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[Use of administrative and economic methods in managing veterinary affairs].

The possibilities are stated of using the administrative and economic methods in the administration of the veterinary service. It is stressed that the two types of methods are applied in combination. Administrative methods are to be employed in the control of epizootics, including zoonoses, and in the veterinary and sanitary control, resp. surveillance and inspection. Both types of methods are equally referred to in the control of parasitic diseases with epizootic course of development as well as in the control of diseases caused by occasionally pathogenic organisms. The use of economic methods is prevailing in the control of noninfectious diseases, and in the administration of bioproduct and drug production.

Animal Diseases↗

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees.

BACKGROUND: Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. RESULTS: Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. CONCLUSION: Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion.

Animals↗

The effects of the use of the morantel sustained release bolus system on calves grazing a highly contaminated pasture in The Netherlands.

The efficacy of the morantel sustained release bolus system for the control of parasitic gastroenteritis in calves was evaluated in the Netherlands. The effect of bolus administration to calves, either on May 1 at the beginning of the summer grazing season or on June 12 after the pasture was mown for silage, was determined in respect of liveweight gain, faecal worm egg output, serum pepsinogen values and worm burdens. In addition, pairs of tracer calves were turned out with each group every four weeks and sacrificed for worm counts in order to monitor pasture larval contamination throughout the grazing period. Compared with nontreated control calves, the worm egg outputs of the bolus-treated calves turned out (Nematodirus helvetianus), while the bolus-treated calves turned out on June 12 had a corresponding reduction of 95 and 100 percent. Over the grazing season the average weight gain of bolus-treated calves turned out on May 1 was 34 kg more than nontreated controls turned out at the same time. Difference in weight gain of the treated and control calves turned out late in the season was 10.5 kg in favour of the treated group. The postmortem worm counts were highest in the control calves turned out early and lowest in the bolus-treated calves turned out late. All tracer calves placed on the paddock grazed by control calves (turned out early) died from parasitic gastroenteritis from July onwards while those from the paddock grazed by the control calves (turned out late) died from parasitic gastroenteritis from September onwards. All the tracer calves placed on the paddocks grazed by bolus-treated calves survived until the intended slaughter date.

Animals↗

Resistance in nematode parasites of livestock to the benzimidazole anthelmintics.

The benzimidazoles have served humans well in the continual battle to control nematode parasites among livestock. However, the value of these drugs has been seriously undermined in various countries, particularly in the southern hemisphere, by the development of resistance in the target parasite species. Scientists in many countries are trying to come to grips with this problem, with studies both in the laboratory and the field. However, there are shortcomings with both approaches, particularly the former, which need to be recognized. In this article, Peter Waller discusses these in relation to research into the experimental and epidemiological aspects of benzimidazole resistance.

Journal Article↗

Echinococcosis--an international public health challenge.

This review aims to summarise some of the recent studies that have been undertaken on parasites of the genus Echinococcus and the diseases which they cause. Although the adult parasite, which inhabits the intestine of various carnivore species is not pathogenic, the larval or metacestode stages can be highly pathogenic, causing economic losses to livestock and various forms of echinococcosis in humans, some of which have a high fatality rate. There is growing evidence that there are at least 5 species of Echinococcus rather than the generally accepted 4 species. Within these species there are a number of genotypes or strains. This can have implications for surveillance and control. In some wealthy countries, cystic echinococcosis caused by Echinococcus granulosus has been successfully controlled or indeed eradicated. However, in most parts of the world it remains a serious threat to human health. In the former Soviet Union, the disease has rapidly increased in incidence after the end of communist administration. Human alveolar echinococcosis, caused by Echinococcus multilocularis, is more sporadic. However, in some Chinese communities there is a disturbingly high human prevalence and in Europe there has been an increase in the detection rate of E. multilocularis in animals in the last 10 years. Echinococcosis can present diagnostic challenges, particularly in the definitive host in areas of low endemicity. Much of the recent work relating to the use of coproantigen and PCR to overcome these difficulties is summarized. New ideas for controlling the parasite are becoming available and these include both the use of vaccination and the application of mathematical models to determine the most cost effective means of control. Effective measures that are affordable are vital if the parasite is to be controlled in poor countries.

Animals↗

A recombinant baculovirus 42-kilodalton C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 protects Aotus monkeys against malaria.

