheep (mean 37) were present on 18.3% of the farms. With regard to management: 74.5% of the farmers turned the calves in their first year onto pasture, 25.5% kept them indoors. The average time on pasture was ca. 5 months. Rational grazing was practise on 81.4% of the farms, on 18.6% calves were set stocked. The first pasture of the calves was mown before turn-out on 72.9% of the farms. On 48.2% of these farms, calves were always moved to mown pastures. With regard to treatments: 33.8% of the farmers vaccinated their calves against lungworm in the years 1993, 1994 and 1995. Despite the withdrawal of the vaccine from the market in 1996, 7.2% of the farmers vaccinated their calves as recommended, with two doses, and 13.1% with a single dose. At turn-out, 41.5% of the farmers gave the calves a preventive anthelmintic treatment. Of these treatments, 66.9% were sustained of pulse release long acting device. During the grazing season, 36.6% of the farmers treated their calves. After housing 50.3% of the farmers gave a treatment. Signs of lungworm infection were noticed on 18.6% of the farms. Of the 'Deventer' group (89 farmers), 96.6% turned the calves out, Of these farmers, 86.0% had used the lungworm vaccine in 1995. In 1996, 52.7% of the farmers had vaccinated the calves:36.5% with a single dose and 16.2% with the double dose. Of the 35 farmers who did not vaccinate in 1996, 62.9% gave a preventive treatment at turn-out. Clinical signs of lungworm infection were not observed on the 12 farms which vaccinated the calves twice. On 11% of the farms which vaccinated once and on 14% of the farms which did not vaccinate, signs of lungworm infection were observed. It is concluded that more than 80% of Dutch dairy cattle farmers take appropriate measures to control gastrointestinal nematode and lungworm infections in calves in their first grazing season by grazing on aftermath, rotational grazing on mown pastures combined or not with preventive anthelmintic treatments. However, combinations of aftermath grazing and preventive treatment occurred on 30% of the farms. This may be overprotective and may prevent sufficient build up of immunity, causing worm problems at a later age. The withdrawal of the lungworm vaccine from the market did not cause a rise in lungworm problems. Some farmers did vaccinate, despite the withdrawal. The majority used other preventive treatment measures, mainly the application of long acting boli.

Animals↗

Immunology of helminth infections, with special reference to immunopathology.

Immune responses resulting in immunity to infection or disease, share the same basic humoral and cellular mechanisms. While immunity to helminth infection has evolved to mediate rapid elimination of the parasite, the strategies evolved by the parasites themselves aim to delay this rejection process and ensure the survival and distribution of their progeny. Ineffective or incomplete immunity results in persistence of parasites or their products within the host tissues, inappropriate or chronic stimulation by parasite antigens, hyper-reactivity and tissue damage or immunopathology. A long standing classification by Gell and Coombs identifies four major types of hypersensitivity responses accounting for most of the immunopathogenesis, three of which are mediated by antibody and one, delayed type hypersensitivity (DTH), by T cells. This paper aims to give a short review of these four classical hypersensitivity reactions with particular reference to infections of large animals with helminth parasites. In addition, in view of the functionally different helper T cell subsets now identified, the existing DTH response is redefined as DTH Type 1 (Th-1 mediated) and two new classes of T cell-dependent DTH responses are proposed; DTH Type II, associated with the Th-2 type cytokines IL-4 and IL-5 and eosinophilic granuloma formation, and DTH Type III, associated with IL-4 and TGF-beta and fibrosis. Finally, some implications of immunopathology on parasite control strategies are discussed.

Animals↗

Cloning and sequence analysis of the candidate nicotinic acetylcholine receptor alpha subunit gene tar-1 from Trichostrongylus colubriformis.

A T. colubriformis genomic library in lambda EMBL3 was screened for sequences homologous to the Caenorhabditis elegans unc-38 nicotinic acetylcholine receptor (nAChR) alpha-subunit gene. The candidate gene tar-1 (for Trichostrongylus acetylcholine receptor subunit gene 1) comprising 13704 base pairs was thus identified. BLAST comparison of the sequenced clone with GenBank, followed by comparison of translated regions in six reading frames with protein databases, identified clearly defined tracts corresponding to 12 putative exons sharing high sequence homology to other nAChR genes and able to code for sequential regions of a putative nAChR alpha-subunit protein (tar-1). Tar-1 shares sequence similarities with over 40 nAChR subunit proteins. The highest similarity (91.6%) is with unc-38, suggesting that nAChR sequences from nematodes are closely related. The sequence includes motifs typical of these molecules including adjacent cysteine residues at the ACh binding site and four transmembrane regions. The DNA sequence presents the longest genomic tract described for this organism and should prove useful as a probe source in the search for nAChR genes from this and other nematodes and for studying the molecular mechanism of resistance to levamisole, a drug which is known to act on nAChRs of worms and which is widely used for parasite control.

