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)

An antigen (LMS) prepared from Leishmania major-like promastigotes was used in an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of human and dog visceral leishmaniasis. The results were compared with those from the indirect immunofluorescent antibody test (IFAT). A total of 1822 canine sera were tested, including sera from dogs with visceral leishmaniasis, transmissible venereal tumors, ehrlichiosis, rickettsiosis, or Chagas' disease and sera from healthy dogs. The antigen was also tested with 227 samples of human sera, including sera from patients with visceral, cutaneous, or diffuse cutaneous leishmaniasis and from noninfected individuals, as well as sera from patients with Chagas' disease, toxoplasmosis, rickettsiosis, hepatitis B, schistosomiasis, ascaridiasis, malaria, rheumatoid factor, leprosy and rheumatoid factor, tuberculosis, or leprosy. All dogs and all human patients had a clinical and/or serological and/or parasitological diagnosis. For detecting antibodies in sera from dogs with leishmaniasis, the antigen showed a sensitivity of 98%, specificity of 95%, and concordance of 93% and when used for detecting antibodies in human sera presented a sensitivity of 92%, specificity of 100%, and concordance of 92%. Comparison between ELISA and IFAT demonstrated that ELISA using the LMS antigen yielded more reliable results than IFAT. The LMS antigen displayed no cross-reactivity with sera from patients or dogs that had any of the other diseases tested.
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PMID:Leishmania major-like antigen for specific and sensitive serodiagnosis of human and canine visceral leishmaniasis. 1241 75

This review focuses on the most significant trends in the development of drugs for the treatment of malaria, African sleeping sickness and toxoplasmosis. In the case of malaria, those include new fixed-dose artemisinin combinations, antifolates and new targets in the apicoplast of Plasmodium falciparum. Targets in the treatment of trypanosomiasis are the biosynthesis of glycosylphosphatidylinositol and enzymes involved in the biosynthesis of trypanothione. Efforts to develop a vaccine against toxoplasmosis are discussed as well.
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PMID:The necessity to develop drugs against parasitic diseases. 1261 Dec 73

Apicomplexan parasites cause severe diseases such as malaria, toxoplasmosis, and coccidiosis (caused by Plasmodium spp., Toxoplasma, and Eimeria, respectively). These parasites contain a relict plastid-termed "apicoplast"--that originated from the engulfment of an organism of the red algal lineage. The apicoplast is indispensable but its exact role in parasites is unknown. The apicoplast has its own genome and expresses a small number of genes, but the vast majority of the apicoplast proteome is encoded in the nuclear genome. The products of these nuclear genes are posttranslationally targeted to the organelle via the secretory pathway courtesy of a bipartite N-terminal leader sequence. Apicoplasts are nonphotosynthetic but retain other typical plastid functions such as fatty acid, isoprenoid and heme synthesis, and products of these pathways might be exported from the apicoplast for use by the parasite. Apicoplast pathways are essentially prokaryotic and therefore excellent drug targets. Some antibiotics inhibiting these molecular processes are already in chemotherapeutic use, whereas many new drugs will hopefully spring from our growing understanding of this intriguing organelle.
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PMID:The apicoplast: a plastid in Plasmodium falciparum and other Apicomplexan parasites. 1272 49

Toxoplasma gondii belongs to the Apicomplexa phylum, which comprises protozoan parasites of medical and veterinary significance, responsible for a wide variety of diseases in human and animals, including malaria, toxoplasmosis, coccidiosis and cryptosporidiosis. During infection in the intermediate host, T. gondii undergoes stage conversion between the rapidly replicating tachyzoite that is responsible for acute toxoplasmosis and the dormant or slowly dividing encysted bradyzoite. The tachyzoite-bradyzoite interconversion is central to the pathogenic process and is associated with the life-threatening recrudescence of infection observed in immunocompromised patients such as those suffering from AIDS. In chronic infections, the bradyzoites are located within tissue cysts found predominantly in brain and muscles. The tissue cyst is enclosed by a wall containing specific lectin binding sugars while the bradyzoites have accumulated large amounts of the storage polysaccharide of glucose, amylopectin. Our recent findings have identified several genes and proteins associated with amylopectin synthesis or degradation and glucose metabolism, including different isoforms of certain glycolytic enzymes, which are stage-specifically expressed during tachyzoite-bradyzoite interconversion. Here, we will discuss how the genes and enzymes involved in carbohydrate metabolisms are used as molecular and biochemical tools for the elucidation of molecular mechanisms controlling T. gondii stage interconversion and cyst formation.
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PMID:Developmentally regulated biosynthesis of carbohydrate and storage polysaccharide during differentiation and tissue cyst formation in Toxoplasma gondii. 1277 Jul 73

