RESUMEN
BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.
Asunto(s)
COVID-19/terapia , Intervención Médica Temprana/métodos , Tiempo de Tratamiento , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/mortalidad , COVID-19/patología , Chile , Progresión de la Enfermedad , Intervención Médica Temprana/estadística & datos numéricos , Femenino , Mortalidad Hospitalaria , Humanos , Inmunización Pasiva/métodos , Inmunización Pasiva/mortalidad , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Respiración Artificial/mortalidad , Respiración Artificial/estadística & datos numéricos , Tiempo de Tratamiento/normas , Resultado del Tratamiento , Sueroterapia para COVID-19RESUMEN
Tuberculosis (TB) is an infectious disease of extremely high epidemiological burden worldwide that is easily acquired through the inhalation of infected respiratory droplets. The complex pathogenesis of this infection spans from subjects never developing this disease despite intense exposure, to others in which immune containment fails catastrophically and severe or disseminated forms of disease ensue. In recent decades, microRNAs (miRNAs) have gained increasing attention due to their role as gene silencers and because of their altered expression in diverse human diseases, including some infections. Recent research regarding miRNAs and TB has revealed that the expression profile for particular miRNAs clearly changes upon Mycobacterium tuberculosis infection and also varies in the different stages of this disease. However, despite the growing number of studies-some of which have even proposed some miRNAs as potential biomarkers-methodological variations and key differences in relevant factors, such as sex and age, cell type analyzed, M. tuberculosis strain, and antimicrobial therapy status, strongly hinder the comparison of data. In this review, we summarize and discuss the literature and highlight the role of selected miRNAs that have specifically and more consistently been associated with M. tuberculosis infection, together with a discussion of the possible gene and immune regulation pathways involved.
Asunto(s)
MicroARNs/metabolismo , Mycobacterium tuberculosis/fisiología , Tuberculosis/genética , Animales , Biomarcadores/metabolismo , Expresión Génica , Humanos , Tuberculosis Latente/genética , Tuberculosis Latente/inmunología , Macrófagos/inmunología , MicroARNs/genética , Viabilidad Microbiana , Mycobacterium tuberculosis/patogenicidad , Transducción de Señal/inmunología , Tuberculosis/inmunologíaRESUMEN
Mycobacterium tuberculosis (Mtb) has the extraordinary ability to persist for decades within granulomas in the human host. These histopathological structures involved in both protection and pathogenesis, are subject to various influences from the host systemically and through micro-niche environments. Despite the fact that vitamin D (VD) has a key role in macrophage activation and mycobacterial clearance in the early stages of Mtb infection, the overall role of VD in granuloma maintenance or functionality has been scarcely studied. VD deficiency has long time been known to influence on gut microbiota composition, and recent studies have shown that it can also impact on respiratory microbiome. The human microbiota plays an important role in pathogen colonization resistance, and it has been proposed to play a potential role in TB pathogenesis. In this article, we have reviewed current knowledge on the interaction between VD, the lung microbiome and TB, and propose mechanisms by which the tuberculous granuloma's outcome could be modulated by these two factors. The determinants of the final fate of lung granulomas are still unclear, and deciphering the underlying drivers of Mtb infection outcome within those structures is of critical importance.
Asunto(s)
Microbioma Gastrointestinal/fisiología , Granuloma/inmunología , Pulmón/microbiología , Mycobacterium tuberculosis/patogenicidad , Tuberculosis/inmunología , Vitamina D/metabolismo , Disbiosis , Microbioma Gastrointestinal/inmunología , Granuloma/patología , Interacciones Huésped-Patógeno , Humanos , Pulmón/patología , Activación de Macrófagos , Tuberculosis/patología , Vitamina D/inmunología , Deficiencia de Vitamina D/complicacionesRESUMEN
The critical role of commensal microbiota in the human body has been increasingly recognized, and our understanding of its implications in human health and disease has expanded rapidly. The lower respiratory tract contains diverse communities of microbes known as lung microbiota, which are present in healthy individuals and in individuals with respiratory diseases. The dysbiosis of the airway microbiota in pulmonary tuberculosis (TB) may play a role in the pathophysiological processes associated with TB disease. Recent studies of the lung microbiome have pointed out changes in lung microbial communities associated with TB and other lung diseases and have also begun to elucidate the profound effects that antituberculous drug therapy can have on the human lung microbiome composition. In this review, the potential role of the human microbiome in TB pathogenesis and the changes in the human microbiome with Mycobacterium tuberculosis infection and TB therapy are presented and discussed.
