RESUMEN

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.

Asunto(s)

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 , Biomarcadores

RESUMEN

Background: Accurate diagnosis of latent tuberculosis infected (LTBI) individuals is important in identifying individuals at risk of developing active tuberculosis. Current diagnosis of LTBI routinely relies on the detection and measurement of immune responses using the Tuberculin Skin Test (TST) and interferon gamma release assays (IGRAs). However, IGRA, which detects Mycobacterium tuberculosis specific IFN-γ, is associated with frequent indeterminate results, particularly in immunosuppressed patients. There is a need to identify more sensitive LTBI point of care diagnostic biomarkers. The aim of this study was to assess the validity of early secreted antigen target 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) stimulated plasma to identify additional cytokines and chemokines as potential biomarkers of LTBI. Method: The levels of 27 cytokines and chemokines were measured by Bio-Plex Pro cytokine, chemokine and growth factor assay in ESAT-6 and CFP-10 co-stimulated plasma from 20 LTBI participants with positive IGRA (Quantiferon TB Gold plus) and 20 healthy controls with negative IGRA. Traditional ELISA was used to validate the abundance of the best performing markers in 70 LTBI and 72 healthy participants. All participants were HIV negative. Results: We found that Interleukin 1 receptor antagonist (IL1ra) (p = 0.0056), Interleukin 2 (IL-2) (p < 0.0001), Interleukin 13 (IL-13) (p < 0.0001), Interferon gamma-induced protein 10 (IP-10) (p < 0.0001), and Macrophage inflammatory protein-1 beta (MIP1b) (p = 0.0010) were significantly higher in stimulated plasma of LTBI compared to healthy individuals. Stimulated plasma IL-2 (cutoff 100 pg/mL), IP-10 (cutoff 300 pg/mL) and IL-13 (5 pg/mL) showed potential in diagnosing LTBI with PPV = 100%, 0.89.4%, and 80.9% and NPV = 86.9%, 0.85.7%, and 84.2%, respectively. Conclusion: Our data shows that co-stimulating whole blood with ESAT-6 and CFP-10 may help distinguish LTBI from healthy individuals. We also identified IL-2 and IP-10 as potential biomarkers that could be added to the currently used IFN-γ release assays in detection of LTBI.

RESUMEN

BACKGROUND: We evaluated the palatability and acceptability of a 100 mg dispersible and a non-dispersible 250 mg levofloxacin (LVX) tablet formulation in children. METHODS: Perform was a randomised, open-label, cross-over trial of the relative bioavailability of LVX dispersible vs. crushed non-dispersible tablets in children aged <6 years routinely receiving TB preventive treatment. Children and caregivers completed Likert- and ranking-type measures on the acceptability of both formulations. We used summary, comparative and ranking statistics to characterise formulation acceptability. RESULTS: A total of 25 children were enrolled (median age: 2.6 years, IQR 1.6-4.0). Caregivers reported frequent challenges with preventive therapy in routine care prior to study entry, including taste of tablets (n = 14, 56%), vomiting/spitting out medicines (n = 11, 44%), and children refusing medicines (n = 10, 40%). Caregivers reported that the dispersible formulation was easier for their child to take than the non-dispersible formulation (P = 0.0253). Mean ranks for caregiver's formulation preferences (dispersible tablets: 1.48, SD ±0.71; non-dispersible tablets: 2.12, SD ±0.67; routinely available formulations: 2.40 SD ±0.82) differed significantly (Friedman's F 11.120; P < 0.0038); post-hoc testing showed dispersible tablets were preferred over non-dispersible (P = 0.018) and routinely available LVX formulations (P < 0.001). CONCLUSIONS: The dispersible LVX 100 mg tablet formulation was preferred and should be prioritised for integration into routine care.

