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Background: Although there is consistent evidence that smoking is a risk factor associated with tuberculosis (TB), whether smoking cessation improves treatment outcomes and reduces the risk of TB recurrence remains understudied. Methods: We conducted a prospective cohort study with a seven-year follow-up in China. We recruited newly-diagnosed TB patients and classified them as non-smokers, ex-smokers, and current smokers. Current smokers were invited to participate in a smoking cessation intervention programme. We used a Cox proportional hazards model to assess the risk of death among TB patients and the risk of recurrence among successfully treated patients. Results: In total, 634 (79.2%) patients completed anti-TB treatments and 115 (14.4%) patients died. We confirmed the existence of a dose-response relationship between smoking frequency and the risk of TB recurrence (the slope of the fitted line >0; P < 0.05). Compared to those who continued smoking, the risk of death and recurrent TB for the patients who quit smoking during treatment decreased. The HR of mortality for smokers who smoked 30 or more cigarettes was 2.943 (95% confidence interval (CI) = 1.035-8.368), while the HR of mortality for those who smoked 30 or more cigarettes, but quit during treatment was 2.117 (95% CI = 1.157-3.871). However, the risk of recurrence remained high for ex-smokers who had a smoking history of 25 years or more. Conclusions: Our study provides further evidence supporting the World Health Organization's call for co-management of smoking and other risk factors as part of routine TB treatment.
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Recurrencia , Cese del Hábito de Fumar , Tuberculosis , Humanos , Cese del Hábito de Fumar/estadística & datos numéricos , China/epidemiología , Masculino , Femenino , Estudios Prospectivos , Adulto , Persona de Mediana Edad , Estudios de Seguimiento , Tuberculosis/mortalidad , Tuberculosis/prevención & control , Factores de Riesgo , Antituberculosos/uso terapéutico , Anciano , Fumar/epidemiología , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
This study investigates the incidence of Class B respiratory infectious diseases (RIDs) in China under the Coronavirus disease 2019 (COVID-19) epidemic and examines variations post-epidemic, following the relaxation of non-pharmaceutical interventions (NPIs). Two-stage evaluation was used in our study. In the first stage evaluation, we established counterfactual models for the pre-COVID-19 period to estimate expected incidences of Class B RIDs without the onset of the epidemic. In the second stage evaluation, we constructed seasonal autoregressive integrated moving average intervention (SARIMA-Intervention) models to evaluate the impact on the Class B RIDs after NPIs aimed at COVID-19 pandemic were relaxed. The counterfactual model in the first stage evaluation suggested average annual increases of 10.015%, 78.019%, 70.439%, and 67.799% for tuberculosis, scarlet fever, measles, and pertussis respectively, had the epidemic not occurred. In the second stage evaluation, the total relative reduction in 2023 of tuberculosis, scarlet fever, measles and pertussis were - 35.209%, - 59.184%, - 4.481%, and - 9.943% respectively. The actual incidence declined significantly in the first stage evaluation. However, the results of the second stage evaluation indicated that a rebound occurred in four Class B RIDs after the relaxation of NPIs; all of these showed a negative total relative reduction rate.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/prevención & control , China/epidemiología , Incidencia , SARS-CoV-2/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/transmisión , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/prevención & control , Escarlatina/epidemiología , Tos Ferina/epidemiología , Tos Ferina/prevención & control , Tos Ferina/transmisión , Sarampión/epidemiología , Sarampión/transmisión , Sarampión/prevención & control , Pandemias/prevención & control , Tuberculosis/epidemiología , Tuberculosis/transmisión , Tuberculosis/prevención & controlRESUMEN
Tuberculosis (TB) is caused by infection with the bacterial pathogen Mycobacterium tuberculosis (M.tb) in the respiratory tract. There was an estimated 10.6 million people newly diagnosed with TB, and there were approximately 1.3 million deaths caused by TB in 2022. Although the global prevalence of TB has remained high for decades and is an annual leading cause of death attributed to infectious diseases, only one vaccine, Bacillus Calmette-Guérin (BCG), has been approved so far to prevent/attenuate TB disease. Correlates of protection or immunological mechanisms that are needed to control M.tb remain unknown. The protective role of antibodies after BCG vaccination has also remained largely unclear; however, recent studies have provided evidence for