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Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis.

It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B(4) production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase(-/-) mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid of Swiss mice treated with MK886. In the lung parenchyma of infected animals, MK886 significantly inhibited synthesis of IL-5 at the beginning of infection, whereas levels of IL-12 increased progressively throughout the postinfection period. However, levels of leukotriene C(4), PGE(2), TNF-alpha, IL-3, IL-4, IFN-gamma, and IL-10 were comparable between the treated and untreated groups. Nevertheless, IgE and IgG1 (but not IgG2a) synthesis was also significantly inhibited by MK886 administration. Therefore, in S. venezuelensis-infected mice, adult worm and egg burdens are leukotriene dependent. These findings indicate potential immunostimulatory strategies involving leukotriene administration, and may serve as an alert to physicians treating Strongyloides stercoralis-infected patients presenting asthma-like symptoms because use of 5-lipoxygenase inhibitors may worsen the infection.

Animals↗

Mice deficient in LRG-47 display enhanced susceptibility to Trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth.

IFN-gamma is known to be required for host control of intracellular Trypanosoma cruzi infection in mice, although the basis of its protective function is poorly understood. LRG-47 is an IFN-inducible p47GTPase that has been shown to regulate host resistance to intracellular pathogens. To investigate the possible role of LRG-47 in IFN-gamma-dependent control of T. cruzi infection, LRG-47 knockout (KO) and wild-type (WT) mice were infected with the Y strain of this parasite, and host responses were analyzed. When assayed on day 12 after parasite inoculation, LRG-47 KO mice, in contrast to IFN-gamma KO mice, controlled early parasitemia almost as effectively as WT animals. However, the infected LRG-47 KO mice displayed a rebound in parasite growth on day 15, and all succumbed to the infection by day 19. Additional analysis indicated that LRG-47-deficient mice exhibit unimpaired proinflammatory responses throughout the infection. Instead, reactivated disease in the KO animals was associated with severe splenic and thymic atrophy, anemia, and thrombocytopenia not observed in their WT counterparts. In addition, in vitro studies revealed that IFN-gamma-stimulated LRG-47 KO macrophages display defective intracellular killing of amastigotes despite normal expression of TNF and NO synthetase type 2 and that both NO synthetase type 2 and LRG-47 are required for optimum IFN-gamma-dependent restriction of parasite growth. Together, these data establish that LRG-47 can influence pathogen control by simultaneously regulating macrophage-microbicidal activity and hemopoietic function.

Animals↗

Treatment of external and internal parasites of cattle.

To control parasitic disease in cattle, one first has to determine what parasites he or she is trying to control--nuisance and biting flies in a milking parlor or ticks on range cattle? The determination may be based on geographic location, class of cattle, and their management. After determining what is there, then if the numbers are sufficient, justify treatment. Each livestock producer has a different array of parasites with which to deal, and in some circumstances, parasitic disease is below the economic threshold. Others may have occasional clinical disease associated with parasites, but most have situations in which the potential of economic loss is high enough to justify control.

Animal Husbandry↗

From the bench to the field: control of parasitic infections within primary health care.

During the last decade there has been a great increase in the number of countries that have endorsed the primary health care (PHC) policy at national level, set up national guidelines for it and launched its large-scale implementation. In addition, there have been many important developments with regard to appropriate, cost-effective technologies, training concepts and approaches to securing community participation. These achievements have produced numerous encouraging results. However, although the control of parasitic infections integrated into PHC systems has often been initially successful, these achievements could often not be sustained. Using case studies, mainly concerning schistosomiasis, as examples, control technologies and their applicability within PHC are discussed at three levels; the identification of public health priorities, the community-based implementation of control and the process of evaluation and monitoring. There is a great potential for the integration of a substantial part of control activities, particularly morbidity control, into PHC, provided that the aims and sequences of control activities are well matched with the felt needs of the communities concerned. This implies that the biomedical researcher, the epidemiologist and the health planner need to consider the indigenous health perspectives of the affected community. For example, recent progress in the laboratory in the development of vaccines against parasites needs to be complemented by field studies that continuously validate, standardize and assess the applicability of the proposed measures. This kind of interplay will form the basis for participatory approaches in health planning and make it possible for control activities to be integrated into existing PHC structures and to respond to the needs of the communities concerned.