Asunto(s)
Antituberculosos/uso terapéutico , Microbiota/efectos de los fármacos , Sistema Respiratorio/microbiología , Tuberculosis/tratamiento farmacológico , Disbiosis , HumanosAsunto(s)
Trazado de Contacto , Tamizaje Masivo/métodos , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Composición Familiar , Salud de la Familia , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Prevalencia , Prueba de Tuberculina , Tuberculosis Pulmonar/microbiología , Adulto JovenAsunto(s)
Vacuna BCG , Tuberculosis/prevención & control , Niño , Chile/epidemiología , Humanos , Tuberculosis/epidemiologíaRESUMEN
Interferon-gamma (IFN-γ) release assays play a pivotal role in tuberculosis infection (TBI) diagnosis, with QuantiFERON-TB Gold Plus-an enzyme-linked immunosorbent assay (ELISA)-among the most widely utilized. Newer QuantiFERON-TB platforms with shorter turnaround times were recently released. We aimed to evaluate these platforms' agreement in the diagnosis of TBI. Blood samples from a prospective cohort of tuberculosis household contacts were collected at baseline and after 12 weeks of follow-up, and tested with LIAISON, an automated chemiluminescence immunoassay (CLIA) system, QIAreach, a lateral flow (QFT-LF) semi-automated immunoassay, and the ELISA QuantiFERON-TB Gold Plus platform. Test concordances were analyzed. ELISA vs CLIA overall agreement was 83.3% for all tested samples (120/144) [Cohen's kappa coefficient (κ): 0.66 (95% CI: 0.54-0.77)]. Samples positive with CLIA provided consistently higher IFN-γ levels than with ELISA (P < 0.001). Twenty-four (16.7%) discordant pairs were obtained, all CLIA-positive/ELISA-negative: 15 (62.5%) had CLIA IFN-γ levels within borderline values (0.35-0.99 IU/mL) and 9 (37.5%) >0.99 IU/mL. QFT-LF showed only 76.4% (68/89) overall agreement with ELISA [κ: 0.53 (95% CI: 0.37-0.68)] with 21 (23.6%) discordant results obtained, all QFT-LF-positive/ELISA-negative. Overall concordance between ELISA and CLIA platforms was substantial, and only moderate between ELISA and QFT-LF. The CLIA platform yielded higher IFN-γ levels than ELISA, leading to an almost 17% higher positivity rate. The techniques do not seem interchangeable, and validation against other gold standards, such as microbiologically-confirmed tuberculosis disease, is required to determine whether these cases represent true new infections or whether CLIA necessitates a higher cutoff. IMPORTANCE: Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.
Asunto(s)
Ensayo de Inmunoadsorción Enzimática , Ensayos de Liberación de Interferón gamma , Interferón gamma , Mycobacterium tuberculosis , Tuberculosis , Humanos , Estudios Prospectivos , Adulto , Mycobacterium tuberculosis/inmunología , Femenino , Masculino , Ensayos de Liberación de Interferón gamma/métodos , Tuberculosis/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Persona de Mediana Edad , Interferón gamma/sangre , Adulto Joven , Composición Familiar , Adolescente , Niño , Anciano , Preescolar , Inmunoensayo/métodosRESUMEN
Intra-amniotic infection with Candida species is an uncommon but severe condition with high fetal morbimortality and no established clinical guidelines for its management. We report a Candida albicans intra-amniotic infection diagnosed in a 25-week pregnant woman, successfully treated with high-dose liposomal amphotericin B. Pregnancy was prolonged until 30 weeks, and despite persistently positive Candida cultures in amniotic fluid, a healthy newborn was delivered without evidence of systemic infection. Amphotericin concentration was determined at birth, revealing levels over 30 times higher in mother's and cord blood than in the amniotic fluid, probably explaining the clinical protection despite failure in obtaining fungal clearance.