Recently introduced rapid nonmicroscopic immunocapture assays for the diagnosis of malaria infection are being evaluated for their sensitivity and specificity in various epidemiological settings. A Plasmodium falciparum histidine-rich protein-2 (PfHRP-2)-based assay (ICT malaria Pf assay) was evaluated for its performance and compared to that of Giemsa-stained thick blood film microscopy. Of the 515 patients tested, 163 were positive for malaria parasites on thick blood film microscopy: 87 were infected with P. vivax; 63 with P. falciparum; 1 with P. malariae; and 12 with both P. falciparum and P. vivax. The ICT assay detected 53 P. falciparum infections and, as expected, failed to detect all but one case of P. vivax. Three cases of mixed infections were also not detected by this assay. The performance of the ICT assay in diagnosing P. falciparum infection was comparable to that of microscopy. The sensitivity of the ICT assay was 82% and the specificity 99.0%. The ICT assay also detected 4 false-positive cases. These patients reported treatment with chloroquine in the previous 2-5 weeks. The specificity of the assay was evaluated in different groups of patients, who had tested negative for malaria infection by microscopy. These patients were selected from different disease groups: rheumatoid arthritis; hepatitis C; toxoplasmosis; schistosomiasis; and hydatid disease. Of the 225 patients studied, 133 were positive for rheumatoid factor. Thirty-five (26%) of the 133 patients had false positive-reactions with the ICT assay, while only four had false positive-reactions with the OptiMAL test. After the rheumatoid factor was absorbed 33 of the 35 false-positive specimens were negative when retested with the ICT assay. Our study shows that the PfHRP-2-based ICT assay gave a false positive-reaction in 26% of the patients who had rheumatoid factors, but were negative for malaria by microscopy. We conclude that new rapid nonmicroscopic methods for the diagnosis of malaria that complement or support blood film microscopy would be of great use in the diagnosis and treatment of patients with malaria and also in epidemiological studies.
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PMID:Performance of rapid malaria Pf antigen test for the diagnosis of malaria and false-reactivity with autoantibodies. 1291 86

The article focuses on the Indian initiative of making kits for diagnosis of various infectious and non-infectious diseases as well as reproductive hormones and hormones in various other endocrine disorders. Indigenous diagnostic kits for the detection of various infections such as filariasis, typhoid, amebiasis, Japanese encephalitis, hepatitis, HIV, dengue, leishmaniasis, malaria, rabies, toxoplasmosis, rotavirus, and group A streptococci have been developed. Agreements to transfer the know-how of some of these leads to industries have been signed. The know-how of enzyme-linked immunosorbent assay (ELISA) for detection of hepatitis C has been successfully transferred to industry and is being commercially produced. For detection of HIV-1 and HIV-2, indigenous diagnostic kits based on three different formats, namely ELISA, Western blot and rapid test have been developed and are being commercially produced by Indian industries. The factors influencing the successful transfer of laboratory-scale diagnostic assays from academia to industry and their commercial exploitation have been discussed. Indian scientists have made seminal contributions in exploring the possibility to develop an effective and safe contraceptive vaccine to control the increasing human population of India. Achieving contraception by means of vaccine is a novel approach, which entails generation of a specific antibody response against antigens critically involved in the process of mammalian reproduction. In India, three major programs on contraceptive vaccines based on the beta-subunit of human chorionic gonadotrophin ((beta)hCG) for women, ovine follicle stimulating hormone (oFSH) for men, and riboflavin carrier protein for both males and females have been initiated. The work at the National Institute of Immunology, New Delhi on contraceptive vaccine for women, based on (beta)hCG, has demonstrated, for the first time, that it is feasible to regulate fertility by such an approach. Basic research being carried out to achieve immunocontraception by interfering at sperm-oocyte interaction level has been briefly discussed. These developments are still at the research stage. In addition to advances in the area of contraceptive vaccines, a non-steroidal contraceptive oral pill has been developed by Central Drug Research Institute, Lucknow, commercially produced by two Indian pharmaceutical companies and has been incorporated in the National Family Welfare Program. Another interesting approach for fertility regulation in male has been developed in India, which involves vas occlusion with styrene maleic anhydride (SMA) and is currently undergoing clinical trials in human subjects.
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PMID:Status of immunodiagnosis and immunocontraceptive vaccines in India. 1293 96