Animals↗

Juvenile hormone synthesis, metabolism, and resulting haemolymph titre in Heliothis virescens larvae parasitized by Toxoneuron nigriceps.

Last instar larvae of the tobacco budworm, Heliothis virescens F., fail to pupate and have little 20-hydroxyecdysone when parasitized by Toxoneuron nigriceps (Viereck). In this paper, we extend these observations to juvenile hormone (JH) to determine if parasitism by this wasp affects other endocrine systems. To this end, we compared the production of JH by corpora cardiaca-corpora allata complexes (CC-CA), the metabolism of JH by haemolymph enzymes, and the haemolymph titre of JH in parasitized and non-parasitized control larvae of H. virescens during the last larval instar. CC-CA from parasitized and control larvae had similar peaks of JH synthesis on day 1 of the fifth instar, with JH II accounting for more than 90% of total JH in both groups. On subsequent days, JH synthesis dropped to undetectable levels more quickly in non-parasitized controls than in parasitized larvae. JH metabolism by haemolymph of parasitized and control animals increased from low levels on day 1 of the fifth instar to high levels on days 2 and 3 of the instar. JH metabolism was significantly higher in control larvae than in parasitized larvae. After day 3, JH metabolism decreased in both groups, but was significantly higher in parasitized larvae. The major metabolite of JH in both groups was JH acid, though traces of JH diol and JH acid diol were also detected. The haemolymph titre of JH in both groups peaked on day 1 of the fifth instar and, similar to the synthesis of JH by CC-CA, decreased more rapidly in control larvae. As a result, non-parasitized animals had significantly lower JH titres on day 2. The higher JH titres observed in parasitized larvae during the early fifth instar may contribute to their developmental arrest. The possible role of these JH alterations in the host developmental and metabolic redirection is discussed and a more comprehensive physiological model accounting for host-parasitoid interactions is proposed.

Animals↗

Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection.

Malaria parasite infection in anopheline mosquitoes is limited by inflammatory levels of nitric oxide metabolites. To assess the mechanisms of parasite stasis or toxicity, we investigated the biochemistry of these metabolites within the blood-filled mosquito midgut. Our data indicate that nitrates, but not nitrites, are elevated in the Plasmodium-infected midgut. Although levels of S-nitrosothiols do not change with infection, blood proteins are S-nitrosylated after ingestion by the mosquito. In addition, photolyzable nitric oxide, which can be attributed to metal nitrosyls, is elevated after infection and, based on the abundance of hemoglobin, likely includes heme iron nitrosyl. The persistence of oxyhemoglobin throughout blood digestion and changes in hemoglobin conformation in response to infection suggest that hemoglobin catalyzes the synthesis of nitric oxide metabolites in a reducing environment. Provision of urate, a potent reductant and scavenger of oxidants and nitrating agents, as a dietary supplement to mosquitoes increased parasite infection levels relative to allantoin-fed controls, suggesting that nitrosative and/or oxidative stresses negatively impact developing parasites. Collectively, our results reveal a unique role for nitric oxide in an oxyhemoglobin-rich environment. In contrast to facilitating oxygen delivery by hemoglobin in the mammalian vasculature, nitric oxide synthesis in the blood-filled mosquito midgut drives the formation of toxic metabolites that limit parasite development.

Allantoin↗

Efficiency of feeding Duddingtonia flagrans chlamydospores to control nematode parasites of first-season grazing goats in France.