their involvement in protection against disease, as biomarkers for the state of infection, and as potential predictors of outcomes. Interestingly, the antibodies generated post-vaccination with BCG are linked to the activation of innate immune cascades, providing further evidence that antibody effector functions are critical for protection against respiratory pathogens such as M.tb. In this review, we aim to provide current knowledge of antibody application in TB diagnosis, prevention, and treatment. Particularly, this review will focus on 1) The role of antibodies in preventing M.tb infections through preventing Mtb adherence to epithelium, antibody-mediated phagocytosis, and antibody-mediated cellular cytotoxicity; 2) The M.tb-directed antibody response generated after vaccination and how humoral profiles with different glycosylation patterns of these antibodies are linked with protection against the disease state; and 3) How antibody-mediated immunity against M.tb can be further explored as early diagnosis biomarkers and different detection methods to combat the global M.tb burden. Broadening the paradigm of differentiated antibody profiling and antibody-based detection during TB disease progression offers new directions for diagnosis, treatment, and preventative strategies. This approach involves linking the aforementioned humoral responses with the disease state, progression, and clearance.
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Anticuerpos Antibacterianos , Vacuna BCG , Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/inmunología , Anticuerpos Antibacterianos/inmunología , Tuberculosis/inmunología , Tuberculosis/prevención & control , Vacuna BCG/inmunología , Animales , Inmunidad Innata , Vacunación , BiomarcadoresRESUMEN
To systematize published laboratory methods to inactivate Mycobacterium tuberculosis (MTB) and to describe their effectiveness. We carried out a review of the scientific literature to identify the publications that reported methods for the inactivation of MTB, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search addressed inactivation methodologies used in Public health laboratories for the treatment of biological material and only included studies reporting the efficacy of the method. The database used were PubMed (National Library of Medicine) and LILACS (Latin American and Caribbean Literature in Health Sciences). We evaluated the quality of the studies with the JBI (Joanna Briggs Institute) Critical Instrument Appraisal Checklist. We included 14 publications meeting the established inclusion and exclusion criteria. These 14 studies actually described a total of 35 inactivation methods. Most of them combined heat treatment with some chemical or enzymatic agent, and there were very few applying a single strategy. Twenty-four (68.57%) methods demonstrated significant efficacy in inactivating MTB. The systematic review identified 35 methods of inactivation of MTB, published in 14 studies. Most of the methods combined physical treatment techniques, especially heat, with chemical and/or enzymatic treatment techniques, obtaining mostly good results in preventing the reproduction of the microorganism. PROSPERO (International Prospective Register of Ongoing Systematic Reviews) (Code CRD42024503621).
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Mycobacterium tuberculosis , Mycobacterium tuberculosis/efectos de los fármacos , Humanos , Tuberculosis/microbiología , Tuberculosis/prevención & control , Viabilidad Microbiana , Desinfección/métodosRESUMEN
Tuberculosis (TB) is one of the leading causes of death from infectious diseases, killing approximately 1.3 million people worldwide in 2022 alone. The current vaccine for TB contains a live attenuated bacterium, Mycobacterium bovis BCG (Bacille Calmette-Guérin). The BCG vaccine is highly effective in preventing severe forms of childhood TB but does not protect against latent infection or disease in older age groups. A new or improved BCG vaccine for prevention of pulmonary TB is urgently needed. In this study, we infected murine bone marrow derived dendritic cells from C57BL/6 mice with M. bovis BCG followed by elution and identification of BCG-derived MHC class I and class II-bound peptides using tandem mass spectrometry. We identified 1436 MHC-bound peptides of which 94 were derived from BCG. Fifty-five peptides were derived from MHC class I molecules and 39 from class II molecules. We tested the 94 peptides for their immunogenicity using IFN- γ ELISPOT assay with splenocytes purified from BCG immunized mice and 10 showed positive responses. Seven peptides were derived from MHC II and three from MHC class I. In particular, MHC class II binding peptides derived from the mycobacterial surface lipoprotein Mpt83 were highly antigenic. Further evaluations of these immunogenic BCG peptides may identify proteins useful as new TB vaccine candidates.
