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Influence of host and parasite genotypes on immunological control of Theileria parasites.

Infections with Theileria parva in the African buffalo are invariably asymptomatic, whereas infections in cattle usually result in clinical disease, the severity of which varies in different populations of cattle. The parasite exhibits antigenic heterogeneity, which in cattle manifests as differences between parasite strains in their cross-protective properties. A series of studies on T cell responses to T. parva in cattle have demonstrated that class I MHC-restricted cytotoxic T lymphocytes (CTL), specific for parasitized lymphoblasts, are important mediators of immunity. Cytotoxic T cell responses frequently display parasite strain-restricted specificities which appear to correlate with the capacity of strains to cross-protect. The strain specificity of CTL responses varies in animals immunized with the same parasite strain and is influenced by both host and parasite genotype. Recent studies have provided evidence that there is competition between epitopes for induction of CTL responses, which can result in a bias to strain-specific epitopes. These properties of the CTL response have important implications for vaccination. Thus, in designing a vaccine, it may be possible, by selecting parasite proteins containing appropriate CTL epitopes, to generate CTL responses that protect against a wide range of parasite strains. Although there are no comparable data on CTL responses in the buffalo, it is considered that the features of the immune response described for cattle would be advantageous for survival of parasite populations in the buffalo. Specifically, a bias in the immune responses to strain-specific determinants should favor establishment of infection in buffalo already carrying the parasite and allow fluctuation in the levels of different parasite strains during the course of persistent infection.

Animals↗

Control of human parasitic diseases: Context and overview.

The control of parasitic diseases of humans has been undertaken since the aetiology and natural history of the infections was recognized and the deleterious effects on human health and well-being appreciated by policy makers, medical practitioners and public health specialists. However, while some parasitic infections such as malaria have proved difficult to control, as defined by a sustained reduction in incidence, others, particularly helminth infections can be effectively controlled. The different approaches to control from diagnosis, to treatment and cure of the clinically sick patient, to control the transmission within the community by preventative chemotherapy and vector control are outlined. The concepts of eradication, elimination and control are defined and examples of success summarized. Overviews of the health policy and financing environment in which programmes to control or eliminate parasitic diseases are positioned and the development of public-private partnerships as vehicles for product development or access to drugs for parasite disease control are discussed. Failure to sustain control of parasites may be due to development of drug resistance or the failure to implement proven strategies as a result of decreased resources within the health system, decentralization of health management through health-sector reform and the lack of financial and human resources in settings where per capita government expenditure on health may be less than $US 5 per year. However, success has been achieved in several large-scale programmes through sustained national government investment and/or committed donor support. It is also widely accepted that the level of investment in drug development for the parasitic diseases of poor populations is an unattractive option for pharmaceutical companies. The development of partnerships to specifically address this need provides some hope that the intractable problems of the treatment regimens for the trypanosomiases and leishmaniases can be solved in the not too distant future. However, it will be difficult to implement and sustain such interventions in fragile health services often in settings where resources are limited but also in unstable, conflict-affected or post-conflict countries. Emphasis is placed on the importance of co-endemicity and polyparasitism and the opportunity to control parasites susceptible to cost-effective and proven chemotherapeutic interventions for a package of diseases which can be implemented at low cost and which would benefit the poorest and most marginalized groups. The ecology of parasitic diseases is discussed in the context of changing ecology, environment, sociopolitical developments and climate change. These drivers of global change will affect the epidemiology of parasites over the coming decades, while in many of the most endemic and impoverished countries parasitic infections will be accorded lower priority as resourced stressed health systems cope with the burden of the higher-profile killing diseases viz., HIV/AIDS, TB and malaria. There is a need for more holistic thinking about the interactions between parasites and other infections. It is clear that as the prevalence and awareness of HIV has increased, there is a growing recognition of a host of complex interactions that determine disease outcome in individual patients. The competition for resources in the health as well as other social sectors will be a continuing challenge; effective parasite control will be dependent on how such resources are accessed and deployed to effectively address well-defined problems some of which are readily amenable to successful interventions with proven methods. In the health sector, the problems of the HIV/AIDS and TB pandemics and the problem of the emerging burden of chronic non-communicable diseases will be significant competitors for these limited resources as parasitic infections aside from malaria tend to be chronic disabling problems of the poorest who have limited access to scarce health services and are representative of the poorest quintile. Prioritization and advocacy for parasite control in the national and international political environments is the challenge.

Animals↗

A survey by questionnaire of parasitic worm control in cattle and sheep at the Glasgow University Lanark practice.

