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1.
Nat Prod Res ; : 1-15, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38832530

RESUMEN

Despite the many advances in drug research, natural products are still being explored as a promising source for discovering new bioactive compounds to treat global diseases such as tuberculosis. However, there is a lack of studies and information about coastal natural products, which thrive in the transitional environment between two different ecosystems and produce unique secondary metabolites. Mangroves, estuaries, and mudflats make up areas for coastal species and have shown promising results in antituberculosis research, some of them are present in hotspot areas. This review focuses on research conducted in coastal environments and explores the reasons why these natural products tend to outperform non-coastal ones against the causative agent of tuberculosis, Mycobacterium tuberculosis.

2.
J Mol Biol ; 436(11): 168577, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38642883

RESUMEN

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.


Asunto(s)
Moléculas de Adhesión Celular , Virus del Dengue , Evolución Molecular , Interacciones Huésped-Patógeno , Receptores de Superficie Celular , Proteínas del Envoltorio Viral , Envoltura Viral , Humanos , Brasil , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/química , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/metabolismo , Interacciones Huésped-Patógeno/genética , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/química , Simulación de Dinámica Molecular , Filogenia , Unión Proteica , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/química , Receptores Virales/metabolismo , Receptores Virales/química , Receptores Virales/genética , Envoltura Viral/metabolismo , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/química
3.
Microbiol Spectr ; 12(6): e0350623, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38651877

RESUMEN

Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of Mycobacterium tuberculosis (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, Mycobacterium abscessus/Mycobacterium chelonae-BiDz, Mycobacterium avium-BiDz, Mycobacterium intracellulare/Mycobacterium chimaera-BiDz, and Mycobacterium kansasii-BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of Mycobacterium tuberculosis and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Micobacterias no Tuberculosas , Reacción en Cadena de la Polimerasa , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/clasificación , Sensibilidad y Especificidad , ARN Ribosómico 16S/genética , Tuberculosis/diagnóstico , Tuberculosis/microbiología , ADN Bacteriano/genética , Técnicas Biosensibles/métodos
4.
Virol J ; 20(1): 286, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049805

RESUMEN

Zika virus (ZIKV) and dengue virus (DENV) share a lot of similarities being both phylogenetically closely related, share the same insect vector passage for reaching the host, affinity for the same carbohydrate receptor domains (CRDs), indicating feasible competition between them on the natural field. Here, we prospected interactions of both envelope proteins with a DC-SIGN, a transmembrane c-type lectine receptor with the most implicated CRD with the Flavivirus infection presents on dendritic cells involved in viruses replication processes into the host, and among rares CRD receptors susceptible to interacting with a broad of subtypes of DENV. Protein-protein docking procedures produced structures for molecular dynamics experiments, suggesting the most energetically favorable complex. The difference found in the deltaG results prompted the experimentation with molecular dynamics. To investigate further specific residues involved with such interactions we produced a decomposition analysis using molecular dynamics of the docked proteins evaluated afterward with the Generalized Born Surface Area method. Solvent-accessible surface area (SASA) analysis for both showed very similar but with a slight reduction for ZIKV_E, which agreed with residues SASA analysis highlighting regions more exposed in the ZIVK protein than in DENV. Despite residues PHE313 is reponsible for most of the interactions with the envelope of these arboviruses, ZIKV interacted with this residue in DC-SIGN with lower energies and using more interactions with not expexted residues GLU241 and ARG386. Taken together these results suggest better competitive interaction of ZIKV with the DC-SIGN receptor, particularly in the CRD portion.