A field trial, conducted over two consecutive years, was aimed at assessing the efficacy of the administration of spores of the nematophagous fungus Duddingtonia flagrans to young goats for the control of nematode parasite infections on a French commercial dairy goat flock. For both years, the first-year grazing kids were divided into two similarly managed groups (fungus and control groups): in 2003 a daily dose rate of 5 x 10(5) spores/kg body weight was given to the fungus-group animals, while in 2004 a daily dose rate of 10(6) spores/kg body weight was used; the other half of the kids, acting as control, did not receive the spores. Parameters measured every 3 weeks included nematode egg excretion, larval development in faecal cultures and pasture larval counts. Additionally, at the beginning, the middle and the end of each grazing season, the goats were weighed and blood samples for pepsinogen determination were collected. In 2003, similar results were recorded for all the measured parameters in the control and fungus groups. In contrast, in 2004, the kids receiving the spores showed lower faecal egg counts and pepsinogen levels at the end of the season and higher growth rate compared to kids of the control group.

Animals↗

Schistosoma mansoni egg specific antibodies and circulating antigens: assessment of their validity in immunodiagnosis of schistosomiasis.

A total of 127 individuals of different age and sex; 92 from Kafr-Sendewa, Qualyobia Governorate, Egypt, in comparison to 23 cases with hydatidosis and fascioliasis as a parasitic control group, and 12 healthy control group from non-endemic area. All cases were screened by clinical examination, urine, stool, rectal snip, abdominal ultrasonographic examination and indirect haemagglutination test (IHAT). Accordingly, they were grouped into active intestinal schistosomiasis group, seropositive group by (IHAT), normal control group from the same endemic area, parasitic control group and normal control group. All cases were subjected to detection of IgG, IgM, IgG4, anti-soluble egg antigen (SEA) and anti-excretory-secretory egg antigen (ESEA) by ELISA tests; and circulating egg antigens by double-sandwich ELISA techniques. The results showed that IgG4 anti-SEA is the best diagnostic test, as it gave the best diagnostic efficacy (90%). Also, it is a good screening test which can be used in endemic area as it gave significant difference between the active intestinal schistosomiasis cases with each of the endemic control group (P < 0.001) and the seropositive cases (P < 0.05). Other valid diagnostic egg specific antibodies tests were IgM anti-SEA and IgG anti-SEA as their diagnostic efficacy were 80% and 76.6% respectively (P < 0.05). The diagnostic efficacy of circulating antigen detection (C.Ag) test was 70% (P < 0.05). In addition, it was the most specific test with 100% specificity. IG4-anti-ESEA gave the least cross-reaction with other parasites (17.3%). The mean optical density (OD) level of circulating antigen detection test was significantly higher in the organomegalic (hepatosplenomegaly) cases than the non-organomegalic cases (P < 0.05).

Adolescent↗

Evaluation of efficacy expectations for novel and non-chemical helminth control strategies in ruminants.

The interest in novel methods of controlling helminth infections in ruminants is driven primarily by the development of parasite resistance to currently available anthelmintics. While the purpose of anthelmintics is to achieve high efficacy, i.e. >90% reduction of adult and/or larval parasites in the target host animal, the purpose of novel parasite control methods is rather to assist in maintaining parasite infections below the economic threshold. The ability to maintain parasite levels below the economic threshold is related not only to the efficacy of the control method, but also to the epidemiology of the parasites, climatic conditions, the livestock management program, and integration in a sustainable parasite control program. Because of this fundamental difference, novel parasite control methods need to be evaluated using efficacy criteria different from that adopted for anthelmintics. Although the efficacy of novel parasite control methods may be demonstrated in classic dose-confirmation studies, the impact on livestock production parameters can only be evaluated when tested on-farm. In this paper, the rationale for evaluating novel methods differently from anthelmintics is reviewed, potential performance expectations are presented, and four novel parasite control methods (vaccines, nematophagous fungi, condensed tannins, and immunonutrition) are assessed based on the potential performance criteria.

Animal Husbandry↗

An Australian network to support the understanding and control of parasites.

The Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC) Research Network for Parasitology will focus and coordinate the fundamental, strategic and applied parasitology research in Australia. It will raise the standing of Australia in the field, assist in the community understanding of parasitology, and maintain and improve the capacity of Australia to keep its stock, crops, wildlife and people free from disease. On an international scale, the ARC/NHMRC Network will work with other countries to develop new technologies for the detection and control of parasites.

Animals↗

Comparative study of early-season prophylaxis using ivermectin with lungworm vaccination in the control of parasitic bronchitis and gastroenteritis in cattle.

Twenty-four first-season calves were randomly allocated to three similar groups (1-non-treated controls; 2 - vaccinated against lungworm; 3 - treated with ivermectin 21, 56 and 91 days after turnout) and set-stocked on separate pastures. Parasitic bronchitis became evident in the controls and signs of parasitic gastroenteritis were seen later in the vaccinates, but the ivermectin-treated calves remained healthy. After autumn housing, all were kept as a single group for the winter. The following summer, six of the ivermectin-treated animals and their matching vaccinates were grazed together, without further prophylaxis, along with six first-season calves. The latter displayed evidence of mild but debilitating pulmonary and gastrointestinal parasitic disease while both groups of yearlings remained healthy (with the exception of one diarrhoeic vaccinate). Thus, the immune status of the ivermectin-treated animals appeared to be comparable to that of the vaccinates. This conclusion was supported by parasitological observations and by artificial challenge at the end of the second grazing season.

Animals↗

Anthelmintic resistance.

Since the first reports of resistance to the broad spectrum anthelmintics were made some three decades ago, this phenomenon has changed from being considered merely as a parasitological curiosity to a state of industry crisis in certain livestock sectors. This extreme situation exists with the small ruminant industry of the tropical/sub-tropical region of southern Latin America where resistance to the entire broad spectrum anthelmintic arsenal now occurs. In contrast, the cattle industry does not appear to be threatened--or so it seems. Although field reports of resistance have been made to the range of broad spectrum anthelmintics in nematode parasites of cattle, it appears that the evolution of resistance in cattle parasites is not as dramatic as for sheep worms. However, one cannot remain confident that this state of affairs will remain static. Concern is shared amongst parasitologists that we have not looked closely enough. In regions of the world where internal parasites are considered a problem in cattle and drenching occurs frequently, no widespread surveys have been carried out. It appears that because of the very high costs and risks associated with taking a new active drug down the development track to marketing, that the pharmaceutical industry has, in general, turned away from this activity. By implication, the international small ruminant industry is too small for these companies to make the necessary investment. This begs two questions: What is the fate of the sheep (and goat) industries in those parts of the world where resistance is rampant and immediate ameliorative parasite control options are required? What will be the response if significant resistance is found in cattle parasites? There is a body of opinion which suggests that if resistance becomes an issue in the control of cattle parasites then the pharmaceutical industry will find it commercially attractive to re-enter the anthelmintic discovery and development business. This is based on the simple commercial fact that by far the greatest anthelmintic sales are associated with the cattle industry. However, this market is specific and sectoral, with by far the greatest sales in North America and Western Europe, where the prevalence of resistance is likely to be low and remain so, more-or-less indefinitely. So the chances of the above scenario occurring must be considered low. Remarkable developments have recently occurred in non-chemotherapeutic parasite control options, for example worm vaccines, host selection and biological control. Also, there seems to be greater acceptance of various grazing management practices designed to reduce the frequency of anthelmintic treatment. However, they collectively cannot be expected to offer immediate salvation to farmers now faced with chemotherapeutic failure to control nematode parasites in their flocks. The future for these farmers must be considered bleak, because compounded with these problems are the poor commodity prices for sheep and goat meat and fibre, resulting in relentless reductions in funding for research to support these industries. Perhaps the major social issues associated with re-structuring and possibly abandonment of sheep and goat farming in affected areas may precipitate action? As veterinary parasitologists, who in general have an interest and expertise in parasite control, we must promote the importance of the problem of anthelmintic resistance and ways to tackle it.

Animals↗