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Antígenos Bacterianos , Vacuna BCG , Proteínas Bacterianas , Células Dendríticas , Ratones Endogámicos C57BL , Mycobacterium bovis , Animales , Antígenos Bacterianos/inmunología , Mycobacterium bovis/inmunología , Ratones , Vacuna BCG/inmunología , Proteínas Bacterianas/inmunología , Células Dendríticas/inmunología , Desarrollo de Vacunas , Femenino , Proteómica/métodos , Linfocitos T/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Lipoproteínas/inmunología , Tuberculosis/prevención & control , Tuberculosis/inmunología , Péptidos/inmunología , Proteínas de la MembranaRESUMEN
BACKGROUND: Tuberculosis (TB) preventive treatment (TPT) is a long-standing recommendation for children exposed to TB but remains poorly implemented. Home-based contact management may increase access and coverage of TPT among children exposed to TB in their households. METHODS: Sixty in-depth interviews were conducted with key informants including program managers, TB providers (known as TB focal persons), health extension workers and caregivers whose children had recently engaged with TB prevention services in Oromia, Ethiopia in 2021 to understand the barriers and facilitators to providing home-based TB prevention services for children aged < 15 years. Thematic content analysis was conducted including systematically coding each interview. RESULTS: Home-based services were considered a family-centered intervention, addressing the time and financial constraints of clients. Stakeholders proposed a task-shared intervention between health extension workers and facility-based TB focal persons. They recommended that TB services be integrated into other home-based services, including HIV, nutrition, and vaccination services to reduce workload on the already overstretched health extension workers. Community awareness was considered essential to improve acceptability of home-based services and TPT in general among community members. CONCLUSIONS: Decentralization of TPT should be supported by task-sharing initiation and follow up between health extension workers and facility-based TB focal persons and integration of home-based services. Active community engagement through several existing mechanisms can help improve acceptability for both home-based interventions and TPT promotion overall for children. TRIAL REGISTRATION: The results presented here were from formative research related to the CHIP-TB Trial (Identifier NCT04369326) registered on April 30, 2020. This qualitative study was separately registered at NCT04494516 on 27 July 2020.
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Accesibilidad a los Servicios de Salud , Tuberculosis , Humanos , Etiopía , Niño , Tuberculosis/prevención & control , Femenino , Masculino , Adolescente , Preescolar , Investigación Cualitativa , Servicios de Atención de Salud a Domicilio/organización & administración , Entrevistas como Asunto , Lactante , CuidadoresRESUMEN
BACKGROUND: Tuberculosis constitutes a public health problem in Morocco. In an environment where results-based management and the evaluation of public policies become an imperative; the evaluation of the performance of the national tuberculosis control program finds its interest. OBJECTIVES: This study aims to analyze the performance of the tuberculosis control program in the Souss Massa region, based on the systemic approach model over a five-year period 2016-2020. METHODS: This is a descriptive secondary data analysis carried out in the Souss-Massa region in southern Morocco over a five year period 2016-2020. Data collection was carried out through the health information system of the NTCP and the various periodic reports produced by the primary health care establishments and diagnostic centers for tuberculosis and respiratory diseases, the delegations and the regional health directorate of the Ministry of Health. RESULTS: The incidence of tuberculosis has fluctuated between 63 and 72 cases/100,000 inhabitants; the average number of cases detected is 1871 cases per year; the survey completion rate is 57.10%; the therapeutic success rate varies between 82% and 89%, the treatment failure rate varies between 0.62% and 2.32%; the death rate varies between 0.63% and 2.92%; the failure rate for tuberculosis/HIV cases is between 3.10% and 6.09%. CONCLUSIONS: The results of the program tracer indicators at the level of the Souss-Massa region show that the latter combs to achieve the target objectives.