The immunogenicity and protective efficacy of baculovirus recombinant polypeptide based on the Plasmodium falciparum merozoite surface protein 1 (MSP-1) has been evaluated in Aotus lemurinus griseimembra monkeys. The MSP-1-based polypeptide, BVp42, corresponds to the 42-kDa C-terminal processing fragment of the precursor molecule. Immunization of Aotus monkeys with BVp42 in complete Freund's adjuvant resulted in high antibody titers against the immunogen as well as parasite MSP-1. Fine specificity studies indicated that major epitopes recognized by these antibodies localize to conserved determinants of the 19-kDa C-terminal fragment derived from cleavage of the 42-kDa processing fragment. Effective priming of MSP-1-specific T cells was also demonstrated in lymphocyte proliferation assays. All three Aotus monkeys immunized with BVp42 in complete Freund's adjuvant showed evidence of protection of protection against blood-stage challenge with P. falciparum. Two animals were completely protected, with only one parasite being detected in thick blood films on a single days after injection. The third animal had a modified course of infection, controlling its parasite infection to levels below detection by thick blood smears for an extended period in comparison with adjuvant control animals. All vaccinated, protected Aotus monkeys produced antibodies which inhibited in vitro parasite growth, indicating that this assay may be a useful correlate of protective immunity and that immunity induced by BVp42 immunization is mediated, at least in part, by a direct effect of antibodies against the MSP-1 C-terminal region. The high level of protection obtained in these studies supports further development of BVp42 as a candidate malaria vaccine.

Animals↗

Molecular approaches to elucidating innate and acquired immune responses to Babesia bovis, a protozoan parasite that causes persistent infection.

For many vector-transmitted protozoal parasites, immunological control of acute infection leads to a state of persistent infection during which parasitemias may cycle unnoticed in infected but otherwise clinically healthy animals. Achieving persistent infection is a strategy that favors parasitism, since both host and, therefore, parasite survive, and endemically infected animal populations provide a reservoir of parasites continually available for subsequent transmission. Examples of the major economically important protozoan pathogens that cause persistent infection in mammals include the related Theileria and Babesia parasites as well as Trypanosoma species. Control of acute infection and maintenance of clinical immunity against subsequent infection are determined by the interplay of innate and acquired immune responses. This review will focus on approaches taken to gain an understanding of the molecular basis for innate and acquired immunity against the hemoprotozoan parasite of cattle, Babesia bovis. Knowledge of mechanisms used by the parasite to survive within infected cattle from acute to persistent infection combined with definition of the correlates of protective immunity in cattle should be applicable to designing effective vaccines.

Animals↗

Evaluation of the effect of the fenbendazole sustained-release intraruminal device on the immunity of calves to lungworm.

Each of 10 set-stocked calves was given a fenbendazole sustained-release intraruminal bolus at turnout for the control of parasitic bronchitis while a group of 10 similar calves was left untreated. The respiratory rates of the control calves were not greatly increased during the grazing season, but persistent coughing was evident from early July when they all had patent lungworm infections. Only occasional coughing was reported from the bolus-treated calves except for a transient increase in its frequency in late September. In mid-August, one of the treated calves was passing lungworm larvae and when they were housed six of the 10 had patent infections. In August tracer calves picked up an average of 23.5 lungworms per day from the control paddock but only 2.1 from the paddock grazed by the treated calves. In September the corresponding figures were 7.6 and 19.2 lungworms per day, respectively, from the control and 'treated' paddocks. After housing, the post mortem worm counts after an experimental challenge with Dictyocaulus viviparus larvae were reduced by 99.2 and 98.7 per cent (P < 0.0001), respectively, for the control and bolus-treated calves in comparison with weight-matched parasite-naive calves. Thus, despite a relatively low level of challenge during the grazing season, the treated animals had developed a considerable degree of protective immunity.

Animals↗

Eosinophil granulocyte proliferation and differentiation in schistosomal granulomas are controlled by two cytokines.

In parasitic diseases, eosinophilia is controlled at the systemic level by soluble, circulating factors. In addition to their medullar production and migration to tissues involved by parasitosis, eosinophil populations in inflammatory infiltrates may be locally amplified by their in situ proliferation. In granulomas induced in liver tissue by eggs of schistosome worms, eosinophil proliferation and differentiation are observed. We have shown that they were under control of two cytokines, the activity of which can be demonstrated in supernatants of isolated granulomas maintained in culture for 24 hours. One of them has been identified as interleukin-5. The other one is secreted by adherent cells obtained from periovular granulomas, among which macrophages represent more than 99% of cells. It is considered to correspond to the previously described factor, secreted by inflammatory macrophages mobilized on intraperitoneal glass implants in mice with chronic schistosomiasis. In acute schistosomiasis, the activity of the interleukin-5 was predominant, whereas in the chronic phase of the disease, the stimulation of peripheral eosinopoiesis is taken over by the factor secreted by adherent cells. During the progression from the acute to the chronic phase of schistosomiasis, the immune reactivity of the host is down-regulated by T suppressor lymphocyte circuits. In addition, a redistribution of cellular controls of the host reaction to parasites may act as a complementary mechanism for establishment of the viable equilibrium between host and parasite.