RESUMEN
Background: Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative diagnostic test result. Understanding factors associated with clinicians' decisions to initiate treatment for individuals with negative test results is critical for predicting the potential impact of new diagnostics. Methods: We performed a systematic review and individual patient data meta-analysis using studies conducted between January/2010 and December/2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies participants were evaluated based on clinical examination and routinely-used diagnostics, and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy, Xpert MTB/RIF). Findings: Multiple factors were positively associated with treatment initiation: male sex [adjusted Odds Ratio (aOR) 1.61 (1.31-1.95)], history of prior TB [aOR 1.36 (1.06-1.73)], reported cough [aOR 4.62 (3.42-6.27)], reported night sweats [aOR 1.50 (1.21-1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23-2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62-0.96)] compared to smear microscopy and declined in more recent years. Interpretation: Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.
RESUMEN
INTRODUCTION: Vitamin D deficiency has been proposed to confer susceptibility to acquiring tuberculosis infection by impairing the innate immune response. METHODS: In an exploratory study, we examined whether the levels of 25-hydroxyvitamin D3 (25(OH)D3) in serum, and cathelicidin - an antimicrobial peptide-induced under calcitriol - in the nasal fluid, would associate with the risk of acquiring tuberculosis infection. RESULTS: Within a prospective cohort of 231 tuberculosis household contacts tested with repeated interferon-gamma release assays, we serially analyzed all the uninfected contacts acquiring tuberculosis infection at follow-up ("converters", n=18), and an age and sex-matched control group of contacts not acquiring tuberculosis infection ("non-converters", n=36). The median levels of serum 25(OH)D3 did not differ between convertors and non-converters at baseline (14.9 vs. 13.2 ng/ml, p=0.41), nor at follow-up (19.0 vs 18.6ng/ml, p=0.83). Similarly, cathelicidin levels did not differ between both groups. CONCLUSION: These data argue against a major role for hypovitaminosis D in tuberculosis infection susceptibility.
RESUMEN
Introduction: Mucosal immunity is strongly elicited in early stages of many respiratory and enteric infections; however, its role in tuberculosis pathogenesis has been scarcely explored. We aimed to investigate Mycobacterium tuberculosis (Mtb) specific IgA levels in saliva in different stages of latent Tuberculosis Infection (TBI). Methodology: A multiplex bead-based Luminex immunoassay was developed to detect specific IgA against 12 highly immunogenic Mtb antigens. A prospective cohort of household contacts (>14 years) of pulmonary TB cases was established in Santiago, Chile. Contacts were classified as Mtb-infected or not depending on serial interferon-γ release assay results. Saliva samples were collected and tested at baseline and at a 12-week follow-up. Results: Mtb-specific IgA was detectable at all visits in all participants (n = 168), including the "non-Mtb infected" (n = 64). Significantly higher median levels of IgA were found in the "Mtb infected" compared to the uninfected for anti-lipoarabinomannan (LAM) (110 vs. 84.8 arbitrary units (AU), p < 0.001), anti-PstS1 (117 vs. 83 AU, p < 0.001), anti-Cell Membrane Fraction (CMF) (140 vs. 103 AU, p < 0.001) and anti-Culture Filtrate Proteins (CFP) (median 125 vs. 96 AU, p < 0.001), respectively. Nonetheless, the discriminatory performance of these specific mucosal IgA for TBI diagnosis was low. Conclusion: Saliva holds Mtb-specific IgA against several antigens with increased levels for anti-LAM, anti-PstS1, anti-CMF and anti-CFP found in household contacts with an established TBI. The role of these mucosal antibodies in TB pathogenesis, and their kinetics in different stages of Mtb infection merits further exploring.