Amino Acid Sequence↗

Preventive health care for pet potbellied pigs.

Many small and exotic animal practitioners decline to see potbellied pigs, possibly because of their challenging behavior and the perception that in order to treat them, one must be very knowledgeable about swine medicine. With some basic information about their unique behavior and their preventive health care needs, however, seeing potbellied pigs in practice is easy and provides a much-needed service in many communities. The behavior of the pig, recommended methods of restraint, physical examination, vaccinations, and parasite control are all discussed.

Animals↗

Polymorphic DNA markers in the genome of parasitic nematodes.

Polymorphic molecular markers are being identified to characterize the genomes of parasitic nematodes. The aim is to construct a map with markers evenly spread over the six chromosomes. With such a map, regions can be identified that are under selection pressure when attempts are being made to eradicate worms, be it by drugs, vaccines or genetic resistance in the sheep. Several types of markers have been developed, microsatellites, transposon-associated markers, amplified fragment length polymorphism (AFLP) and expressed sequence tag (EST) markers. Linkage groups can be constructed using several genetic crosses between inbred and drug resistant strains. EST markers will be especially important for comparative mapping with the genome of Caenorhabditis elegans, and therefore localization of the linkage group on a chromosome. It will then be possible to identify functional genes close to markers that have changed allele frequencies under selection pressure and identify the mechanisms of resistance to parasite control.

Animals↗

Comparative disposition kinetics of albendazole in sheep following oral and intraruminal administration.

The pharmacokinetics of albendazole was studied in sheep following single oral and intraruminal administration at nematocidal dose rates. The disposition curves of its metabolites indicated increased uptake of the drug in sheep following intraruminal as compared to oral dosing (p < 0.05). The increased bioavailability of benzimidazole anthelmintics given by the intraruminal route could be exploited for optimizing the use of anthelmintic for sustained parasite control in small ruminants.

Administration, Oral↗

Alpha CD 2 mAb treatment safely attenuates adoptive transfer colitis.

Increased proliferation, defective apoptosis, and cytokine dysregulation of T lymphocytes are thought to be important for the pathogenesis of inflammatory bowel disease. Since these phenomena can be corrected by alpha CD 2 mAb, we asked whether CD2 directed immunotherapy safely prevents and/or ameliorates adoptive transfer colitis. Colitis was induced by transfer of CD4(+) T cell blasts to syngenic RAG 1(-/-) mice or CD 45 RB(high) CD4(+) T cells to SCID mice. The alpha CD 2 mAb 12-15 or rat IgG was given, starting either initially or upon first signs of colitis. Disease activity was assessed by clinical monitoring, microscopic scoring, hemoccult, endoscopy, and blood count analysis. Cytokine production of stimulated LPL was measured by ELISA and cell proliferation by [(3)H]-thymidine incorporation. Parasite control was analyzed in a murine model of infection with Toxoplasma gondii. The alpha CD 2 mAb significantly increased mean survival time when starting at transfer of blasts (survival >35 days: alpha CD 2 69% vs 0% of controls, P<0.001). In the SCID colitis model hematochezia and macroscopic colitis were delayed. When used in established T-cell blast colitis, the benefit was less pronounced, even in combination with dexamethasone (mean survival+/-s.e.m.: alpha CD 2+dexa: 13.5+/-2.9 vs dexa+IgG: 6.3+/-1.0, P<0.05). In the preventive experiment the alpha CD 2 mAb markedly reduced IL-2 secretion and T-cell proliferation. The immune response towards Toxoplasma gondii was not impaired. These studies show for the first time that CD2 directed immunotherapy can attenuate or delay adoptive transfer colitis and ameliorate established colitis. Most likely inhibition of IL-2 secretion and T-cell proliferation are responsible for these effects. Still, immune defence towards T. gondii is maintained.

Adoptive Transfer↗

Balancing immunity and pathology in visceral leishmaniasis.