The results of a questionnaire circulated in 1984 concerning parasitic worm control on cattle and sheep farms in a veterinary practice in the west of Scotland are reported. Control by grazing management or anthelmintic treatment was used in 92 per cent of the cattle herds and in all the sheep flocks. The use of anthelmintic drugs was greatest on farms where grazing control was also practised. Benzimidazoles were the most frequently used anthelmintic drugs.

Animals↗

Pivotal role of interleukin-12 and interferon-gamma axis in controlling tissue parasitism and inflammation in the heart and central nervous system during Trypanosoma cruzi infection.

The role of cytokines in the control of tissue parasitism and pathogenesis of experimental Chagas' disease was investigated. Wild-type and different cytokine as well as inducible nitric oxide synthase (iNOS) knockout mice were infected with the Colombian strain of Trypanosoma cruzi, and the kinetics of tissue parasitism, inflammatory reaction, parasitemia, and mortality were determined. We demonstrate the pivotal role of the interleukin (IL)-12/interferon (IFN)-gamma/iNOS axis and the antagonistic effect of IL-4 in controlling heart tissue parasitism, inflammation, and host resistance to acute infection with T. cruzi. Further, the heart and central nervous system were shown the main sites of reactivation of T. cruzi infection in mice lacking functional genes for IFN-gamma and IL-12, respectively. Our results also show that in contrast to IFN-gamma knockout (KO) mice, splenocytes from IL-12 KO mice infected with T. cruzi produced low levels of IFN-gamma upon stimulation with antigen. Consistently, high levels of anti-T. cruzi IgG2a antibodies were detected in the sera from IL-12 KO, but not from IFN-gamma KO mice, infected with the Colombian strain of T. cruzi. Thus, our results suggest that the level of IFN-gamma deficiency is a major determinant of the site of reactivation of T. cruzi infection in immunocompromised host.

Animals↗

Examination of serum total IgG1 concentration in atopic and non-atopic dogs.

In this study, serum immunoglobulin G1 (IgG1) concentrations were examined in atopic and non-atopic dogs receiving different levels of parasite control. Significantly lower serum total IgG1 concentrations were found in non-atopic dogs receiving stringent parasite control than in atopic dogs or non-atopic dogs receiving less stringent parasite control. Examination of serum total IgG1 concentrations of atopic dogs after six months of allergen specific immunotherapy (ASIT) showed a significant increase in serum total IgG1 concentrations. It is proposed that serum total IgG1 concentrations are affected by parasitism, atopic dermatitis and ASIT.

Allergens↗

Theoretical and empirical issues in benefit identification, measurement and valuation related to parasitic disease control in poor countries.

Considerable resources have been allocated over the years to parasitic disease eradication or control, e.g. malaria and schistosomiasis. Decision-makers in recent years have increasingly appealed to economists seeking an economic justification in order to continue or renew support for such programmatic efforts. Often economists when facing such an analytical task have employed benefit-cost or cost-effectiveness analytical techniques. This paper reviews the theoretical and empirical rationale employed in the conduct of such studies, focusing particularly on the benefits or impact indicators used. The review identifies many problems encountered in identifying benefits, and then measuring and valuing them.

Communicable Disease Control↗

Sociocultural factors in the control and prevention of parasitic diseases.

Control and prevention of parasitic disease depends on an adequate knowledge of interactions among factors such as human behavior, the environment, and the life cycles of parasites. Sociocultural factors in large part determine transmission and persistence of parasites. The main determinants are poverty, low educational level, deficiencies in home technologies, high demographic density, and ruralism. Selected interventions designed to improve any of these situations may fail if they are applied in an isolated manner. The holistic implementation of interventions has proved successful in the control and prevention of parasitic infections in several parts of the word. The implementation of several kinds of interventions simultaneously, that is, a holistic approach, combined with an awareness of a society's infrastructure, can produce favorable results. For such an awareness--when it provokes action--can improve the overall quality of life.

Adolescent↗

Multiple helminth infections in children: impact and control.

Parasitic worm infections are amongst the most widespread of all chronic human infections. It is estimated that there are more than 3 billion infections in the world today. In many low income countries it is often more common to be infected than not to be. Indeed, a child growing up in an endemic community can expect be infected soon after weaning, and to be infected and constantly reinfected for the rest of her or his life. Infection is most common amongst the poorest and most disadvantaged communities, and is typically most intense in children of school going age. As the risk of morbidity is directly related to intensity of infection, it follows that children are the most at risk from the morbid effects of disease. Multiparasite infections are also common in such communities and there is evidence that individuals harbouring such infections may suffer exacerbated morbidity, making children even more vulnerable. Thus, these infections pose a serious threat to the health and development of children in low income countries. For many years, the need to control these infections has lain uncontested, and with the advent of broad-spectrum anthelminthic drugs that are cheap, safe and simple to deliver, control has at last become a viable option for many communities. Furthermore, there is now increased emphasis being placed on a multispecies approach as a cost-effective mechanism to control the morbidity of virtually all the major helminthic infections of humans.