Animals↗

Effect of permethrin impregnated plastic strips on Dermanyssus gallinae in loose-housing systems for laying hens.

The effect of permethrin impregnated plastic strips (Die No Mite Strips) was evaluated on Dermanyssus gallinae populations in aviary systems for layers in Sweden. Two application strategies of the strips were tested: (A) attached in the housing system, allowing the birds to rub against the strips and thereby get the acaricide released onto their plumage, and (B) attached out of reach of the hens, at two different sites (perches and egg-belt lids) of the inner surfaces of the system, where the mites sheltered during the day. On two farms with 2030 (A) and 3384 (B) hens, and existing mite populations, strips were mounted for 20 and 10 weeks, respectively, and mite numbers were monitored by traps. With application A an overall mite reduction of 53% was observed, while with B the mean mite numbers decreased by 39% at the perches and 92% at the egg-belt lid. The strips were originally designed for caged hens afflicted by ectoparasites that stay on the host for most of their life cycle. However, since D. gallinae spends most of its time off the host, it was not possible to control the parasite with application A. Resistance tests performed on mites from both treated and control compartments where application A was used showed no indication of resistance to permethrin, while 95% of the mites survived a 48 h exposure to the compound where application B was performed. Thus, permethrin resistant mites appeared to be the main reason for the failure to control D. gallinae with application B.

Administration, Topical↗

Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy.

The antifolate combination pyrimethamine/sulphadoxine (PYR/SDX; Fansidar) is frequently used to combat chloroquine-resistant malaria. Its success depends upon pronounced synergy between the two components, which target dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) in the folate pathway. This synergy permits clearance of parasites resistant to either drug alone, but its molecular basis is still unexplained. Plasmodium falciparum can use exogenous folate, which is normally present in vivo, bypassing SDX inhibition of DHPS and, apparently, precluding synergy under these conditions. However, we have measured parasite inhibition by SDX/PYR combinations in assays in which folate levels are strictly controlled. In parasites that use exogenous folate efficiently, SDX inhibition can be restored by levels of PYR significantly lower than those required to inhibit DHFR. Isobolograms show that the degree of synergy between PYR and SDX is highly dependent upon prevailing folate concentrations and are indicative of PYR acting to block folate uptake and/or utilization. No significant synergy was observed at physiological drug levels when PYR/SDX acted on purified DHFR, whether wild type or mutant. We conclude that the primary basis for antifolate synergy in these organisms arises from PYR targeting a site (or sites) in addition to DHFR, which restores DHPS as a relevant target for SDX.

4-Aminobenzoic Acid↗

Some haematological parameters in plasmodial parasitized HIV-infected Nigerians.

BACKGROUND: Nigeria is highly burdened by malaria and HIV-infection, yet researchers know little about the impact of this co-infection on the haematological profile of HIV-infected adult Nigerians. This case control study is an attempt to investigate the effect that HIV/malaria co-infection has on some haematological parameters of HIV-infected Nigerians. METHODS: Complete blood count (CBC) of 30 plasmodium parasitized HIV-infected subjects and 70 non-parasitized controls were studied. RESULTS: Of the 30 parasitized subjects, 28 (93.3%) were positive for falciparum malaria and 2 (6.7%) for vivax malaria. The incidence of anaemia, thrombocytopenia, neutropenia and leucopenia were significantly higher in parasitized subjects compared to non-parasitized controls 66.7%, 60%, 36.7% and 63.3% versus 32.9%, 42.9%, 24.3% and 24.3% respectively. A statistically significant difference was observed between the haemoglobin, platelet count and the erythrocyte sedimentation rate (ESR) of parasitized and non- parasitized individuals (p < 0.05) respectively. A significant positive correlation was observed between the level of parasitaemia and anaemia (r = 0.37, p < 0.04) in parasitized subjects. The incidence of anaemia was two times higher in parasitized subjects compared to non-parasitized controls (66.7% versus 32.9%). Red cell morphology showed a normocytic and normochromic picture in 40% and 67.1% of parasitized and non- parasitized individuals respectively. Microcytic, hypochromic picture was observed in 60% and 23% respectively in parasitized and non- parasitized individuals. Striking eosinophilia was seen in 5 (16.7%) of parasitized and 3 (4.3%) of non-parasitized individuals. CONCLUSION: Incidence of cytopenia appear significantly higher in parasitized subjects compared to non-parasitized control and bring to bare the need for regular anti-malaria prophylaxis for HIV-infected patients particularly in Nigeria.