RESUMEN
The upper respiratory tract is an obliged pathway for respiratory pathogens and a healthy microbiota may support the host's mucosal immunity preventing infection. We analyzed the nasopharyngeal microbiome in tuberculosis household contacts (HHCs) and its association with latent tuberculosis infection (TBI). A prospective cohort of HHCs was established and latent TBI status was assessed by serial interferon-γ release assay (IGRA). Nasopharyngeal swabs collected at baseline were processed for 16S rRNA gene sequencing. The 82 participants included in the analysis were classified as: (a) non-TBI [IGRA negative at baseline and follow-up, no active TB (n = 31)], (b) pre-TBI [IGRA negative at baseline but converted to IGRA positive or developed active TB at follow-up (n = 16)], and (c) TBI [IGRA positive at enrollment (n = 35)]. Predominant phyla were Actinobacteriota, Proteobacteria, Firmicutes and Bacteroidota. TBI group had a lower alpha diversity compared to non-TBI (padj = 0.04) and pre-TBI (padj = 0.04). Only TBI and non-TBI had beta diversity differences (padj = 0.035). Core microbiomes' had unique genera, and genus showed differential abundance among groups. HHCs with established latent TBI showed reduced nasopharyngeal microbial diversity with distinctive taxonomical composition. Whether a pre-existing microbiome feature favors, are a consequence, or protects against Mycobacterium tuberculosis needs further investigation.
Asunto(s)
Tuberculosis Latente , Microbiota , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis Latente/microbiología , Estudios Prospectivos , ARN Ribosómico 16S/genética , Ensayos de Liberación de Interferón gamma , Mycobacterium tuberculosis/genéticaRESUMEN
Introduction: Research activities have a positive impact on the performance of residents. However, information on research conducted by residents from developing countries is scarce. Our study sought to identify the barriers and facilitators for developing research in medical residency programs in a Latin-American faculty of medicine. Methods: A mixed methodology study design was carried out. We used a grounded theory approach for the qualitative phase, collecting data through semi-structured interviews and focus groups with faculty and residents. For the quantitative phase, surveys were administered to residents and teachers. We used factor analysis and scree plot (validity), Cronbach's alpha, and Intraclass correlation coefficient (reliability) to evaluate the surveys' psychometric properties. Results: Focus groups involving ten faculty members and 15 residents were conducted, and the following domains were identified: a) facilitators for resident participation, b) barriers, c) strategies for introducing research into the curriculum, d) arguments supporting research activities throughout medical residency, and e) profile of research-motivated residents. Both residents and faculty members identified a lack of protected time and adequate mentoring as the major barriers. A gender gap was found related to international publications (34% vs. 66% women/men); women perceived that research activities 'compete with other activities' (OR: 2.04, 95% CI 1.03 to 4.07). Conclusions: Research is highly valued by both residents and faculty members at a Latin-American university with a strong academic output. Major barriers to promoting research in this context include lack of protected time and effective mentoring, and gender gaps. Strategies proposed to improve research within medical residency programs include: establishing an interdisciplinary mentoring program between residents and researchers, promoting elective rotations, and rewarding proposals that consider gender equity.
Introducción: Las actividades de investigación tienen un impacto positivo en el rendimiento de los médicos residentes. Falta información sobre investigaciones desarrolladas por residentes de países en vías de desarrollo. Nuestro objetivo fue evaluar las barreras y facilitadores para la investigación en programas de residencia en una Facultad de Medicina de América Latina. Métodos: Se llevó a cabo un diseño de estudio de metodología mixta. Utilizamos un enfoque de teoría fundamentada para la fase cualitativa, recopilando los datos a través de entrevistas semiestructuradas y grupos focales con profesores y residentes. Para la fase cuantitativa, se administraron encuestas a residentes y profesores. Para evaluar las propiedades psicométricas de las encuestas utilizamos análisis factorial y scree plot (validez); alfa de Cronbach y coeficiente de Correlación Intraclase (confiabilidad). Resultados: Se realizaron grupos focales que incluyeron diez profesores y quince residentes, y se identificaron los siguientes dominios: a) facilitadores para la participación de los residentes, b) barreras, c) estrategias para introducir la investigación en el currículo, d) argumentos que respaldan las actividades de investigación durante la residencia, y e) perfil de los residentes motivados en la investigación. Tanto los residentes como el profesorado identificaron la falta de tiempo protegido y la ausencia de tutoría adecuada como las principales barreras. Se encontró una brecha de género relacionada con las publicaciones internacionales (34% vs 66% mujeres/hombres), las mujeres percibieron que las actividades de investigación 'compiten con otras actividades' (OR: 2.04, IC 95% 1.03 a 4.07). Conclusiones: Los residentes y profesores de una universidad latinoamericana de alta productividad valoran mucho la investigación. La presencia de brecha de género, la falta de tiempo protegido y de tutorías destacan como las principales barreras. Las estrategias propuestas para mejorar la investigación dentro de los programas de residencia son: establecer un programa de tutoría interdisciplinario entre residentes e investigadores; promover las rotaciones electivas; y premiar propuestas que consideren la equidad de género.