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Tuberculosis , Humanos , Marruecos/epidemiología , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Tuberculosis/diagnóstico , Evaluación de Programas y Proyectos de Salud , Incidencia , Programas Nacionales de Salud/organización & administración , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/diagnóstico , Infecciones por VIH/epidemiologíaRESUMEN
Tuberculosis (TB) is one of the main contributors to global mortality and morbidity. Prevalence of TB is more in developing countries. It is one of the airborne diseases that has always been a major health problem. It is caused by organisms of the Mycobacterium tuberculosis (MTB) complex affecting different organ systems. The proverb prevention is better than cure best applies to TB and it has been practiced from ancient periods. However, modalities of prevention have varied much depending upon the advancement in research and technology. TB preventive practice reduces the load of TB significantly and it was used as the theme for world TB Day for the year 2013. Bacille Calmette-Guérin (BCG) vaccination is one of the modalities to prevent TB and it's been practiced for decades with a lot of modifications from synthesis, schedule and method of administration. BCG mainly prevents serious TB with a less known effect on TB prevention. Other uses of BCG vaccination are being studied. In the modern era, heterologous effects of BCG vaccination have brought BCG once again into the limelight. TB prevention strategies start from basic health education and vaccination. Newer vaccines are under trial to improve the efficacy of TB vaccination and yet to be used for general practice. Prevention and immunization against TB have been modified in immunocompromised children. The concept of drug resistance has to be kept in mind before using anti tubercular drugs without any bacteriological evidence for tuberculosis. National Tuberculosis Elimination Programme (NTEP) focuses on contact tracing and treatment of latent TB infection as a resort to prevent further spread of TB in India. This review article has been authored following an exhaustive examination of the existing literature, with the aim of enhancing comprehension regarding tuberculosis prevention and immunization.
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Vacuna BCG , Tuberculosis , Humanos , Vacuna BCG/uso terapéutico , Niño , Tuberculosis/prevención & control , Tuberculosis/epidemiología , India/epidemiología , VacunaciónRESUMEN
The BCG vaccine, Bacille Calmette Guerin, holds the distinction of being the most widely administered vaccine. Remarkably, a century has passed since its discovery; however, puzzlingly, questions persist regarding the effectiveness of the immune response it triggers. After years of diligent observation, it has been deduced that BCG imparts immunity primarily to a specific age group, namely children. This prompts a significant query: the rationale behind BCG's limited efficacy against TB in particular age groups and populations remains elusive. Beyond vaccinations, drug therapy has emerged as an alternative route for TB prevention. Nonetheless, this approach faces challenges in the contemporary landscape, marked by the emergence of new instances of MDR-TB and XDR-TB, compounded by the financial burden of treatment. It's noteworthy that BCG remains the sole WHO-approved vaccine for TB. This comprehensive review delves into several aspects, encompassing the immune response during infection, the shortcomings of BCG in conferring immunity, and the various factors contributing to its limitations. Within this discourse, we explore potential explanations for the observed deficiencies of the BCG vaccine and consider how these insights could catalyze the development of future vaccines. The current landscape of novel vaccine development for TB is illuminated, including a spotlight on the latest vaccine candidates.