AIDS-Related Opportunistic Infections↗

The use of antisense oligonucleotides as chemotherapeutic agents for parasites.

Although several approaches to the control of human parasites are possible, the prevention and therapy of the corresponding diseases still remain a difficult task. The development of vaccines has been hampered by the poor immunological response to or the high variability of parasitic antigens. Problems also arise for chemotherapy where differences in the biochemistry of host and parasite must be exploited. The increasingly difficult search for new drugs is always challenged by the appearance of resistance.

Journal Article↗

Prevalence of parasitic diseases among nomadic Fulanis of south-eastern Nigeria.

A study was carried out to determine the prevalence of parasitic infections among the nomadic Fulanis of south-eastern Nigeria between September 2003-March 2004. Urine, stool and blood specimens were collected from each of 231 subjects. Of these, 98 (42.4%) were infected with one or more of 14 parasitic species, of which Plasmodium malariae had the highest prevalence (15.3%). Others included 6 intestinal helminth parasites: Ascaris lumbricoides, hookworm, Strongyloides stercoralis, Schistosoma mansoni, Enterobius vermicularis, Trichocephalus trichiurus, 2 protozoan parasites: Entamoeba histolytica and E. coli, 4 blood parasites: Mansonella perstans, Loa loa, Trypanosoma sp, Plasmodium falciparum, as well as Schistosoma haematobium recovered in the urine. Prevalence of these parasitic infections varied significantly among bush encampments, sexes, and age groups. They had evidence of onchocerciasis. Their occupational imperatives, beliefs and general life style are contributing factors to the prevalence of parasitic infections among the nomadic Fulanis of south eastern Nigeria. Aspects of prevalence and control of parasitic infections are discussed.

Adolescent↗

The use of a molluscicide, in conjunction with chemotherapy, to control Schistosoma haematobium at the Barombi Lake foci in Cameroon. I. The attack on the snail hosts, using N-tritylmorpholine, and the effect on transmission from snail to man.

The background and strategy of a campaign to control the transmission of Schistosoma haematobium at the isolated crater-lake villages of Barombi Mbo and Barombi Kotto are outlined. A two-pronged attack was envisaged, using N-tritylmorpholine (Frescon) to control the snail host, and niridazole (Ambilhar) to control the parasite in man. The lake villages and their environs are described. Observations, relevant to control, are recorded on the biology of Bulinus rohlfsi and B. camerunensis. Snail populations were sampled by hand picking, and by the use of basket traps baited with dead leaves. Some experiments on the susceptibility of both snails to S. haematobium are described, together with observations on the strains of schistosome developing in monkeys exposed to cercariae from naturally-infected snails from the lakes. Frescon was applied through a tube to the bottom layers at the edge of the lakes, where the snails lived. Concentrations of 2 ppm down to 0.5 ppm N-tritylmorpholine proved necessary for adequate kills. Intervals of 6 weeks between treatments sufficed to control B. rohlfsi, but applications every 2 weeks were needed for B. camerunensis. The numbers of egg-masses, of snails, and of infective snails of both species were recorded before, during and after Frescon/Ambilhar control; and snail transmission rates and indices have been calculated. Control operations reduced transmission by R. rohlfsi to 2.4% of the pre-control level, or to below the detectable threshold. They were most effective at Mbo, where B. rohlfsi was the only intermediate host. At Kotto, despite excellent B. rohlfsi control, transmission of the residual infections in the human population by B. camerunensis persisted during control operations, until the intervals between Frescon applications were cut to 2 weeks.

Animals↗

Metabolic fate of alanine in an insect Manduca sexta: effects of starvation and parasitism.

