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Coinfecção Trypanosoma cruzi/HIV e reativação da Doença de Chagas em uma coorte submetida à avaliação parasitológica entre 1995 e 2019 no Hospital de Clínicas da Universidade Federal do Triângulo Mineiro, Uberaba/Minas Gerais

Fri, 10 Dec 2021 00:00:00 GMT

Título: Coinfecção Trypanosoma cruzi/HIV e reativação da Doença de Chagas em uma coorte submetida à avaliação parasitológica entre 1995 e 2019 no Hospital de Clínicas da Universidade Federal do Triângulo Mineiro, Uberaba/Minas Gerais Abstract: Trypanosoma cruzi is the etiologic agent of Chagas disease that occurs between 6 and 8 million people, most of them in Latin America. Human Immunodeficiency Syndrome / AIDS or Acquired Immune Deficiency Syndrome / AIDS is a chronic degenerative infection currently detected in 38 million people and caused by human immunodeficiency viruses 1 (HIV-1) and 2 (HIV-2). The spread of HIV in endemic regions for Chagas disease generated the Trypanosoma cruzi / HIV coinfection. In this study, the profile of Chagas disease reactivation was evaluated in a cohort of individuals with the Trypanosoma cruzi / HIV coinfection detected among chagasic individuals who underwent parasitological examinations for the detection of Trypanosoma cruzi at the Hospital de Clínicas da UFTM / Uberaba / Minas Gerais between 1995 and 2019. Coinfection was identified in 6.6% (99/1501) of these individuals, who had a mean age of 51.6 ± 10.5 years, with no difference in terms of gender and age (p>0.05). These came mainly from the states of Minas Gerais (64.6%) and São Paulo (24.2%). In the group of coinfected individuals, there was no significant difference between the means of LT-CD4+ in males and females (p=0.17), however, the viral load was lower in males (p=0.0208). Chagas disease reactivation occurred in 23.2% (23/99) of the individuals, with a reactivation rate of 24.2% (24/99), 2 reactivations / 1 case. The parasite was detected in blood in 54.2%, in blood and cerebrospinal fluid in 29.1%, and cerebrospinal fluid in 16.7%. Among the reactivated individuals, there was no difference between the distribution according to gender (p> 0.05) and mean age, however, the non-reactivated, presented a higher mean age (p=0.024). The mortality rate was higher (p=0.0050) in the group with reactivation and was associated with invasion of the central nervous system in 71.4% of cases, in females (p=0.0017), LT-CD4+ < 200 cells/mm3 and higher viral load. The LT-CD4+ count in the non-reactivated group was higher compared to the reactivated group (p= 0.0186). The distribution of viral load between individuals with reactivation and without reactivation showed no difference, however, the p-value was at the threshold of significance (p=0.0510). Regarding the distribution by gender, it was found that the average of LT-CD4+ in the reactivated group was lower (p=0.0109) in the male gender, with no difference (p>0.05) in viral load. In the non-reactivated group, the mean LTCD4+ did not differ between genders (p=0.4480), however, the viral load was lower in males (p=0.0462). Coinfected individuals had 47.3% of blood culture samples positive, associated with higher viral load and lower LT-CD4+ count (p<0.0001), and negative ones with higher levels of LT-CD4+ and lower viral load. Blood culture positivity was higher (p=0.0008) among samples from reactivated individuals (63.1%) than among non-reactivated individuals (40.9%), the reactivated group had lower LT-CD4+ and higher viral load than the non-reactivated. In Trypanosoma cruzi / HIV coinfection, three profiles of Chagas disease reactivation were identified according to LT-CD4+ values and viral load: Group A: without immunosuppression (LT-CD4+ > 204 cells/mm3) and low/ moderate viral load; Group B: immunosuppression (LT-CD4+ ≤ 215 cells/mm3) and high viral load; Group C: immunosuppression (LT-CD4+ < 200 cells/mm3) and low/moderate viral load. The data found open new perspectives for better classification and monitoring of disease reactivation in Trypanosoma cruzi / HIVAIDS coinfection. Tipo: Dissertação

A riqueza de espécies de reservatórios prediz taxas locais de mortalidade por doença de Chagas?