Experimental visceral leishmaniasis (VL) caused by infection with Leishmania donovani results in the development of organ-specific immunity in the two main target tissues of infection, the spleen and the liver. The liver is the site of an acute resolving infection associated with the development of inflammatory granulomas around infected Kupffer cells, and resistance to reinfection. Paradoxically, the spleen is an initial site for the generation of cell-mediated immune responses, but ultimately becomes a site of parasite persistence with associated immunopathological changes. These include splenomegaly and a breakdown in tissue architecture that is postulated to contribute to the immunocompromized status of the host. The progressive development of splenic pathology is largely associated with high levels of TNF and interleukin (IL)-10. Follicular dendritic cell (DC) networks are lost, whereas TNF mediates the destruction of marginal zone macrophages and gp38(+) stromal cells, and IL-10 promotes impaired DC migration into T-cell areas with consequent ineffective T-cell priming. Splenic stromal cell function is also altered, promoting the selective development of IL-10-producing DC with immunoregulatory properties. Ultimately, a fine immunological balance determines responses that effectively promote parasite clearance in the liver and those that promote pathology in the spleen, and future investigation aims to separate these responses to offer further means of parasite control in chronically infected VL patients.

Animals↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Gates, GAVI, the glorious global funds and more: all you ever wanted to know.

Global immunization programmes have achieved some remarkable successes. In 1977, Frank Fenner's Commission declared smallpox to have been eradicated by an 11-year-long intensive campaign. The Expanded Programme on Immunization encompassed six important childhood vaccines and reached over three-quarters of the world's children. Polio eradication has gone remarkably well, with only 10 out of 200 countries reporting residual cases. But amidst all the good news, there is also bad news. Coverage is variable; infrastructure is crumbling; and newer vaccines are not being incorporated in many country programmes. The Bill and Melinda Gates Foundation has introduced a new dynamic here. From their initial gift of $100 million in December 1998, their commitment to date is US$1.5 billion - and rising. At the centre is a Global Children's Vaccine Fund which permitted the launch, in January 2000, of the Global Alliance for Vaccines and Immunization. This is targeted to the 74 poorest countries of the world and is designed to improve vaccination infrastructure, to purchase newer vaccines and to support research and development. Even before we know how successful this programme will be, it has had its imitators. The Global Fund to Fight AIDS, TB and Malaria borrowed many concepts from GAVI. The Global Alliance for Improved Nutrition announced in May 2002 does so as well, and is heavily supported by Gates. Highly effective parasite control programmes antedate all this but will be much strengthened. However, we still face a sizeable budgetary gap both for research and for bringing the best advances to all people who need them.

Acquired Immunodeficiency Syndrome↗

[Protein traffic in Plasmodium infected-red blood cells].

To survive within erythrocytes, Plasmodium parasites have to put into place different membrane and sub-cellular compartments in order to import different nutrients and to export proteins/antigens. Infected cells pose not only a major world health risk by killing two million people per year, but also a very interesting cell biology problem, as within the erythrocyte the parasite resides inside a vacuole called the parasitophorous vacuole and as a consequence, it is separated from the blood stream by three membrane barriers, its own plasma membrane, the parasitophorous vacuole membrane and the erythrocyte plasma membrane. In spite of these three barriers the parasite is capable of secreting antigens and importing nutrients, and to do this, it has developed a complex vesicular system that extends into the red blood cell cytoplasm to the plasma membrane. Understanding how the parasite controls this extensive vesicular traffic has driven research into Plasmodium Rabs, whose potential role is discussed.

Animals↗

[Estimation of the prevalence of bovine hydatid cyst in the south Pyrenees].

Since 1994 "Réseau VEGA" (veterinary survey network) has organized a record of sanitary information in 14 slaughterhouses in the Midi-Pyrénées. Data about hydatidosis in cattle are centralized, analysed, then sent namely to each stockbreeder concerned. Estimation of the prevalence rate from 1994 to 1996 is 0.28% for animals and 2.5% for livestock. A marked decrease of rates was noticed during this three year monitoring period. Nevertheless, the Pyrenean area remains more affected than the North of the region. In an outbreak of hydatidosis, a few animals are carriers. Bovine infestation must be considered as revealing a rural cycle. Moreover, the link between bovine hydatidosis and ovine transhumance seems to be confirmed. Using livestock as epidemiological units is innovative in terms of hydatidosis. This approach allows a better adjustment of parasitism control and introduces the notions of the outbreak and the risk of human contamination. In the Midi-Pyrénées region, local human cases of hydatidosis are few. However, the absence of compulsory notification and of databases, on the one hand, and the extreme difficulty of confirming the autochthonous nature of the contamination, on the other hand, limit the reliability of data. A better collaboration between physicians and veterinarians would reduce animal prevalence and the risk of human contamination.

