IS1245 genotypic analysis of Mycobacterium avium isolates from patients in Brazil

AbstractObjective: Disseminated Mycobacterium avium infection is an emerging opportunistic disease among patients with acquired immunodeficiency syndrome (AIDS) in Brazil. The mode of transmission of M. avium in a developing country setting needs to be better characterized.Methods: Mycobacterium avium strain collections in São Paulo and Rio de Janeiro were analyzed according to the strains' IS1245 DNA gel electrophoretic migration patterns. Medical records of the patients from whom M. avium isolates were available were reviewed, and their demographic characteristics were stratified according to the isolates' IS1245 DNA fingerprint patterns.Results: Of 105 patients, 33 (31 %) with M. avium isolated between 1990 and 1994 had strains having IS1245 patterns identical in patterns seen in isolates from two or more patients (designated as cluster pattern strains). Cluster pattern strains were isolated from 21 (39%) of 54 patients with disseminated infection (defined as infection due to M. avium isolated from a sterile site in an adult patient). Six of the cluster pattern strains were isolated only from sterile sites. In São Paulo, cluster pattern strains were significantly more likely to be isolated from patients with disseminated disease.Conclusions: These preliminary observations suggest that in large cities of Brazil, a high proportion (at least 39%) of disseminated M. avium infections in patients with AIDS results from a recent transmission. Some strains of M. avium may be more likely to cause disseminated disease than others after an infection

Increase of cd4+cd25highfoxp3+ cells impairs in vitro human microbicidal activity against mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

50204076]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 Stringari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb. Methods We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv). Results The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. Conclusions Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.publishersversionpublishe

Mycobacterium tuberculosis progresses through two phases of latent infection in humans

Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.publishersversionpublishe

Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

11 páginas, 2 figuras, 1 tablaInappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)Peer reviewe

Perfil epidemiológico dos casos de tuberculose multirresistente do Espírito Santo

Estudo retrospectivo de perfil dos casos de TBMR do Espírito Santo, entre 2000 e 2004. Identificou-se 61 pacientes com TBMR, sendo a amostra composta por 57 casos, que tiveram seus prontuários revisados para obtenção das variáveis estudadas. Estimou-se como prevalência para a TBMR combinada 0,87% (0,66 - 1,13; IC95%). O teste anti-HIV foi feito em 78,9% dos casos, sendo 11,1% positivos. Investigando co-morbidades, destacaram-se etilismo e tabagismo. Encontrou-se 11 casos de resistência primária (RI) e 46 de resistência adquirida (RA), com média de 2,3 &plusmn; 1,3 tratamentos anteriores. Em 35,1% dos casos houve relato de contato prévio conhecido com doente de tuberculose, enquanto em 67,9% não houve ou nega-se ter havido. Dez pacientes (17,5%) foram tratados com o esquema de 1ª linha, 18 (31,6%) com o de 2ª linha e 27 (47,4%) com o de 3ª linha. Dezoito (31,6%) tiveram tratamento auto-administrado, e 39 (68,4%) supervisionado. Quanto ao desfecho, houve cura em 33 casos (71,7%), abandono em 7 (15,2%) e óbito em 5 (10,9%), 1 caso de falência e 11 (19,3%) estão em tratamento. Dos 10 casos encerrados de RI, 80% (8/10) foram curados, contra 69,4% (25/36) dos casos de RA. Concluímos que a prevalência de TBMR é baixa no ES. A cura foi alcançada em 70% dos casos. As co-morbidades podem ser importante fator interveniente para um desfecho satisfatório do tratamento. Os resultados enfatizam a necessidade de busca, diagnóstico e realização de TSA para identificação da RI e a supervisão do tratamento de todos os casos de tuberculose