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Vacuna BCG , Vacunas contra la Tuberculosis , Humanos , Vacuna BCG/inmunología , Vacunas contra la Tuberculosis/inmunología , Tuberculosis/prevención & control , Desarrollo de Vacunas , Tuberculosis Resistente a Múltiples Medicamentos/prevención & controlRESUMEN
Key learnings from some landmark studies that the author has been associated with and their implications on program strategies are highlighted. Learnings from prevalence surveys provide justification for active TB Case finding (ACF), role of Chest X-ray screening, justification of the elderly as a key vulnerable population and suggest re-think of the methods of sub-national certification for progress towards tuberculosis free status. Risk of infection studies suggest 14 million people acquiring new tuberculous infection each year in India suggesting a re-think on the targets for TB elimination. Justification is given for 'TB deaths averted' as a parameter for monitoring program impact, reviving risk of infection surveys using CyTB and higher emphasis on careful analysis of routine surveillance data for monitoring epidemiological trends rather than oft-repeated surveys. The modelling outputs suggest higher focus on reducing transmission of infection in urban and reducing treatment delay in rural areas and the need to scale up active case finding and TB preventive treatment in order to achieve End TB targets. Case finding studies justify upfront molecular diagnostics, need to confirm a single sputum result by another specimen or radiology during ACF and futility of X-ray based diagnosis during ACF. High rates of recurrence with intermittent treatment regimen providing evidence in favor of daily regimen, role of family centric approach to nutritional supplementation to prevent TB mortality and reduce TB incidence among household contacts are highlighted besides the need to address high proportion of families suffering catastrophic expenses during pre-treatment period.
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Tuberculosis Pulmonar , Humanos , India/epidemiología , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Tuberculosis/diagnóstico , Prevalencia , Tamizaje Masivo/métodos , IncidenciaRESUMEN
Tuberculosis and Coronaviral disease-19 had a global impact in 2020 and still predominating, both infectious diseases similar to the lethal pandemics spread in one route, likely airborne transmission, the infected person could spread to healthy people. However, tuberculosis slightly varies from COVID-19. Though the primordial disease of the tuberculosis epidemic has had a vast impact on this society, besides the COVID-19 pandemic with other co-morbidities, conditions faced numerous complications. This review exemplified the impact of two lethal diseases in changing patient care, diagnostic issues, and forensic sciences roles. The diagnosis of tuberculosis with a massive concern due to standard testing methods, leading to inaccuracy, sensitivity, and prolonged time consumption. In addition, unavailability of testing kits, equipment failure, over-crowd in hospitals and fewer healthcare workers, a prolonged testing period, and finally, anxiety about COVID-19. Also, the contribution of forensic sciences in the autopsy of the exact cause of infectious diseases is crucial. Likewise, during this pandemic, there has been a drastic reduction in tuberculosis incidence in high-burden countries and a synergistic effect of both diseases. So, this review summarized the overall burden of tuberculosis management during COVID-19 and followed the guidelines of various nations' healthcare authorities to mitigate the consequences of tuberculosis diagnosis and prognosis during the pandemic.
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COVID-19 , Medicina Legal , Tuberculosis , Humanos , COVID-19/epidemiología , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/prevención & control , SARS-CoV-2RESUMEN
Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). While BCG protects against TB in children, its protection against pulmonary TB in adults is suboptimal, and the development of a better TB vaccine is a global health priority. Previously, we reported two recombinant BCG strains effective against murine TB with low virulence and lung pathology in immunocompromised mice and guinea pigs. We have recently combined these two recombinant BCG strains into one novel vaccine candidate (BCGΔBCG1419c::ESAT6-PE25SS) and evaluated its immunogenicity, efficacy and safety profile in mice. This new vaccine candidate is non-inferior to BCG in protection against TB, presents reduced pro-inflammatory immune responses and displays an enhanced safety profile.