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CONTEXTE: Nous avons évalué la palatabilité et l'acceptabilité d'un comprimé dispersible de 100 mg et d'un comprimé non dispersible de 250 mg de lévofloxacine (LVX) chez les enfants. MÉTHODES: Perform était un essai randomisé, ouvert et croisé de la biodisponibilité relative des comprimés dispersibles LVX par rapport aux comprimés non dispersibles écrasés chez des enfants âgés de moins de 6 ans recevant régulièrement un traitement préventif contre la TB. Les enfants et les soignants ont rempli des questionnaires de type Likert et de classement sur la tolérance des deux formulations. Nous avons utilisé des statistiques sommaires, comparatives et de classement pour caractériser la tolérance à la formulation. RÉSULTATS: Au total, 25 enfants ont été recrutés (âge médian : 2,6 ans ; IQR 1,6­4,0). Les soignants ont signalé des problèmes fréquents liés au traitement préventif dans le cadre des soins de routine avant le début de l'étude, notamment le goût des comprimés (n = 14, 56%), le fait de vomir ou de recracher les médicaments (n = 11, 44%) et le fait que les enfants refusent les médicaments (n = 10, 40%). Les soignants ont déclaré que la formulation dispersible était plus facile à prendre pour leur enfant que la formulation non dispersible (P = 0,0253). Les classements moyens pour les préférences de formulation des soignants (comprimés dispersibles : 1,48 ; SD ±0,71 ; comprimés non dispersibles : 2,12 ; SD ±0,67 ; formulations couramment disponibles : 2,40 ; SD ±0,82) différaient de manière significative (Friedman's F 11,120 ; P < 0,0038) ; les tests post-hoc ont montré que les comprimés dispersibles étaient préférés aux comprimés non dispersibles (P = 0,018) et aux formulations LVX couramment disponibles (P < 0,001). CONCLUSION: La formulation dispersible des comprimés de LVX 100 mg a été préférée et devrait être intégrée en priorité dans les soins de routine.

RESUMEN

BACKGROUND: The Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases. METHODS: We conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering. RESULTS: Our study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering. CONCLUSION: While the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.

Asunto(s)

Genotipo , Tuberculosis Latente , Mycobacterium tuberculosis , Humanos , Masculino , Mycobacterium tuberculosis/genética , Femenino , Tuberculosis Latente/epidemiología , Tuberculosis Latente/microbiología , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Factores de Riesgo , Adolescente , Análisis por Conglomerados , Anciano , Prevalencia , Tuberculosis/epidemiología , Tuberculosis/microbiología , Niño , Preescolar , Lactante , Florida/epidemiología

RESUMEN

Tuberculous pericardial effusion is uncommon in the developed countries. However, it remains one of the main causes of presentation with a pericardial presentation with pericardial effusion in the developing world. We present the case of a 24-year-old male patient who presented with a weekly history of diarrhoea, vomiting, shortness of breath and feeling hot. Chest computed tomography revealed a large pericardial effusion with significant haemodynamic compromise. The patient underwent emergency pericardiocentesis, and the pericardial fluid interferon-gamma assay result was positive for tuberculosis. He was unable to tolerate endobronchial biopsy under ultrasound despite heavy sedation and was commenced on anti-tuberculous therapy following a discussion in a multidisciplinary team meeting. He was started on four standard anti-tuberculosis medications, including rifampicin, isoniazid, pyrazinamide, ethambutol and prednisolone. The patient had re-accumulation of pericardial fluid on repeat echocardiography in the first few weeks, which eventually resolved with anti-tuberculous therapy.

RESUMEN

Data on alcohol use and incident Tuberculosis (TB) infection are needed. In adults aged 15+ in rural Uganda (N=49,585), estimated risk of incident TB infection was 29.2% with alcohol use vs. 19.2% without (RR: 1.49; 95%CI: 1.40-1.60). There is potential for interventions to interrupt transmission among people who drink alcohol.

RESUMEN

We report that unsuccessful treatment outcomes were 11.8% for tuberculosis (TB) disease and 21.8% for TB infection among persons deprived of liberty in Uganda Prisons Service facilities. Remedial efforts should include enhancing referral networks to ensure treatment continuity, strengthening data systems for complete outcome documentation, and prioritizing short-course treatment regimens.