Asunto(s)
Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Humanos , Simulación de Dinámica Molecular
5.
J Infect Dev Ctries ; 17(10): 1373-1386, 2023 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-37956372

RESUMEN

INTRODUCTION: Mycobacterium tuberculosis genotyping has impacted evolutionary studies worldwide. Nonetheless, its application and the knowledge generated depend on the genetic marker evaluated and the detection technologies that have evolved over the years. Here we describe the timeline of main genotypic methods related to M. tuberculosis in Latin America and the main findings obtained. METHODOLOGY: Systematic searches through the PubMed database were performed from 1993 to May 2021. A total of 345 articles met the inclusion criteria and were selected. RESULTS: Spacer oligonucleotide typing (spoligotyping) was the most widely used method in Latin America, with decreasing use in parallel with increasing use of mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) and whole genome sequencing (WGS). Among the countries, Brazil, Mexico, and Argentina had the most publications, and a considerable part of the articles were in collaboration with Latin American or non-Latin American institutions; a small proportion of studies needed partnerships to perform the genotypic methods. The genotypic methods allowed the identification of M. tuberculosis genotypes with greater capacity for clonal expansion and revealed the predominance of the Euro-American lineage in Latin America. There was a notable presence of the Beijing family in Peru and Colombia. CONCLUSIONS: The data obtained demonstrated the importance of expanding collaborative networks of tuberculosis (TB) research groups to countries with low productivity in this area, the commitment of the few Latin American countries to advance TB research, as well as the inestimable value of building a Latin America database, considering ease of population mobility between countries.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , América Latina/epidemiología , Genotipo , Polimorfismo de Longitud del Fragmento de Restricción , Técnicas de Tipificación Bacteriana/métodos , Tuberculosis/epidemiología , Tuberculosis/microbiología , Mycobacterium tuberculosis/genética , Repeticiones de Minisatélite
6.
Perfusion ; : 2676591231164877, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36940319

RESUMEN

INTRODUCTION: Transport on extracorporeal membrane oxygenation (ECMO) is a risky and complex procedure. Although most published data support the feasibility of interhospital transport on ECMO, data concerning intra-facility transportation and frequency and severity of complications during ECMO transport of adult patients are still scarce. The aim of this study was to assess transport arrangements and complications during intra and interhospital ECMO-supported patients transport at a high-volume ECMO center. METHODS: Retrospective single-center descriptive study evaluating the prevalence and severity of complications associated with the transportation of adult patients on ECMO support between 2014 and 2022 in our ECMO center. RESULTS: We performed 393 transfers of patients on ECMO support. Those comprised 206 intra-facility, 147 primary, 39 secondary and one tertiary transports. For primary and tertiary transportations, the average transfer length was 118.6 km (range 2.5-1446) and the mean total transport time was 5 h 40 min. The majority of transportations were made by ambulance (93.2%). Complications occurred in 12.7% of all transports and were more frequent in intra-facility and primary/tertiary transfers. Most complications were patient (46%) and staff related (26%). Risk category two was the most frequent (50%), and only five complications were classified as risk category 1 (10%). No deaths occurred during all patient transport. CONCLUSIONS: Most transports carry minor problems that entail a negligible risk to the patient. When ECMO-supported transport is performed by an experienced team, the severe complications are not related with an increased morbimortality.

7.
Ciênc. Saúde Colet. (Impr.) ; 27(12): 4461-4466, Dec. 2022. tab, graf
Artículo en Portugués | LILACS-Express | LILACS | ID: biblio-1404203

RESUMEN

Resumo A tuberculose (TB) apresenta incidências elevadas em todo o mundo, sendo ainda mais grave em pessoas privadas de liberdade (PPL). Foi avaliada a completude das notificações de TB de PPL no SINAN realizadas por equipes de atenção primária prisional (eAPP) ou por outros estabelecimentos de saúde do RS. Estudo descritivo, transversal, utilizando dados de notificações de PPL feitas no SINAN TB pelas eAPP ou por outros estabelecimentos de saúde, de janeiro de 2014 a novembro de 2018. Foi analisado o percentual de completude das variáveis: sexo, raça/cor, escolaridade, HIV, tipo de entrada, baciloscopia de escarro, cultura do escarro, Aids, tratamento antirretroviral durante o tratamento para a TB, tratamento diretamente observado (TDO), baciloscopia de 6º mês e situação de encerramento. Praticamente 53% dos casos de TB em PPL foram notificados por eAPP, e 47,1% foram notificados por outros estabelecimentos de saúde. Oitenta por cento das variáveis foram classificadas na categoria 4 (75,1% a 100% de completude). No entanto, as variáveis TDO e baciloscopia de 6º mês foram classificadas na categoria 3 (50,1% e 75% de completude). Embora não comprometa a notificação da TB no SINAN, a ausência de dados pode prejudicar a qualidade das informações sobre a doença.