Asunto(s)
Internado y Residencia , Masculino , Humanos , Femenino , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Curriculum , InvestigaciónRESUMEN
Chile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19-related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Prueba Serológica para COVID-19 , COVID-19 , Mutación Missense , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Sustitución de Aminoácidos , Animales , COVID-19/sangre , COVID-19/genética , Chile , Chlorocebus aethiops , Femenino , Células HEK293 , Humanos , Masculino , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/sangre , Glicoproteína de la Espiga del Coronavirus/genética , Células VeroRESUMEN
We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml-1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml-1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml-1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml-1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml-1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.
Asunto(s)
Trazado de Contacto/métodos , Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/inmunología , Tuberculosis Latente/diagnóstico , Mycobacterium tuberculosis/inmunología , Adulto , Anciano , Antígenos Bacterianos/inmunología , Linfocitos T CD8-positivos/inmunología , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Sensibilidad y Especificidad , Tuberculosis/diagnósticoRESUMEN
BACKGROUND: Mycobacterial diseases are very important both clinically and epidemiologically. Mycobacterium tuberculosis complex (MTBc) infections confer higher morbidity and mortality rate than non-tuberculous mycobacteria (NTM) infections. Traditional species identification techniques are based on phenotypic characteristics which take a long time by laborious processes and in occasions are no conclusive. Currently, most used techniques are based on molecular methods, which are accurate but are expensive and complex. Matrix Assisted Laser Desorption/Ionization Time-of-Flight mass spectrometry (MALDI-TOF MS) is a simple, cheap and fast identification method based on comparing protein spectra with a reference database. AIM: To assess the performance of MALDI-TOF MS in the identification of MTBc and NTM, compared with molecular methods. METHODS: For that purpose, 28 isolates of 9 different species were analyzed through MALDI-TOF MS. RESULTS: 78.5% (22/28) of isolates were correctly identified, 100% (9/9) of rapidly growers NTM, 60% (9/15) of slow growing NTM and 100% (4/4) of MTBc. Every unidentified isolate (6/6) corresponded to M. avium/intracellulare complex. CONCLUSION: MALDI-TOF MS is fast, simple and cheaper than molecular methods and also has adequate accuracy.
Asunto(s)
Mycobacterium , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , TuberculosisRESUMEN
BACKGROUND: A simple blood test for detecting active tuberculosis (TB) could be key to this epidemic containment, given that a large proportion of patients are unable to produce sputum for testing. Currently available interferon-γ release assays (IGRAs) are inadequate to diagnose active TB, with reported pooled sensitivity and specificity both under 81%. OBJECTIVE: To explore whether cytokines/chemokines other than interferon-γ in response to long-term cell stimulation could improve the ability to distinguish between different TB infection status. METHODS: We prospectively enrolled subjects with newly diagnosed pulmonary TB and their household contacts in Santiago. All contacts were tested with IGRA. Peripheral blood mononuclear cells were obtained and antigen-specific stimulated for 72â¯h before collecting their culture supernatants. RESULTS: Subjects with active TB displayed markedly low cytokines/chemokines secretion upon PBMC stimulation, with lower GM-CSF being the best differentiator from IGRA(+) contacts, with 71% (95% CI 53-85) sensitivity, 86% (95% CI 65-97) specificity and AUC = 0.79 (p = 0.0003). On the other hand, when compared to the uninfected IGRA(-) contacts, higher level of IL-2 secretion was the best indicator of active TB, with 73.5% (95% CI 56-87) sensitivity, 85% (95% CI 66-96) specificity and AUCâ¯=â¯0.79 (pâ¯=â¯0.0001). No single cytokine/chemokine released upon stimulation could accurately differentiate between active TB and all TB contacts grouped together. CONCLUSION: GM-CSF and IL-2 provided the best yield to differentiate active TB from latent TB and from TB uninfected, respectively, with higher specificities than that reported for IGRAs. However, none of both resulted sensitive enough to be used as a stand-alone biomarker for active TB.