Asunto(s)

Antituberculosos , Tuberculosis , Humanos , Uganda/epidemiología , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Adulto , Masculino , Femenino , Resultado del Tratamiento , Antituberculosos/uso terapéutico , Adulto Joven , Persona de Mediana Edad , Adolescente , Prisioneros

RESUMEN

Authors present a pilot study of the development of innovative flow cytometry-based assay with a potential for use in tuberculosis diagnostics. Currently available tests do not provide robust discrimination between latent tuberculosis infection (TBI) and tuberculosis disease (TB). The desired application is to distinguish between the two conditions by evaluating the production of a combination of three cytokines: IL-2 (interleukin-2), IFNɣ (interferon gamma) and TNFɑ (tumor necrosis factor alpha) in CD4+ and CD8+ T cells. The study was conducted on 68 participants, divided into two arms according to age (paediatric and adults). Each arm was further split into three categories (non-infection (NI), TBI, TB) based on the immune reaction to Mycobacterium tuberculosis (M.tb) after a close contact with pulmonary TB. Each blood sample was stimulated with specific M.tb antigens present in QuantiFERON tubes (TB1 and TB2). We inferred TBI or TB based on the predominant cytokine response of the CD4+ and/or CD8+ T cells. Significant differences were detected between the NI, TBI and the TB groups in TB1 in the CD4+TNFɑ+parameter in children. Along with IL-2, TNFɑ seems to be the most promising diagnostic marker in both CD4+and CD8+ T cells. However, more detailed analyses on larger cohorts are needed to confirm the observed tendencies.

Asunto(s)

Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Citometría de Flujo , Interferón gamma , Interleucina-2 , Tuberculosis Latente , Mycobacterium tuberculosis , Humanos , Niño , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/inmunología , Tuberculosis Latente/microbiología , Citometría de Flujo/métodos , Adulto , Mycobacterium tuberculosis/inmunología , Linfocitos T CD8-positivos/inmunología , Masculino , Femenino , Linfocitos T CD4-Positivos/inmunología , Interleucina-2/sangre , Proyectos Piloto , Adolescente , Adulto Joven , Persona de Mediana Edad , Interferón gamma/sangre , Interferón gamma/inmunología , Preescolar , Citocinas/sangre , Citocinas/metabolismo , Biomarcadores/sangre , Factor de Necrosis Tumoral alfa/sangre , Diagnóstico Diferencial , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/sangre , Valor Predictivo de las Pruebas , Antígenos Bacterianos/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Anciano

RESUMEN

BACKGROUND: The latent TB infection (LTBI) is an asymptomatic infection caused by Mycobacterium tuberculosis (M.bt). Previous studies have shown a host-protective role for Heme oxygenase-1 (HO-1) during Mtb infection and an important involvement of Glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggested a crucial role for Glutathione in the granulomatous response to M. tb infection, with altered GSH levels associated to decreased host resistance. The aim of this study was to provide additional tools for discriminating the pathologic TB state and the asymptomatic infection. METHODS: We analyzed the gene expression of HO-1 and Gpx4 enzymes in blood of subjects with LTBI, active TB and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with the evaluation of GCL expression, the gene responsible for the GSH de novo synthesis. RESULTS: Our findings highlight a shift of glutathione homeostasis towards a more reducing conditions in LTBI, and a different modulation of GSH-dependent genes and HO-1 expression respect to active TB. CONCLUSION: This study can provide useful tools to understand the redox background that address the infection toward the asymptomatic or active disease.

RESUMEN

Lung underdevelopment is a rare congenital anomaly with variable clinical significance and presenting symptoms. It usually manifests during childhood. We present two cases of developmental lung anomaly subtypes and discuss clinical presentation and outcomes in such patient populations. LEARNING POINTS: Pulmonary underdevelopment is a challenging diagnosis and should be considered in patients with unilateral opacification on chest radiograph.Childhood developmental history is critical for diagnosis as delayed, or misdiagnoses are common. Definitive diagnosis can be made by computed tomography scan.Management is watchful waiting with close monitoring, with long term prognosis remaining unclear.

RESUMEN

BACKGROUND: Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. METHODS: We conducted a prospective multicentric observational study in Catalonia (Spain) from June 2017 to December 2019. We enrolled children aged < 15 years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21 days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8-12 weeks post-return. LTBI was defined as a TST ≥5 mm and/or a positive QFT-Plus. RESULTS: Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU, 95%CI = 8.8-28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3-9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU, 95%CI = 3.9-20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1-13.3). CONCLUSIONS: The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions.