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Vacuna BCG , Huésped Inmunocomprometido , Vacunas Sintéticas , Animales , Vacuna BCG/inmunología , Vacuna BCG/efectos adversos , Vacuna BCG/genética , Ratones , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Femenino , Tuberculosis/prevención & control , Tuberculosis/inmunología , Mycobacterium bovis/inmunología , Mycobacterium bovis/genética , Mycobacterium bovis/patogenicidad , Modelos Animales de Enfermedad , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Ratones Endogámicos C57BL , Pulmón/microbiología , Pulmón/patología , Pulmón/inmunología , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Eficacia de las VacunasRESUMEN
BACKGROUND: China has made remarkable achievements in tuberculosis (TB) prevention and control, but it still takes long way to achieve the End TB goal especially in underdeveloped Southwest China. TB healthcare workers (HCWs) are core forces in TB prevention and control but often face job burnout. This study aimed to explore the burden and associated factors of job burnout among TB HCWs in Southwest China. METHODS: This cross-sectional study used both survey questionnaires and semi-structured interviews, to assess job burnout among TB HCWs based on Malasch Model and explore the associated factors based on Herzberg's two-factor theory (different hygiene and motivation factors). Quantitative data analysis adopts multiple linear regression to in SPSS 22.0, and qualitative data were analyzed through a framework approach. RESULTS: A total of 1140 TB HCWs were included in questionnaire surveys. The overall job burnout rates of TB HCWs in Centers for Disease Control and Prevention (CDC), designated hospitals and Primary Health Care (PHC) sectors were 55%, 70.1% and 67.5%, respectively. TB HCWs in CDC who scored lower in interpersonal factors had a higher risk of depersonalization (DP) [B(95%CI): -0.89 (-1.71 to -0.80)]. TB HCWs in designated hospitals who scored lower in doctor-patient relationship factors [B (95%CI): 6.63 (-12.06 to -1.20)] were more likely to have emotional exhaustion (EE). TB HCWs who were less satisfied with training, supervision and assessment in PHC sectors [B(95%CI): 0.65 (0.03 to 1.26)] had less personal accomplishment (PA). Interviews with nine TB HCWs showed that poor environment could lead to high infection and heavy workload could lead to work pressure among TB HCWs in Chongqing. It is also found that performance assessment and management of TB HCWs, communication and cooperation and so on are related to job burnout. CONCLUSIONS: TB HCWs had different levels of job burnout in CDC, designated hospitals, and PHC sectors of Chongqing, which were affected by different hygiene and motivation factors. Governments, organizations and individuals should take cooperative measures such as strengthening communication to deal with job burnout among TB HCWs.
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Agotamiento Profesional , Personal de Salud , Tuberculosis , Humanos , Agotamiento Profesional/psicología , Agotamiento Profesional/epidemiología , Masculino , Estudios Transversales , Femenino , Adulto , China/epidemiología , Personal de Salud/psicología , Encuestas y Cuestionarios , Tuberculosis/psicología , Tuberculosis/prevención & control , Persona de Mediana Edad , Investigación CualitativaRESUMEN
We report here on the characterisation in mice of a noninvasive bacille Calmette-Guérin (BCG) skin challenge model for assessing tuberculosis (TB) vaccine efficacy. Controlled human infection models (CHIMs) are valuable tools for assessing the relevant biological activity of vaccine candidates, with the potential to accelerate TB vaccine development into the clinic. TB infection poses significant constraints on the design of a CHIM using the causative agent Mycobacterium tuberculosis (Mtb). A safer alternative is a challenge model using the attenuated vaccine agent Mycobacterium bovis BCG as a surrogate for Mtb, and intradermal (skin) challenge as an alternative to pulmonary infection. We have developed a unique noninvasive imaging system based on fluorescent reporters (FluorBCG) to quantitatively measure bacterial load over time, thereby determining a relevant biological vaccine effect. We assessed the utility of this model to measure the effectiveness of 2 TB vaccines: the currently licenced BCG and a novel subunit vaccine candidate. To assess the efficacy of the skin challenge model, a nonlinear mixed-effects models was built describing the decline of fluorescence over time. The model-based analysis identified that BCG vaccination reduced the fluorescence readout of both fluorophores compared to unvaccinated mice (p < 0.001). However, vaccination with the novel subunit candidate did not alter the fluorescence decline compared to unvaccinated mice (p > 0.05). BCG-vaccinated mice that showed the reduced fluorescent readout also had a reduced bacterial burden in the lungs when challenged with Mtb. This supports the fluorescence activity in the skin as a reflection of vaccine induced functional pulmonary immune responses. This novel noninvasive approach allows for repeated measurements from the challenge site, providing a dynamic readout of vaccine induced responses over time. This BCG skin challenge model represents an important contribution to the ongoing development of controlled challenge models for TB.