Abstract Tuberculosis (TB) has a high incidence in several countries and is even more severe in prisoners. We evaluated the completeness of prisoners TB notifications in the Notifiable Disease Information System (SINAN) carried out by prison primary care teams (eAPP) or by other health facilities in the state of Rio Grande do Sul (RS). This descriptive cross-sectional study used prisoners data notifications in the SINAN TB by the eAPP or other health facilities from January 2014 to November 2018. We analyzed the percentage of completeness of the variables: gender, ethnicity, schooling, HIV, entry type, sputum smear, sputum culture, AIDS, ART during TB treatment, directly observed treatment (DOT), sixth-month smear, and closure status. Around 52.9% of TB cases in prisoners were reported by eAPP, and other health facilities reported 47.1% of the cases. Eighty percent of the variables were classified in category 4 (75.1% to 100% completeness). However, the DOT and sixth-month smear variables were classified into category 3 (50.1% and 75% completeness). While it does not compromise the notification of TB in the SINAN, the lack of data can impair the quality of information about the disease.

8.
J. Health Biol. Sci. (Online) ; 10(1): 1-5, 01/jan./2022. ilus
Artículo en Inglés | LILACS | ID: biblio-1411474

RESUMEN

Objective: The study aimed to evaluate molecular and immunological methods and to propose a workflow using them for tuberculosis (TB) diagnosis routine. Methods: A cross-sectional retrospective study was performed, including 121 liquid cultures from a TB laboratory located in the extreme south of Brazil. All cultures were positive for Mycobacterium tuberculosis complex (MTBC) by in-house Polymerase Chain Reaction (PCR) using DNA extracted by the CTAB method (PCR-CTAB) for IS6110 detection. These cultures were subjected to faster tests than this one, the immunological MPT64 assay and the PCR using DNA extracted by thermal lysis method (PCR-TL), and these were evaluated for MTBC identification using PCR-CTAB as a reference method. Results: The sensitivity of MPT64 assay and PCR-TL to identify MTBC in positive cultures by PCR-CTAB were 73.6% (89/121) and 98.3% (119/121), respectively. We proposed a workflow based on the use of MPT64 assay in liquid cultures suggestive of MTBC, and in case of a negative result, we suggest the performance of PCR-TL. The PCR-CTAB is suggested only if faster tests are negative. Conclusions: Methods capable of confirming MTBC in cultures should continue to be standardized, tested, and optimized to meet the ideal requirements of simplicity, quickness, and effectiveness. The molecular and immunological methods evaluated have differences in the execution and detection of MTBC in cultures, but they are rapid tools for laboratory TB diagnosi


Objetivos: O estudo objetivou avaliar métodos molecular e imunológico e propor um fluxo de trabalho utilizando-os para a rotina de diagnóstico da tuberculose (TB). Métodos: Foi realizado um estudo transversal retrospectivo, incluindo 121 culturas líquidas de um laboratório de TB localizado no extremo sul do Brasil. Todas as culturas foram positivas para o complexo Mycobacterium tuberculosis (CMTB) por Reação em Cadeia da Polimerase (PCR) in-house para detecção do IS6110, usando DNA extraído pelo método CTAB (PCR-CTAB). Essas culturas foram submetidas a testes mais rápidos que este, o ensaio imunológico MPT64 e a PCR com DNA extraído pelo método de lise térmica (PCR-LT), e estas foram avaliadas para identificação de CMTB usando PCR-CTAB como método de referência. Resultados: A sensibilidade do ensaio MPT64 e da PCR-LT para identificar o CMTB em culturas positivas pela PCRCTAB foi de 73,6% (89/121) e 98,3% (119/121), respectivamente. Propusemos um fluxo de trabalho baseado no uso do ensaio MPT64 em culturas líquidas sugestivas de CMTB e, em caso de resultado negativo, sugerimos a realização de PCR-LT. Sugere-se a PCR-CTAB apenas se os testes mais rápidos forem negativos. Conclusões: Os métodos capazes de confirmar o CMTB em culturas devem continuar sendo padronizados, testados e otimizados para atender aos requisitos ideais de simplicidade, rapidez e eficácia. Os métodos molecular e imunológico avaliados apresentam diferenças na execução e detecção do CMTB em culturas, mas são ferramentas rápidas para o diagnóstico laboratorial da TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , ADN , Reacción en Cadena de la Polimerasa , Pruebas Diagnósticas de Rutina , Cetrimonio , Mycobacterium
9.
Rev Soc Bras Med Trop ; 55: e00602022, 2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36417620