Adolescent↗

Prospects for biological control of nematode parasites of ruminants.

Control of nematode parasites in ruminants is directed almost exclusively at the parasitic stage in the host using conventional anthelmintic therapy. However, to complete their life cycle, parasites have to develop through a series of free-living stages on pasture. It is within this environment that there is a vast range of cohabiting micro-organisms, some of which are known to infect or prey on nematodes. These include bacteria, protozoa, viruses and fungi. To date, most interest has been focused on those organisms producing chemical toxins which have been developed as anthelmintics, e.g. Streptomyces/avermectins. Yet the potential of predacious and nematoxic fungi and bacteria for the biological control of nematode parasites of livestock remains largely untapped. These organisms may well offer a cheaper and more sustainable approach to reducing the impact of parasitism in livestock.

Journal Article↗

Current concerns about control programs in temperate climates.

Efforts to control cyathostome nematodes in temperate climates have not been uniformly successful, as evidenced by contemporary reports of clinical disease and widespread anthelmintic failure. Indeed, effective control is confounded by numerous factors, including ignorance of local transmission patterns, confusing or conflicting control recommendations, and use of ineffective anthelmintics or regimens. Most of these problems are universal rather than being climatically unique, and it is important to recognize that they are mere symptoms of larger and more comprehensive problems. The most basic problem in managing cyathostomes is inadequate knowledge of biological factors that influence control recommendations. These include population dynamics, arrested development, host resistance, and regional bionomics. Another hindrance is the absence of objective criteria to define effective control. Target fecal egg counts are arbitrary and subjective, and parameters to measure the subclinical impact of cyathostome infection in well-managed horses have not been identified. The final general challenge to effective parasite control is motivation and education of equine practitioners and horse owners, who currently receive much of their parasite control information in the form of biased advertising. Ultimately, more effective equine parasite control will result from collaborative efforts of basic research, clinical application, and improved information transfer.

Animals↗

Toxoplasma gondii: mechanism of the parasitostatic action of 6-thioxanthine.

In contrast to the cytocidal effect of 6-thiopurines on mammalian cells, the action of 6-thioxanthine on Toxoplasma gondii was only parasitostatic. 6-Thioxanthine was a substrate of the parasite's hypoxanthine-guanine phosphoribosyltransferase. That enzyme converted 6-thioxanthine to 6-thioxanthosine 5'-phosphate which accumulated to near millimolar concentrations within parasites incubated intracellularly in medium containing the drug. 6-Thioxanthosine 5'-phosphate was the only detectable metabolite of 6-thioxanthine. The absence of 6-thioguanine nucleotides explains the lack of a parasitocidal effect because the incorporation of 6-thiodeoxyguanosine triphosphate into DNA is the mechanism of the lethal effect of 6-thiopurines on mammalian cells. Extracellular parasites that had accumulated a high concentration of 6-thioxanthosine 5'-phosphate incorporated more labeled hypoxanthine or xanthine into their nucleotide pools than did control parasites. The basis for this increased nucleobase salvage remains unexplained. It was not due to up-regulation of hypoxanthine-guanine phosphoribosyltransferase and could not be explained by reduced use of labeled nucleotides for nucleic acid synthesis. Extracellular parasites that had accumulated a high concentration of 6-thioxanthosine 5'-phosphate used labeled hypoxanthine almost entirely to make adenine nucleotides while control parasites made both adenine and guanine nucleotides. Both extracellular parasites that had accumulated a high concentration of 6-thioxanthosine 5'-phosphate and control parasites efficiently used labeled xanthine to make guanine nucleotides. These observations suggested that inosine 5'-phosphate-dehydrogenase was inhibited while guanosine 5'-phosphate synthase was not. Assay of inosine 5'-phosphate dehydrogenase in soluble extracts of T. gondii confirmed that 6-thioxanthosine 5'-phosphate was an inhibitor. We conclude that 6-thioxanthine blocks the growth of T. gondii by a depletion a guanine nucleotides.

Animals↗

Epidemiology and control of parasites in northern temperate regions.

The serious and widespread problem of drug resistance has forced a re-thinking of basic philosophy regarding control of equine parasites. It has illustrated the dangers of total reliance on chemical control and stimulated the use of alternate strategies. Two new approaches are described. Prophylactic treatments in the spring and summer provide effective strongyle and colic control with less selection pressure for drug resistance. A nonchemical approach of pasture cleaning twice a week offers the same advantages with the added bonus of a 50 per cent increase in grazing area.

Age Factors↗