The fate of [3-13C]alanine administered to last instar larvae of an insect Manduca sexta was investigated in vivo by 13C-NMR spectroscopy. Following injection of the isotopically substituted substrate and conversion to [3-13C]pyruvate 13C was principally incorporated into C2, C3 and C4 of glutamate and glutamine in unparasitized ad libitum-fed larvae, insects starved 48 hr prior to injection and larvae parasitized by the insect parasite Cotesia congregata. Selective labeling at C2 and C3 of glutamate/glutamine resulted from carboxylation of [3-13C]pyruvate to [2,3-13C]oxaloacetate catalyzed by pyruvate carboxylase, randomization of the label in fumarate, and synthesis of glutamate and glutamine after condensation with acetyl CoA to [2 proR,3-13C]citrate. In contrast, enrichment at C4 of glutamate and glutamine resulted from oxidation [3-13C]pyruvate to [2-13C]acetyl CoA catalyzed by pyruvate dehydrogenase followed by condensation with oxaloacetate. The ratio of enrichment (C2 + C3): C4 provided a measure of the relative contributions of the pyruvate dehydrogenase and pyruvate carboxylase catalyzed pathways of substrate utilization by the tricarboxylic acid cycle. The mean ratio was 0.6 and 0.7 in control and parasitized larvae, respectively, and 2.4 in starved insects. The latter result demonstrated that substrate utilization by the TCA cycle was markedly altered by starvation. In addition, the rate of labeled alanine metabolism was significantly reduced by starvation. The concentrations of glutamate and glutamine in the blood (hemolymph) were similar in all three groups of insects. No evidence for gluconeogenesis was observed in any group. Starved larvae incorporated label into C6 of glucose and trehalose but no complementary enrichment at C1 was observed. This result was consistent with the activity of the non-oxidative phase of the pentose phosphate pathway during which labeled glyceraldehyde-3-phosphate arising from [3-13C]alanine reacts with sedoheptulose-7-phosphate yielding erythrose-4-phosphate and [6-13C]fructose-6-phosphate catalyzed by transaldolase. Specifically labeled fructose-6-phosphate then gives rise to glucose and trehalose labeled at C6. Preliminary analysis of the hemolymph of starved insects indicated the presence of several hexose phosphates labeled at C6. The hemolymph level of trehalose was significantly reduced in both starved and parasitized insects. Lipogenesis from [3-13C]alanine was evident in unparasitized control larvae but was absent in parasitized and starved insects. The pattern of labeling in fatty acid was consistent with de novo pathway utilizing [2-13C]acetyl CoA derived by oxidation of [3-13C]alanine.

Alanine↗

Effects of anti-Leishmania monoclonal antibodies on the development of Leishmania major in Phlebotomus duboscqi (Diptera: Psychodidae).

BACKGROUND: Research in our laboratory has previously shown that immune-mediated transmission blocking may be applied to Leishmania infections and that the LPG molecule and anti-LPG monoclonal antibodies was found to be an excellent candidate against L. major infections. OBJECTIVE: To test the effect of monoclonal antibodies (MABs) raised against different species of Leishmania for their ability to inhibit development of Leishmania major in Phlebotomus duboscqi sand flies. DESIGN: A laboratory based study. SETTING: Centre for Biotechnology Research and Development, Kenya Medical Research Institute, Nairobi. RESULTS: Sand fly dissections on days two, four and six post-feeding showed that monoclonal antibodies against L. donovani (Ld2cb and Ld3A3) were the most effective at inhibiting L. major development than those raised against L. aethiopica, L. major or L. tropica. Ld2cb inhibited L. major development by 82% in sand flies fed on 1 x 10(6) amastigotes while Ld3A3 inhibited by 72%; 58% and 74% in those fed on 1 x 10(5) amastigotes respectively. Monoclonal antibodies against L. aethiopica (Lae 3c6) inhibited L. major development by 28% and 40% for sand flies fed on 1 x 10(6) and 1 x 10(5) amastigotes respectively. Anti-L. major monoclonal antibody (Lm5A5) inhibited L. major development by 16% in sand flies fed on 1 x 10(6) amastigotes and 25% in sand flies fed on 1 x 10(5) amastigotes. Anti-L. tropica antibody (Lt2c8) inhibited L. major development in P. duboscqi fed on 1 x 10(6) by 28 %and 33% in those fed on 1 x 10(5) amastigotes. Most of the parasites seen in sand flies which fed on L. donovani mABs (Ld2cb and Ld3A3) were nectomonads and a few haptomonads. In all the control groups, parasite development followed the normal developmental stages up to the metacyclic stage. In sand fly groups fed on monoclonal antibodies raised against L. aethiopica, L. major or L. tropica there was limited parasite development inhibition, and the promastigotes developed and migrated forward in a normal pattern as observed in the controls. CONCLUSIONS: These results suggests a possible role of humoral mechanisms in protection against leishmaniasis and potentially useful in reducing parasite development in the sand fly.

Animals↗