We evaluated industrially prepared Western blot strips designed to avoid the cross-reactions observed with indirect immunofluorescence and enzyme-linked immunosorbent assays used for the serodiagnosis of trichinellosis. The antigen preparations were crude extracts of Trichinella spiralis. The Western blot profile characteristic of trichinellosis was characterized by comparing 60 sera from patients infected by Trichinella to 11 sera from healthy subjects, 51 sera from patients with other proven parasitic diseases (cysticercosis, schistosomiasis, strongyloidosis, fascioliasis, toxocariasis, liver amebiasis, anisakiasis, filariasis, toxoplasmosis, hydatidosis, or malaria), and 23 sera from patients with autoantibodies. Specific 43- to 44-kDa and 64-kDa bands were obtained with all of the sera from 51 patients with acute trichinellosis, in 4 out of 9 patients at the early stages of the disease, and in only 1 control patient, who had suspected anisakiasis and in whom trichinellosis could not be ruled out by muscle biopsy.
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PMID:Development and evaluation of a Western blot kit for diagnosis of human trichinellosis. 1296 6

Members of the phylum Apicomplexa are obligate intracellular parasites that invade erythrocytes, lymphocytes, macrophages or cells of the alimentary canal in various vertebrate species. Organelles within the apical complex of invasive stages facilitate host cell invasion. Parasites in this phylum cause some of the most debilitating diseases of medical and veterinary importance. These include malaria, toxoplasmosis, babesiosis, theileriosis (East Coast fever), and coccidiosis in poultry and livestock. In recent years, opportunistic infections caused by Cryptosporidium parvum, and recrudescent Toxoplasma gondii infections in AIDS patients have prompted intensified efforts in understanding the biology of these parasites. In this review, Tobili Sam-Yellowe examines the unifying and variant molecular features of rhoptry proteins, and addresses the role of multigene families in organelle function: the biogenesis of the rhoptries will also be examined, in an attempt to understand the sequence of events leading to successful packaging, modification and processing of proteins within the organelle.
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PMID:Rhoptry organelles of the apicomplexa: Their role in host cell invasion and intracellular survival. 1527 82