Abattoirs↗

Differences in plasma and abomasal kinetics of albendazole and its metabolites in calves grazed on pasture or fed a grain-based diet.

We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) and its metabolites in calves either grazing on pasture or fed a grain-based concentrate diet. Six male Holstein calves (weight 180 to 200 kg) were allowed to graze on lush pasture for three weeks before intraruminal administration of ABZ at 10 mg kg-1(pasture group). After a three-week wash-out period, the same animals were housed and fed on a grain-based concentrate diet for three weeks prior to receiving the same ABZ treatment (concentrate group). Jugular blood and abomasal fluid samples were collected over 120 hours post-treatment. Plasma and abomasal fluid samples were analysed by high performance liquid chromatography (HPLC). The digesta transit time was measured using cobalt (Co) as a fluid marker; abomasal fluid and faecal samples were collected and Co concentrations measured by atomic absorption spectrophotometry. Complementary studies of the in vitro dissolution of ABZ particles at different pH values were also conducted. The pH of abomasal fluid collected from animals kept under both feeding conditions was registered. Increased concentrations of ABZ sulphoxide (ABZSO) and sulphone (ABZSO2) in plasma, resulting in significantly higher Cmax and area under the curve (AUC) values for both metabolites, were obtained in calves fed on the concentrate diet compared to those grazing on pasture. Enhanced abomasal fluid levels of ABZ and ABZSO were observed in concentrate-fed calves. The mean retention time of the digestive fluid marker in the gastrointestinal (GI) tract was significantly longer in the animals fed the grain-based diet. The in vitro dissolution of ABZ at a pH value equivalent to that obtained in the abomasum of the concentrate-fed calves (1.75) was significantly greater than that obtained at the pH registered in pasture-fed animals (2.00). The characterisation of the kinetic/metabolic behaviours and the resultant efficacy of antiparasitic drugs in animals reared under different management conditions may be relevant in increasing parasite control in livestock.

Abomasum↗

Risk factors for iron-deficiency anaemia among pregnant women living in rural Vietnam.

OBJECTIVE: To assess the prevalence of anaemia in rural Vietnam and to determine its risk factors. DESIGN: A cross-sectional survey. SETTING: Vietnam, Nghe An Province. STUDY POPULATION: The total number of participants was 439. Of these participants, one was excluded from the study due to a mental disorder. Forty-seven did not participate in the test for parasites and 68 did not complete at least one of the questions. RESULTS: The prevalence of anaemia (haemoglobin (Hb) <11.0 g dl(-1)) was 43.2% and of severe anaemia (Hb <8.0 g dl(-1)) was 0.5%. Taking iron tablets, the consumption of eggs and the preference for Western medicine significantly and positively correlated with Hb concentration in the pregnant women in a multiple regression analysis. Pregnancy duration and hookworm infestation significantly and negatively correlated with Hb concentration in the pregnant women. CONCLUSION: The prevalence of anaemia in rural Vietnam has remained as high as that found in the national anaemia survey in 2000. The results of the present study could aid in the development of an iron-deficiency anaemia programme among pregnant women in rural Vietnam that emphasises iron supplementation, parasite control and improved diet, including the consumption of eggs. The programme's focus should be on women who prefer traditional medicine to Western medicine.

Adult↗

Responding to the crisis in sub-Saharan Africa: the role of nutrition.

In the chapter dealing with education and health, the report of the influential Commission for Africa prioritises basic health systems, HIV/AIDS, malaria and tuberculosis. In contrast, nutrition is given less than half a page and is reduced to parasite control and micronutrient support. Such neglect of nutrition is hard to understand in the context of increasing hunger and malnutrition across the continent. Sub-Saharan Africa is the only region in the world where the proportion of underweight children has stagnated and the absolute numbers have actually increased in the last decade. It has been pointed out that if current trends continue sub-Saharan Africa will achieve the Millennium Development Goal for child mortality around 2115 - one century after the target date. Quite clearly those concerned with nutrition need to more powerfully advocate the role of nutrition in lifting Africa out of the spiral of poverty. The present paper argues that to achieve this requires an understanding not just of the critical role of nutrition for health and development (both individual and national), but also of how recent global changes are interacting with changes in food production and supply, other determinants of maternal and child health, and the role and capacity of the state to tackle malnutrition in Africa. It concludes by suggesting some responses that nutritionists could now be making.