RESUMEN

Tuberculosis (TB) is a serious infectious disease, and its control is considered a challenge, especially among vulnerable populations such as prisoners. The occurrence of TB in prisons is an alarming public health problem in many countries. This integrative review aims to describe the epidemiology of TB and control strategies for this disease in countries with the largest prison populations. Studies have shown that it is essential to know the prevalence of TB in prisons of each country. This is because it can serve as an indication of the need for action in prisons to reduce TB rates, including improving the structure of prison environments, rapidly and accurately diagnosing new cases, identifying drug-resistant strains, and implementing effective and directly observed treatment for TB.


Asunto(s)
Prisioneros , Tuberculosis , Humanos , Prisiones , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Prevalencia , Poblaciones Vulnerables
10.
Cien Saude Colet ; 27(12): 4461-4466, 2022 Dec.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-36383859

RESUMEN

Tuberculosis (TB) has a high incidence in several countries and is even more severe in prisoners. We evaluated the completeness of prisoners TB notifications in the Notifiable Disease Information System (SINAN) carried out by prison primary care teams (eAPP) or by other health facilities in the state of Rio Grande do Sul (RS). This descriptive cross-sectional study used prisoners data notifications in the SINAN TB by the eAPP or other health facilities from January 2014 to November 2018. We analyzed the percentage of completeness of the variables: gender, ethnicity, schooling, HIV, entry type, sputum smear, sputum culture, AIDS, ART during TB treatment, directly observed treatment (DOT), sixth-month smear, and closure status. Around 52.9% of TB cases in prisoners were reported by eAPP, and other health facilities reported 47.1% of the cases. Eighty percent of the variables were classified in category 4 (75.1% to 100% completeness). However, the DOT and sixth-month smear variables were classified into category 3 (50.1% and 75% completeness). While it does not compromise the notification of TB in the SINAN, the lack of data can impair the quality of information about the disease.


A tuberculose (TB) apresenta incidências elevadas em todo o mundo, sendo ainda mais grave em pessoas privadas de liberdade (PPL). Foi avaliada a completude das notificações de TB de PPL no SINAN realizadas por equipes de atenção primária prisional (eAPP) ou por outros estabelecimentos de saúde do RS. Estudo descritivo, transversal, utilizando dados de notificações de PPL feitas no SINAN TB pelas eAPP ou por outros estabelecimentos de saúde, de janeiro de 2014 a novembro de 2018. Foi analisado o percentual de completude das variáveis: sexo, raça/cor, escolaridade, HIV, tipo de entrada, baciloscopia de escarro, cultura do escarro, Aids, tratamento antirretroviral durante o tratamento para a TB, tratamento diretamente observado (TDO), baciloscopia de 6º mês e situação de encerramento. Praticamente 53% dos casos de TB em PPL foram notificados por eAPP, e 47,1% foram notificados por outros estabelecimentos de saúde. Oitenta por cento das variáveis foram classificadas na categoria 4 (75,1% a 100% de completude). No entanto, as variáveis TDO e baciloscopia de 6º mês foram classificadas na categoria 3 (50,1% e 75% de completude). Embora não comprometa a notificação da TB no SINAN, a ausência de dados pode prejudicar a qualidade das informações sobre a doença.


