WHO technical report series, ISSN 0512-3054 905
vi, 109 s. : tab., grafy, mapy ; 22 cm
- MeSH
- Chagas Disease * MeSH
- Philately MeSH
- Medicine in the Arts * MeSH
- Publication type
- Biography MeSH
- Historical Article MeSH
Annales de la Société Belge de Médecine Tropicale, ISSN 0365-6527 vol. 65, suppl. 1, 1985
232 s. : il., tab. ; 24 cm
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- cestovní a tropická medicína
BACKGROUND: Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. METHODS/PRINCIPAL FINDINGS: To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. CONCLUSIONS/SIGNIFICANCE: Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease.
- MeSH
- Apoptosis MeSH
- Autoimmune Diseases prevention & control MeSH
- Chagas Cardiomyopathy prevention & control MeSH
- Chagas Disease therapy MeSH
- Immunization MeSH
- DNA, Kinetoplast genetics MeSH
- Chickens genetics MeSH
- Mutation MeSH
- Myocardium pathology MeSH
- Graft Rejection MeSH
- Bone Marrow Transplantation * MeSH
- Trypanosoma cruzi genetics immunology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Technical report series ; no. 202
21 s.
- Conspectus
- Buněčná biologie. Cytologie
- NML Fields
- parazitologie
- veřejné zdravotnictví
[1st ed.] vi, 93 s. : il.
- MeSH
- Communicable Diseases MeSH
- Tropical Medicine MeSH
- Geographicals
- Bolivia MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- cestovní a tropická medicína
- infekční lékařství
Chagas disease (CD) is a neglected disease caused by Trypanosoma cruzi Chagas, 1909. Causative treatment can be achieved with two drugs: benznidazole or Nifurtimox. There are some gaps that hinder progress in eradicating the disease. There is no test that can efficiently assess cure control after treatment. Currently, the decline in anti-T. cruzi antibody titres is assessed with conventional serological tests, which can take years. However, the search for new markers of cure must continue to fill this gap. The present study aimed to evaluate the decline in serological titres using chimeric proteins after treatment with benznidazole in chronic patients diagnosed with CD. It was a prospective cross-sectional cohort study between 2000 and 2004 of T. cruzi-positive participants from the Añatuya region (Argentina) treated with benznidazole. Serum samples from ten patients were collected before treatment (day zero) and after the end of treatment (2, 3, 6, 12, 24 and 36 months). For the detection of anti-T. cruzi antibodies, an indirect ELISA was performed using two chimeric recombinant proteins (IBMP-8.1 and IBMP-8.4) as antigens. The changes in reactivity index within the groups before and after treatment were evaluated using the Friedman test. All participants experienced a decrease in serological titres after treatment with benznidazole, especially IBMP-8.1. However, due to the small number of samples and the short follow-up period, it is premature to conclude that this molecule serves as a criterion for sustained cure. Further studies are needed to validate tests based on these or other biomarkers to demonstrate parasitological cure.
Insecticide-impregnated nets can kill triatomine bugs, but it remains unclear whether they can protect against Chagas disease transmission. In a field trial in Quequeña, Peru, sentinel guinea pigs placed in intervention enclosures covered by deltamethrin-treated nets showed significantly lower antibody responses to saliva of Triatoma infestans compared with animals placed in pre-existing control enclosures. Our results strongly suggest that insecticide-treated nets prevent triatomine bites and can thereby protect against infection with Trypanosoma cruzi. Anti-salivary immunoassays are powerful new tools to evaluate intervention strategies against Chagas disease.
- MeSH
- Chagas Disease prevention & control MeSH
- Insect Control methods MeSH
- Immunoassay MeSH
- Insect Bites and Stings immunology prevention & control MeSH
- Guinea Pigs MeSH
- Parasitology methods MeSH
- Insecticide-Treated Bednets MeSH
- Saliva immunology MeSH
- Triatoma immunology MeSH
- Animals MeSH
- Check Tag
- Guinea Pigs MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Geographicals
- Peru MeSH