Tue, 23 Jan 2024 00:00:00 GMT

Título: A riqueza de espécies de reservatórios prediz taxas locais de mortalidade por doença de Chagas? Abstract: The dilution effect hypothesis postulates an inverse relationship between host diversity and the probability of disease transmission. However, the amplification effect hypothesis proposes that there is a direct relationship between pathogen transmission and greater host diversity. Understanding the diversity of vectors, hosts and reservoirs of the etiologic agent Trypanosoma cruzi can contribute to the development of epidemiological surveillance of Chagas disease. We aimed to test the dilution and amplification hypotheses, considering the possible relationship between mortality rates from Chagas disease and the biodiversity of reservoir species of the disease. We used Chagas disease mortality data for each municipality in the country for the years 2018, 2019 and 2020; geographical coordinates for each city, human population density data and HDI for each municipality; rasters indicating species richness and environmental variables based on the literature; and polygons with centroids, using QGIS software. Generalized Estimated Equation Models were used in the statistical analysis, with statistical significance set at p<0.001. We obtained an association between bird and mammal species richness and mortality from Chagas disease. The diversity of mammalian hosts increased the risk of transmission through the amplification effect. For birds, our results revealed the occurrence of the dilution effect. The results also point to the influence of geographical variation through the distribution of vectors and the prevalence of different host species. We found a positive relationship between HDI and Chagas mortality rates, denoting an urgent need to develop public health strategies. Thus, this study showed that a significant increase in the risk of transmission of Chagas disease is associated with a greater diversity of mammal species and indicated that a lower risk of transmission of the disease is associated with a greater diversity of bird species. Our study also showed that municipalities with higher human development indices had, on average, higher Chagas mortality rates. Our findings contribute to an understanding of the specific epidemiology of Chagas disease and prompt discussion of more effective approaches to the control and prevention of vector-borne infectious diseases in a comprehensive context that encompasses biological, social and economic variables. Tipo: Dissertação

Papel do óxido nítrico no transplante alogênico de células mesenquimais estromais na Doença Inflamatória Intestinal

Mon, 24 Sep 2012 00:00:00 GMT

Título: Papel do óxido nítrico no transplante alogênico de células mesenquimais estromais na Doença Inflamatória Intestinal Abstract: 1 Inflammatory Bowel Diseases (IBD) are chronic relapsing diseases that result in diarrhea, 2 abdominal pain, rectal bleeding and malnutrition. The inflammation in ulcerative colitis (UC) 3 is restricted to the colonic mucosa, whereas Crohn's disease (CD) is characterized by 4 transmural infiltration that may affect any part of the gastrointestinal tract. CD is 5 characterized by a Th1 response and UC presents an atypical Th2 response, while Th17 is 6 present in elevated levels in inflamed mucosa of both CD and UC. The treatment routinely 7 used in IBD includes various drugs and surgeries; however, no currently available therapy 8 represents the cure for IBD, which may also predispose to colorectal cancer. Then, new 9 therapeutic approaches are necessary for better control of IBD. Mesenchymal stromal cells 10 (MSC) are multipotent cells that have immunoregulatory properties and are therefore 11 considered as important therapeutic tool for various chronic inflammatory diseases, including 12 IBD. These cells suppress the immune response by several mechanisms, such as by the 13 production of nitric oxide (NO) induced by activation of inducible Nitric Oxide Synthase 14 (iNOS). In this context, this study aimed to assess the therapeutic potential of MSC from WT 15 or iNOS-/- mice in IBD. IBD was induced in BALB/c mice by intrarretal enema of 16 trinitrobenzene sulfonic acid (TNBS). Animals were treated with allogeneic MSC derived from 17 the bone marrow of WT or iNOS-/- C57BL/6 mice and were euthanized 3, 7 or 14 days later. 18 The results showed that both MSC showed surface markers and plasticity inherent to this cell 19 type although MSC iNOS-/- were not able to differentiate into osteoblasts. Treated animals 20 had decreased disease clinical signs and increased survival, besides normalization of 21 systemic leukocyte counts and changes in populations of neutrophils and eosinophils in the 22 intestine. Both MSC led to decreased local inflammation and reestablishment of intestinal 23 architecture. However, the local inflammation was differentially modulated by MSC 24 depending on the presence of NO, since WT MSC controlled the Th17 response and led to 25 increased IL-10 levels while the iNOS-/- MSC induced a shift to the Th2 response in the gut. 26 Finally, this study contributed to the elucidation of the mechanisms that mediate the 27 therapeutic potential of MSC in IBD. Tipo: Dissertação

