Present status of chemotherapy and chemoprophylaxis of human trypanosomiasis in the Western Hemisphere.
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Biomedical subjects
Publications and source records attributed to Z Brener.
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Epimastigotes and trypomastigotes of T. cruzi obtained from acellular culture as well as bloodstream trypomastigotes agglutinate with concanavalin A (Con A). Con A-binding sites were also localized on the cell membrane by using the Con A-horseradish peroxidase-diaminobenzidine method. Passage of epimastigotes and trypomastigotes from acellular culture through DEAE-cellulose column did not affect Con A-binding sites as detected by agglutination and electron miscroscopy.
The uptake and further development of bloodstream forms from T. cruzi Y and CL strains in mouse peritoneal macrophages have been investigated. Parasites from the Y strain (which present predominance of slender forms) are 20 to 30-fold more infective to macrophages than those from CL strain in which stout forms highly predominate. A complete amastigote-trypomastigote cycle is observed in normal or thioglycollate-induced macrophages infected with parasites from both strains.--Opsonization significantly increases the uptake by normal macrophages of parasites from both strains. The fate of the opsonizated parasites is, however, different: the Y trypomastigotes present a normal cycle which culminates with the release of newly formed trypomastigotes whereas CL parasites are extensively destroyed by normal macrophages.--The differences in the uptake and fate displayed by both T. cruzi populations are not well understood. They are apparently related to parasite membrane components or macrophage receptors differences, which are probably influencing endocytosis and the further intracellular development of the parasites.
First stage nymphs of Triatoma infestans and Dipetalogaster maximus which had never fed after egg hatching, were allowed to ingest by artificial feeding a blood-free suspension of Trypanosoma cruzi trypomastigotes collected from experimentally infected mice. A high percentage of the vectors acquired a normal infection and produced infective stages. The parasite's development in the vector did not require blood but may have needed the presence of unknown factors secreted and/or excreted in the insect's digestive tract.
A systematic study of the distribution of intracellular parasites in the organs and tissues was performed in groups of mice inoculated with 4 different Trypanosoma cruzi strains. An extremely high parasitism of spleen, liver, and bone marrow was observed in mice inoculated with Y and Berenice strains; with CL strain, however, parasites were almost absent in those organs. Bloodstream forms apparently present differences which facilitate or prevent their uptake by macrophages from the mononuclear phagocytic system. Parasitism of the smooth muscle from hollow organs was significantly higher with ABC and Berenice strains than with Y and CL. The importance of the distribution of intracellular stages in the pathogenesis of the disease is discussed.
A dramatic reduction in the total number of dense vesicles in Auerbach's plexus of the mouse colon was observed during the acute phase of experimental American Trypanosomiasis (Chagas' disease). A significant decrease in substance P activity of the colon of inoculated animals was also measured. It is suggested that this decrease in substance P activity could be related to the reduction in the number of dense vesicles in Auerbach's plexus.
A 48-hr drug screening test is described which evaluates inhibition of exponential growth of T. cruzi culture forms by electronic cell count. About 80% of drugs active in vivo produced a greater than 50% growth inhibition, whereas among compounds inactive in vivo, only 19.6% induced such inhibition. Advantages of this test are low cost, rapid results, small amounts of drugs needed, and feasibility without animal facilities. Comparative studies showed that culture forms are not suitable for screening additives to prevent transmission of T. cruzi by banked blood.
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Inhibition of T. cruzi amastigote-trypomastigote differentiation in tissue culture at 37 C is a strain-dependent event. When eight T. cruzi strains were submitted to two environmental temperatures (33 and 37 C), the following patterns of differentiation were obtained: in three strains, transformation was inhibited at 37 C but readily occurred at 33 C; in three other strains differentiation took place at both temperatures; finally, in the two remaining strains, a partial inhibition was detected at 37 C. The authors discuss the meaning of this intraspecific variation and the possible relationship with the occurrence of temperature-sensitive mutants among protozoa.
Leptomonas pessoai from the reduviid hemipteron Zelus leucogrammus, was cloned. The original strain (ATCC 30252) and clones can differentiate from promastigote to opisthomastigote. Differentiation is faster at high temperature (37 C) and in a defined medium as compared with a complex medium. It is suggested that Leptomonas pessoai be designated Herpetomonas samuelpessoai.
Temperature strongly influenced morphogenesis of intracellular trypomastigotes in cell culture infected with 2 different strains of T. cruzi. With the Gilmar strain the amastigote-to-trypomastigote differentiation readily occurred at 33 and 37 C, whereas the CL strain differentiation took place at 33C but was inhibited at 37 C. The possiblity of this selective thermosensitivity resulting from mutational adaptation of the parasite is discussed.
The action of immune sera from animals with chronic Chagas disease on Trypanosoma cruzi bloodstream forms (Y and CL strains) was investigated. Y strain trypomastigotes were agglutinated by anti-CL or anti-Y immune sera and their infectivity was decreased when inoculated into normal mice. CL strain trypomastigotes, however, remained apparently unchanged, with neither agglutination nor decline of infectivity being observed after incubation with both immune sera. Sera from three patients with chronic Chagas disease clearly agglutinated and two of them decreased the infectivity of Y strain trypomastigotes. Passive transfer of immunity was achieved in mice that recieved anti-CL or anti-Y immune sera and that were challenged with Y strain parasites. These results suggest that humoral immunity participates in the protective immune response against T. cruzi and that bloodstream trypomastigotes represent a more suitable model for studies of antigenic variation in these infections.
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