Whereas parasitic diseases are always a heavy burden for humanity, few are the new antiparasitic molecules marketed during the last 25 years. Thus on the 1393 new molecules marketed between 1975 and 1999, only 7 have antiprotozoan properties. This talk will detail the progress made in the treatment of the intestinal protozoa, malaria, visceral leishmaniasis and toxoplasmosis, problems with which are especially confronted the European parasitologists. The treatment of Giardia and intestinal amoebas is based on 5-nitro-imidazoles derivatives. Single-dose treatments can be used with tinidazole or secnidazole. Resistance to these compounds of Giardia were described and in these cases, treatment by quinacrine or nitazoxanide are possible alternatives. Nitazoxanide is marketed in the United States and in Australia. It seems to be a well tolerated antiparasitic agent with a broad spectrum because it is active on a lot of intestinal protozoa and helminths. It acts on the same metabolic way as the 5-nitro-imidazoles (inhibition of the ferredoxine reductase) but without synthesis of free radicals and DNA deterioration of the target cell. It is thus neither teratogenic nor mutagenic. Artemisinin derivatives allowed considerable progress in the treatment of malaria. They have short half-lifes, allowing a fast parasitic clearance and these derivatives do no provoke resistance. They are first line drugs for the treatment of malaria in areas of drug resistance. The arthemeter-lumefantrine association (Riamet, Coartem) ensures a rapid disappearance of the circulating parasites and is well tolerated. Atovaquone-proguanil (Malarone) is usable in the treatment of acute malaria but also in disease prevention with the advantage of continuing drug intake for only 7 days after having left the infected area. The treatment of leishmaniasis is always delicate and is characterized by the worrying development of antimony resistances, probably related in the European zones to the treatment of dogs. Liposomal amphotricin is an alternative of choice but remains very expensive. The heating of amphotericin to 70 degrees C during 20 minutes gives it experimental properties and efficacies comparable with that of liposomal amphotericin, but at a less cost. Miltefosine, an alkyl-phospholipide antimetabolite, is very active on visceral leishmaniasis resistant to antimonial treatment. However, its long half-life could induce the emergence of resistances. Miltefosine induces much less side effects than conventional amphotericin B. The commonly used anti-toxoplasmic drugs (sulphadiazine and pyrimethamine) were marketed some 50 years ago and are only active on the rapid forms in multiplication. No drug is really efficient on the cysts although preliminary tests with atovaquone are encouraging to treat ophthalmologic forms in immunocompetent patients. To conclude, it is important to continue to search for new antiprotozoan molecules because, for some parasites, drug resistance is an important problem. Moreover, the treatment of the pregnant women, particularly during the first trimester, is often impossible and there is a lack of galenic forms easily usable in children. A better knowledge of the metabolic pathways of protozoa (particularly the apicoplast of Apicomplexa parasites) would certainly open the posssibility to identify new drugs. To reduce and delay the appearance of resistances, mass-treatments of mass should be avoided and targeted treatments prefered as well as the use of associations of molecules having different modes of action.
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PMID:[New drugs for the treatment of human parasitic protozoa]. 1530 92

Recently, the term of clinical immunoparasitology has been coined to indicate the application of immunological methods to the laboratory diagnosis of parasitic infections. In particular, serological diagnosis (indirect diagnosis) is useful especially in the cases of toxocarosis, trichinellosis, echinococcosis, cysticercosis, toxoplasmosis, amoebic abscess, some filariasis, visceral leishmaniasis, schistosomiasis. When possible, for infections caused by protozoa or helminths, the "gold standard" is represented by direct diagnosis performed by microscopic and/or macroscopic observation of the parasite. In any case, immunological results must be interpreted in consideration of the clinical picture of the patient and confirmed possibly by finding the parasite or its genome, even using molecular methods. Furthermore, since the presence of specific antibodies can reveal an acquired infection, but not necessarily a disease, it is particularly helpful, in addition to a qualitative evaluation, a quantitative one, by determining the serum antibody titre. After recovery, the antibody levels decrease, however, they may persist for long periods, for this reason they do not help in evaluating the treatment outcome. Interpretation of serological results may be difficult when the patients originate from areas where the suspected infection is endemic, in that case, a serum positivity could reflect an old exposition to the parasite, therefore it is not related to the present clinical status. Furthermore, serology may frequently result falsely negative in not immunocompetent subjects (organ transplanted, HIV positive individuals, premature babies, diabetics). Clinicians can interpret correctly the serological results only if the Parasitology laboratory inform them about the significant diagnostic values, the sensitivity and the specificity of the test in use. At present time, many diagnostic kits for immunoparasitology are commercially available, and industries are developing newer and newer ones (which are not always validated). In relation to this aspect, it should be helpful, for each of parasitic infection, to establish reference centers, not only to control the quality of commercial kits, but also as a reference point to those laboratories which use "in house" kits. To this regard, the recent establishment of a European Centre for Control of Infectious Diseases will help. The antigen characteristics (crude, E/S, recombinant, synthetic) for assays searching for antibodies (IHA, IFA, EIA, WB) of different classes, the controls to choose for these assays, the specimen requirements will be discussed. The recent findings on the serological diagnosis of intestinal protozoa infections, malaria, leishmaniasis, echinococcosis, cysticercosis, trichinellosis, toxocariasis, schistosomiasis, strongyloidiasis will be presented.
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PMID:[The serodiagnosis of parasitic infections]. 1530 4


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