Asunto(s)
Antígenos Bacterianos/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Pruebas Inmunológicas , Interleucina-2/metabolismo , Tuberculosis Latente/diagnóstico , Leucocitos Mononucleares/metabolismo , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Chile , Trazado de Contacto , Diagnóstico Diferencial , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Interacciones Huésped-Patógeno , Humanos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Ensayos de Liberación de Interferón gamma , Interleucina-2/inmunología , Tuberculosis Latente/inmunología , Tuberculosis Latente/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/microbiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores de Tiempo , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/metabolismo , Adulto JovenRESUMEN
Introducción Las actividades de investigación tienen un impacto positivo en el rendimiento de los médicos residentes. Falta información sobre investigaciones desarrolladas por residentes de países en vías de desarrollo. Nuestro objetivo fue evaluar las barreras y facilitadores para la investigación en programas de residencia en una Facultad de Medicina de América Latina. Métodos Se llevó a cabo un diseño de estudio de metodología mixta. Utilizamos un enfoque de teoría fundamentada para la fase cualitativa, recopilando los datos a través de entrevistas semiestructuradas y grupos focales con profesores y residentes. Para la fase cuantitativa, se administraron encuestas a residentes y profesores. Para evaluar las propiedades psicométricas de las encuestas utilizamos análisis factorial y scree plot (validez); alfa de Cronbach y coeficiente de Correlación Intraclase (confiabilidad). Resultados Se realizaron grupos focales que incluyeron diez profesores y quince residentes, y se identificaron los siguientes dominios: a) facilitadores para la participación de los residentes, b) barreras, c) estrategias para introducir la investigación en el currículo, d) argumentos que respaldan las actividades de investigación durante la residencia, y e) perfil de los residentes motivados en la investigación. Tanto los residentes como el profesorado identificaron la falta de tiempo protegido y la ausencia de tutoría adecuada como las principales barreras. Se encontró una brecha de género relacionada con las publicaciones internacionales (34% vs 66% mujeres/hombres), las mujeres percibieron que las actividades de investigación 'compiten con otras actividades' (OR: 2.04, IC 95% 1.03 a 4.07). Conclusiones Los residentes y profesores de una universidad latinoamericana de alta productividad valoran mucho la investigación. La presencia de brecha de género, la falta de tiempo protegido y de tutorías destacan como las principales barreras. Las estrategias propuestas para mejorar la investigación dentro de los programas de residencia son: establecer un programa de tutoría interdisciplinario entre residentes e investigadores; promover las rotaciones electivas; y premiar propuestas que consideren la equidad de género.
Introduction Research activities have a positive impact on the performance of residents. However, information on research conducted by residents from developing countries is scarce. Our study sought to identify the barriers and facilitators for developing research in medical residency programs in a Latin-American faculty of medicine. Methods A mixed methodology study design was carried out. We used a grounded theory approach for the qualitative phase, collecting data through semi-structured interviews and focus groups with faculty and residents. For the quantitative phase, surveys were administered to residents and teachers. We used factor analysis and scree plot (validity), Cronbach's alpha, and Intraclass correlation coefficient (reliability) to evaluate the surveys' psychometric properties. Results Focus groups involving ten faculty members and 15 residents were conducted, and the following domains were identified: a) facilitators for resident participation, b) barriers, c) strategies for introducing research into the curriculum, d) arguments supporting research activities throughout medical residency, and e) profile of research-motivated residents. Both residents and faculty members identified a lack of protected time and adequate mentoring as the major barriers. A gender gap was found related to international publications (34% vs. 66% women/men); women perceived that research activities 'compete with other activities' (OR: 2.04, 95% CI 1.03 to 4.07). Conclusions Research is highly valued by both residents and faculty members at a Latin-American university with a strong academic output. Major barriers to promoting research in this context include lack of protected time and effective mentoring, and gender gaps. Strategies proposed to improve research within medical residency programs include: establishing an interdisciplinary mentoring program between residents and researchers, promoting elective rotations, and rewarding proposals that consider gender equity.