Avaliação do efeito da saliva de triatomíneos (Heteroptera: Reduviidae) sobre a biologia de células dendríticas murinas

Mon, 07 Jul 2014 00:00:00 GMT

Título: Avaliação do efeito da saliva de triatomíneos (Heteroptera: Reduviidae) sobre a biologia de células dendríticas murinas Abstract: Triatomines are blood-sucking arthropods of great medical interest because they are vectors of Trypanosoma cruzi, the ethiological agent of Chagas disease. During feeding triatomines need to overcome two major barriers imposed by the host defense systems: hemostasis and the immune system. While it is known that several molecules are capable of subverting the host hemostatic barriers, only few molecules capable of subverting the immune system have been characterized by these ectoparasites. Dendritic cells (DCs), present in the skin of all vertebrates, are key components of the innate immune response playing a crucial role in the induction of acquired immunity to many aggressive agents, including bloodsucking arthropods, and are of great interest to understand whether triatomines evade the responses by modulating these cells. Thus, the purpose of this study was to investigate the effect of the saliva from triatomines Panstrongylus herreri, Meccus pallidipennis, Rhodnius prolixus and Triatoma lecticularia on differentiation, maturation (expression of stimulatory and costimulatory molecules and cytokine production) and apoptosis of DCs. In this work we also try to identify if the saliva of these species have prostaglandin E2 (PGE2) in its constitution. Saliva from adult triatomines were obtained by dissection of salivary glands and the DCs were obtained from the differentiation of mouse bone marrow precursor cells in the presence of GM-CSF (25 ng/mL). The influence of saliva on DCs differentiation was analyzed by incubation of stem cells from C57BL/6 mice for 7 days in the presence of saliva and after this time the expression of molecular markers CD11c, CD11b, MHC-II, CD40, and CD86 were evaluated by flow cytometry. To assess the cell maturation, differentiated DCs were stimulated with LPS in the presence or absence of saliva and the expression of MHC-II, CD40, CD80 and CD86 was evaluated by flow cytometry and the production of cytokines TNF-α, IL-12p40, IL-10 and IL-6 was evaluated by ELISA. The differentiation of DCs was inhibited by the four tested saliva and this inhibitory activity (dilution 1:30 v / v) reached 79% for the specie P. herreri, 57% for M. pallidipennis, 38% for T. lecticularia and 76% for R. prolixus. The expression of MHC-II, CD40 and CD86 in DCs was differentially modulated depending on the saliva from each species. Regarding maturation, saliva differentially inhibited the expression of MHC-II, CD40, CD80 and CD86 in LPS-matured DCs but the CD40 molecule was the only inhibited by the saliva of the four species. Except for the saliva of R. prolixus, that induced IL-6 cytokine production, TNF-α, IL-12 and IL-6 were inhibited and IL-10 was increased in the saliva of the other three species tested. It is noteworthy that the saliva, per se, depending on the species, induced the production of IL-12, IL-6 and IL-10. The saliva of R. prolixus was the only one that induced DCs apoptosis. The presence of PGE2 in the saliva of the four evaluated triatomines was not detected. These results demonstrate that triatomines saliva has molecules that modulate the biology of DCs and this effect is PGE2- independent. We believe that the decrease in differentiation, the modulation of stimulatory and co-stimulatory molecules and the inhibition of pro-inflammatory cytokines and the induction of IL-10 generates a much less aggressive environment for the feeding that could also facilitate the transmission of pathogens, including T. cruzi. Tipo: Dissertação