Asunto(s)
Prisioneros , Tuberculosis , Humanos , Brasil/epidemiología , Estudios Transversales , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Sistemas de Información
11.
Pharmaceutics ; 14(10)2022 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-36297456

RESUMEN

Despite a considerable number of new antibiotics under going clinical trials, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The use of lipid nanocarriers provides several advantages such as protection from compound degradation, increased bioavailability, and controlled and targeted drug release. Wheat germ agglutinin (WGA) is known to have its receptors on the alveolar epithelium and increase phagocytosis. The present study aimed to produce nanostructured lipid carriers with novel glycosylated amphiphilic employed to attach WGA on the surface of the nanocarriers to improve intracellular drug delivery. High-pressure homogenization was employed to prepare the lipid nanocarriers. In vitro, high-content analysis and flow cytometry assay was employed to study the increased uptake by macrophages when the nanocarriers were grafted with WGA. A lipid nanocarrier with surface-functionalized WGA protein (~200 nm, PDI > 0.3) was successfully produced and characterized. The system was loaded with a lipophilic model compound (quercetin; QU), demonstrating the ability to encapsulate a high amount of compound and release it in a controlled manner. The nanocarrier surface functionalization with the WGA protein increased the phagocytosis by macrophages. The system proposed here has characteristics to be further explored to treat intracellular pathogens.

12.
Rev Soc Bras Med Trop ; 55: e00522022, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36287468

RESUMEN

BACKGROUND: Tuberculosis is a worldwide public health problem and is more prevalent in specific populations, such as prisoners. The aim of this study was to analyze the epidemiological and operational indicators of tuberculosis in prisoners in a southern region of Brazil. METHODS: This was a descriptive, observational study, utilizing secondary data from the Notifiable Diseases Information System on tuberculosis cases diagnosed in prisoners in the state of Rio Grande do Sul, southern Brazil, from 2014 to 2018. Prisoner data used to calculate incidence were extracted from reports by the National Penitentiary Department. RESULTS: From 2014 to 2018, 3,557 tuberculosis cases were reported in Rio Grande do Sul prisoners. The incidence rate of tuberculosis in prisoners was 1,235/100,000 individuals in 2014 and 1,430/100,000 individuals in 2018. The proportion of new TB cases tested for HIV was high, 83.4% in this period; among those tested, 12.9% were HIV coinfected. The proportion of new cases of pulmonary tuberculosis confirmed by laboratory criteria was 52.6% in this period. In total, 18.4% of new pulmonary tuberculosis cases were initiated on directly observed treatment in this period, and 36.4% of contacts of new cases of pulmonary tuberculosis with laboratory confirmation were examined. Among retreatment pulmonary tuberculosis cases, 82.4% were laboratory-confirmed. CONCLUSIONS: Tuberculosis incidence is increasing on a per-capita and absolute basis in Rio Grande do Sul. Laboratory confirmation, HIV testing, directly observed treatment, and contact investigation rates were all low, indicating the need to improve medical and public health measures for tuberculosis control in prisons.


Asunto(s)
Infecciones por VIH , Prisioneros , Tuberculosis Pulmonar , Tuberculosis , Humanos , Brasil/epidemiología , Prisiones , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología
13.
Tuberculosis (Edinb) ; 136: 102252, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36063660

RESUMEN

Due to several obstacles in treating tuberculosis (TB), the search for new therapeutic alternatives remains a global priority. The nitrogenous heterocyclic compounds are promising in searching for new anti-Mycobacterium tuberculosis molecules, and our previous results highlight the potential of tetrahydropyridines. After exploring the antimycobacterial potential and putative mechanism of action of a tetrahydropyridine derivative (NUNL02), we seek to measure the oxidative stress caused by NUNL02 inside the extracellular replicating M. tuberculosis since it could be the reason for the NUNL02 bactericidal effect against replicating and starved M. tuberculosis; and to evaluate the anti-M. tuberculosis activity of NUNL02 against the intracellular bacillus (even combined with an anti-TB drug) to explore the potential of this tetrahydropyridine as a promising adjuvant for TB therapy. Briefly, we assessed the activity of NUNL02 against the H37Rv strain and evaluated the combination of NUNL02 and rifampicin (RIF), at previously defined subinhibitory concentrations, against intramacrophage M. tuberculosis. NUNL02, in addition to promote the oxidative stress inside the extracellular replicating M. tuberculosis as a possible indirect mechanism of action, also presented bactericidal potential as promising as RIF against intracellular bacilli. Thus, our findings reinforce NUNL02 as a promising scaffold for the development of new options for TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Ganglionar , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Pirrolidinas/farmacología , Rifampin/farmacología
14.
Mem Inst Oswaldo Cruz ; 117: e220031, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35920498