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Vacuna BCG , Modelos Animales de Enfermedad , Mycobacterium tuberculosis , Piel , Animales , Vacuna BCG/inmunología , Ratones , Mycobacterium tuberculosis/inmunología , Femenino , Piel/microbiología , Piel/inmunología , Tuberculosis/prevención & control , Tuberculosis/inmunología , Tuberculosis/microbiología , Eficacia de las Vacunas , Ratones Endogámicos C57BL , Carga Bacteriana , Vacunas contra la Tuberculosis/inmunología , Vacunación/métodos , Mycobacterium bovis/inmunología , HumanosRESUMEN
X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.
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Subunidad gamma Común de Receptores de Interleucina , Tuberculosis , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X , Humanos , Lactante , Masculino , Vacuna BCG/administración & dosificación , Vacuna BCG/efectos adversos , Vacuna BCG/inmunología , Exones , Subunidad gamma Común de Receptores de Interleucina/genética , Mutación , Mycobacterium bovis/inmunología , Mycobacterium bovis/patogenicidad , Tuberculosis/inmunología , Tuberculosis/prevención & control , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/complicaciones , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/diagnóstico , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/inmunologíaRESUMEN
BACKGROUND: In 1993, WHO declared tuberculosis (TB) as a global health emergency considering 10 million people are battling TB, of which 30% are undiagnosed annually. In 2020 the COVID-19 pandemic took an unprecedented toll on health systems in every country. Public health staff already engaged in TB control and numerous other departments were additionally tasked with managing COVID-19, stretching human resource (HR) capacity beyond its limits. As part of an assessment of HR involved in TB control in India, The World Bank Group and partners conducted an analysis of the impact of COVID-19 on TB human resources for health (HRH) workloads, with the objective of describing the extent to which TB-related activities could be fulfilled and hypothesizing on future HR requirements to meet those needs. METHODS: The study team conducted a Workload Indicators and Staffing Needs (WISN) analysis according to standard WHO methodology to classify the workloads of priority cadres directly or indirectly involved in TB control activities as over-, adequately or under-worked, in 18 districts across seven states in India. Data collection was done via telephone interviews, and questions were added regarding the proportion of time dedicated to COVID-19 related tasks. We carried out quantitative analysis to describe the time allocated to COVID-19 which otherwise would have been spent on TB activities. We also conducted key informant interviews (KII) with key TB program staff about HRH planning and task-shifting from TB to COVID-19. RESULTS: Workload data were collected from 377 respondents working in or together with India's Central TB Division (CTD). 73% of all respondents (n = 270) reported carrying out COVID-19 tasks. The average time spent on COVID-19 tasks was 4 h / day (n = 72 respondents). Multiple cadres highly instrumental in TB screening and diagnosis, in particular community outreach (ASHA) workers and CBNAAT/TrueNAAT laboratory technicians working at peripheral, block and district levels, were overworked, and spending more than 50% of their time on COVID-19 tasks, reducing time for TB case-finding. Qualitative interviews with laboratory technicians revealed that PCR machines previously used for TB testing were repurposed for COVID-19 testing. CONCLUSIONS: The devastating impact of COVID-19 on HR capacity to conduct TB case-finding in India, as in other settings, cannot be overstated. Our findings provide clear evidence that NTEP human resources did not have time or essential material resources to carry out TB tasks during the COVID pandemic without doing substantial overtime and/or compromising on TB service delivery. To minimize disruptions to routine health services such as TB amidst future emerging infectious diseases, we would do well, during periods of relative calm and stability, to strategically map out how HRH lab staff, public health resources, such as India's Health and Wellness Centers and public health cadre, and public-private sector collaboration can most optimally absorb shocks to the health system.