Africa South of the Sahara↗

Malaria transmission by Anopheles punctulatus in the highlands of Irian Jaya, Indonesia.

A 21-month (1991-1992) assessment of malaria and the relative contribution of Anopheles punctulatus and An. koliensis to its transmission was conducted in Oksibil, a highland community in Irian Jaya, Indonesia. Nearly all (98%) of the 2577 Anopheles from indoor or outdoor human-landing collections were An. punctulatus. Nineteen (0.75%) of the 2518 An. punctulatus tested were positive when tested for malaria circumsporozoite protein (CSP) by ELISA: nine (45% of positives) for Plasmodium vivax-210, six (30%) for Plasmodium falciparum, three (15%) for P. vivax-247 and two (10%) for P. malariae. One mosquito was positive for both P. vivax 210 and P. falciparum. All 59 An. koliensis tested were negative. All mosquitoes positive for CSP were from indoor collections, 89% from the main houses and the remaining 11% from the traditional dwellings (bokams). These findings are discussed with respect to highland malaria epidemiology and transmission in the Oksibil Valley.

Animals↗

Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine and albendazole, in various combinations.

Repeated, single, oral doses of combinations of ivermectin, diethylcarbamazine (DEC) or albendazole are recognized as important tools for parasite control in lymphatic filariasis. In order to assess the effects of re-treatment using these combinations in Brugia malayi infections, 40 asymptomatic microfilaraemics were re-treated at the end of the first year, with an additional, single, dose of the combination they had previously received. They were then followed-up for another year. The subjects, of both sexes and aged 14-70 years, each received a two-drug combination: ivermectin (200 micrograms/kg) with DEC (6 mg/kg); ivermectin (200 micrograms/kg) with albendazole (400 mg); or DEC (6 mg/kg) with albendazole (400 mg). The kinetics of microfilarial clearance were similar to that seen during the first treatment, the members of the two groups given DEC having less intense microfilaraemias, 1 year after the re-treatment, than those given ivermectin with albendazole (P < 0.001 for each comparison). At this time, the two DEC groups also had a higher proportion of amicrofilaraemic individuals (22 of 26) than the ivermectin + albendazole group (three of nine). There were fewer adverse reactions in all the groups after re-treatment than seen after the first treatment. In countries such as India, where there is no co-endemicity of onchocerciasis or loiasis, the options for control programmes in areas where brugian filariasis is endemic are DEC alone or DEC in combination with ivermectin or albendazole. Where there is no access to ivermectin, transmission control must be based on DEC alone or in combination with albendazole.

Adolescent↗

A survey of anthelmintic usage for sheep: a time for change.

A sample survey of anthelmintic usage and farmers; drenching policies was conducted on 614 sheep farms, in the North and South Islands, selected from among those carrying 1500 or more breeding ewes. The survey was based on information for the 1978179 and 1979/80 farming years recorded on questionnaires completed during personal interviews between Livestock Officers and the farmers concerned. Results show that there were no significant between-Island differences in mean drenching frequencies for any age class of sheep. In 1979/80, the overall New Zealand drenching frequencies were 6.3 for lambs, 1.8 for 1-2-year-olds and 1.2 for sheep older than 2 years. Of the farmers surveyed, 20% did not drench 1-2-year-old sheep and 29% did not drench sheep older than 2 years. There were also no between-Island differences in timing of drenches and alternation of drench brands. Sixty-nine per cent of the farmers followed a pre-determined drenching programme whereas 27% stated that they drenched if and when necessary. For lambs, some drenching was carried out in all months of the year hut fewer farmers drenched during the mid-winter to mid-spring period (July-October). Older stock were drenched in all months also but there was a general acceptance by farmers of the practices of pre-tupping and pre or post-lambing drenching. At the time of the survey, 48% of the farmers were using three or more brands of drench with a maximum of nine. Analysis of data relating to brands of drench used shows that whereas 39% of the farmers w,ere alternating drench families [i.e. benzimidazoles (BZ) c.f. non-benzimidazoles (NBZ)] within a single farming year, only 3% were practising a strict alternation of drench families between years. General comments by the farmers surveyed indicate a disturbing degree of misunderstanding and misconception regarding the properties and limitations of current anthelmintics. The survey also revealed a lack of appreciation of the rationale of prophylactic (;preventive;) parasite control. These aspects are discussed in relation to currently recommended control strategies and the problem of anthelmintic resistance.

Journal Article↗