RESUMEN

BACKGROUND: Non-tuberculous mycobacteria (NTMs) cause diseases known as mycobacteriosis and are an important cause of morbidity and mortality. The diagnosis of pulmonary disease caused by NTM is hampered by its clinical similarity with tuberculosis (TB) and by the lack of an accurate and rapid laboratory diagnosis. OBJECTIVES: Detect DNA from NTMs directly from lung samples using real-time polymerase chain reaction (qPCR) for amplification of 16S rRNA. Additionally, DNA sequencing (hsp65 and rpoB genes) was used to identify the species of MNTs. METHODS: A total of 68 sputum samples (54 with suspected NTMs and 14 with TB) from patients treated at a referral hospital were used. FINDINGS: Of these, 27/54 (50%) were qPCR positive for NTMs and 14/14 TB patients (controls) were qPCR negative with an almost perfect concordance (Kappa of 0.93) with the Mycobacterium spp. culture. Sequencing confirmed the presence of NTM in all positive samples. The most common species was Mycobacterium gordonae (33%), followed by Mycobacterium abscessus (26%), Mycobacterium fortuitum (22%), Mycobacterium avium (15%) and Mycobacterium peregrinum (4%). MAIN CONCLUSIONS: The qPCR technique for detecting NTMs targeting 16S rRNA has the potential to detect NTMs and rapidly differentiate from Mycobacterium tuberculosis. However, it is necessary to identify the species to help in the differential diagnosis between disease and contamination, and to guide the choice of the therapeutic scheme.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Tuberculosis , Humanos , Pulmón , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium tuberculosis/genética , Micobacterias no Tuberculosas/genética , ARN Ribosómico 16S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
15.
Rev Soc Bras Med Trop ; 55: e0198, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35976335

RESUMEN

BACKGROUND: Tuberculosis (TB) remains a serious public health problem, with approximately 10 million new cases reported annually. Knowledge about the quantitative evolution of theses and dissertations (T&Ds) examining human TB in Brazil can contribute to generating strategic planning for training professionals in this field and disease control. Therefore, this study highlights the role of T&Ds on TB in national scientific disclosures. METHODS: An integrative review related to TB was performed, including T&Ds produced in Brazil and completed between 2013 and 2019. RESULTS: A total of 559,457 T&Ds were produced, of which 1,342 were associated with TB, accounting for 0.24% of the total number of T&Ds in Brazil. This was evidenced by a predominance of themes such as attention/health care, epidemiology, and TB treatment, and 80.2% of the T&Ds on TB were related to the large areas of health and biological sciences. Only 19.7% of T&Ds were associated with groups of patients considered at risk for TB, and 50.9% were produced in southeastern Brazil. The 1,342 T&Ds on TB were developed in 416 postgraduate programs linked to 121 higher education institutions (HEIs). We highlight that 72.7% of T&Ds on TB were produced in federal HEIs, 27.4% in state HEIs, and 8.5% in private HEIs. CONCLUSIONS: Strategic themes, such as TB control, require public policies that aim to increase the number of doctors and masters with expertise in TB, with geographic uniformity, and in line with the priorities for disease control.


Asunto(s)
Tuberculosis , Brasil/epidemiología , Atención a la Salud , Humanos , Tuberculosis/epidemiología
16.
Rev. epidemiol. controle infecç ; 12(2): 61-68, abr.-jun. 2022. ilus
Artículo en Inglés | LILACS | ID: biblio-1417324

RESUMEN

Background and objectives: to understand the impact of the COVID-19 pandemic on tuberculosis (TB) diagnosis in different settings is essential to guide the establishment of appropriate TB control strategies. This study aimed to assess the influence of COVID-19 pandemic in laboratory diagnosis of TB in patients tested and diagnosed for TB. Methods: a data survey was carried out in the database of laboratories that perform TB diagnosis for the public health system in Rio Grande city (Rio Grande do Sul, Brazil). Results: there was a decrease of 1,368 to 735 (reduction of 46.3%) in the number of patients tested for TB in public diagnostic services in 2019 and 2020, respectively, and a decrease of 197 to 119 (reduction of 39.6%) in the number of new TB cases diagnosed. In contrast, the positivity rate was 14.4% in 2019 and 16.2% in 2020. Moreover, it was observed that the laboratory that performs the diagnostic service for Primary Health Care was the most affected, when compared to Tertiary Health Care. Conclusion: as a consequence of measures to control the spread of SARS-CoV-2, there was a reduction in TB testing and in the detection of new cases, especially in Primary Health Care, where patients with less need for hospitalization are received.(AU)


