Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporin A (CsA), a cyclic undecapeptide with powerful properties of immunosuppression, acts on parasitic infections in laboratory animals in various ways. The outcome of drug administration in vivo varies with timing of treatment relative to infection, route of administration, dose and number of treatments applied. CsA is clearly antiparasitic against malaria, schistosomes, adult tapeworms, metacestodes and filarial nematodes. By contrast, it acts as an immunomodulator against trypanosomes and Giardia, by exacerbating infection; in the case of Leishmania spp. the drug acts variously. In some other infections CsA acts both as an antiparasite drug and as an immunosuppressant (Toxoplasma, avian coccidiosis and gastrointestinal nematodes). This range of activities is reviewed and possible modes of action discussed in the light of emerging data on in vitro drug activity and on putative receptor binding. The potential value of a non-immunosuppressive analogue of CsA in the control of parasitic infections of humans and domestic animals is considered but this paper lays particular stress on the seminal role of CsA as a laboratory tool.
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PMID:Cyclosporin A: antiparasite drug, modulator of the host-parasite relationship and immunosuppressant. 130 27

Coccidiosis, caused by Eimeria spp., is a major disease of economic importance to the poultry industry. The cloning and characterisation of genes coding for antigens of those species infecting chickens is an initial step in the identification of protective antigens suitable for the development of a genetically engineered vaccine. This report describes the molecular characterisation of an antigen of E. tenella produced by the recombinant lambda amp3 bacteriophage EtHL6. Three native polypeptides corresponding to the EtHL6 antigen, with sizes between 110 and 94 kDa, have been identified on both sporozoites and second generation merozoites of E. tenella by mouse antisera raised against the EtHL6 fusion protein. The DNA insert is a 722-bp EcoRI fragment encoding a polypeptide comprising three tandem blocks of amino acids which are highly homologous to each other. Each region, A, B and C, contains a strongly hydrophilic domain and two pairs of cysteine residues. Computer analysis has identified similarities with a group of proteins which include the circumsporozoite antigen and thrombospondin-related anonymous protein (TRAP) of malaria parasites, human thrombospondin, mouse properdin and the terminal components of the complement pathway.
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PMID:Regions of an Eimeria tenella antigen contain sequences which are conserved in circumsporozoite proteins from Plasmodium spp. and which are related to the thrombospondin gene family. 220 33

The characteristics of AIDS in Africa differ sharply from those in North America with respect to diagnosis and epidemiology, and in a clinical sense. The study of 78 patients treated in Kinshasa, Zaire during the period of October 1983-July 1984 yielded the following results: 159 out of a total of 1051 hospitalized patients were suspected of having AIDS, and there were 78 proven cases (54 of them died). The average age of 40 women and 38 men was 27 and 31 years, respectively, and the ratio of married people was 35% and 74%, respectively, with a lot of men living in polygamous relationships. In the first stage of the disease weight loss appeared in 100%, recurrent diarrhea in 83.3%, significant loss of strength in 75.6%, febrile conditions in 68.3%, and skin lesions in 58.9%. The ratio of men to women was 5:5, since heterosexuality and polygamy prevailed. Cigarette smoking was the main addition, thus drug addition per se did not appear as a risk factor. Blood transfusions occurred frequently (for instance, in malaria), but hemophilic patients receiving lyophilized preparations were rare. Haitians visited in fairly large numbers after the 1960's propagating the risk of AIDS. Black Africans accounted for 100% of cases. The number of concomitant, opportunistic diseases in AIDS patients in Zaire were: 34 cases of tuberculosis, 32 cases of candidiasis, 30 fungal infections, 21 Herpes labialis and/or genitalis, 19 cases of dermal and cerebral cryptococcosis, 12 cases of cryptosporidiosis, 9 cases of Kaposi's sarcoma, 5 cases of Herpes zoster, 3 cases of aseptic cerebral infections, 3 cases of coccidiosis, 2 cases of toxoplasmosis, and 1 case of pneumonia (Pneumocystis). Tuberculosis, cryptococcosis, cryptosporidiosis, and toxicosis were more frequent opportunistic diseases in Zaire than in the U.S.A., while pneumonia caused by Pneumocystis and Kaposi's sarcoma were relatively rare.
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PMID:[Acquired immunodeficiency syndrome (AIDS) in the African environment]. 382 54

In summary, it appears that giardiasis, coccidiosis, cryptosporidiosis, strongyloidiasis, capillariasis and perhaps P. falciparum malaria are the only parasitic diseases which cause malabsorption of many nutrients. D. latum and A. lumbricoides interfere with vitamin B12 and vitamin A absorption, respectively. In view of the increasing use of immunosuppressive therapy, it is likely that malabsorption caused by intestinal parasites may become even more evident in the future.
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PMID:Parasites and malabsorption. 640 70

A novel fungal metabolite, apicidin [cyclo(N-O-methyl-L-tryptophanyl-L -isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal activity in vitro against Apicomplexan parasites has been identified. It is also orally and parenterally active in vivo against Plasmodium berghei malaria in mice. Many Apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and new therapeutic agents are urgently needed. Apicidin's antiparasitic activity appears to be due to low nanomolar inhibition of Apicomplexan histone deacetylase (HDA), which induces hyperacetylation of histones in treated parasites. The acetylation-deacetylation of histones is a thought to play a central role in transcriptional control in eukaryotic cells. Other known HDA inhibitors were also evaluated and found to possess antiparasitic activity, suggesting that HDA is an attractive target for the development of novel antiparasitic agents.
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PMID:Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. 891 58