RESUMEN
INTRODUCCIÓN: El tratamiento de la tuberculosis (TB) ocular es un tema que genera controversia en el mundo. Para el correcto manejo de estos pacientes, es necesario el desarrollo de guías que consideren la epidemiología de la TB ocular en cada nación. El objetivo de este consenso fue discutir de forma interdisciplinaria la epidemiología, fisiopatología, clínica, diagnóstico, estudio y tratamiento de los pacientes con TB ocular, para establecer un algoritmo de tratamiento y proponer qué pacientes deben ser tratados en Chile y con qué tratamiento. Además, se establecieron acuerdos para efectuar quimioprofilaxis de los pacientes con TB latente que tienen indicación de tratamiento inmunosupresor por enfermedades inflamatorias oculares.
The treatment of ocular tuberculosis (TB) remains controversial worldwide. The development of guidelines for ocular TB can facilitate the approach and management of these patients. These guidelines should be developed regionally, considering the local TB epidemiology. The objectives of this consensus are: to initiate an interdisciplinary discussion about the epidemiology, pathophysiology, clinical presentation, diagnosis, workup and treatment of patients with ocular TB, to establish a treatment algorithm and define which patients should be treated in Chile and how and, to analyze and discuss the published data regarding chemoprophylaxis for patients with latent TB who need to start immunosuppressive treatment due to inflammatory ocular conditions.
Asunto(s)
Humanos , Tuberculosis Ocular/diagnóstico , Tuberculosis Ocular/terapia , Tuberculosis Ocular/epidemiología , Fenotipo , Uveítis/diagnóstico , Chile/epidemiología , Escleritis/diagnóstico , Tuberculosis Ocular/fisiopatología , Factores de Riesgo , Quimioprevención , Vasculitis Retiniana/diagnóstico , Consenso , Diagnóstico DiferencialRESUMEN
OBJECTIVES: Vitamin D (VD) enhances the immune response against Mycobacterium tuberculosis in vitro, and VD deficiency has been described in patients with active tuberculosis (TB). However, the role of hypovitaminosis D in the pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate the association of VD deficiency, season of the year, and latent TB infection in household contacts (HHC), given that this is a potentially modifiable condition often related to nutritional deficiencies and lack of sun exposure. METHODS: We prospectively enrolled new pulmonary TB cases (n = 107) and their HHC (n = 144) over a 2-year period in Santiago, Chile. We compared plasma 25-hydroxycholecalciferol (25OHD) levels and examined the influence of season, ethnic background, living conditions, and country of origin. RESULTS: Over 77% of TB cases and 62.6% of HHC had VD deficiency (<20 ng/ml). Median 25OHD concentration was significantly lower in TB cases than in HHC (11.7 vs. 18.2 ng/ml, p<0.0001). Migrants HHC had lower 25OHD levels than non-migrants (14.6 vs. 19.0 ng/ml, p = 0.026), and a trend towards a higher burden of latent TB infection (52.9% vs. 35.2%, p = 0.066). Multivariate analysis found VD deficiency in HHC was strongly associated with being sampled in winter/spring (adOR 25.68, 95%CI 7.35-89.7), corresponding to the seasons with lowest solar radiation exposure. Spring enrollment-compared with other seasons-was the chief risk factor for latent TB infection in HHC (adOR 3.14, 95%CI 1.28-7.69). CONCLUSIONS: Hypovitaminosis D was highly prevalent in TB cases and also in HHC. A marked seasonality was found for both VD levels and latent TB in HHC, with winter being the season with lowest VD levels and spring the season with the highest risk of latent TB infection.