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COVID-19 , SARS-CoV-2 , Tuberculosis , Carga de Trabajo , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , India/epidemiología , Tuberculosis/epidemiología , Tuberculosis/terapia , Tuberculosis/prevención & control , Personal de Salud , Fuerza Laboral en Salud/organización & administración , Pandemias/prevención & controlRESUMEN
INTRODUCTION: Food insecurity and undernutrition both contribute to the large tuberculosis burden in India. Indian government rolled out the direct benefit transfer (DBT) programme "Nikshay Poshan Yojana" on a national scale on April 1, 2018 largely to provide nutritional support. Hence, it was proposed to take up this study in Western Maharashtra (Pune district) to study the coverage, delays and implementation challenges of 'Direct Benefit Transfer' in the National Tuberculosis Elimination Programme as there have only been a limited number of studies conducted regarding the same. METHODOLOGY: This mixed methods study was conducted at Tuberculosis Units (TUs) under District Tuberculosis Officer (DTO) in Western Maharashtra (Pune district) for the duration August 2020 to September 2022. A total of 3373 participants were included for the quantitative component. For qualitative component In-depth interviews of key informants (healthcare providers involved in the implementation of Direct Benefit Transfer) and Focus Group Discussion (FGD) for patients and care givers was done and explored using thematic analysis. RESULTS: The total coverage was found to be 76.81%. The health providers reported staff related challenges (overburden and non-cooperative staff), bank related issues (local and cooperate banks not involved in the Public Financial Management System (PFMS) loop and lack of bank account), patient related issues (fear of being scammed), the DBT process (lengthy and complex) and software related issues as major hurdles involved in the scheme's implementation. The challenges to the implementation of DBT reported by the beneficiaries (TB patients) were lack of awareness and disbelief about the scheme, bank related issues (lack of bank account and necessary documents to open account), financial challenges (job insecurity, loans), physical challenges (weakness) and delays in delivering the benefit due to software errors. CONCLUSION: In the present study the DBT coverage was very encouraging. The common challenges identified by the staff members and patients in the implementation of the scheme were lack of awareness about the scheme, bank related issues and software issues. To increase the coverage of DBT, it is vital that these issues be resolved.
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Tuberculosis , Humanos , India/epidemiología , Tuberculosis/prevención & control , Programas Nacionales de Salud , Inseguridad Alimentaria , Femenino , Erradicación de la Enfermedad/métodos , Masculino , Desnutrición/prevención & control , Personal de Salud , Grupos FocalesRESUMEN
BACKGROUND: District-based public private mix (DPPM) tuberculosis in Purwakarta district was strengthened by the MitraTB application. This research is aimed to explore perception of user about MitraTB application and measure their perception of this application in dimensions; design, usefulness, ease of use, and acceptance. METHODS: This study was exploratory sequential mixed methods research. A qualitative study was first conducted in order to gain an in-depth understanding about user's perception of MitraTB application through in-depth interviews. Data were analyzed through coding and categorizing. Based on qualitative finding, a questionnaire was developed and used in the following quantitative study. A cross sectional study was then conducted in quantitative phase. Data were analyzed using Rasch modeling. RESULT: The design of the MitraTB application looks simple and attractive to users. This application is useful to make it easier for private practitioners to report TB cases and it is easy to use. Respondents can accept the MitraTB application well. Most respondents have good perception about MitraTB application in dimensions; design (56.25%), usefulness (69.79%), ease of use (55.20%), and acceptance (73.96%). CONCLUSIONS: MitraTB application has a good design feature, useful, easy to use, and acceptable. This application facilitates the private sector to be involved in the TB program by reporting TB cases. Follow-up and local regulations are required for the continued use of this application.