This review presents short information on the present status and some future perspectives of vaccination against parasitoses of domestic animals. For the control of such parasitoses in some European countries only a few vaccines are registered: Paracox and Livacox (for coccidiosis in chickens), Toxovax (for toxoplasmosis in sheep), Pirodog (for babesiosis in dogs) and Dictol (for dictyocaulosis in cattle). These are live vaccines containing attenuated parasites, except Pirodog. As a world-wide innovation in 1994 a vaccine against ixodid tick infestation (Boophilus microplus) in cattle was marketed in Australia under the trade name TickGARD which contains a recombinant protein antigen. A recombinant vaccine against Taenia ovis cysticercosis in sheep was developed in Australia/New Zealand but has not yet been registered. The development of vaccines against further parasitoses of domestic animals is a fascinating and promising field. Present research activities are focussed on molecular antigen vaccines and vector vaccines. First reports (for example regarding leishmaniosis and malaria) indicate that nucleic acid vaccines represent a new potential of development.
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PMID:[Vaccines against parasitic diseases of domestic animals]. 901 13

Coccidiosis is the most important parasitic infection in poultry worldwide and also causes problems in cattle, sheep and goats. Control is largely limited to good husbandry and prophylactic chemotherapy using a range of drugs against which resistance is rapidly acquired. Attempts at vaccination using conventional vaccines have been disappointing and there is now a need for a new approach. Research into the immunology of coccidiosis has lagged behind that of other sporozoans and there are useful lessons that might be learned from studies on toxoplasmosis, cryptosporidiosis, theileriosis and malaria. In these infections the emphasis has turned to the cytokine network that drives the response towards protection. Central to these studies are the roles of interferon-gamma, interleukin-12 and activated macrophages with the involvement of nitric oxide in parasite killing. Cytotoxic T cells have also increasingly been implicated. Research has shown that different immune responses can be elicited by manipulating the cytokine system and these new concepts can be applied to the design of peptide or recombinant vaccines, and the possibilities of developing such vaccines against coccidiosis will be discussed.
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PMID:Control of coccidiosis: lessons from other sporozoa. 950 43

Parasites of the phylum Apicomplexa (Sporozoa) cause diseases such as malaria, toxoplasmosis, or intestinal coccidiosis. Invasive stages possess typical apical organelles such as dense granules that harbor a broad range of polypeptides that are believed to take part in the parasite-host cell interaction. In previous studies a 26-kDa polypeptide of dense granules from Sarcocystis muris cyst merozoites (bradyzoites) was characterized as a thiol (cysteine) proteinase. In this paper a method is demonstrated to amplify DNA fragments from genomic DNA of S. muris cyst merozoites by polymerase chain reaction, which probably code for the 26-kDa antigen.
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PMID:Amplification of genomic DNA fragments of Sarcocystis muris (Apicomplexa) cyst merozoites encoding a thiol (cysteine) proteinase. 969 76

The phylum Apixomplexa includes obligate intracellular parasites that are of enormous medical and veterinary significance, as they are responsible for a wide variety of diseases including malaria, toxoplasmosis, coccidiosis, cryptosporidiosis, theileriosis and babesiosis. The EST sequencing projects in Toxoplasma gondii and the Plasmodium falciparum genome sequencing project have greatly accelerated gene discovery, revealing for example novel coding sequences restricted to the Apicomplexa. However, easy acquisition of sequence is almost useless if the function of any given gene cannot be tested. The establishment of transfection systems in Toxoplasma gondii, Neospora and in several Plasmodium species has provided us with the reverse genetics methods appropriate to the functional analysis of genes. Over the past few years, the discovery of novel genes coupled to the ability to introduce or modify genes has already contributed to a better understanding of cell biology and pathogenesis of these obligate intracellular parasites. Some insights into the complex processes of parasite invasion, differentiation, regulation of gene expression and protein trafficking are emerging although identification of the exact functional roles for many molecules is still awaiting more investigation. This review summarizes progress in this area. It also emphasises the tight link and synergy between Toxoplasma and malaria research. The use of reverse genetics does not guarantee the answer to gene function, so we can learn from both failed and successful experiments about how better and more efficiently to use 'genomics' to accelerate discoveries relevant to the understanding of parasitism by Apicomplexa.
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PMID:The importance of reverse genetics in determining gene function in apicomplexan parasites. 1046 37

Apicomplexan protozoan parasites have complex life cycles that involve phases of asexual and sexual reproduction. Some genera have intermediate insect hosts, for example, Plasmodium spp. (the cause of malaria), but related genera such as Eimeria spp. (causative agents of coccidiosis in poultry) have a direct life cycle occurring in only a single host. Mechanisms that regulate the life cycles of apicomplexan parasites are unknown, but the intracellular growth of avian Eimeria spp. is easily shortened by serial selection for the first parasites to complete the transition from asexual to sexual reproduction (to yield so-called precocious lines). To investigate the genetic basis of such an abbreviated life cycle, we have used the species E. tenella and analyzed the inheritance of 443 polymorphic DNA markers in 22 recombinant cloned progeny derived from a cross between parents that had selectable phenotypes of precocious development or resistance to an anticoccidial drug. The markers were placed in 16 linkage groups (which defined 12 chromosomes) and a further 57 unlinked groups. Two linkage groups showed an association (P =.0105) with the traits of precocious development or drug-resistance and were mapped to chromosome 2 (ca 1.2 Mbp) and chromosome 1 (ca 1.0 Mbp), respectively. The map provides a framework for further studies on the identification of genetic loci implicated in the regulation of the life cycle of an important protozoan parasite and a representative of a major taxonomic group. [A table with the segregation data is available as an online supplement at http://www.genome.org.]
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PMID:A genetic linkage map of the apicomplexan protozoan parasite Eimeria tenella. 1104 56


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