Asunto(s)

Tuberculosis Latente , Prueba de Tuberculina , Humanos , Masculino , España/epidemiología , Estudios Prospectivos , Femenino , Niño , Tuberculosis Latente/epidemiología , Tuberculosis Latente/diagnóstico , Preescolar , Incidencia , Adolescente , Viaje , Factores de Riesgo , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Tuberculosis/diagnóstico , Familia , Amigos , Lactante

RESUMEN

Tuberculosis (TB), an aerosol-transmitted infection caused by Mycobacterium tuberculosis (Mtb), remains the commonest cause of death globally, from an infectious bacterial disease. Nine years on from the launch of the World Health Organization (WHO)'s END-TB strategy, disease incidence rates are stubbornly unchanged [1]. While this represents, in part, a reversal of improving trends caused by the COVID-19 pandemic, it also reflects the fragility and inadequacy of healthcare systems to sustain TB control [2]. Although multifactorial, a key reason for this is the ineffectiveness of existing clinical tools to meet the two key objectives of the END-TB strategy-(i) early diagnosis and treatment of TB disease (to limit onward transmission); and (ii) disease prevention through screening for asymptomatic TB infection (TBI). Meeting both objectives will rely on the development of new biomarkers with high accuracy, but the global nature of the TB problem also requires that new tests are rapid, low cost and can be measured in patients by sampling from universally accessible sites. In this review, we will present the accumulating evidence for circulating Mtb in both TB disease and asymptomatic TBI and discuss the potential utility of novel bacteriophage-based technology for blood-based detection of Mtb.

Asunto(s)

Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Pandemias , Tuberculosis/microbiología

RESUMEN

BACKGROUND: Management of newborns and healthcare workers (HCWs) exposed to congenital tuberculosis (TB) in the neonatal intensive care unit (NICU) has been reported rarely. AIM: To outline a contact investigation process for individuals exposed to congenital TB in the NICU and investigate nosocomial transmission. Additionally, to assess the efficacy and safety of window prophylaxis in exposed newborns. METHODS: A baby, born at a gestational age of 28 + 1 weeks, was diagnosed with isoniazid-resistant congenital TB on the 39th day of admission to the level IV NICU. Newborns and HCWs exposed cumulatively for ≥8 h underwent contact investigation and follow-up for a year. FINDINGS: Eighty-two newborns underwent contact investigation. All newborns displayed normal chest X-rays, and 42 hospitalized newborns tested negative for acid-fast bacilli stain and Xpert® MTB/RIF assay in their endotracheal sputum or gastric juices. Eighty received window prophylaxis: six of 75 on rifampin experienced mild adverse events, and none of the five on levofloxacin. After 12 weeks, five (6.1%) had a positive tuberculin skin test, all of whom had already received the Bacillus Calmette-Guérin vaccine and tested negative on TB interferon-gamma releasing assay. Of 119 exposed HCWs, three (2.5%) were diagnosed with latent TB infection and completed a four-month rifampin therapy. There was no active TB disease among exposed newborns and HCWs during a one-year follow-up. CONCLUSION: Timely diagnosis of congenital TB is crucial for minimizing transmission among exposed neonates and HCWs in the NICU setting. In cases of isoniazid-resistant index patients, even premature newborns may consider the use of rifampin or levofloxacin for window prophylaxis.

Asunto(s)

Antituberculosos , Infección Hospitalaria , Personal de Salud , Unidades de Cuidado Intensivo Neonatal , Isoniazida , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Isoniazida/uso terapéutico , Femenino , Masculino , Antituberculosos/uso terapéutico , Personal de Salud/estadística & datos numéricos , Infección Hospitalaria/prevención & control , Rifampin/uso terapéutico , Adulto , Trazado de Contacto , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control , Tuberculosis/transmisión