Justificativa e objetivos: compreender o impacto da pandemia COVID-19 no diagnóstico da tuberculose (TB) em diferentes locais é essencial para orientar o estabelecimento de estratégias adequadas de controle da TB. O objetivo deste estudo foi avaliar a influência da pandemia de COVID-19 no diagnóstico laboratorial de TB, em pacientes testados e diagnosticados com TB. Métodos: foi realizado um levantamento de dados no banco de dados de laboratórios que realizam diagnóstico de TB para o sistema público de saúde na cidade de Rio Grande (Rio Grande do Sul, Brasil). Resultados: houve redução de 1.368 para 735 (redução de 46,3%) no número de pacientes testados para TB nos serviços públicos de diagnóstico em 2019 e 2020, respectivamente, e redução de 197 para 119 (redução de 39,6%) no número de novos casos de TB diagnosticados. Em contrapartida, a taxa de positividade foi de 14,4% em 2019 e 16,2% em 2020. Além disso, observou-se que o laboratório que realiza o serviço de diagnóstico para a Atenção Primária à Saúde foi o mais afetado, quando comparado com a Atenção Terciária à Saúde. Conclusão: como consequência das medidas de controle da disseminação do SARS-CoV-2, houve redução na testagem de TB e na detecção de novos casos, principalmente na atenção primária à saúde, onde são recebidos pacientes com menor necessidade de internação.(AU)


Justificación y objetivos: comprender el impacto de la pandemia Covid-19 en el diagnóstico de tuberculosis (TB) en diferentes lugares es fundamental para orientar el establecimiento de estrategias adecuadas de control de la TB. El objetivo de este estudio fue evaluar la influencia de la pandemia de COVID-19 en el diagnóstico de laboratorio de TB, en términos de pacientes examinados y diagnosticados de TB. Métodos: los datos fueron recolectados de la base de datos de los laboratorios que realizan el diagnóstico de TB para el sistema público de salud en la ciudad de Rio Grande (Rio Grande do Sul, Brasil). Resultados: hubo una reducción de 1.368 a 735 (reducción del 46,3%) en el número de pacientes sometidos a pruebas de TB en los servicios públicos de diagnóstico en 2019 y 2020, respectivamente, y una reducción de 197 a 119 (reducción del 39,6%) en el número de nuevos casos de TB diagnosticados. Por otro lado, la tasa de positividad fue de 14,4% en 2019 y 16,2% en 2020. Además, se observó que el laboratorio que realiza el servicio de diagnóstico para la Atención Primaria de Salud fue el más afectado, en comparación con la Atención Terciaria de Salud. Conclusiones: como consecuencia de las medidas para el control de la propagación del SARS-CoV-2, hubo una reducción en las pruebas de TB y en la detección de nuevos casos, especialmente en la Atención Primaria de Salud, donde se encuentran los pacientes con menor necesidad de hospitalización.(AU)


Asunto(s)
Humanos , Tuberculosis/diagnóstico , COVID-19 , Pandemias , Servicios de Salud
17.
Chem Biodivers ; 19(5): e202100846, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35290725