RESUMEN

Activin A strongly influences immune responses; yet, few studies have examined its role in infectious diseases. We measured serum activin A levels in two independent tuberculosis (TB) patient cohorts and in patients with pneumonia and sarcoidosis. Serum activin A levels were increased in TB patients compared to healthy controls, including those with positive tuberculin skin tests, and paralleled severity of disease, assessed by X-ray scores. In pneumonia patients, serum activin A levels were also raised, but in sarcoidosis patients, levels were lower. To determine whether blockade of the activin A signaling axis could play a functional role in TB, we harnessed a soluble activin type IIB receptor fused to human IgG1 Fc, ActRIIB-Fc, as a ligand trap in a murine TB model. The administration of ActRIIB-Fc to Mycobacterium tuberculosis-infected mice resulted in decreased bacterial loads and increased numbers of CD4 effector T cells and tissue-resident memory T cells in the lung. Increased frequencies of tissue-resident memory T cells corresponded with downregulated T-bet expression in lung CD4 and CD8 T cells. Altogether, the results suggest a disease-exacerbating role of ActRIIB signaling pathways. Serum activin A may be useful as a biomarker for diagnostic triage of active TB or monitoring of anti-tuberculosis therapy. IMPORTANCE: Tuberculosis remains the leading cause of death by a bacterial pathogen. The etiologic agent of tuberculosis, Mycobacterium tuberculosis, can remain dormant in the infected host for years before causing disease. Significant effort has been made to identify biomarkers that can discriminate between latently infected and actively diseased individuals. We found that serum levels of the cytokine activin A were associated with increased lung pathology and could discriminate between active tuberculosis and tuberculin skin-test-positive healthy controls. Activin A signals through the ActRIIB receptor, which can be blocked by administration of the ligand trap ActRIIB-Fc, a soluble activin type IIB receptor fused to human IgG1 Fc. In a murine model of tuberculosis, we found that ActRIIB-Fc treatment reduced mycobacterial loads. Strikingly, ActRIIB-Fc treatment significantly increased the number of tissue-resident memory T cells. These results suggest a role for ActRIIB signaling pathways in host responses to Mycobacterium tuberculosis and activin A as a biomarker of ongoing disease.

Asunto(s)

Mycobacterium tuberculosis , Neumonía , Sarcoidosis , Tuberculosis , Humanos , Ratones , Animales , Ligandos , Tuberculina , Activinas , Inmunoglobulina G , Biomarcadores

RESUMEN

In Indonesia, the implementation of tuberculosis (TB) contact investigation is limited, with low detection rates. We report the yield of and risk factors for TB disease and infection for household contacts (HHCs) investigated using chest X-ray (CXR) screening. We identified HHCs aged five years and above of bacteriologically confirmed index cases from 2018 to 2022 in Yogyakarta City and Kulon Progo. All HHCs were offered screening for TB symptoms; TB infection testing with either tuberculin skin testing or interferon gamma release assay; and referral for CXR. Sputum from those with symptoms or CXR suggestive of TB was tested with Xpert MTB/RIF. Risk factors for active TB disease and latent TB infection (LTBI) were identified by logistic regression models. We screened 2857 HHCs for TB between June 2020 and December 2022, with 68 (2.4%) diagnosed with active TB. Of 2621 HHCs eligible for LTBI investigation, 1083 (45.7%) were diagnosed with LTBI. The factors associated with active TB were age, being underweight, diabetes mellitus, urban living, and sleeping in the same house as an index case. Factors associated with LTBI were increasing age and male gender. Conclusions: Screening for HHC including CXR and TST/IGRA yielded a moderate prevalence of TB disease and infection.

RESUMEN

BACKGROUND: Tuberculosis in the UK is more prevalent in people with social risk factors- e.g. previous incarceration, homelessness - and in migrants from TB endemic countries. The management of TB infection is part of TB elimination strategies, but is challenging to provide to socially excluded groups and the evidence base for effective interventions is small. METHODS: We evaluated a TB infection screening and treatment programme provided by a peer-led service (Find&Treat) working in inclusion health settings (e.g. homeless hostels) in London. IGRA (interferon-gamma release assay) testing and TB infection treatment were offered to eligible adults using a community-based model. The primary outcome was successful progression through the cascade of care. We also evaluated socio-demographic characteristics associated with a positive IGRA. RESULTS: 42/312 (13.5%) participants had a positive IGRA and no one had evidence of active TB. 35/42 completed a medical evaluation; 22 started treatment, and 17 completed treatment. Having a positive IGRA was associated with previous incarceration and being born outside of the UK. DISCUSSION: Provision of TB infection diagnosis and management to this socially excluded population has several challenges including maintaining people in care and drug-drug interactions. Peer-support workers provided this service safely and effectively with appropriate support. Further work to generate data to inform risks and benefits of treatment for TB infection in this group is needed to facilitate joint decision making.

Asunto(s)

Tuberculosis Latente , Tuberculosis , Adulto , Humanos , Prueba de Tuberculina , Londres/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Ensayos de Liberación de Interferón gamma

RESUMEN

OBJECTIVE: The objective of this study was to assess the incidence of tuberculosis (TB) and find the risk factors of TB patients with a high burden of TB in socioeconomic level, the high level of TB incidence and the great changes of economic and social factors, explore the possible factors, construct scientific and robust prediction model, and analyse whether the task of stopping TB can be accomplished by the expected global deadline. STUDY DESIGN: This was an ecological study. METHODS: Descriptive analysis, spatial and space-time scan, correlation analysis, and regression analysis were carried out, based on cases of TB in Sichuan Province and ecological data from 2006 to 2017, to explore the characters of TB and ecological factors, using the transfer function-noise model to forecast the trend of TB until 2035. RESULTS: Factors affecting the incidence of TB, increasing per capita green area, reporting status of TB among Tibetans and Yi minorities, comprehensive treatment management, total cost of TB per capita for urban residents, proportion of males with high school education, 20 to 20 h of 24-h accumulated precipitation, reducing HIV at the same time as AIDS deaths, the increase in the proportion of males in junior high school education, and the increase in the number of registered TB cases can reduce the incidence of TB. CONCLUSIONS: There was concentration mainly on enhanced control of the environment and society measures, helpful in guiding government planning to control TB. Reinforcement is required to reduce the TB of population aged 15-24 and aged 25-64 in socioeconomic level by 2035.

Asunto(s)

Pueblos del Este de Asia , Factores Socioeconómicos , Tuberculosis , Humanos , Masculino , China/epidemiología , Incidencia , Factores de Riesgo , Tuberculosis/epidemiología

RESUMEN

The yield of contact investigation on relapsed tuberculosis (TB) cases can guide strategies and resource allocation in the TB control programme. We conducted a retrospective cohort study to review the yield of contact investigation in relapsed TB cases and identify factors associated with TB infection (TBI) among close contacts of relapsed TB cases notified between 2018 and 2022 in Singapore. TB infection positivity was higher among contacts of relapsed cases which were culture-positive for Mycobacterium tuberculosis complex compared to those who were only polymerase chain reaction (PCR)-positive (14.8% vs. 12.3%). On multivariate analysis, after adjusting for age and gender of the index, gender, and existing comorbidities of contacts, factors independently associated with TBI were culture and smear positivity of the index (AOR 1.41, 95%CI 1.02-1.94), higher odds with every 10 years of increase in age compared to contacts below aged 30, contacts who were not Singapore residents (AOR 2.09, 95%CI 1.46-2.97), and household contacts (AOR 2.19, 95%CI 1.44-3.34). Although the yield of screening was higher for those who were culture-positive compared to only PCR-positive relapsed cases, contact tracing for only PCR-positive cases may still be important in a country with moderate TB incidence, should resources allow.

Asunto(s)

Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Trazado de Contacto , Estudios Retrospectivos , Singapur/epidemiología , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Tuberculosis Latente/epidemiología

RESUMEN

Some individuals exposed to Mycobacterium tuberculosis develop a latent infection and remain at a lifelong risk of developing tuberculosis (TB) disease, a state called as TB infection (TBI). TB preventive treatment (TPT) aims to treat TBI and prevent progression to active TB in an exposed or infected person. Currently, it is not possible to confirm TBI microbiologically, but can be identified indirectly by means of immune-based tests [Tuberculin skin test (TST), interferon-gamma release assays (IGRAs)]. It is crucial to rule out active TB before initiating TPT. TPT regimens have evolved with time. The most widely used regimen is 6 mo of daily Isoniazid (INH) (6H). Another regime in pipeline for persons >2 y, but not yet widely available, is 3HP (3 mo of weekly Isoniazid and Rifapentine). TPT to contacts of drug resistant TB (DR-TB) patients needs to be tailored depending on the resistance pattern in the index case, and relies on a bacteriological confirmation of the same. Individuals receiving TPT should be closely monitored for emergence of any signs or symptoms suggestive of active TB disease while on TPT.