RESUMEN

Microalgae, due to its rapid growth, low nutritional requirements, and versatility of adaptation to different environmental conditions, has aroused the biotechnological interest, synthesizing novel molecules with antioxidant, anticoagulant, anti-inflammatory, antitumor, and antimicrobial activities. In this sense, we carried out the bioprospection of Chaetoceros muelleri, a marine diatom employed in aquaculture, as a candidate to the development of new drugs for the treatment of bacterial infections. The chemical profile of extracts in different solvents (hexane, chloroform, methylene chloride, ethyl acetate, methanol, and acetone) were analyzed by 1 H-NMR. The hexane extract was the most active against all bacteria species tested, including Mycobacterium tuberculosis, with a minimum inhibitory concentration of 100 µg/ml. Contrarily, the methanol extract was inactive against all tested microorganisms and, in addition, was the only one with IC50 >800 µg/mL, showing no cytotoxicity in VERO cell lines. All other extracts showed antibacterial potential and IC50 values varying between 267.58 and 142.47 µg/ml. The fact that C. muelleri is a microalga easily grown on bioreactors on a large scale may promote its biotechnological use, especially as scaffolds for the development of new compounds against bacterial species of clinical and public health interest.


Asunto(s)
Diatomeas , Antibacterianos/química , Antioxidantes/farmacología , Diatomeas/metabolismo , Hexanos , Metanol/metabolismo , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química
19.
Mem. Inst. Oswaldo Cruz ; 117: e220031, 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1386342

RESUMEN

BACKGROUND Non-tuberculous mycobacteria (NTMs) cause diseases known as mycobacteriosis and are an important cause of morbidity and mortality. The diagnosis of pulmonary disease caused by NTM is hampered by its clinical similarity with tuberculosis (TB) and by the lack of an accurate and rapid laboratory diagnosis. OBJECTIVES Detect DNA from NTMs directly from lung samples using real-time polymerase chain reaction (qPCR) for amplification of 16S rRNA. Additionally, DNA sequencing (hsp65 and rpoB genes) was used to identify the species of MNTs. METHODS A total of 68 sputum samples (54 with suspected NTMs and 14 with TB) from patients treated at a referral hospital were used. FINDINGS Of these, 27/54 (50%) were qPCR positive for NTMs and 14/14 TB patients (controls) were qPCR negative with an almost perfect concordance (Kappa of 0.93) with the Mycobacterium spp. culture. Sequencing confirmed the presence of NTM in all positive samples. The most common species was Mycobacterium gordonae (33%), followed by Mycobacterium abscessus (26%), Mycobacterium fortuitum (22%), Mycobacterium avium (15%) and Mycobacterium peregrinum (4%). MAIN CONCLUSIONS The qPCR technique for detecting NTMs targeting 16S rRNA has the potential to detect NTMs and rapidly differentiate from Mycobacterium tuberculosis. However, it is necessary to identify the species to help in the differential diagnosis between disease and contamination, and to guide the choice of the therapeutic scheme.

20.
Rev. Soc. Bras. Med. Trop ; 55: e0052, 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1406960

RESUMEN

ABSTRACT Background: Tuberculosis is a worldwide public health problem and is more prevalent in specific populations, such as prisoners. The aim of this study was to analyze the epidemiological and operational indicators of tuberculosis in prisoners in a southern region of Brazil. Methods: This was a descriptive, observational study, utilizing secondary data from the Notifiable Diseases Information System on tuberculosis cases diagnosed in prisoners in the state of Rio Grande do Sul, southern Brazil, from 2014 to 2018. Prisoner data used to calculate incidence were extracted from reports by the National Penitentiary Department. Results: From 2014 to 2018, 3,557 tuberculosis cases were reported in Rio Grande do Sul prisoners. The incidence rate of tuberculosis in prisoners was 1,235/100,000 individuals in 2014 and 1,430/100,000 individuals in 2018. The proportion of new TB cases tested for HIV was high, 83.4% in this period; among those tested, 12.9% were HIV coinfected. The proportion of new cases of pulmonary tuberculosis confirmed by laboratory criteria was 52.6% in this period. In total, 18.4% of new pulmonary tuberculosis cases were initiated on directly observed treatment in this period, and 36.4% of contacts of new cases of pulmonary tuberculosis with laboratory confirmation were examined. Among retreatment pulmonary tuberculosis cases, 82.4% were laboratory-confirmed. Conclusions: Tuberculosis incidence is increasing on a per-capita and absolute basis in Rio Grande do Sul. Laboratory confirmation, HIV testing, directly observed treatment, and contact investigation rates were all low, indicating the need to improve medical and public health measures for tuberculosis control in prisons.

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